Veterinary Surgical Oncology [2 ed.] 9781119089124, 9781119090229, 9781119089094, 1119089123, 1119090229, 1119089093

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Table of Contents Cover Title Page Copyright Page Dedication Page List of Contributors Preface Foreword About the Companion Website 1 Principles of Surgical Oncology Preoperative Considerations Surgical Planning Postoperative Considerations References 2 Multi-modal Therapy Introduction Surgery Radiation Therapy Surgery and Radiation Chemotherapy Electrochemotherapy Molecular and Targeted Therapies Complications of Chemotherapy Complications of Radiation Therapy References 3 Interventional Oncology Imaging

Instrumentation and Implants Approaches Nonvascular Interventional Oncology Techniques Vascular Interventional Oncology Techniques References 4 Skin and Subcutaneous Tumors Skin Tumors General Principles General Approach to the Diagnosis and Staging of Skin Tumors Treatment Options for Skin Tumors Mast Cell Tumors Mesenchymal Tumors and Melanoma References 5 Head and Neck Tumors Lymph Node Staging Nasal Planum Tumors Tumors of the Pinna Tumors of the External Ear Canal Tumors of the Middle Ear Salivary Gland Tumors Tumors of the Lip References 6 Oral Tumors Introduction Diagnosis and Clinical Staging General Surgical Considerations Surgical Approach to Tumors of the Mandible Surgical Approach to Tumors of the Maxilla Mandibular and Maxillary Tumors in Dogs

Surgical Approach to Tumors of the Hard Palate Surgical Approach to Tumors of the Tongue Multimodal Management of Oral Tumors Prognosis References 7 Alimentary Tract Esophagus Stomach Liver and Gallbladder Pancreas Small Intestine Colorectal Tumors Perianal Tumors References 8 Respiratory Tract and Thorax Rhinotomy Laryngeal Tumors Thoracotomy Tracheal Tumors Lung Metastasectomy for Sarcomas Thoracic Wall Resection References 9 Cardiovascular System Heart and Heart-Base Tumors Pericardial Tumors Carotid Body Tumors Vascular Oncologic Surgery – Tumor Thrombus Excision References

10 Reproductive System Female Reproductive System Histologic Tumor Types Prognosis Adjuvant Therapy Uterine Tumors Vaginal and Vulvar Tumors Histologic Tumor Types Prognosis Adjuvant Therapy Tumors of the Clitoris Canine Mammary Tumors Feline Mammary Tumors Male Reproductive System Testicular Tumors Prognosis Prostatic Tumors Surgical Techniques and Outcomes Radiation Therapy Histologic Tumor Types and Prognosis Penile Tumors Surgery References 11 Urinary Tract Biopsy Procedures for Urinary Tumors Laparoscopy FNA and Needle Core Biopsy Incisional Biopsy Imaging Techniques

Kidney Bladder Palliative Procedures References 12 Eyelids, Eye, and Orbit Introduction Clinical Workup and Biopsy Principles Imaging Techniques Eyelid Neoplasia V-plasty and Four-sided Excision Advancement Flap Rotational Flap Semicircular Flap Mucocutaneous Subdermal Plexus Flaps (Lip-to-lid) Bucket Handle or Bridge Flap Conjunctival, Nictitans, and Scleral Neoplasia Eye Neoplasia Orbital Neoplasia References 13 Endocrine System Pituitary Tumors Adrenal Tumors Thyroid Tumors: Feline Hyperthyroidism Thyroid Glands: Canine Thyroid Tumors Parathyroid Tumors Cats Endocrine Pancreatic Tumors References 14 Hemolymphatic System

Lymph Nodes Spleen Thymus Tonsils References 15 Nervous System Introduction Clinical Workup Preoperative Imaging Techniques Intracranial and Calvarial Tumors Vertebral and Spinal Cord Tumors Nerve Sheath Tumors References 16 Musculoskeletal Tumors Osteosarcoma Other Musculoskeletal Tumors Metastatic Tumors of Bone Primary BoneTumors of Cats Diagnostic Workup Surgical Principles Limb Amputation Hemipelvectomy Scapulectomy Ulnectomy Limb-sparing Surgery Digit-Metacarpus-Metatarsus Amputation Vertebral Tumors Joint Tumors Muscle Tumors

Adjunctive Therapies References 17 Ethics and Surgical Limits of Surgical Oncology Introduction Surgical Limits References Index End User License Agreement

List of Tables Chapter 1 Table 1.1 Factors affecting the goal of surgery and consequently the dose o... Chapter 2 Table 2.1 Epithelial. Table 2.2 Round cell. Table 2.3 Mesenchymal. Chapter 4 Table 4.1 WHO TNM staging system for tumors in animals. Table 4.2 WHO Clinical staging system for canine mast cell tumors. Table 4.3 Common features of STS (as described by Liptak and Forrest 2013). Table 4.4 TNM staging and grading system for soft tissue sarcomas. Chapter 6 Table 6.1 Clinical staging (TNM) of oral tumors in dogs and cats.

Table 6.2 Suggested analgesic options for oral surgery in cats and dogs. Table 6.3 Summary of common oral tumors in the dog and cat. Chapter 7 Table 7.1 Hepatic lesion characterization relative to normal liver using MR... Table 7.2 Relative weight of individual liver lobes in dogs. Table 7.3 Literature summary of the frequency of morphologic classi ication... Table 7.4 Differential diagnosis for hypoglycemia in dogs. Table 7.5 Reported survival times for dogs with insulinoma treated with sur... Table 7.6 Staging for insulinoma. Chapter 8 Table 8.1 Median Overall Survival (OS) and/or ProgressionFree Interval (PF... Table 8.2 Access to the main thoracic structures for tumor excision. Table 8.3 Percent functional volume of each lung lobe for dogs in the stand... Table 8.4 Clinical stages of primary lung tumors. Table 8.5 Clinical stages adapted from human staging system of primary lung... Chapter 11 Table 11.1 Reported survival times with total cystectomy. Table 11.2 Stent sizes available. Chapter 12 Table 12.1 Third eyelid glandular neoplasms in dogs and cats – data from a ...

Chapter 14 Table 14.1 Tumors involving the canine spleen. Table 14.2 Disorders associated with thymomas in dogs and cats. Table 14.3 Clinical staging of thymoma. Chapter 15 Table 15.1 List of intra-axial and extra-axial nervous system tumors in dog... Table 15.2 Medications and dosing schemes commonly used for neuropathic pai... Chapter 17 Table 17.1 Anatomic structures or organs that can be sacri iced acutely in ...

List of Illustrations Chapter 1 Figure 1.1 Diagram illustrating the different doses of surgery: marginal, wi... Figure 1.2 Diagram showing the extension of tumor into the grossly normal-lo... Figure 1.3 (a) Automated needle core biopsy instrument. (b) The tip of the n... Figure 1.4 Punch biopsy instrument, 8 mm in diameter. Figure 1.5 (a) Jamshidi needle (left) with the two stylets (middle and right... Chapter 2 Figure 2.1 (a) Standard or conventional linear accelerator. Most of the mach...

Figure 2.2 (a) Conventional (i.e. standard) radiation plan for a nasal tumor... Figure 2.3 (a) Anal sac adenocarcinomas treated with adjuvant megavoltage ra... Figure 2.4 (a) focal necrosis on the antebrachium following extravasation of... Figure 2.5 Mix breed canine with an incompletely resected mast cell tumor on... Figure 2.6 Beagle canine with an incompletely resected soft tissue sarcoma o... Figure 2.7 American Staffordshire with an incompletely resected soft tissue ... Figure 2.8 Late radiation therapy side effects. Image (a) shows a dog with a... Chapter 3 Figure 3.1 Interventional oncology instrumentation. From left to right: (a) ... Figure 3.2 Urethral stent placement (neoplastic obstruction). (a) An area of... Figure 3.3 Colorectal stent (neoplastic obstruction). In this dog, a stent w... Chapter 4 Figure 4.1 (a, b) Noncontrast and contrast CT scan imaging of an interscapul... Figure 4.2 (a) Preoperative margins marked on skin with marking pen. (b) En ... Figure 4.3 Surgical en bloc resection of cutaneous tumor with planned recons... Figure 4.4 Range of cutaneous mast cell tumor appearances. (a) Ulcerated gra...

Figure 4.5 Darier’s sign secondary to vasoactive substance release of an MCT... Figure 4.6 Cytological appearance of canine cutaneous MCT showing degranulat... Figure 4.7 Excision of STS at distal medial aspect of the metatarsus using a... Figure 4.8 (a) Wide excision of a feline injection-siteassociated sarcoma. ... Figure 4.9 Radical excision of a feline injection-site-associated sarcoma. (... Chapter 5 Figure 5.1 Squamous cell carcinoma of the nasal planum in a golden retriever... Figure 5.2 Preoperative appearance of a nasal planum SCC in a cat. The deepl... Figure 5.3 The typical appearance of an SCC of the pinna in a cat. Note the ... Figure 5.4 Immediate postoperative appearance following nasal planum resecti... Figure 5.5 Cosmetic appearance six weeks after nasal planum resection in a c... Figure 5.6 Cosmetic appearance following nasal planum resection in a golden ... Figure 5.7 A MCT along the medial border of the helix of the pinna. Incision... Figure 5.8 (a) Pinnectomy in a cat with multifocal head and neck SCC. Note t... Figure 5.9 Immediate postoperative appearance of the reconstructed pinna fol... Figure 5.10 Partial pinnectomy of the affected pinna in Figure 5.3. Minimum ...

Figure 5.11 (a) A 1.7 × 1.9 × 1 cm luid- illed mass on the convex surface o... Figure 5.12 (a) Ceruminous gland adenocarcinoma in the horizontal ear canal ... Figure 5.13 (a) Ceruminous gland cysts affecting the pinna and external ear ... Figure 5.14 (a) Vertical ear canal resection for ceruminous adenoma of the v... Figure 5.15 Traction-avulsion of a nasopharyngeal polyp extending into the e... Figure 5.16 Traction-avulsion of a large nasopharyngeal polyp in a cat. Note... Figure 5.17 (a, b) Salivary adenoma of a minor salivary gland in the lip of ... Figure 5.18 (a) MCT affecting the cheek of a seven-year-old female spayed Be... Figure 5.19 (a) Local recurrence of an SCC on the dorsolateral lip of an 11-... Figure 5.20 (a) A MCT involving the rostral lip of an adult mixed breed dog.... Figure 5.21 (a) A buccal rotation lap was used to repair the lip of a seven... Figure 5.22 Super icial temporal axial pattern lap. (a) A cutaneous istula... Figure 5.23 (a, b) A 3.2 × 1.8 × 1.2 cm squamous cell carcinoma con ined to ... Figure 5.24 (a) Buccal SCC in an 11-year-old male neutered west highland whi... Chapter 6 Figure 6.1 Computed tomography scan of a dog with a zygomatic squamous cell ...

Figure 6.2 Computed tomography scan of a dog with a multilobular osteochondr... Figure 6.3 Sentinel lymph node mapping and biopsy as described by Brissot an... Figure 6.4 Bone tunnels have been drilled into the hard palate to provide a ... Figure 6.5 Anatomy of the mandible. The inferior alveolar artery, vein, and ... Figure 6.6 Anatomy of the mandible showing the muscles of mastication. (a) P... Figure 6.7 Unilateral rostral mandibulectomy. (a) The labial and gingival mu... Figure 6.8 Bilateral rostral mandibulectomy. (a) A malignant melanoma involv... Figure 6.9 Segmental mandibulectomy. (a) The labial and gingival mucosa are ... Figure 6.10 Rim mandibulectomy. (a) The labial and gingival mucosa are incis... Figure 6.11 Subtotal and total hemimandibulectomy. (a) A skin incision may b... Figure 6.12 Ventral approach for segmental mandibulectomy in a dog with a ma... Figure 6.13 Vertical ramus or caudal mandibulectomy. (a) The dotted line rep... Figure 6.14 It is important that a feeding tube be inserted following any ma... Figure 6.15 (a and b) The typical postoperative appearance of a dog followin... Figure 6.16 The typical postoperative appearance of a dog following bilatera...

Figure 6.17 The typical postoperative appearance of a dog following subtotal... Figure 6.18 Reconstruction of a segmental mandibulectomy in a cat with a cus... Figure 6.19 A ranula-like lesion (arrow) in a dog one day following subtotal... Figure 6.20 Dehiscence of the commissure of the lips and rostral end of the ... Figure 6.21 Mandibular drift following subtotal hemimandibulectomy for a man... Figure 6.22 Anatomy of the maxilla and skull. (a and b) A number of maxillec... Figure 6.23 (a) A benign acanthomatous ameloblastoma arising from the period... Figure 6.24 Unilateral rostral maxillectomy. (a) The labial and gingival muc... Figure 6.25 Bilateral rostral maxillectomy. (a) Bilateral rostral maxillecto... Figure 6.26 (a and b) Typical drooped nose cosmetic appearance following bil... Figure 6.27 (a) For the cantilever suture technique, a 3–5 cm skin incision ... Figure 6.28 (a) Bilateral rostral maxillectomy combined with nasal planum re... Figure 6.29 An 18-day postoperative image of a dog with a nasal planum resec... Figure 6.30 Radical maxillectomy. (a and b) The labial and gingival mucosal ... Figure 6.31 (a) Caudal maxillectomy through an intraoral approach is recomme...

Figure 6.32 (a) A caudal maxillectomy through combined approach is recommend... Figure 6.33 Segmental maxillectomy in a dog with a biologically high-grade, ... Figure 6.34 Caudal maxillectomy through a combined approach in a cat with a ... Figure 6.35 (a) The typical appearance of a dog following caudal maxillectom... Figure 6.36 (a) The postoperative appearance of a dog following unilateral r... Figure 6.37 The typical appearance of a dog following bilateral rostral maxi... Figure 6.38 (a–c) The typical postoperative appearance following radical max... Figure 6.39 Dehiscence of the intraoral incision following caudal maxillecto... Figure 6.40 The oronasal istula has been debrided and repaired with a trans... Figure 6.41 A free auricular cartilage autograft for treatment of a central ... Figure 6.42 (a) A caudal midline oronasal istula following segmental maxill... Figure 6.43 Ulceration of the upper lip in a cat following unilateral hemime... Figure 6.44 (a) A melanotic malignant melanoma of the caudal mandible in a d... Figure 6.45 Squamous cell carcinoma can have a variable gross appearance. Ul... Figure 6.46 A ibrosarcoma in the caudal maxilla of a dog. Note the typical ...

Figure 6.47 An acanthomatous ameloblastoma arising from the periodontal liga... Figure 6.48 A peripheral odontogenic ibroma arising from the periodontal li... Figure 6.49 (a) A squamous cell carcinoma arising from the alveolar ridge of... Figure 6.50 An inductive ibroameloblastoma arising from the rostral maxilla... Figure 6.51 An eosinophilic granuloma in a cat. These lesions are non-neopla... Figure 6.52 (a) Full-thickness excision of the hard palate is indicated for ... Figure 6.53 (a) A ibrosarcoma on the free portion of the tongue of a dog ha... Figure 6.54 (a) A primary glossal soft tissue sarcoma in a dog; (b) The soft... Figure 6.55 (a and b). The tumor is removed with a wedge of the tongue. The ... Figure 6.56 (a) A benign extramedullary plasmacytoma of the tongue in a dog;... Figure 6.57 (a and b) A full-thickness incision is made transversely across ... Figure 6.58 (a) A full-thickness longitudinal incision is made along the mid... Figure 6.59 (a) A benign extramedullary plasmacytoma of the tongue in a dog;... Chapter 7 Figure 7.1 (a) Lateral and (b) ventrodorsal radiograph of a dog with an esop... Figure 7.2 CT of an esophageal tumor located in the region of the cardia....

Figure 7.3 Esophagoscopy of a carcinoma diagnosed by endoscopic-assisted bio... Figure 7.4 Endoscopic view of an esophageal leiomyosarcoma. Figure 7.5 An abdominal approach has been used for a leiomyoma involving the... Figure 7.6 (a) Resection and anastomosis of an esophageal leiomyoma depicted... Figure 7.7 Precontrast helical CT image of a dog with a midbody gastric neop... Figure 7.8 (a) Intraoperative image of the initial dissection for a gastric ... Figure 7.9 Postcontrast helical CT image of a dog with a multilobular, cavit... Figure 7.10 (a) Illustration demonstrating the guillotine technique for proc... Figure 7.11 (a, b) Intraoperative image of TA-90 linear stapling device used... Figure 7.12 Postoperative image of a central division liver lobectomy after ... Figure 7.13 Picture of inside of the vena cava seen from the right side. The... Figure 7.14 Schematic representation of canine hepatic venous system. The gr... Figure 7.15 (a, b) Postoperative image of canine (a) and feline (b) HCC, bot... Figure 7.16 (a, b) Postmortem images of a cat with a massive cystadenoma ori... Figure 7.17 Intraoperative image of a cat with bile duct carcinoma and secon... Figure 7.18 Anatomy of the canine pancreatic duct system and vascular system...

Figure 7.19 Enucleation of a pancreatic mass (insulinoma) using blunt dissec... Figure 7.20 (a) Insulinoma within the body of the pancreas (black arrow) and... Figure 7.21 (a) Intraoperative image of a dog undergoing a functional end-to... Figure 7.22 Phases of FNA of enlarged sublumbar lymph nodes. (a) After the l... Figure 7.23 The rectal mass is exposed by traction on four stay sutures appl... Figure 7.24 Endoscopic view of (a) a rectal leiomyosarcoma (the same as in F... Figure 7.25 (a) Megacolon caused a colorectal adenocarcinoma in a dog; (b) b... Figure 7.26 (a) Intraoperative view of an in iltrative colorectal adenocarci... Figure 7.27 (a) Intraoperative view of a small cecal gastrointestinal stroma... Figure 7.28 (a) Colocolonic end-to-end anastomosis obtained in a dog using a... Figure 7.29 Pull-out procedure. (a) Application of a stay suture 1–2 cm cran... Figure 7.30 Endoscopic polypectomy. The polypectomy snare is opened and the ... Figure 7.31 Following pull-out (on the left) and exteriorization of a relati... Figure 7.32 Pull-out (prolapse) and stapling procedure. (a) The rectum has b... Figure 7.33 Transanal pull-through procedure. (a) Eversion of the rectum by ...

Figure 7.34 a) and (b) CT scan appearance of a leiomyoma dorsal to the rectu... Figure 7.35 a) Blunt undermining of a leiomyoma in a dog through a dorsal ap... Figure 7.36 Rectal pull-through procedure. (a) Circumferential skin incision... Figure 7.37 Rectal pull-through procedure for a rectal adenocarcinoma 2 cm f... Figure 7.38 Green line shows site of osteotomy for symphyseal separation. Re... Figure 7.39 Both the pubis and ischium are spread apart with a Finocchietto ... Figure 7.40 The phases of the osteotomy of both the pubis and ischium to rem... Figure 7.41 Reconstruction following pelvic osteotomy and colorectal resecti... Figure 7.42 (Same case as Figure 7.23; see also Figures 7.26d and 7.49.) (a)... Figure 7.43 Illustration of Swenson's pull-through (a) an intraabdominal ap... Figure 7.44 (See also Figure 7.26) (a) Enlarged metastatic sublumbar lymph n... Figure 7.45 (a) The clinical appearance of the perianal/perineal region in a... Figure 7.46 Balloon dilation in a small dog that developed a stricture follo... Figure 7.47 In this case, the pull-through procedure was performed for an in... Figure 7.48 (a) The clinical appearance of a prolapsed rectal mast cell tumo...

Figure 7.49 Phases of colorectal resection for a colorectal adenocarcinoma i... Figure 7.50 Three different clinical presentations of canine hepatoid adenom... Figure 7.51 (a and b) Two different presentations of canine perianal adenoca... Figure 7.52 Hepatoid perianal adenocarcinoma in an 11-yearold male German s... Figure 7.53 (a) Right anal sac adenocarcinoma in a dog, and (b) in a cat.... Figure 7.54 Lateral abdominal radiograph which shows an enlargement of the s... Figure 7.55 Multiple lung metastases from an anal sac adenocarcinoma in a do... Figure 7.56 The CT appearance of an extensive iliac internal lymphoadenopath... Figure 7.57 (a) CT scan of a large sublumbar lymph node that caused a signif... Figure 7.58 (a) CT scan of a large medial iliac lymph node secondary to a pe... Figure 7.59 (a–d) Marginal excision of a large perianal adenoma. Figure 7.60 (a) Multiple perianal adenomas. (b) Postoperative view after mar... Figure 7.61 Phases of anoplasty. (a) The anal region, together with both ana... Figure 7.62 Phases of the excision of a perianal soft tissue sarcoma in a do... Figure 7.63 (a) The clinical appearance of an anal carcinoma causing fecal o...

Figure 7.64 (a) The clinical presentation of a recurrent perianal adenocarci... Figure 7.65 Advancement lap in a rectocutaneous plasty. These laps have th... Figure 7.66 (a) Marginal excision of an anal sac adenocarcinoma in a dog. (b... Figure 7.67 Clinical (a) and CT view (b) of a large anal sac adenocarcinoma ... Figure 7.68 Wide excision of an anal sac adenocarcinoma in a cat. (a) The ar... Figure 7.69 Macroscopic view of several sublumbar lymph nodes after excision... Figure 7.70 (a) Intraoperative appearance of an enlarged medial iliac node i... Figure 7.71 The region of both the medial iliac (on the lateral aspect of th... Figure 7.72 (a) This male German shepherd dog experienced a wound dehiscence... Figure 7.73 (a) Anoplasty; (b) following a partial dehiscence, healing has o... Figure 7.74 Incontinent dog two years after surgery. Figure 7.75 Anoplasty in a German shepherd dog 10 days after surgery. In thi... Figure 7.76 This dog has been operated several times for bilateral perineal ... Figure 7.77 (a) Ulcerated hepatoid adenoma of the “tail gland” in a dog. The... Figure 7.78 The clinical appearance of a preputial hepatoid adenoma at the l... Figure 7.79 Perianal adenoma in a spayed bitch. This followed a similar exci...

Figure 7.80 Ventral vertebral changes caused by an adjacent metastatic sublu... Figure 7.81 Humeral metastasis secondary to an anal sac adenocarcinoma in a ... Figure 7.82 Squamous cell carcinoma of the anal region in two different Germ... Figure 7.83 The clinical (a) and post-excisional (b) appearance of a melanom... Figure 7.84 Lymphoma of the anal region in a seven-year-old female mongrel d... Figure 7.85 Large hemangioma located between the anus and the tail base in a... Figure 7.86 (a) The clinical appearance of an ventrally located plasma cell ... Figure 7.87 (a) The clinical appearance of a large soft tissue sarcoma invol... Chapter 8 Figure 8.1 (a) Gross appearance of a cat with a nasal tumor. (b) Gross appea... Figure 8.2 Nasal biopsy with cannula. (a) The dog is positioned in sternal r... Figure 8.3 (a) Rostrocaudal view of the frontal sinuses in a dog. A radioden... Figure 8.4 Contrast-enhanced CT imaging of the nasal cavity. (a) Some hyperd... Figure 8.5 Endoscopic view of nasal masses in dog. This imaging technique pe... Figure 8.6 Dorsal rhinotomy. (a) Dorsal view of the canine skull. Osteotomie... Figure 8.7 Ventral rhinotomy in a dog. (a) Ventral view of the canine skull....

Figure 8.8 Ventral rhinotomy in a cat. The procedure is similar to that desc... Figure 8.9 Temporary carotid artery occlusion in a dog. After a blunt dissec... Figure 8.10 Intraoperative view demonstrating the Rumel tourniquet placed ar... Figure 8.11 (a) Positioning of a dog undergoing adjuvant unilateral dorsal r... Figure 8.12 Flow chart of the decision-making process for the diagnosis and ... Figure 8.13 Endoscopic image of an arytenoid chondrosarcoma in a nine-year-o... Figure 8.14 Oral examination of a dog with a laryngeal rhabdomyosarcoma. Figure 8.15 Lateral radiograph of a dog with a laryngeal rhabdomyosarcoma.... Figure 8.16 CT examination of a dog with a laryngeal rhabdomyosarcoma. Figure 8.17 CT reconstruction of a dog with laryngeal chondrosarcoma. From t... Figure 8.18 Ten-year-old malamute with a grade II mast cell tumor of the ary... Figure 8.19 Images from a dog with ibrosarcoma of the epiglottis. (a) Oral ... Figure 8.20 Total laryngectomy specimen from a Sheltie with a laryngeal squa... Figure 8.21 Laryngeal chondrosarcoma in a 10-year-old dog. The trachea dista... Figure 8.22 Same dog as in Figure 8.21. En bloc resection of the larynx incl...

Figure 8.23 Photograph of a Sheltie seven days after surgery with a laryngea... Figure 8.24 Chest radiographs. (a) Ventrodorsal view of a dog with an intrat... Figure 8.25 CT images of a canine thorax. (a) Contrastenhanced CT is a more... Figure 8.26 Intercostal thoracotomy. (a) An incision in the skin, subcutaneo... Figure 8.27 (a) The thoracic drain is applied by making a stab incision two ... Figure 8.28 Median sternotomy. (a) The skin and subcutaneous tissues are inc... Figure 8.29 (a) The closure of the sternum is achieved by preplacing some i... Figure 8.30 Figure-of-eight suture pattern for sternotomy closure. The wires... Figure 8.31 Lateral radiograph of a dog with a tracheal chondrosarcoma. Figure 8.32 (a, b) CT scan of a dog with a tracheal chondrosarcoma. (c) Reco... Figure 8.33 (a) Intraoperative photograph of a cat with a tracheal squamous ... Figure 8.34 (a) Intraoperative photograph of a dog with a tracheal chondrosa... Figure 8.35 Surgical approach to the bronchus (between the two forceps) by l... Figure 8.36 Bronchial mass has been resected, and an anastomosis of the bron... Figure 8.37 A postoperative neck lexion harness is being used to prevent ne...

Figure 8.38 (a) Preoperative radiograph of a tracheal carcinoma causing trac... Figure 8.39 Anatomy of the canine lungs. Figure 8.40 Postoperative view of lung cancer. Note the presence of necrotic... Figure 8.41 Thoracic radiographs taken in (a) right lateral, (b) left latera... Figure 8.42 (a) Right lateral and (b) left lateral (projections of the thora... Figure 8.43 Intraoperative view of an enlarged tracheobronchial lymph node.... Figure 8.44 Partial lung lobectomy (a). A pair of crushing forceps are place... Figure 8.45 Operative view of partial lung lobectomy. The affected lobe is g... Figure 8.46 Postoperative thoracic radiograph to evaluate pneumothorax and t... Figure 8.47 Operative view of a partial lung lobectomy performed with surgic... Figure 8.48 Hand suture technique for lung lobectomy. (a) Ligation of the ve... Figure 8.49 Intraoperative view of complete lung lobectomy performed with st... Figure 8.50 Postoperative view of the left lung after pneumonectomy. Figure 8.51 Thoracoscopic view of (a) a total lung lobectomy in a cat before... Figure 8.52 Biopsy samples are obtained through a keyhole procedure via thor... Figure 8.53 11-year-old domestic shorthair cat affected by digit lung syndro...

Figure 8.54 (a) Lateral thoracic projection of an 11-year-old mixed dog with... Figure 8.55 (a) A ventrodorsal projection radiograph of a dog with a rib cho... Figure 8.56 Postcontrast transverse CT of anosteosarcoma involving the ifth... Figure 8.57 Resection of a subcutaneous hemangiosarcoma. In this case, skin ... Figure 8.58 The previous biopsy tract is removed with the resection; however... Figure 8.59 Intraoperative photograph of a dog with a rib chondrosarcoma. Th... Figure 8.60 Intraoperative photograph of a dog with a rib chondrosarcoma aft... Figure 8.61 Adhesion between a lung lobe and the rib tumor. A TA stapler is ... Figure 8.62 Intraoperative photograph of mesh that is used to reconstruct a ... Figure 8.63 Intraoperative photograph of a dog with a rib chondrosarcoma. Th... Figure 8.64 Outline of the borders of the latissimus dorsi myocutaneous lap... Figure 8.65 (a) Intraoperative photograph showing elevation of the latissimu... Figure 8.66 The omentum has been placed over the thoracic defect to provide ... Figure 8.67 (a) Intraoperative picture of a dog with a mass over the caudola... Figure 8.68 CT scan of a cat with a sternal chondrosarcoma. Figure 8.69 (a) Preoperative picture of a cat with a sternal chondrosarcoma ...

Figure 8.70 (a) Intraoperative photograph of a sternectomy for soft tissue s... Chapter 9 Figure 9.1 Echocardiogram identifying pericardial effusion (PE). RV, right v... Figure 9.2 Right auricular mass (arrow) is seen in association with a perica... Figure 9.3 A TA 30 stapler is placed across the base of the right auricle an... Figure 9.4 Placement of tangential forceps on the right auricle to remove a ... Figure 9.5 Right auricle specimen after excision. Figure 9.6 PTFE is being used to bypass a heart-base tumor that is inducing ... Figure 9.7 The diaphragm insertion is underlined with a blue line. The scope... Figure 9.8 The pericardium is grasped under thoracoscopic visualization. Figure 9.9 (a) Thoracoscopic pericardial biopsy. The white arrows are showin... Figure 9.10 (a) Contrast-enhanced sagittal and (b) transverse T1 MRI of a ca... Figure 9.11 A soft tissue nodule (17 × 16 × 20 mm, DV × LM × CrCd, pink arro... Figure 9.12 Surgical resection of a carotid body tumor at the carotid bifurc... Figure 9.13 Carotid body tumor after resection. Figure 9.14 Sagittal and transverse CT angiograms demonstrating a caval thro...

Figure 9.15 (a) Adrenal mass with caval thrombus. The thrombus is being mani... Chapter 10 Figure 10.1 Ovarian tumor. These tumors can grow very large, and extreme car... Figure 10.2 Use of episiotomy to improve exposure of vaginal resection. A ur... Figure 10.3 Vaginal leiomyoma. (a) These tumors can grow quite large. Arrow ... Figure 10.4 (a) Perivaginal dissection for vulvovaginectomy. Dissection is p... Figure 10.5 Illustration of the extent of the excision and the tissues remov... Figure 10.6 Bilateral caudal regional mastectomy in the dog reconstructed wi... Figure 10.7 Bilateral mastectomy in the cat. (a) The cat is placed in dorsal... Figure 10.8 Sertoli cell tumor of a cryptorchid testicle with torsion. Figure 10.9 Sertoli cell tumor (left) after castration. Note the size differ... Figure 10.10 Gynecomastia in a male dog with a Sertoli cell tumor. Figure 10.11 (a) Approach to the prostate (arrow), which involved a pubic sy... Figure 10.12 (a) Cystourethrogram demonstrating a markedly narrowed prostati... Figure 10.13 Cystoscopic image of the prostatic urethra in iltrated with TCC... Figure 10.14 Elliptical incision around the prepuce and penis prior to a pen...

Figure 10.15 Dissection of the penis from the body wall during a penile ampu... Figure 10.16 Multilobular osteochondrosarcoma of the penis. Figure 10.17 Preputial excision and reconstruction using the epithelium of t... Chapter 11 Figure 11.1 Ultrasonographic images (cranial is left, caudal right) of two d... Figure 11.2 Intraoperative view of a renal hemangiosarcoma affecting the cra... Figure 11.3 Intraoperative view of a large canine nephroblastoma. Figure 11.4 Intraoperative view of a canine renal carcinoma. A TA-30V stapli... Figure 11.5 (a) Intraoperative view of the cranial pole of a canine kidney (... Figure 11.6 Radiographs of a dog with a retroperitoneal mass (metastatic sem... Figure 11.7 Metastatic carcinoma to the sublumbar lymph nodes. Figure 11.8 Intraoperative view of a canine urinary bladder TCC following cy... Figure 11.9 Excised section of a canine bladder wall with multifocal TCC. Th... Figure 11.10 View of a canine TCC of the trigone through a ventral cystotomy... Figure 11.11 Following excision of the mass in Figure 11.10 with approximate... Figure 11.12 A CO2 laser is being used to dissect deep into the bladder subm...

Figure 11.13 Ventral view of a dog with TCC of the bladder following cystoto... Figure 11.14 Bladder, prostate, and pelvic portion of the urethra from a dog... Figure 11.15 (a) Intraoperative image following complete cystectomy/prostate... Figure 11.16 Fluoroscopic image of intra-arterial chemotherapy. After an art... Figure 11.17 Vagino-urethroplasty being performed on a dog with TCC of the c... Figure 11.18 CT image of a urethral stent (small arrow; large arrow points t... Figure 11.19 Stereotactic radiosurgery (SRS) treatment plan for a dog with u... Chapter 12 Figure 12.1 A wedge (a) or rectangular four-sided (b) excision may be perfor... Figure 12.2 Two-layer closure for an eyelid defect. (a) Upper eyelid full-th... Figure 12.3 Advancement graft. (a) Proposed skin incisions following tumor e... Figure 12.4 Rotation lap. Medial canthus is to the right of the picture. (a... Figure 12.5 Semicircular lap technique. Medial canthus is to the left. (a) ... Figure 12.6 Mucocutaneous subdermal plexus laps (lip-tolid). (a) A full-th... Figure 12.7 Mucocutaneous subdermal plexus laps (lip-tolid). (a) The propo... Figure 12.8 Bucket handle lap. (a) The bucket handle lap is prepared by ma...

Figure 12.9 Axial pattern lap based on the cutaneous branch of the super ic... Figure 12.10 Cryosurgery is performed on a tumor of the lower eyelid. A chal... Figure 12.11 Sebaceous adenoma of the lower eyelid in a dog. Figure 12.12 Benign tumors of the eyelid in dogs. (a) Benign melanoma; (b) h... Figure 12.13 Subconjunctival approach to enucleation, left eye. (a) A latera... Figure 12.14 Transpalpebral enucleation, left eye. (a) A sharp incision is m... Figure 12.15 Photographs depicting the portion of the skull that is excised ... Figure 12.16 Total orbitectomy performed on a cadaver. (a) A skin incision i... Figure 12.17 Depiction of the landmarks for the osteotomy of the medial wall... Figure 12.18 (a) Surgical site following total orbitectomy. Large arrow poin... Figure 12.19 Photographs depicting the portion of the skull that is excised ... Figure 12.20 Photographs depicting the portion of the skull that is excised ... Figure 12.21 Immediate postoperative appearance of a dog following an extens... Figure 12.22 Appearance of a dog one week following orbitectomy (caudal maxi... Figure 12.23 (a, b) Appearance of a dog one month after hemimaxillectomy and... Figure 12.24 Appearance of a cat two weeks after total orbitectomy for a ib...

Chapter 13 Figure 13.1 (a and b) Skull photographs showing the hamular process of each ... Figure 13.2 Drawing showing the positioning of the dog on the surgery table.... Figure 13.3 Image from CT in a dog showing tumor arising from the right adre... Figure 13.4 Photograph of an adrenocortical carcinoma of the right adrenal g... Figure 13.5 Photograph of an adrenocortical carcinoma from a dog. Figure 13.6 Photograph of a thyroid adenoma (arrow) in a cat. Cranial is to ... Figure 13.7 Photograph showing the position of the animal on the surgery tab... Figure 13.8 (a) and (b) Noninvasive thyroid carcinomas in dogs. Figure 13.9 Images from CT in a dog showing ectopic thyroid tumor involving ... Figure 13.10 Intraoperative photographs of excision of ectopic thyroid tumor... Figure 13.11 Photographs of a parathyroid adenoma in dogs. (a) The parathyro... Figure 13.12 Different intraoperative appearances that an insulinoma can hav... Chapter 14 Figure 14.1 Example of direct lymphography. Methylene blue was instilled in ... Figure 14.2 Examples of methylene blue dye and luorescein indirect lymphogr...

Figure 14.3 Example of lipiodol indirect lymphography. Lipiodol was instille... Figure 14.4 Example of thoracoscopic indocyanine green indirect lymphography... Figure 14.5 Example of computed tomography indirect lymphography. (a) Lohexo... Figure 14.6 Example of gadolinium magnetic resonance indirect lymphography. ... Figure 14.7 Example of regional lymphoscintigraphy. (a) Dog is positioned in... Figure 14.8 Example of single agent indirect lymphography utilizing methylen... Figure 14.9 Example of regional lymphoscintigraphy, intraoperative vital dye... Figure 14.10 (a and b) Clinical appearance of lymphangiosarcoma in two dogs.... Figure 14.11 Diagram showing the sites of ligation for the hilar splenic lig... Figure 14.12 Splenectomy. Notice omental adhesions (a) to the splenic mass a... Figure 14.13 Example of (a) fatal splenic portal vein thrombosis with portal... Figure 14.14 Cytology from a thymoma (500X). Note the heterogeneous populati... Figure 14.15 Different imaging modalities that can be used to image a thymom... Figure 14.16 (a and b) Example of precaval syndrome. Note the profound cervi... Figure 14.17 Transverse CT image of a large thymoma invading the cranial ven... Chapter 15

Figure 15.1 Landmarks for craniotomy borders (dotted line) for the cat (a) a... Figure 15.2 Example of a titanium mesh plate for cranioplasty. For some cran... Figure 15.3 A durotomy can be performed using microforceps and a No. 12 blad... Figure 15.4 Incision (a) and craniotomy window placement in the cat (b) and ... Figure 15.5 An example of a dog after excision of a multilobular osteochond... Figure 15.6 Position of the head for the caudal tentorial craniotomy approac... Figure 15.7 Position of the head for the suboccipital craniotomy approach wi... Figure 15.8 Ventral skull anatomy and craniotomy borders (a) for the ventral... Figure 15.9 Anatomy of the extracranial branches of the trigeminal nerve (ye... Figure 15.10 Example of the neuronavigation screen during planning for resec... Figure 15.11 Muscle anatomy of the caudal cervical spine in cross-sectional ... Figure 15.12 Vascular anatomy of the cervical spine, with the vertebral arte... Figure 15.13 Illustrations of the Funkquist type A (a), Funkquist type B (b)... Figure 15.14 Illustration of the deep muscular anatomy encountered during th... Figure 15.15 Once the pedicle is exposed, the foraminotomy can be performed ...

Figure 15.16 Illustration of lumbar vertebrae in a dog, showing the three co... Figure 15.17 Nerve sheath tumors often begin distally and branch along the n... Figure 15.18 Illustration of the nerve root entry zones visible upon durotom... Chapter 16 Figure 16.1 A multilobular osteochondrosarcoma (MLO) of the skull of a dog. ... Figure 16.2 A whole-body bone scan in a dog presenting with a thoracic limb ... Figure 16.3 A myelogram of a dog with a vertebral osteochondroma involving t... Figure 16.4 An intraoperative image of a pathologic fracture through a biops... Figure 16.5 Bone biopsies should be collected from the center of the bone le... Figure 16.6 (a) The Jamshidi bone biopsy needle with cannula and screw-on ca... Figure 16.7 A Jamshidi bone biopsy needle with multiple core biopsies from a... Figure 16.8 Three-view thoracic radiographs are important in the clinical st... Figure 16.9 Computed tomography scans are signi icantly more sensitive for t... Figure 16.10 Magnetic resonance imaging has superior soft tissue detail and ... Figure 16.11 (a) A whole-body bone scan of a dog with a proximal humeral ost... Figure 16.12 (a) For forequarter amputation, the animal is positioned in lat...

Figure 16.13 (a) For coxofemoral disarticulation, the animal is positioned i... Figure 16.14 (a) A Bull Mastiff one day after forequarter amputation (and su... Figure 16.15 (a) Transverse CT images of a hemangiosarcoma of the proximal f... Figure 16.16 Hemipelvectomy techniques. External pelvectomy entails amputati... Figure 16.17 (a) Intraoperative photograph of dog with a large proximal femo... Figure 16.18 (a) and (b) The radiographic changes in dogs with primary tumor... Figure 16.19 (a) A CT scan of a dog with a primary osteosarcoma of the scapu... Figure 16.20 A distal scapular osteotomy (arrow) for partial scapulectomy ha... Figure 16.21 Postoperative specimens following partial scapulectomy (a) and ... Figure 16.22 Tenodesis of the biceps tendon to the proximal humerus has been... Figure 16.23 (a) The soft tissue defect following partial scapulectomy. (b) ... Figure 16.24 (a) Lateral preoperative radiograph of a dog with an osteosarco... Figure 16.25 Photograph of a Great Dane considered a good candidate for limb... Figure 16.26 Lateral (a) and caudal (b) aspect of the distal radius of a poo... Figure 16.27 Craniocaudal radiographic image of a good candidate for limb-sp...

Figure 16.28 (a) Nuclear scintigraphy of the same dog as in Figure 16.27. No... Figure 16.29 A T1 sagittal magnetic resonance image of a canine osteosarcoma... Figure 16.30 (a) The cephalic vein (arrow) should be preserved if possible t... Figure 16.31 (a) Intraoperative photograph of the medial aspect of an allogr... Figure 16.32 (a) Photograph of the irst-generation 122 mm radial endoprosth... Figure 16.33 (a) Lateral radiographic projection of a distal radial allograf... Figure 16.34 (a) A photograph of a dog with a severe postoperative infection... Figure 16.35 (a) A postoperative radiograph following limbsparing surgery w... Figure 16.36 (a) Local tumor recurrence in the distal antebrachium of a dog ... Figure 16.37 Lateral postoperative radiograph of a pasteurized autograft for... Figure 16.38 (a) Illustrations of the ulna roll-over technique. Proximal and... Figure 16.39 (a) Illustrations of the lateral manus translation technique. R... Figure 16.40 Radiographs showing bone transport osteogenesis (BTO) to ill a... Figure 16.41 A dog with a tarsal osteosarcoma treated with partial amputatio... Figure 16.42 Advances in 3D printing techniques have the potential to revolu...

Figure 16.43 (a) A squamous cell carcinoma of the digit in a dog. Note the t... Figure 16.44 Lateral and dorsopalmar/plantar radiographs should be taken of ... Figure 16.45 (a) An inverted Y-shape incision is made with the stem of the Y... Figure 16.46 The postoperative appearance following amputation of the fourth... Figure 16.47 (a) A lateral radiograph of a dog with an osteosarcoma of the s... Figure 16.48 A lateral radiograph of a dog with an osteochondroma arising fr... Figure 16.49 Advanced imaging modalities provide more accurate information o... Figure 16.50 (a) The Weinstein-Boriani-Biagnini (WBB) Surgical Staging Syste... Figure 16.51 A total en bloc multiple segment vertebrectomy of T9 to T12 has... Figure 16.52 An en bloc sagittal resection has been performed in a dog with ... Figure 16.53 (a) A contrast-enhanced MRI of a dog with an osteosarcoma arisi... Figure 16.54 A lateral radiographic projection of the tibiotarsal joint in a... Figure 16.55 A ventrodorsal radiographic projection of the pelvis in a dog w... Figure 16.56 A CT scan of a dog with an in iltrative lipoma of the thoracic ... Figure 16.57 Surgical planning for a dog with a hypodermal hemangiosarcoma. ...

Figure 16.58 (a) A CT scan of a dog with an intramuscular mast cell tumor of... Figure 16.59 (a) An intraoperative image of a hemangiosarcoma arising from t... Figure 16.60 (a) The typical appearance of an intermuscular lipoma in a dog ...

Veterinary Surgical Oncology Second Edition Edited by

Simon T. Kudnig Animal Referral Hospital Victoria, Australia Bernard Séguin Colorado State University Fort Collins, CO, USA

This edition irst published 2022 © 2022 John Wiley & Sons, Inc. Edition History John Wiley & Sons (1e, 2017) All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by law. Advice on how to obtain permission to reuse material from this title is available at http://www.wiley.com/go/permissions. The right of Simon T. Kudnig and Bernard Séguin to be identi ied as the authors of the editorial material in this work has been asserted in accordance with law. Registered Of ice John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, USA Editorial Of ice 111 River Street, Hoboken, NJ 07030, USA For details of our global editorial of ices, customer services, and more information about Wiley products visit us at www.wiley.com. Wiley also publishes its books in a variety of electronic formats and by print-on-demand. Some content that appears in standard print versions of this book may not be available in other formats. Limit of Liability/Disclaimer of Warranty The contents of this work are intended to further general scienti ic research, understanding, and discussion only and are not intended and should not be relied upon as recommending or promoting scienti ic method, diagnosis, or treatment by physicians for any particular patient. In view of ongoing research, equipment modi ications, changes in governmental regulations, and the constant low of information relating to the use of medicines, equipment, and devices, the reader is urged to review and evaluate the information provided in the package insert or instructions for each medicine, equipment, or device for, among other things, any changes in the instructions or indication of usage and for added warnings and precautions. While the publisher and authors have used their best efforts in preparing this work, they make no representations or warranties with respect to the accuracy or completeness of the contents of this work and speci ically disclaim all warranties, including without limitation any implied warranties of merchantability or itness for a particular purpose. No warranty may be created or extended by sales representatives, written sales materials or promotional statements for this work. The fact that an organization, website, or product is referred to in this work as a citation and/or potential source of further information does not mean that the publisher and authors endorse the information or services the organization, website, or product may provide or recommendations it may make. This work is sold with the understanding that the publisher is not engaged in rendering professional services. The advice and strategies contained herein may not be suitable for your situation. You should consult with a specialist where appropriate. Further, readers should be aware that websites listed in this work may have changed or disappeared between when this work was written and when it is read. Neither the publisher nor authors shall be liable for any loss of pro it or any other commercial damages, including but not limited to special, incidental, consequential, or other damages. Library of Congress Cataloging-in-Publication Data Names: Kudnig, Simon T., editor. | Séguin, Bernard, editor. Title: Veterinary surgical oncology / edited by Simon T. Kudnig, Bernard Séguin.

Description: Second edition. | Hoboken, NJ : Wiley-Blackwell, [2022] | Includes bibliographical references and index. Identi iers: LCCN 2021038703 (print) | LCCN 2021038704 (ebook) | ISBN 9781119089056 (hardback) | ISBN 9781119089094 (adobe pdf) | ISBN 9781119090229 (epub) Subjects: MESH: Neoplasms–surgery | Neoplasms–veterinary | Surgery, Veterinary–methods Classi ication: LCC SF910.T8 (print) | LCC SF910.T8 (ebook) | NLM SF 910.T8 | DDC 636.089/6994–dc23 LC record available at https://lccn.loc.gov/2021038703 LC ebook record available at https://lccn.loc.gov/2021038704 Cover Design: Wiley Cover Image: Courtesy of Simon T. Kudnig and Bernard Séguin

To my late father, Philip, whose life has inspired me, and to my mother, Judy, who is always so proud of our achievements. To my wife, Narelle, and to my children, Samantha and Andrew, who I cherish and who give me unending support. S.K. To my late dad, who led by example, and my mom for always believing in me and for their endless support. To my brother for his encouragement. To my wife Lisa and children Alexandre and Gabrielle for teaching me so much more. B.S. To our colleagues who are a motivation to push ourselves to always do better. S.K. and B.S.

List of Contributors Sara A. Ayres, DVM, DVSc, Diplomate ACVS Mapleview Animal Clinic Barrie, ON, Canada Head and Neck Tumors Nicholas J. Bacon, MA, VetMB, CertVR, CertSAS, Diplomate ECVS, Diplomate ACVS, FRVS Professor, Surgical Oncology School of Veterinary Medicine University of Surrey Guildford UK AND Clinical Director Fitzpatrick Referrals Oncology and Soft Tissue Surrey Research Park Guildford UK Urinary Tract Tania A. Banks, BVSc, FANZCVS, GCHEd, PhD Veterinary Specialist Services 104 Eastlake Street Carrara Queensland Australia Multimodal Therapy, Alimentary Tract: Pancreas Sarah Boston, DVM, DVSc, Diplomate ACVS ACVS Founding Fellow of Surgical Oncology ACVS Founding Fellow of Oral and Maxillofacial Surgery VCA Canada Mississauga-Oakville Veterinary Hospital Oakville, ON, Canada

Respiratory Tract and Thorax: Chest Wall Tumors, Laryngeal Tumors, Tracheal Tumors Jonathan P. Bray MVSc MSc(ClinOnc) PhD MACVSc MRCVS Diplomate ECVS Senior Consultant Surgeon Fitzpatrick Referrals Oncology and Soft Tissue 70 Priestley Road Surrey Research Park Guildford Surrey UK Musculoskeletal System Tara A. Britt, VMD, Diplomate ACVS, ACVS Founding Fellow Surgical Oncology Four Seasons Veterinary Specialists Loveland CO,USA Reproductive System: The Male Lisa Brownlee, DVM, MS, Diplomate ACVIM (Internal Medicine) Staff Internist Four Seasons Veterinary Specialists Loveland CO, USA Endocrine System Paolo Buracco, DVM, Diplomate ECVS Professor of Veterinary Surgery Department of Veterinary Science University of Torino Grugliasco (Turin) Italy Alimentary Tract: Colorectal Tumors and Perianal Tumors Earl F. Calfee, III, DVM, MS, Diplomate ACVS Nashville Veterinary Specialists Nashville, TN, USA

Alimentary Tract: Stomach, Liver and Gall Bladder, Pancreas, Small Intestine Ryan P. Cavanaugh, DVM, DACVS-SA, ACVS Founding Fellow, Surgical Oncology Associate Professor Small Animal Surgery Department of Clinical Sciences Ross University School of Veterinary Medicine St. Kitts West Indies Alimentary Tract: Stomach, Liver and Gall Bladder, Pancreas, Small Intestine Craig A. Clifford. DVM. MS, Diplomate ACVIM (Oncology) Medical Oncologist Hope Veterinary Specialists/Blue Pearl Malvern, PA, USA Multimodal approaches to Surgical Oncology William T.N. Culp, VMD, Diplomate ACVS ACVS Founding Fellow, Surgical Oncology ACVS Founding Fellow, Minimally Invasive Surgery ACVS Founding Fellow, Oral and Maxillofacial Surgery Professor, Small Animal Surgery (Surgical Oncology/Interventional Radiology) Department of Surgical and Radiological Sciences School of Veterinary Medicine University of California-Davis Davis CA, USA Principles of Surgical Oncology Interventional Oncology Alimentary Tract: Esophagus Michael Davidson, DVM, Diplomate ACVO Professor, Ophthalmology North Carolina State University College of Veterinary Medicine

1053 William Moore Drive Raleigh, NC, USA Eyelids, Eye, and Orbit William S. Dernell, DVM, MS, Diplomate ACVS Director of External Clinical Training Programs Department of Veterinary Clinical Sciences College of Veterinary Medicine Washington State University Pullman, WA, USA Musculoskeletal System Nicole Ehrhart, VMD, MS, Diplomate ACVS Professor, Surgical Oncology Department of Clinical Sciences College of Veterinary Medicine and Biomedical Sciences Colorado State University Fort Collins, CO, USA Principles of Surgical Oncology James P. Farese, DVM, Diplomate ACVS ACVS Founding Fellow Surgical Oncology Golden Gate Veterinary Specialists San Rafael, CA, USA Urinary Tract, Musculoskeletal System Jolle Kirpensteijn, DVM, PhD, Diplomate ACVS, Diplomate ECVS Chief Veterinary Of icer Hill’s Pet Nutrition US 400 SW 8th Avenue Topeka, KS, USA Skin and Subcutaneous Tumors: Skin Tumors General Principles, Soft Tissue Sarcomas Simon T. Kudnig BVSc, MVS, MS, FACVSc, Diplomate ACVS ACVS Founding Fellow, Surgical Oncology Animal Referral Hospital Essendon Fields

Victoria, Australia Cardiovascular System B. Duncan X. Lascelles, BSc, BVSc, PhD, FRCVS, CertVA, DSAS(ST), Diplomate ECVS, Diplomate ACVS Professor of Comparative and Translational Pain Research Surgery Section North Carolina State University College of Veterinary Medicine Raleigh, NC, USA Oral Tumors Eyelids, Eye, and Orbit Julius M. Liptak, BVSc, MVetClinStud, FACVSc, Diplomate ACVS, Diplomate ECVS ACVS Founding Fellow, Surgical Oncology ACVS Founding Fellow, Oral and Maxillofacial Surgery Capital City Small Animal Mobile Surgery Ottawa, Ontario, Canada Head and Neck Tumors Oral Tumors Musculoskeletal System, Ethics and Limits of Surgical Oncology Marina Martano, DMV, PhD Professor of Veterinary Surgery Department of Medical – Veterinary Sciences University of Parma Italy Respiratory Tract and Thorax: Thoracotomy, Rhinotomy Eric Monnet, DVM, PhD, Diplomate ACVS, Diplomate ECVS Professor, Small Animal Surgery Department of Clinical Sciences Colorado State University College of Veterinary Medicine and Biomedical Sciences Fort Collins, CO, USA Cardiovascular System Emanuela Morello, DMV, PhD Associate Professor of Veterinary Surgery Department of Veterinary Science University of Torino

Grugliasco (Turin) Italy Respiratory Tract and Thorax: Lung Christine Mullin, VMD, Diplomate ACVIM (Oncology) Medical Oncologist Hope Veterinary Specialists - Blue Pearl Malvern Malvern, PA, USA Multimodal Therapy Rebecca A. Packer, MS, DVM, Diplomate ACVIM (Neurology) Veterinary Neurologist/Neurosurgeon Blue Pearl Specialty and Emergency Pet Hospital Lafayette, CO, USA Cassandra Y. Prpich, BVSc, MANZCVS, Diplomate ACVS ACVS Fellow, Surgical Oncology Medical Director Colorado Animal Specialty and Emergency Boulder, CO, USA Eyelids, Eye, and Orbit Stewart Ryan, BVSc, MS, Diplomate ACVS, Diplomate ECVS Senior lecturer, Department of Clinical Sciences, Melbourne Veterinary School The University of Melbourne Werribee, VIC, Australia Skin and Subcutaneous Tumors: Skin Tumors General Principles, Mast Cell Tumors Bernard Séguin, DVM, MS, Diplomate ACVS ACVS Founding Fellow, Surgical Oncology ACVS Founding Fellow, Oral and Maxillofacial Surgery Professor of Surgical Oncology Flint Animal Cancer Center Department of Clinical Sciences College of Veterinary Medicine and Biomedical Sciences Colorado State University

Fort Collins, CO, USA Endocrine System Maurine J. Thomson, BVSc, FACVSc Specialist, Surgical Oncologist Animal Referral Hospital Sinnamon Park QLD, Australia Reproductive System: The Female Sebastiaan (Bas) A. van Nimwegen, DVM, PhD, Diplomate ECVS Assistant Professor Department of Clinical Sciences Faculty of Veterinary Medicine Utrecht University Utrecht The Netherlands Skin and Subcutaneous Tumors: Skin Tumors General Principles, Soft Tissue Sarcomas Deanna R. Worley, DVM, Diplomate ACVS-SA ACVS Founding Fellow, Surgical Oncology ACVS Founding Fellow, Oral and Maxillofacial Surgery Small Animal Professor Surgical Oncology Department of Clinical Sciences College of Veterinary Medicine and Biomedical Sciences, Colorado State University Fort Collins, CO, USA Hemolymphatic System Erik G.H. Wouters, DVM, Diplomate ECVS AniCura Dierenziekenhuis Drechtstreek Referral Clinics Dordrecht & Rijswijk The Netherlands Skin and Subcutaneous Tumors: Skin Tumors General Principles, Skin Tumors, Soft Tissue Sarcomas

Preface As stated in the irst edition of Veterinary Surgical Oncology, the impetus to write the book was to ful ill the goals of the Veterinary Society of Surgical Oncology (VSSO), which includes to “disseminate knowledge to help provide the highest possible standard of surgical treatment for cancer and to encourage and promote education in surgical oncology for professional veterinary students, graduate students and house of icers, and graduated veterinarians and veterinary surgeons.” As evidenced by the number of book sales, the translation into different languages, and the listing of the book on several reading lists for specialist surgery colleges, including the American College of Veterinary Surgeons (ACVS), these goals appear to have been met. Veterinary Surgical Oncology has proudly become the most comprehensive resource in this ield and is an integral tool for surgeons performing both basic and advanced surgical oncology procedures. The ield of Veterinary Surgical Oncology, however, is an ever-evolving science, and to maintain currency, the second edition was completed. Some signi icant changes in the second edition include expansion of the interventional oncology chapter and inclusion of these techniques in different chapters due to the rapid growth of this discipline and the recruitment of specialist medical oncologists and neurologists to enhance the multimodal therapy and nervous system chapters, respectively. New igures, additional surgical procedures, and updated information are included in the second edition. The underlying importance of a multidisciplinary approach to cancer, with a high level of understanding of diagnostic imaging, chemotherapy, radiation therapy, alternative therapies, and cancer biology, remains a consistent feature in this textbook, as it is integral to surgical success and overall patient outcome. Surgical oncologists are also cognizant of the fact that their procedures can be invasive, with signi icant alteration to cosmesis and function, and to this end, an additional chapter, entitled “Ethics and Surgical

Limits of Surgical Oncology,” was added. Controversy can sometimes exist with regard to performing some more invasive procedures, and this chapter addresses this issue with a discussion of anatomic, functional, and ethical limits of surgical oncology procedures. The goal of our surgical intervention remains the same, which is to improve the quality and life expectancy of animals with cancer while minimizing harm. This can, however, require a large “surgical dose” or surgical intervention. To allow these invasive surgeries to bene it our patients, excellent communication skills with owners regarding the expected outcome, potential morbidity and complications, and survival time are imperative. The objectives of the second edition remain the same as those for the irst edition: this book is not meant to be a full review of small animal oncology. We wanted to concentrate on the surgical procedures, such as those that are not well covered in other textbooks, and importantly to assist with decision making by providing information such as complications, prognoses, and adjuvant or alternative therapies. The reader is expected to have a basic knowledge of general surgical principles and surgical techniques. Without the excellent contribution and collaboration by the chapter authors, all of whom are leaders in the ield of surgical oncology, the second edition of this textbook would not have been possible. We are indebted to our colleagues who have tirelessly reviewed the irst edition and any feedback from readers to correct any shortfalls in their chapters, as well as to add newer and pertinent information. We also want to thank Justinia Wood, Catriona Cooper, Teri Jensen, Erica Judisch, Jayadivya Saiprasad, and particularly Merryl Le Roux and Susan Engelken, from Wiley-Blackwell, for their assistance, guidance, and patience during the process of updating the irst edition. We also want to thank Molly Borman and Kip Carter for creating new illustrations, Maddi Funk for photography and technical assistance with new igures. Finally, and most importantly, we want to thank our families who have again lived through the creation of the second edition, which has encompassed trying times in world health, and we sincerely appreciate their resilience and support. We are con ident that Veterinary Surgical

Oncology will remain the textbook of choice for students, interns, residents, and veterinary surgeons with interest in surgical oncology. Simon T. Kudnig and Bernard Séguin

Foreword It is my honor to write a foreword for the second edition of Veterinary Surgical Oncology. Having spent most of my career in this discipline, it is rewarding to see an evidence-based approach to surgical oncology being emphasized. It should go without saying that surgical oncology could not have developed to the specialty it is today without the parallel growth of advanced imaging, anesthesia, analgesia, blood products, pathology, critical care, and hemostatic/stapling equipment. Close integration with medical and radiation oncology has been crucial to optimizing patient care. Surgery probably cures more patients than any other discipline but must be tempered with acceptable cosmesis and function. The old adage of “to cut is to cure” should not dominate decisions and outcomes. More radical procedures in the chest, abdomen, and brain are being slowly supplemented with skilled minimally invasive procedures in select instances. Surgical judgment may be the wild card. Determining when, how, and why to operate remains the art of the discipline. The establishment of ACVS fellowship training in surgical oncology has established minimal training guidelines. On a personal note, I have been involved with the training of 22 of the 32 authors of this text. I couldn’t be prouder of their efforts to optimize Veterinary Surgical Oncology and congratulate the editors: Dr. Bernard Séguin and Dr. Simon Kudnig. Stephen J. Withrow, DVM, diplomate ACVS, ACVS Founding Fellow, Surgical Oncology University Distinguished Professor Stuart Chair in Oncology – Emeritus Founding Director, Flint Animal Cancer Center Colorado State University

Fort Collins, CO

About the Companion Website The companion website for this book is at

www.wiley.com/go/kudnig/veterinary The website contains – Figures Video Clips

1 Principles of Surgical Oncology William T.N. Culp and Nicole Ehrhart Cancer treatment is a rapidly changing and evolving area involving multiple diagnostic and therapeutic modalities to achieve the most optimal outcome. Surgical intervention remains a pivotal aspect of the treatment of cancer. Surgery cures more solid cancers than any other single modality. Nonetheless, the optimal treatment pathway for any given animal patient with cancer most often involves several adjuvant treatment modalities. Adjuvant treatments signi icantly affect the success of surgery, and likewise, surgery affects the outcome of adjuvant treatments. It is widely recognized in human cancer centers that patient outcome is greatly improved when surgery is performed by a surgeon with specialized training in oncologic procedures. Surgeons trained in these programs have expertise in the selection of surgical treatment options in combination with other forms of cancer treatment, as well as knowledge of the bene its and risks associated with a multidisciplinary approach beyond what can be mastered within a three-year surgery residency training program. This level of expertise requires an understanding of the fundamental biology of cancer, clinical pharmacology, tumor immunology, and endocrinology, as well as a thorough understanding of potential complications of multimodality therapy. Veterinary training programs in surgical oncology have been in existence for almost 20 years. With the development of novel treatments, the role of the surgical oncologist is constantly evolving and changing (O’Reilly et al. 1997; Drixler et al. 2000). Therapeutic goals (e.g. curative-intent, cytoreduction, or palliation) for each case should be established with owners before surgery is initiated. The ef icacy of surgical therapy in any patient with cancer is heavily dependent upon the surgeon’s global understanding of the patient’s general health status, lifestyle and activity level, type and stage of cancer, adjuvant therapies available, alternatives to surgery, and expected prognosis. To maximize effectiveness, the optimal treatment pathway for each case should be strategically assessed prior to initiating treatment. This planning should always include a frank and thorough discussion with the owner regarding preoperative diagnostic tests, stage of cancer, palliative options, surgical options, adjuvant treatments likely to be needed, costs, postoperative care and expected function, cosmesis, and prognosis including risks of complications. The goal of this discussion is to provide the owner with enough information to help them make an informed choice regarding the best treatment pathway for their companion. Highly individualized initial planning will allow for the best overall outcome for each patient.

Preoperative Considerations Signalment The patient’s age, gender, breed, and weight are important factors in the determination of appropriate recommendations. Advanced age is not necessarily a negative prognostic factor. Comorbidities common to geriatric veterinary patients such as renal insuf iciency, hepatic disease, or osteoarthritis may limit or change speci ic treatment recommendations; however, the age of the patient alone should not. Certain neoplastic diseases are common in a particular gender or breed. The surgical oncologist should always bear in mind the role that gender and breed play in the diagnosis of neoplasia. As an example, the differential list for a lat-coated retriever with a femoral bony lesion noted on radiographs that has been referred for a suspected diagnosis of osteosarcoma should be expanded to include histiocytic sarcoma; other diagnostics such as an abdominal ultrasound would be recommended to look for other foci of histiocytic disease. Other portions of the signalment are also important to note, including the patient’s weight and body condition. Patients that are morbidly obese or those in poor body condition may not be able to function effectively or may be more severely debilitated by a major surgery. For example, a patient with cancer

cachexia can have such profound alterations of their carbohydrate, protein, and fat metabolism that recovery may be compromised (Ogilvie 1998).

Staging/Concomitant Disease Staging diagnostics such as a complete blood count, chemistry pro ile, urinalysis, thoracic radiographs and abdominal ultrasound, and/or thoracic and abdominal computed tomography (CT) are essential components for the preoperative assessment of veterinary oncologic patients. While there is debate about the timing of some of these diagnostics (i.e. before or after biopsy), for many patients, thorough preoperative staging diagnostics can unmask an underlying condition that may alter the plan or better assist the surgeon in providing a more accurate prognosis. Alternative surgical dose may also be recommended based on the results of staging.

Neoadjuvant Therapy The surgical oncologist is often presented with extremely large tumors or tumors located in dif icult anatomic locations. It is important to consider neoadjuvant treatments, if available and warranted, such as chemotherapy and radiotherapy before proceeding with surgery. In some cases, these treatments may decrease the overall surgical dose needed to achieve local control. Most commonly, recommendations about chemotherapy and/or radiation therapy are made after the grade of the tumor and the surgical margins have been determined. In tumors that are suspected to be sensitive to chemotherapy based on published literature or previous experience, a postoperative protocol can be discussed prior to surgery. Neoadjuvant chemotherapy is rarely pursued in veterinary medicine. However, for certain tumor types, this may prove to be a bene icial adjunct to surgery. In human cases of osteosarcoma, neoadjuvant chemotherapy is commonly used prior to surgery and local tumor response (as measured by percent tumor necrosis) has been shown to be associated with increased survival. A veterinary study showed that neoadjuvant chemotherapy with prednisone administered to a group of dogs with intermediategrade mast cell tumors resulted in tumor size reduction; surgical excision of very large mast cell tumors or tumors that were in an anatomic site that precluded wide (3 cm lateral and one facial plane deep) excision was more successful (Stanclift and Gilson 2008). Microscopically complete margins were achieved in many of the pretreated cases. These patients would not likely have had complete surgical margins otherwise (Stanclift and Gilson 2008). Long-term follow-up was not the focus of this study, however, and controversy exists as to the risk of local recurrence in patients where neoadjuvant chemotherapy is used to shrink gross tumor volume with a view to allow a less aggressive surgical margin. Further study is needed to assess the bene it of neoadjuvant chemotherapy in veterinary cancer patients. Neoadjuvant radiation therapy has also been advocated as a method of treating neoplastic disease to reduce the need for radical surgery (McEntee 2006). Advantages to neoadjuvant radiation therapy include a smaller radiation ield, intact tissue planes, better tissue oxygenation, and a reduction in the number of viable neoplastic cells that may be left within a postoperative seroma or hematoma following microscopically incomplete margins. Complications such as poor wound healing may occur more commonly in irradiated surgical sites than in nonirradiated tissue due to the effects of radiation on ibroblasts and blood vessels (Seguin et al. 2005). Even so, surgery in previously irradiated ields can be quite successful, provided care is taken to ensure minimum tension, careful surgical technique, and appropriate timing (either before or after acute effects have occurred). Consultation with a radiation oncologist prior to surgery can help the surgeon identify those patients who may be good candidates. Considerations such as whether or not preoperative radiation will diminish the surgical dose and what type of reconstruction will be needed to ensure a tension-free closure in an irradiated surgical ield should be discussed at length prior to deciding if neoadjuvant radiation is warranted.

Surgical Planning

The irst decision in the surgical planning in removing a tumor is to determine the “surgical dose.” The surgical dose refers to how aggressive the excision is with respect to the edges of the tumor. The surgical dose has been divided into: intracapsular, marginal, wide, and radical (Figure 1.1). An intracapsular excision is where the capsule of the organ where the tumor arises from (e.g. thyroid gland) or the pseudocapsule of the tumor (e.g. soft tissue sarcoma) is disrupted and the tumor is removed in pieces. A marginal excision is where the removal is done just outside or on the capsule or pseudocapsule. Oftentimes, the tumor is “shelled out.” A wide excision is when the tumor and its capsule are never entered and grossly normal tissue surrounds the specimen. This is often de ined as 2–3 cm of normal tissue around the edges of the tumor and one fascial place beneath the cutaneous and subcutaneous tumors. The 2–3 cm of normal tissue is in situ and not histological. A radical excision is the removal of the entire compartment or structure where the tumor is arising from. An example of a radical excision is a limb amputation.

Figure 1.1 Diagram illustrating the different doses of surgery: marginal, wide, and radical being an amputation in this example. Intracapsular is not shown. Source: Illustrated by Molly Borman.

When removing a tumor, there can be three different goals: curative, palliative, and cytoreductive. These goals will dictate the dose of surgery and several factors will guide which goal should be pursued. The irst factor is tumor type. Because benign tumors are limited to their capsule and do not extend into the normal-appearing tissues, a marginal excision is performed. Malignant tumors, however, have the ability to extend into the grossly normal-looking tissue at the microscopic level (Figure 1.2). Other factors need to be considered to determine the goal and consequently the dose of surgery. With (most) malignant tumors, when the goal is curative, a wide or radical excision is required. For a palliative or cytoreductive goal, a marginal excision is performed. An intracapsular excision is rarely indicated.

Figure 1.2 Diagram showing the extension of tumor into the grossly normal-looking tissue. These extensions are most typically at the microscopic level. This is the reason to perform a wide excision (2), as opposed to a marginal excision (1), with the goal to achieve a complete excision. Source: Illustrated by Molly Borman.

The additional factors to consider to determine the goal of the surgery are: tumor size and location, stage of the cancer, overall health of the patient, risk of the surgery, prognosis, and goals of the owners. Table 1.1 provides examples of how these factors come into play, understanding there are always exceptions or nuances (see section on margins and palliative and cytoreductive surgery). Because knowing the tumor type is essential in most instances, methods to get a diagnosis are a ine needle aspirate (FNA) or biopsy.

Fine Needle Aspirate Fine needle aspiration is often the most minimally invasive technique for obtaining critical information about a newly identi ied mass prior to surgery. The accuracy of a FNA is dependent on many factors including the tumor type, location, and amount of in lammation. Overall sensitivity and speci icity of cytology have been reported to be 89% and 100%, respectively (Eich et al. 2000; Cohen et al. 2003). Imaging tools such as ultrasound and luoroscopy can increase the chance of obtaining a diagnostic sample. In most patients, an FNA of cutaneous or subcutaneous lesions can be obtained with no sedation and a minimal amount of discomfort. Fine needle aspiration has been compared to histopathologic samples in several studies. In one study of the correlation between cytology generated from ine needle aspiration and histopathology in cutaneous and subcutaneous masses, the diagnosis was in agreement in close to 91% of cases (Ghisleni et al. 2006). Cytology was 89% sensitive and 98% speci ic for diagnosing

neoplasia, and these numbers varied slightly based on tumor type (Ghisleni et al. 2006). For example, both the sensitivity and speci icity were 100% for mast cell tumors (Ghisleni et al. 2006). In one study looking at the accuracy of cytology of lymph nodes in dogs and cats, cytology had a sensitivity of 67%, speci icity of 92%, and accuracy of 77% for a diagnosis of neoplasia (Ku et al. 2017). In that study, 31% of metastatic lymph nodes secondary to a mast cell tumor were falsely negative (Ku et al. 2017). In another study evaluating the value of cytology of lymph nodes to detect metastasis of solid tumors, the sensitivity of needle aspirates of the lymph node was 67% for sarcomas, 100% for carcinomas, 63% for melanomas, 75% for mast cell tumors, and 100% for other round cell tumors. The speci icity varied between 83 and 96%; also, 20% of nondiagnostic samples were metastatic (Fournier et al. 2018). Table 1.1 Factors affecting the goal of surgery and consequently the dose of surgery Tumor type

stage

Size location

Owner’s prognosis Overall goals health of patient

Goal of surgery

Benign

Marginal Metastasis present Small Trunk

Malignant

Dose of surgery

Good to excellent

Palliative

Marginal

Good

Curative

Wide

Curative

Radical

No metastasis Signi icant Limb Owners Good to accept excellent Good amputation for function Signi icant Limb Owners refuse amputation but accept surgeries with higher morbidity and risks

Good for local control Good and long term survival

Signi icant Limb Owners refuse amputation or surgeries with higher morbidity and risks

Good with adjuvant Good therapy

Curative

Wide (with reconstructive surgery)

Cytoreductive Marginal

Signi icant coPalliative morbidities

Marginal

The goal of ine needle aspiration is to differentiate between an in lammatory or neoplastic process and, if neoplastic, whether the tumor is benign or malignant. In some cases, the speci ic tumor type can be determined (e.g. mast cell tumor). In other cases, the class of tumor may be identi ied (e.g. sarcoma), but the speci ic diagnosis requires histopathology (e.g. chondrosarcoma versus osteosarcoma). The overall purpose of obtaining the FNA is to guide the staging diagnostics (where to look for metastasis or paraneoplastic diseases) and surgical dose. For example, an FNA of a mass showing normal adipocytes would indicate the mass is not in lammatory, rather it is a neoplastic process and it is benign (lipoma). Based on the knowledge of the biologic behavior of this tumor, no other staging tests would be performed and minimal surgical dose would be prescribed (marginal resection). Alternatively, if the FNA of a mass indicated carcinoma cells, more advanced staging (three-view thoracic radiographs, abdominal ultrasound and/or thoracic and abdominal CT, lymph node aspirates) would be indicated and a larger surgical dose would be prescribed. Fine needle aspiration of internal organs can also be performed and may be helpful in guiding diagnostic and treatment choices. Image guidance should be utilized when obtaining FNAs of masses within a body cavity. Aspirates of lung and other thoracic organs can be performed safely in most cases. In one study, ine needle aspiration of lung masses had a sensitivity of 77% and a speci icity of 100% (DeBerry et al. 2002). The aspiration of cranial mediastinal masses is bene icial, as thymomas can be diagnosed by cytology (Rae et al. 1989; Atwater et al. 1994; Lana et al. 2006). Cytologic diagnosis of thymoma requires the presence of a population of unequivocal malignant epithelial cells. The presence of mast cells is also common in thymoma and often supports the diagnosis (Atwater et al. 1994). Flow cytometry is another diagnostic tool that will differentiate thymoma from lymphoma using an FNA sample. Thymomas will contain both CD4+ and CD8+ lymphocytes, whereas lymphoma would typically contain a clonal expansion of one lymphocyte type (Lana et al. 2006). Fine needle aspiration of hepatic and splenic neoplasia has been described in several studies (Osborne et al. 1974; Hanson et al. 2001; Roth 2001; Wang et al. 2004). Successful diagnosis of hepatic neoplasia with ine needle aspiration is variable. A study has reported diagnostic rates for liver cytology of multiple pathologies (including neoplasia) as high as 80% (Roth 2001); however, another study demonstrated less success with diagnostic rates of 14% in dogs and 33% in cats for ine needle aspiration of hepatic neoplasia (Wang et al. 2004). In cases of suspected splenic hemangiosarcoma, ine needle aspiration is generally not recommended, as an accurate diagnosis is unlikely due to the abundance of blood- illed cavities. Additionally, complications may include severe bleeding from the aspiration site. Fine needle aspiration of splenic neoplasia such as lymphoma and mast cell tumors is often diagnostic (Hanson et al. 2001). Other tumors in which ine needle aspiration has been utilized to obtain diagnostic information include gastrointestinal tumors and bony tumors. The accuracy of ine needle aspiration in the diagnosis of gastrointestinal neoplasia is often dependent on the type of neoplasia present. For instance, ine needle aspiration of gastrointestinal lymphoma tends to have a higher sensitivity than aspiration of gastrointestinal carcinoma/adenocarcinoma or leiomyoma/leiomyosarcoma (Bonfanti et al. 2006). The speci icity of the diagnosis is similar among these neoplastic diseases with ine needle aspiration (Bonfanti et al. 2006). In one study, ultrasound-guided ine needle aspiration of osteosarcoma lesions was found to have a sensitivity of 97% and speci icity of 100% for the diagnosis of a sarcoma (Britt et al. 2007). Another study found that cytology after ine needle aspiration agreed with incisional and excisional biopsies of bony lesions in 71% of cases (Berzina et al. 2008). In a more recent study, histology of a bone lesion was superior to cytology (Sabattini et al. 2017). Histology of a biopsy had a sensitivity of 72%, speci icity of 100%, and accuracy of 82%, whereas cytology had a sensitivity of 83%, speci icity of 80%, and accuracy of 83% (Sabattini et al. 2017). As with any procedure, FNAs are not without risk. In certain cases, bleeding or luid leakage can be problematic, especially within a closed body cavity where it cannot be easily controlled. Tumor seeding and implantation along the needle tract is a rare occurrence, but in certain tumors has been reported more frequently. Localized tumor implantation following ultrasound-guided FNA of transitional cell carcinoma of the bladder has been reported (Nyland et al. 2002) and should be a consideration when deciding on methods for diagnosing bladder masses. Fine needle aspiration of mast cell tumors brings

the risk to cause degranulation, and clinicians should be prepared to treat untoward systemic effects following aspiration of a suspicious or known mast cell tumor. Despite the risks associated with needle aspiration, it remains an effective, inexpensive, and valuable tool in the preoperative planning process.

Biopsy Clinicians often use the term “biopsy” as a nonspeci ic description of obtaining a tissue sample for histopathologic interpretation. Because of this, two major categories of biopsy have been designated: pretreatment biopsy (tissue obtained before treatment initiation) or posttreatment biopsy (tissue obtained at the time of de initive tumor resection). All biopsy procedures, whether pretreatment or posttreatment, should be carefully planned with several factors in mind. These factors include known patient comorbidities, anatomic location of the mass, differential diagnoses, biopsy technique, eventual de initive treatment, and any neoadjuvant/adjuvant therapies that may need to be incorporated. Pretreatment Biopsy Needle Core Biopsy This technique is commonly used for soft tissue, visceral, and thoracic masses (Osborne et al. 1974; Atwater et al. 1994; deRycke et al. 1999). Image guidance is recommended when using this technique in closed body cavities. Most patients require sedation and local anesthesia but may not need general anesthesia. Instrumentation includes a needle core biopsy instrument (automated or manual) (Figure 1.3), #11 scalpel blade, local anesthetic, and a 22 g hypodermic needle. To perform the procedure, the area surrounding the mass is clipped free of fur and prepared with aseptic technique. If intact skin is to be penetrated and the animal is not anesthetized, the skin overlying the area to be penetrated is anesthetized with lidocaine or bupivacaine. A 1–2 mm stab incision is made over the mass to allow for placement of the needle core biopsy instrument. The instrument is oriented properly and ired, and the instrument is withdrawn. The 22 g needle can be used to gently remove the biopsy from the trough of the needle core instrument. This identical procedure is performed for masses within a body cavity; however, it is necessary to use image guidance (most commonly ultrasound) for proper placement of the instrument within the desired tissue. Imaging can be used to determine the depth of penetration and to safely avoid nearby vital structures. Punch Biopsy This technique is most effective for cutaneous lesions as well as intraoperatively for biopsies of masses within organs such as the liver, spleen, and kidney. Subcutaneous lesions can be biopsied using this method, but it is best to incise the skin overlying the mass and then obtain the sample using the biopsy instrument.

Figure 1.3 (a) Automated needle core biopsy instrument. (b) The tip of the needle has an indentation, which is illed with the tumor tissue when inserted. There is a sleeve with a cutting edge (red arrow), which cuts the piece of tissue in the indentation of the needle. Instrumentation includes a punch biopsy instrument (Figure 1.4), which typically comes in sizes of 2, 4, 6, and 8 mm; #11 scalpel blade; local anesthetic; Metzenbaum scissors; forceps; and suture. The area containing the mass is clipped free of fur and prepared with aseptic technique. If intact skin will be penetrated and the animal is not anesthetized, the skin overlying the lesion is anesthetized with lidocaine or bupivacaine. For cutaneous masses, an incision is not necessary. For subcutaneous masses, make an incision in the skin over the mass and dissect tissues overlying the mass if present to allow for the procurement of a better sample. The skin incision should be large enough for the punch biopsy instrument to be placed and allow it to be twisted without engaging skin. Twist the punch biopsy instrument until the device is embedded into the mass to the hub. The punch biopsy instrument is then withdrawn from the mass to expose the tissue sample. Gently grasp the sample with forceps, utilize Metzenbaum scissors to sever the deep aspect of the sample from the rest of the tissue, and remove the sample. A single suture is generally suf icient to close the incision. The same procedure can be performed on visceral organs. Incisional (Wedge) Biopsy This technique is effective for masses in all locations and generates a larger sample for histopathologic evaluation as compared to the needle core biopsy. The location of the incision should be carefully planned, as the biopsy incision will need to be removed during the de initive treatment. Care should be taken to avoid dissection and prevent hematoma or seroma formation as these may potentially seed

tumor cells into the adjacent subcutaneous space. Although the junction of normal and abnormal tissue is often mentioned as the ideal place to obtain a biopsy sample, one should take care to avoid entering uninvolved tissues. The most important principle to consider is to obtain a representative sample of the mass. It is also important to obtain a sample that is deep enough and contains the actual tumor, rather than just the ibrous capsule surrounding the mass. Incisional biopsy has a higher potential for complications such as bleeding, swelling, and infection due to the increase in incision size and dissection.

Figure 1.4 Punch biopsy instrument, 8 mm in diameter. Instrumentation includes a scalpel blade, local anesthetic, Metzenbaum scissors, forceps, suture, and hemostats. A Gelpi retractor or similar self-retaining retractor aids in visualization if the mass is covered by skin. If the skin is intact and moveable over the mass, a single incision is made in the skin. Once the tissue layer containing the tumor is exposed, two incisions made in a parallel direction are started super icially and then meet at a deep location to form a wedge. The wedge is then grasped with forceps

and removed. If the deep margin of the wedge is still attached, the Metzenbaum scissors can be used to sever the biopsy sample free of the parent tumor. The wedge site is then closed with a suture. Excisional Biopsy The approach to an excisional biopsy is variable based on location, goal of surgery, and predetermined adjuvant therapy. An excisional biopsy has the advantage of being both a diagnostic technique as well as a treatment modality. A great deal of caution should be exercised in cases where the diagnosis is unclear. At a minimum, an FNA should be obtained to discern if a given mass is in lammatory or neoplastic and, if neoplastic, whether benign or malignant. This information is imperative in order to determine surgical dose. There are cases where an excisional biopsy may be a reasonable option, if doubt or absence of knowledge of the tumor type remains after ine needle aspiration (e.g. nondiagnostic results from cytology), depending on the size and location of the tumor. In these instances, the surgeon must contemplate if an excisional biopsy will compromise the ability to enact a cure by wide excision. If it is deemed that an excisional biopsy can be performed while leaving this option, an excisional biopsy can be considered. For example, a 1 cm in diameter mass on the trunk of a large breed dog can be interrogated by excisional biopsy, whereas a 1 cm in diameter mass on the distal extremity of a dog should be interrogated by incisional biopsy (wedge or punch). Once an excision is performed, the local anatomy is forever altered, tissue planes both deep and wide to the tumor are invaded, providing an opportunity for the tumor cells to extend and seed deeper and wider into tissues. For this reason, the best chance for complete excision is at the time of the irst surgical excision. In order to perform a curative surgery, the surgeon must take the appropriate margin of tissue for the tumor type. In some cases (lipoma), this margin is minimal or even intralesional. In other cases (soft tissue sarcoma), the margin should be more extensive. Unless the tumor type is known at the time of excision, the surgeon may compromise the patient by doing too little or too much surgery. Specific Biopsy Techniques Bone Biopsy The clinician performing the bone biopsy procedure should consider the eventual de initive treatment that is likely to be pursued for each case. The biopsy tract or incision needs to be in a location that can be removed during the de initive treatment. A reactive zone of bone exists in the periphery of most bone tumors, and samples taken from this region are more likely to result in an incorrect diagnosis (Wykes et al. 1985;, Liptak et al. 2004). The surgeon should target the anatomic center of the bony lesion. Two radiographic views of the involved bone should be available during the procedure as this will aid in optimal sampling. The majority of bone biopsies are performed utilizing either a Michele trephine or a Jamshidi needle (Wykes et al. 1985; Powers et al. 1988; Liptak et al. 2004). A trephine instrument provides a large sample and has been associated with 93.8% diagnostic accuracy (Wykes et al. 1985). The disadvantages of the trephine technique include increased likelihood of fracture as compared to other techniques, requirement of a surgical approach, and a more lengthy decalci ication time prior to sectioning (Wykes et al. 1985; Ehrhart 1998). Michele trephines are available in variable diameters. As a small surgical approach is required, a simple surgical pack is needed for the procedure. The biopsy site is clipped free of fur, and the patient is prepared with aseptic technique and draped. A 1–3 cm incision is made over the bony lesion, and the soft tissues are dissected from the surface of the tumor. The trephine is then seated into the tumor using a twisting motion. The trephine is advanced through the cis cortex. An effort should be made to not penetrate both the cis and trans cortex as fracture of the bone is more likely (Liptak et al. 2004). Once the trephine is within the medullary cavity, the trephine is rocked backed and forth to loosen the sample and then removed. A stylet is introduced into the trephine to push the sample out of the trephine onto a gauze square. The Jamshidi needle technique is considered a less invasive means of obtaining a bone biopsy as compared to a Michele trephine. A small stab incision is necessary to introduce this device and fractures

are unlikely. Although a more recent study suggests bone biopsies with a Jamshidi needle are only 82% accurate (Sabattini et al. 2017), an earlier study found that in approximately 92% of cases, a correct diagnosis of tumor versus nontumor is achieved when using a Jamshidi needle (Powers et al. 1988). Instrumentation includes a #11 blade and a Jamshidi needle (Figure 1.5). The surgical site is clipped free of fur, and the patient is prepared with aseptic technique and draped. A 1–2 mm stab incision is made over the bony lesion. The Jamshidi needle is introduced into the stab incision and pressed onto the bony lesion. The stylet is then removed from the needle, and the needle is twisted until the cis cortex is penetrated. The Jamshidi needle is rocked back and forth to loosen the sample and then removed. The stylet is reintroduced into the needle in the opposite direction of the initial location. As the stylet is moved through the Jamshidi needle, the biopsy will be ejected from the base of the Jamshidi needle. For lesions that are large enough to be palpated, image guidance is not necessary. However, for small nonpalpable lesions, image guidance is recommended to document that the biopsy samples were indeed acquired from the lesion, preferably the center of the bone lesion. Fluoroscopy and radiography can be used and sometimes even CT-guidance can be helpful. Lymph Node Biopsy Treatment and biopsy of lymph nodes in neoplastic disease remain controversial (Gilson 1995). It is demonstrated that lymph node size (Langenbach et al. 2001; Williams and Packer 2003) and needle aspirates are not great at detecting metastases (Ku et al. 2017; Fournier et al. 2018). Removing a lymph node or performing an incisional biopsy of a lymph node can aid in staging the patient and assist in the determination of prognosis or treatment options. The surgical oncologist should have a thorough knowledge of the anatomic location of the probable draining lymph node for a mass in a particular location. Alternatively, sentinel lymph node detection techniques such as lymphography and scintigraphy can be used (see Chapter 14). The excisional biopsy of super icial lymph nodes such as the mandibular, super icial cervical (prescapular), axillary, inguinal, or popliteal lymph nodes is described below. For removal of lymph nodes within the thorax or abdomen, an exploration of that body cavity is performed and the lymph nodes are removed by careful dissection and maintenance of hemostasis. Instrumentation includes a #10 or #15 blade, Metzenbaum scissors, forceps, Mayo scissors, and suture. The surgical site is clipped free of fur, and the patient is prepared with aseptic technique and draped. An incision slightly larger than the palpable lymph node is made parallel to the axis of the lymph node. The super icial tissue overlying the lymph node is bluntly and sharply dissected. The lymph node capsule is then grasped with the forceps and blunt and/or sharp dissection is performed around the lymph node to free it from the surrounding tissue. Vessels that are encountered may need to be ligated. The lymph node is then removed, and the subcutaneous tissue and skin are closed. Many “lymph nodes” are actually lymphocenters. The implication is that multiple lymph nodes can be present in one location, for example, the mandibular lymphocenter often has two to three lymph nodes.

Figure 1.5 (a) Jamshidi needle (left) with the two stylets (middle and right). The stylet in the middle is used to approach the bone. The stylet to the right is used to remove the sample from the needle after being acquired. (b) The end of the needle is tapered, helping to keep the sample in the needle when the needle is removed from the bone. (c) To remove the sample from the needle, the stylet is introduced through the tip of the needle and the sample is pushed to exit the base at the handle. In some instances, there is too much resistance to push the sample out of the handle end, in which case the irst stylet is used to push the sample out through the tip. It is not ideal because in theory the sample can suffer some damage going through the narrowed end, but sometimes it is necessary. Endoscopic Biopsy Esophagoscopy, gastroscopy, duodenoscopy, and colonoscopy are routinely performed in veterinary medicine as minimally invasive techniques to attain biopsies of the gastrointestinal tract. Biopsies attained during these procedures are generally smaller than what can be achieved with an open procedure; however, the biopsies are often diagnostic, and the morbidity associated with these procedures is reduced over open procedures (Magne 1995; Moore 2003). Laparoscopy and thoracoscopy are still relatively underutilized modalities, but successful procurement of kidney, bladder, liver, spleen, adrenal gland, pancreas, stomach, intestine, and lung biopsies have been described by the use of these procedures (Rawlings et al. 2002; Lansdowne et al. 2005; Vaden 2005; Barnes et al. 2006). Case selection is essential when considering these minimally invasive alternatives,

as cases that have excessively large tumors or other potential contraindications should undergo an open procedure. Laparoscopy and thoracoscopy may have a role in the staging of veterinary patients as the use of these techniques increases. In cases where lymph node evaluation and biopsy would assist in predicting outcome or determining treatment, these procedures could be performed by minimally invasive techniques (Fagotti et al. 2007; Steffey et al. 2015; Lim et al. 2017).

Surgical Considerations for Curative‐Intent Surgery Certain surgical technical principles will improve the chance of success and minimize the risk of local or distant seeding of tumor cells. The tumor should be draped off from the rest of the surgical ield. Surgeons should attempt to not contact ulcerated or open areas of tumor with gloves or instruments. Sharp dissection is preferred over blunt dissection, when possible, as this will decrease the likelihood of leaving neoplastic cells within the patient and decrease the risk of straying from the preestablished margin. Tension on skin closures should be avoided whenever possible, especially in cases that have undergone radiotherapy. Proper knowledge of tension-relieving techniques such as tension-relieving sutures and laps can assist in closure (Soderstrom and Gilson 1995; Aiken 2003); however, tensionrelieving skin incisions are contraindicated after removal of a neoplasm. If an indwelling drain is deemed necessary in a tumor resection site, the drain should be located in an area that can be resected during a subsequent surgery or in an area that will not compromise radiation therapy and can easily be included in the radiation ield. Lastly, control of hemostasis and prevention of seroma or abscess development due to dead space is encouraged. Seromas or hematomas following an incomplete resection allow tumor cells to gain access to areas beyond the surgical ield as these luids may be widely dispersed throughout the subcutaneous space during movement. To decrease the risk of recurrence after tumor resection, there are several techniques that the surgeon should practice. For tumors that have been previously biopsied or for which a drain has been placed, the biopsy tract and/or drain hole need to be removed en bloc with the tumor. Similarly, adhesions should be removed en bloc with the tumor, when possible. Leaving any of these can result in an increased risk of tumor recurrence. Additionally, when establishing a margin during surgical dissection, this margin must be maintained around the periphery of the tumor down to the deep margin. Straying from this may result in an incomplete resection. Similarly, the pseudocapsule present around a tumor should not be penetrated, as this pseudocapsule is constructed of a compressed layer of neoplastic cells (Soderstrom and Gilson 1995). Seeding of these cells will likely result in recurrence, and healing may be inhibited. Lastly, it is important that a new set of instruments, gloves, and possibly drapes be utilized for closure of a wound created by tumor removal or reconstruction of a wound. This principle applies to the removal of subsequent tumors on the same patient, as these items should not be transferred from one surgical site to another.

Defining and Evaluating Surgical Margins The evaluation of surgical margins of an excised specimen is an essential component to appropriate care in a cancer patient. A surgical margin denotes a tissue plane established at the time of surgical excision, the tissue beyond which remains in the patient. Excised masses should be submitted in their entirety for evaluation of the completeness of excision. The surgeon should indicate the margins with ink or some other method prior to placing the specimen in formalin to aid the pathologist in identifying the actual surgical margin. Because the larger tumor specimen is trimmed by a technician to it on a microscope slide, the pathologist may not be oriented as to what represents a surgical margin versus a sectioning “margin.” Tissue ink on the surgical margin allows there to be orientation throughout sectioning. The ink is present throughout the processing of the tumor specimen and is visible on the slide. If tumor cells are seen at the inked margin under the microscope, the surgical margin is by de inition “dirty” or incomplete. There is considerable confusion and controversy surrounding the issue of appropriate surgical margins and clinical decision-making when histologically incomplete margins are obtained. Prior dogma has

suggested that an overly generous margin is likely to be curative. In order to ensure a good oncological outcome, surgical oncologists have been trained to be as aggressive as possible. While it is well-accepted that aggressive surgical margins tend to lead to better local control, this is not true in every case. Even extensive, complete surgical margins do not always lead to a cure. Local recurrence and/or metastasis may occur despite a histologically complete margin. Mounting evidence in the human sarcoma literature seems to suggest that a planned and executed “widest” surgical margin has not resulted in suf icient improvements in disease-free intervals to justify the morbidity incurred with such resections. This opinion among human surgeons is confounded by the routine use of adjuvant radiation therapy in traditionally dif icult-to-resect tumors such as extremity sarcomas. In veterinary medicine, adjuvant radiation therapy may not be available or affordable. As we know from experience and from the veterinary literature, not every patient with a histologically positive margin will experience recurrence. To confound things further, different malignancies and grades of malignancy (mast cell tumor vs. soft tissue sarcoma, low grade vs. high grade) may require speci ic and separate guidelines for margin planning. Veterinary surgical oncology has traditionally followed the adage that for most malignant solid tumors, a 2–3 cm surgical margin and an additional tissue plane deep is the desired intraoperative goal to achieve wide excision, and is most likely to result in a histologically clean excision. Nonetheless, many surgical oncologists bend these “rules” based on tumor-speci ic evidence in the literature and personal experience. Examples of this include using proportional margins in mast cell tumor resection (Pratschke et al. 2013) or less generous margins for speci ic anatomic areas, where 2–3 cm could result in undesirable functional morbidity (e.g. head and neck, spinal column). Many, based on experience, feel comfortable with smaller margins in speci ic tumor types (anal sac tumors, thyroid tumors, low-grade sarcomas) and in some cases, this is supported in the veterinary literature by indings of no difference in local recurrence between one “width of margin” and a lesser one. However, the minimum safe distance necessary to reduce the chance of local recurrence is currently unknown. Regardless of what is actually performed in the operating room, most of the published literature agrees that a histologic margin free of tumor cells is considered the best predictor of improved local recurrence. Varying Definitions of “Margin” There are several considerations that make the comparison of evidence in the literature and subsequent adjustment of surgical planning dif icult. There are distinct and widely different concepts of what constitutes the de inition of a “margin” and how the quality or magnitude of margins are reported. Margins may refer to: (i) the intraoperative margin (i.e. the normal tissue margin as measured in situ between palpable tumor and the planned incision), (ii) the width of normal tissue beyond palpable tumor and the resected edges as measured after resection and before ixation, (iii) the measured width of tissue beyond the palpable tumor after ixation, and (iv) the measured width of normal tissue between the nearest microscopic tumor cell and the resected edge as seen by a pathologist on the slide. Each of the above margin assessment methods represents very different measurements, yet it is rare for veterinary journal articles to report which of these margin assessment methods is being used or even the magnitude of the resected margin beyond a description of “wide,” “marginal,” or “incomplete.” A recent study (Terry et al. 2017) showed that there was signi icant difference in the measured grossly normal surgical margins following sarcoma removal after resection compared to the planned intraoperative excision margin. Therefore, surgeon intent (wide or marginal) should not be considered an acceptable means of reporting margins obtained. In addition, these same authors noted that comparison of subgross evaluation of tumor-free margins, once sectioned and placed on a slide, was not at all comparable to the magnitude of the pathologist-reported histological tumor-free margin. In human medicine, there has been a shift in margin assessment schemes from a traditional Ennekingstyle margin assessment (intralesional, marginal, wide, or radical) to either a distance method (reporting the minimum distance between the nearest observed tumor cell and the inked surgical margin) or a qualitative method, where resected specimens are classi ied as R0 (no tumor at the inked edge), R1 (microscopic tumor at the inked edge), and R2 (residual gross disease left in patient). This highlights the important difference between surgical margins in situ versus histologic margins. Recent reports comparing the distance method to the qualitative method indicate that with osteosarcoma the

distance method in combination with tumor response to chemotherapy (>90% or 1 million electron volts of photon energy = high energy; maximum dose to tumor rather than skin) and orthovoltage (150–500 kVp = low energy; maximum dose to skin surface) external beam radiation, brachytherapy (interstitial placement of radioactive isotopes), or systemic or cavitary injection of radioisotopes (e.g. iodine131). Megavoltage irradiation has advanced with 3D imaging and planning, multi-leaf collimators, and custom-made blocks (Figures 2.1– 2.3).

Surgery and Radiation Radiation can be used post-operatively, pre-operatively, or intraoperatively, depending on tumor type and location. For example, radiation can be used post-operatively (adjuvantly) to treat a solid tumor in a location where wide complete margins cannot be achieved without limb amputation to save the limb. In this scenario, the radiation oncologist should be involved prior to surgery so that he or she can see if this approach is feasible; appreciate the size, ixation, and exact location of mass; plan the radiation ield size and shape; determine how to spare normal tissue and include a large enough ield; meet the owners; discuss complications, costs, expected outcome; etc. The surgeon’s role in this setting is a delicate, minimal surgery with the intent to preserve blood and oxygen supply to the tissue to increase the effectiveness of radiation. A marginal resection to remove all macroscopic tumor and allow primary closure is performed, and radiation therapy is used with surgery to provide long-term tumor control or cure. This approach differs greatly from a failed curativeintent surgery and a poorly healed or open, hypoxic, radiation-resistant

wound and a delayed start to radiation therapy: a situation that is avoided by a team approach and good planning. When adjuvant radiation is planned, the surgeon can help the radiation oncologist by decreasing wound complications such as infection, dehiscence, and seroma formation. Preservation of blood supply, gentle tissue handling, aseptic technique, attention to hemostasis, use of ine, non-irritating (inert) suture material in minimal amounts, obliteration of dead space in the wound, avoidance of tension, post-operative rest, and use of bandages are all important. Drains should be avoided if possible, and if they are used, drainage entry and exit holes are included in the radiation ield. Hemoclips can be placed in the wound intraoperatively to delineate the boundaries of the excised gross tumor burden to assist the radiation oncologist in planning the radiation ield (McEntee 2004, 2008).

Figure 2.1 (a) Standard or conventional linear accelerator. Most of the machines used in veterinary medicine produce electrons of varying energies as well as 6–20 MV photons. (b) Cobalt-60 machine. This type of radiation-producing machine relies on a Cobalt-60 radiation source inside the head of the gantry. The half-life of Cobalt-60 is 5.27 years, necessitating replacement when the source decays to a negligible level. These types of machines are decreasing in popularity in veterinary medicine. (c) Linear accelerator with on-board imaging. These linear accelerators are equipped with a cone-beam CT in order to image a patient immediately prior to a radiation treatment. This is done in order to accurately localize a tumor in relation to surrounding anatomy and ensure precise dose delivery. These machines are often capable of conventional radiotherapy, intensity modulated radiation therapy (IMRT), stereotactic radiosurgery (SRS), and electron therapy. Photo courtesy of AAPM.org.

(d) CyberKnife Stereotactic Radiosurgical unit. A CyberKnife is a linear accelerator mounted on a robotic arm. This allows delivery of radiation from thousands of angles around a tumor. KV x-ray sources are positioned at orthogonal angles above the CyberKnife, which allow for accurate tumor localization with sub-millimeter accuracy. Source: Photo courtesy of Accuray.com.

Figure 2.2 (a) Conventional (i.e. standard) radiation plan for a nasal tumor (outlined in orange). In order to deliver the prescribed dose of radiation to the tumor, the right eye (outlined in blue) needed to be included in the radiation treatment ield. Source: Image courtesy of Siobhan Haney, DVM, MS, DACVIM (Radiation Oncology); Veterinary Cyberknife Cancer Center, Malvern, PA.

(b) Stereotactic body radiation therapy (SBRT) plan for a nasal tumor, which demonstrates how the dose can be sculpted to treat the tumor with a high dose of radiation (red areas) and the normal tissues receive a signi icantly lower dose (blue areas). The graph in the top right corner is a dose volume histogram. The tumor (red line: gross tumor volume [GTV], orange line: clinical target volume [CTV], purple line: planning target volume [PTV]) receives a high dose of radiation while the normal tissues (bue lines: eyes, light yellow lines: lenses, pink line: brain, and dark yellow: skin) receive a signi icantly lower dose. Source: Image courtesy Bernard Séguin, technical assistance Dr. Erin Trageser.

Chemotherapy Chemotherapy can sometimes be used neoadjuvantly to “down-stage” (shrink) a primary tumor prior to surgery, and thus make it more amenable to surgical resection with clean margins. This may be appropriate for cutaneous and subcutaneous masses such as hemangiosarcoma (Wiley et al. 2010). Similarly, corticosteroids may be used to pre-operatively down-stage mast cell tumors with good success, although it is unknown if local recurrence is less likely with this

approach (Stanclift et al. 2008). In this setting, the surgeon needs to involve the medical oncologist prior to surgery. Chemotherapy also can prolong life post-operatively by addressing systemic metastasis; the classic example is appendicular osteosarcoma in dogs. Chemotherapy can be used immediately post-operatively or once the wound has healed, at the discretion of the medical oncologist and the surgeon. Surgery may have only a small role, such as for diagnostic biopsy, with the sole treatment being chemotherapy, as is the case with lymphoma. Metronomic chemotherapy uses standard chemotherapy agents in a continuous administration, which requires lower doses to be used. The target of the drug is the tumor’s continually proliferating microvasculature, which is susceptible to chemotherapeutic effects with minimal systemic toxicity (Gately and Kerbel 2001; Mutsaers 2009; Biller 2014). Bisphosphonates concentrate within areas of active bone remodeling and induce osteoclast apoptosis, which is of therapeutic bene it in managing pathological bone resorptive conditions such as osteosarcoma, multiple myeloma, and metastatic bone cancer. Bone pain is decreased, quality of life is improved, and progression of bone lesions is delayed (Fan et al. 2005, 2007, 2008, 2009; Fan 2007, 2009; Spugnini et al. 2009; Oblak et al. 2012). Embolization treatments include “bland arterial embolization” (without chemotherapy) and chemoembolization (embolization with chemotherapeutic agents) that can be used as a sole therapy or preoperatively to decrease tumor mass and size. Chemoembolization delivers chemotherapy to the tumor, allowing prolonged contact of the tumor to the chemotherapy without high systemic toxicity (Granov et al. 2005) and augmenting tumor ischemia (Weisse et al. 2002a). There are several experimental studies of embolization treatments in healthy dogs, including chemoembolization with gemcitabine (Granov et al. 2005), carboplatin (Chen et al. 2004; Song et al. 2009), and cisplatin (Nishioko et al. 1992). Bland arterial embolization resulted in decreased tumor growth, pain palliation, and control of hemorrhage in two dogs and one goat (Weisse et al. 2002a) and decreased primary tumor size in a dog with a soft tissue sarcoma (Sun et al. 2002). A recent review of veterinary interventional oncology discusses embolization treatments (Weisse 2015).

Figure 2.3 (a) Anal sac adenocarcinomas treated with adjuvant megavoltage radiation. (b) Lead block used to spare normal tissue from RT. (c) Final setup including a tissue-equivalent “bolus” to allow the maximum dose of radiation to reach the tumor. Source: Courtesy of Mary-Kay Klein.

Figure 2.4 (a) focal necrosis on the antebrachium following extravasation of doxorubicin. (b, c) Surgical debridement of the necrotic tissue.

Electrochemotherapy Electrochemotherapy (ECT) involves the systemic or local delivery of lipophobic drugs (chemotherapeutics including Cisplatin and Bleomycin) in combination with permeabilizing electric pulses which promotes the uptake of these drugs by cancer cells (Spugnini et al. 2016). Normally, these drugs use protein receptors to enter the cell membrane thus uptake is generally low under normal conditions (Spugnini et al. 2017). The permeabilizing electric pulses enhance the uptake of these drugs by an estimated factor of 700-fold for bleomycin and 4–8 times for cisplatin (Spugnini and Baldi 2019). When the cancer cell is exposed to the permeabilizing pulses, it will either return to its previous state or reverse the ion luxes and thereby activating a caspase-induced apoptosis. Once returning to its steady state with said drug present internally, cell death is instituted by each drug’s respective mechanism of action.

Heavy sedation or anesthesia (if intraoperative) is required for ECT and protocols have been established. Many resources are available and depending upon geography courses may be available to aid in training. When used in the post-operative setting, the number of ECT sessions is generally two treatments at q 2-week intervals (Spugnini et al. 2016; Spugnini and Baldi 2019). In the gross disease setting, ECT is continued until either complete response is obtained or tumor progression (Spugnini and Baldi 2019). Published data exists for canine soft tissue sarcoma, canine perineal and anal sac tumors, canine melanoma, canine mast cell tumor, feline soft tissue sarcoma, and feline head and neck carcinomas among others (Spugnini and Baldi 2019).

Molecular and Targeted Therapies These therapies include gene therapy (e.g. viral and non-viral vectors); targeting signal transduction that regulates cell growth, differentiation, survival, and death (e.g. via inhibition of protein kinase); antiangiogenic factors (including metronomic chemotherapy and cyclooxygenase-2 inhibitors); agents that can inhibit DNA methyltransferase-1 function; histone deacetylases; proteasome inhibitors; heat shock protein 90 inhibitors; Poly adenosine diphosphate (ADP)-ribose polymerase (PARP) inhibitors; and carbonic anhydrase IX inhibitors (Argyle et al. 2013). A thinking surgical oncologist is always aware of the animal as a whole and how the behavior of the speci ic cancer in the speci ic patient in luences the surgeon’s role. The surgeon is cognizant of paraneoplastic syndromes, appropriate imaging and staging prior to and during surgery, appropriate support and follow-up care, and how various modalities can be used synergistically to achieve the maximal outcome with minimal morbidity. Tables 2.1–2.3 outline various treatment modalities and published outcomes of these treatments for various types of cancers in dogs and cats.

Complications of Chemotherapy Chemotherapy Extravasation

Extravasation is one of the most common immediate risks to the patient during chemotherapy administration. The extent of resultant injury is dictated by the vesicant potential of the leaked drug, as well as its volume and concentration (Villalobos 2006). Extravasation of vesicant chemotherapeutic agents including doxorubicin, vinca alkaloids (vincristine/vinblastine/vinorelbine), dactinomycin, and mechlorethamine may cause local pain, regional edema and erythema, and in severe cases, extensive tissue necrosis and sloughing (Figure 2.4a). Mild to moderate extravasation reactions have also been reported anecdotally with other agents that are considered irritants including carboplatin, cyclophosphamide, dacarbazine, mitoxantrone, gemcitabine, and 5- luorouracil (Villalobos 2006). Extravasations can occur as a result of multiple punctures of the same vein, coagulopathies, systemic in lammation and vasculitis, inadequate restraint of patients leading to catheter dislodgement, and negligence of the person administering the drug. In order to avoid extravasation, all patients should be properly restrained. If any question exists regarding the ability to properly restrain the animal for safe chemotherapy administration, then sedation should be utilized. Furthermore, exact needle/catheter placement is imperative when administering vesicants. Potent vesicants (doxorubicin, dactinomycin, vinca alkaloids) should be lushed with a minimum of 6 ml of saline before removing the intravenous (IV) needle or catheter. Doxorubicin should always be administered via an in-dwelling IV catheter, while less severe vesicants and irritants may be safely administered through a carefully placed butter ly catheter. Some oncologists advocate for administration of all agents via an IV catheter. As a rule, vesicant chemotherapeutics should never be administered via an unattended/unmonitored luid or syringe pump. Instead, the catheter site must be visually monitored for continued proper placement and periodically checked for patency with aspiration/saline lushes prior to, during, and after vesicant drug administration.

Table 2.1 Epithelial. Neoplasia

Researched Treatment Options and Outcomes

Cutaneous Squamous Cell Carcinoma

Modalities include surgery, radiation therapy, surgery combined with radiation therapy, photodynamic therapy, imiquimod, intralesional chemotherapy (alone or combined with hyperthermia or radiation), electrochemotherapy (ECT) with bleomycin, ECT with bleomycin and doxorubicin, vitamin A–related synthetic retinoids. Cryosurgery is used for small lesions, and there are partial responses with piroxicam in dogs.

Intranasal Carcinoma

Median survival time (MST) without treatment is 95 days; MST of 107 dogs with epistaxis was 88 days versus 224 days for 32 dogs without epistaxis (Rassnick et al. 2006). For curative-intent radiation therapy (RT), MST is approximately 8–20 months (Adams et al. 1987, 1998, 2005; Evans et al. 1989; Theon et al. 1993; LaDue et al. 1999; Nadeau et al. 2004). However, in one study the MST for nasal carcinomas treated with curative intent RT was only 4.4 months, and dogs with unilateral intranasal involvement without bone destruction beyond the turbinates on computed tomography (CT) had a MST of 23.4 months, versus 6.7 months for dogs with CT evidence of cribriform plate involvement (Adams et al. 2009). Curative-intent RT followed by surgical debulk (13 dogs) has MST of 47 months in one study (Adams et al. 2005), and 15 months in another (Bowles et al. 2014). In another study, 42 dogs with nasal tumors treated with surgical cytoreduction and orthovoltage RT had a MST of 7.4 months (Northrup et al. 2001). Curative–intent RT with CT planning has MST of approximately 11–20 months. Coarse-fraction RT (56 dogs) has MST of 7 months (Mellanby et al. 2002), 4.8 months in another study of 48 dogs (Gieger et al. 2008), 16.8 months

Neoplasia

Researched Treatment Options and Outcomes (although the majority were carcinomas, there were several sarcomas in the study) (Fujiwara et al. 2013), and 6.5 months (with no signi icant difference with or without cribriform plate involvement) (Maruo et al. 2011). Hypofractionated image-guided robotic stereotactic radiotherapy either with or without adjunctive treatment for nasal tumors (79% were carcinomas) resulted in a MST of 13.5 months (Glasser et al. 2014), and 10.4 months for nasal carcinomas in another study (Kubicek et al. 2016). In another study of non-lymphomatous nasal tumors in dogs treated with hypo-fractionated image-guided robotic stereotactic radiotherapy without adjunctive chemotherapy, the MST was 19.3 months, and was not signi icantly different for carcinomas versus sarcomas, or dogs with intracranial extension of disease (Gieger and Nolan 2017). In another study of 12 dogs (75% of dogs had intranasal carcinomas) treated with intensity-modulated RT, the MST was 15.3 months (Hunley et al. 2010), and at least one eye could be saved in all dogs treated with intensitymodulated RT in another study (Vaudaux et al. 2007), and both eyes were spared in another study with MST of 13.8 months (Lawrence et al. 2010). Palliative 3D conformal RT (38 dogs) has overall median progression-free interval of 10 months (Buchholz et al. 2009). Palliative RT in another study resulted in 10.2 months MST (although 39% of the dogs in this study had nasal sarcomas) (TanColeman et al. 2013). Chemotherapy alone (small numbers of dogs) is investigational (Hahn et al. 1992; Langova et al. 2004). In a study of 37 dogs with reirradiation of nasal carcinomas, the MST from the irst dose of RT was 14.9 months and 5.9 months from the irst dose of the second course of RT (Gieger et al. 2013). Reirradiation in another study

Neoplasia

Researched Treatment Options and Outcomes resulted in an overall MST of 2.5 years (Bommarito et al. 2011). Use of radiation sensitizers (some investigational) is generally not better than RT alone. Other treatments include brachytherapy, immunotherapy, cryotherapy, and PDT (all investigational) (MacEwen et al. 1977; White et al. 1990; Thompson et al. 1992; Lucroy et al. 2003b). Slow-release cisplatin and RT for nasal tumors resulted in MST of 15.6 months (35% of tumors were sarcomas in this study) (Lana et al. 2004). High-dose-rate brachytherapy in 15 dogs (not of which had nasal carcinomas) resulted in a 17-month MST (Klueter et al. 2006). Primary frontal sinus squamous cell carcinoma in three dogs treated with piroxicam combined with carboplatin or toceranib (investigational in 3 dogs) (de Vos et al. 2012). Nasal carcinoma treated with RT and irocoxib was safe and improved life quality in dogs with nasal carcinomas (Cancedda et al. 2015b).

Transitional Cell Bladder/urethra (dogs): Carcinoma Surgery: Surgery includes debulk, stent, bypass (e.g. (Urogenital) pre-pubic cystostomy catheter for palliation if obstructed), total cystectomy and urinary diversion, resection of proximal urethra and bladder neck and bilateral ureteroneocystostomy (Saulnier-Troff et al. 2008), partial cystectomy alone or in combination with unilateral or bilateral ureteral reimplantation (Stone et al. 1996; Marvel et al. 2017). Rarely is there complete excision due to urethral, prostatic, or ureteral involvement. Surgery is generally combined with chemotherapy to improve survival; MST chemotherapy and surgery 475 days, versus chemotherapy alone MST 31 days, versus surgery alone MST 240 days, versus no treatment MST 7 days (Molnar and Vajdovich 2012).

Neoplasia

Researched Treatment Options and Outcomes Partial cystectomy: 14 dogs treated with partial cystectomy with or without any adjuvant treatment, the MST was 113 days (Norris et al. 1992). Partial cystectomy and long-term piroxicam (92%) or carprofen (8%) +/− various chemotherapeutic agents were used in 37 dogs with bladder TCC, achieving a MST was 348 days (Marvel et al. 2017). Total cystectomy: Total cystectomy followed by ureterocolonic anastomosis was performed in 10 dogs with TCC the overall prognosis was poor with adverse effects such as severe vomiting and neurologic signs (Montgomery and Hankes 1987; Stone et al. 1988). Total cystectomy and urinary diversion to the vagina have been reported, although persistent urinary incontinence is expected (Boston and Singh 2014; Saeki et al. 2015). Total cystectomy and urinary diversion to vagina or prepuce (with post-operative chemotherapy) resulted in a MST of 385 days in 10 cases, and although there were fewer gastrointestinal and neurologic complications compared to ureterocolic anastomosis, dehiscence of ureterostomy, pyelonephritis, oliguria, azotemia, ureteral obstruction, and persistent urinary incontinence were reported post-operative issues (Saeki et al. 2015). Total cystectomy and bilateral cutaneous ureterostomy in 4 dogs had a MST of 279 days (Ricardo Huppes et al. 2017). Resection of proximal urethra and bladder neck and bilateral ureteroneocystostomy: One dog treated with this surgery and adjuvant chemotherapy survived 580 days (Saulnier-Troff et al. 2008). Debulking surgery: Debulking surgery alone for bladder TCC had a MST of 109 days (Lengerich et al. 1992). Debulking surgery performed by ultrasoundguided endoscopic diode laser ablation of TCC bladder/urethra in dogs and post-operative

Neoplasia

Researched Treatment Options and Outcomes carprofen or piroxicam (given for an unknown duration) had MST 380 days, however, complications included stranguria, hematuria, stenosis, spread of TCC within the lower urinary tract, urethral perforation, and bacterial cystitis (Cerf and Lindquist 2012). Debulking surgery using carbon dioxide laser ablation of bladder TCC (via laparotomy) combined with mitoxantrone and piroxicam achieved a MST of 299 days, with rapid resolution of clinical signs (Upton et al. 2006). In another study, 34 dogs with TCC of the urinary bladder and/or prostate and/or urethra were treated with between one and six doses of doxorubicin concurrently with piroxicam, and 50% of these cases also had surgery (mostly curative intent). Of the 23 dogs with measurable disease, 14 had stable disease, 7 had progressive disease and 2 had a partial response. After documented progression of disease, 15 dogs received additional chemotherapy, consisting of carboplatin (n = 8), mitoxantrone (n = 6), vinorelbine (n = 1) or silibinin (n = 1). Overall median progression-free survival was 103 days, and MST was 168 days. Cytoreductive surgery did not result in prolongation of progression-free survival, but signi icantly prolonged overall survival, with chemotherapy and surgery resulting in a MST of 217 days versus chemotherapy alone MST 133 days (Robat et al. 2013a). Stenting: Stenting of 12 dogs with malignant urethral obstructions; 7 had good to excellent outcome, 3 had fair outcome, and 2 had poor outcome (Weisse et al. 2006). Self-expanding nitinol stents were successfully placed in 17 of 19 dogs with urethral obstruction due to TCC, MST 78 days, complications included incontinence in 7 dogs,

Neoplasia

Researched Treatment Options and Outcomes reobstruction from continued growth of urethral TCC (3 dogs), acute reobstruction shortly after the procedure (1 dog), and stent migration (2 dogs) (McMillan et al. 2012). In 42 dogs with obstructive carcinoma (TCC, prostatic adenocarcinoma [ADC], or urinary carcinoma) of the urethra treated with a self-expanding metallic stent, resolution of urinary tract obstruction was achieved in 41 dogs, in one dog the stent dislodged from the urethra and migrated to the bladder. Severe incontinence occurred in 11 dogs and stranguria in 2 dogs. Stent length, diameter, and location were not associated with incidence of incontinence or stranguria. MST after stent placement was 78 days, and treatment with NSAIDs before and chemotherapeutics (carboplatin, adriamycin, mitoxantrone, Cytoxan, gemcitabine, or vinblastine) after stent placement increased MST to 251 days (Blackburn et al. 2013). Permanent cystostomy: for palliation of obstruction also reported (Smith et al. 1995). Long-term urethral diversion using a low-pro ile gastrostomy tube was used to relieve urethral obstruction in a dog with granulomatous urethritis (Salinardi et al. 2003). Abdominal wall TCC: TCC of the urinary tract, as well as abdominal wall TCC occurred in 24 dogs, and developed signi icantly more often in dogs that had undergone cystotomy (18/177 or 10%) compared to dogs that had not (6/367 or 1.6%). In 1 dog that had not undergone cystotomy, TCC had invaded through the urinary bladder wall and spread down the median ligament to the abdominal wall. None of the 18 dogs that received anti-cancer drugs had remission of the abdominal wall TCC, MST after abdominal wall TCC detection was 57 days. It is crucial to minimize the risk of TCC seeding at surgery. Percutaneous sampling of TCC should be

Neoplasia

Researched Treatment Options and Outcomes avoided (Higuchi et al. 2013). Radiation: Complications of urinary incontinence and cystitis occur with whole-bladder intraoperative radiation (Walker and Breider 1987; Withrow et al. 1989). Coarse fractionation external beam radiation (with mitoxantrone-piroxicam) showed no bene it over mitoxantrone-piroxicam chemotherapy alone (Poirier et al. 2004b). Laparoscopically implanted tissue-expander radiotherapy shows promise in reducing radiation damage to surrounding tissues (one dog still alive at 21 months) (Murphy et al. 2008). Neoadjuvant chemotherapy, external beam radiation therapy, and adjuvant chemotherapy were reported in 4 dogs (Marconato et al. 2012). Adaptive radiotherapy techniques spared rectal irradiation and maximized bladder irradiation (Nieset et al. 2014). Intensity-modulated and image-guided radiation therapy for treatment of genitourinary carcinomas (bladder, prostate, urethra) in 21 dogs resulted in a MST of 654 days (Nolan et al. 2012). Medical: Mitoxantrone-piroxicam combination with minimal toxicity has a MST of 291 days (Henry et al. 2003). Cisplatin-piroxicam is not recommended (Greene et al. 2007). For piroxicam alone, MST is 181 days (Knapp et al. 1994). For deracoxib alone, MST is 323 days (McMillan et al. 2011). Gemcitabine-piroxicam combination – MST was 230 days (Marconato et al. 2011), and carboplatinpiroxicam combination –MST was 161 days (Boria et al. 2005), and vinblastine alone, MST 147 days (Arnold et al. 2011). In another study there was no signi icant difference in MST of dogs treated with mitoxantrone-piroxicam versus carboplatinpiroxicam combination; however, dogs with prostatic involvement had shorter MST than TCC in other locations (Allstadt et al. 2015). In 14 dogs

Neoplasia

Researched Treatment Options and Outcomes treated with cisplatin- irocoxib combination, the remission rate was 57% and MST 179 days, in 15 dogs treated with cisplatin the remission rate was 13% and MST 338 days, and in 15 dogs treated with irocoxib alone the remission rate was 20% and MST 152 days. Renal and gastrointestinal toxicoses were common in dogs receiving cisplatin or cisplatin/ irocoxib (Knapp et al. 2013). In another study of 30 dogs, most of which had failed other treatments, metronomic chlorambucil resulted in partial remission in 1 dog, stable disease in 20 dogs, and progressive disease in 9 dogs. The MST of dogs from the time of the start of chlorambucil treatment was 221 days (Schrempp et al. 2013). Subcutaneous 5-azacitidine treatment – MST not reported, 18 dogs – partial remission in 4, stable disease in 9, and progressive disease in 4 (Hahn et al. 2012). Intravesical administration of mitomycin C in 13 dogs with bladder TCC – 2 dogs had severe myelosuppression, 5 had partial remission, 7 had stable disease (Abbo et al. 2010). Intralesional interleukin-2 injected via ultrasound guidance or after surgical debulking in combination with meloxicam, piroxicam, or irocoxib, +/− mitoxantrone resulted in an overall MST of 170 days (Konietschke et al. 2012). Folate-targeted vinblastine conjugate (EC0905) (investigational). Scintigraphy showed folate uptake in both primary and metastatic lesions, partial remission occurred in 56% of dogs (5 dogs), and stable disease in 44% of dogs (4 dogs) (Dhawan et al. 2013). Intra-arterial carboplatin chemotherapy may be preferable compared to the intravenous route for rapid reduction in tumor volume, however, follow-up is short and MST is not reported (Culp et al. 2015). Concurrent antibiotics are commonly needed

Neoplasia

Researched Treatment Options and Outcomes (Budreckis et al. 2015). PDT: PDT is currently under investigation (Lucroy et al. 2003c; Ridgway and Lucroy 2003). Prostatic carcinoma: Prostatectomy is performed for early-stage disease con ined to prostate capsule (but there is a high rate of urinary incontinence) (Hardie et al. 1984; Basinger et al. 1989). Other treatment modalities include transurethral resection (TUR) (electrosurgical and investigational; relieves urethral obstruction, but 2 of 3 dogs had perforated urethra) (Liptak et al. 2004a); Nd:YAG laser (investigational: 8 dogs had MST of 103 days; 3 died from complications within 16 days) (L'Eplattenier et al. 2006); stenting (investigational but very promising, with good to excellent outcome in 8 dogs) (Weisse et al. 2006); bypass obstruction (prepubic catheter); chemotherapy (investigational); non steroidal anti-in lammatories (NSAIDs) (MST 6.9 months in 16 dogs, compared to 0.7 months with no cancer therapy in 15 dogs) (Sorenmo et al. 2004b); intraoperative prostatic radiation (MST for 10 dogs was 114 days) (Turrel 1987a); PDT (investigational) (Lucroy et al. 2003a; L'eplattenier et al. 2008); and palliative radiation for skeletal metastasis. One dog with ductus deferens and prostate TCC treated with removal of both ductus deferens and long-term meloxicam lived for 9 months (Guerin et al. 2012). Cats: Bladder TTC in 11 cats treated with meloxicam had a MST of 311 days (Bommer et al. 2012), in another paper of 20 cats with bladder TCC treated with piroxicam, chemotherapy, or surgery, the MST was 261 days (Wilson et al. 2007).

Neoplasia

Researched Treatment Options and Outcomes

Solitary Primary Surgery (lung lobectomy) is performed, and regional Lung Mass lymph nodes should be biopsied and ideally removed. Clinical stage is an important prognostic indicator with MST 555 days for papillary T1NoMo versus 72 days for the rest (Polton et al. 2008). Lung lobectomy via thoracoscopy reported, smaller tumors are more amenable to thoracoscopic surgery (Mayhew et al. 2013; Bleakley et al. 2015). All adjuvant chemotherapy is investigational at this stage: systemic chemotherapy (vinorelbine) (Poirier et al. 2004a; Wouda et al. 2015); inhalational chemotherapy (Hershey et al. 1999; Vail et al. 2000); intrapleural chemotherapy for malignant pleural effusion (Moore et al. 1991a), a single case report exists of a dog with grade III bronchoalveolar ADC with vascular in iltration and lymph node metastasis treated with tumor removal, chaperone-rich cell lysate (CRCL) vaccine administered weekly, topical imiquimod for the irst 12 treatments, and a single injection of bacillus Calmette-Guerin (BCG) at week 30 of treatment, with a survival of 50+ weeks postdiagnosis (Epple et al. 2013).

Neoplasia

Researched Treatment Options and Outcomes

Thymoma

Resection is done if possible (89% are resectable) (Gores et al. 1994; Zitz et al. 2008; Robat et al. 2013b), along with chemotherapy (Willard et al. 1980; Aronsohn 1985; Martin et al. 1986; Atwater et al. 1994; Robat et al. 2013b); especially if concurrent megaesophagus relating to a poor surgical candidate; radiation therapy has complete to partial responses, and many also received concurrent surgery or chemotherapy (Hitt et al. 1987; KaserHotz et al. 2001; Smith et al. 2001; Robat et al. 2013b). Median survival time with and without surgical treatment was 635 and 76 days, respectively, although a small percentage of surgical cases also received chemotherapy and radiation therapy. Recurrent disease after surgery occurred in 15–17%, and prognosis good after second surgery (Zitz et al. 2008; Robat et al. 2013b). Overall MST with surgery alone 790 days (Zitz et al. 2008). Treatment of concurrent myasthenia gravis is accomplished with immunosuppressive and or anticholinesterase therapy, H2 blockers, other supportive care. Portal site metastasis has been reported after thoracoscopic resection of a malignant thymoma in a dog (Alwen et al. 2015). Thymoma-associated exfoliative dermatitis has been reported in cats and dogs, which resolves with the removal of the thymoma (Forster-Van Hijfte et al. 1997; Rottenberg et al. 2004; Singh et al. 2010; Tepper et al. 2011; Cavalcanti et al. 2014).

Alimentary

Esophageal: Palliative PDT for esophageal carcinoma in a dog allowed a 9-month survival time (Jacobs and Rosen 2000). Esophagogastroscopy and loop electrocautery debulking of an esophageal carcinoma with polypoid hyperplasia resulted in at least a 6-month ST in one dog, and another dog with

Neoplasia

Researched Treatment Options and Outcomes esophageal ADC was euthanazed after one week after gastrostomy tube placement due to poor quality of life (Arnell et al. 2013). Stenting of an obstructed esophagus due to SCC resulted in effective palliation for 3 months (Hansen et al. 2012). Primary carcinomas of the esophagus were reported in 2 cats (Gualtieri et al. 1999a). Gastric: Localized gastric carcinoma treated with marginal resection and adjunctive carboplatin chemotherapy is potentially curative (Lee et al. 2014), although partial gastrectomy is usually indicated. It is rare that all local disease is resected and metastasis usually occurs early, leading to a poor prognosis after surgery in most cases. In several studies, the median survival time was only 55 days for 29 dogs with gastric ADC treated with surgery (Fonda et al. 1989; Gualtieri et al. 1999b; Swann and Holt 2002). Small Intestinal: usually solitary intestinal masses, treatment is surgery with wide margins (at least 5 cm), biopsy of liver and lymph node at surgery should be done, adjuvant chemotherapy may be considered. Debilitation and hypoproteinemia may complicate treatment. In a study of 18 cats diagnosed with small intestinal ADC, the MST of cats with ADC that underwent surgery was 365 days versus 22 days for those with that did not undergo surgery, and the MST was 843 days for those without evidence of metastatic disease at surgery, versus 358 days for those with metastatic disease at surgery (Green et al. 2011). Cats with advanced disease (including carcinomatosis) treated with surgery can have long-term survival (Kosovsky et al. 1988). No proven chemotherapy for ADC, but combination of 5- luorouracil and cisplatin may be effective (Stanclift and Gilson 2004), second-look surgery

Neoplasia

Researched Treatment Options and Outcomes recommended for evaluation of response to chemotherapy (Stanclift and Gilson 2004). Overall MST in dogs treated with surgical resection was 233 days, sex was a prognostic factor with MST for male dogs 272 days v 28 days for female dogs. In this study, only 2 of 15 dogs received adjuvant chemotherapy (Paoloni et al. 2002). Reported adjuvant chemotherapies in dogs include doxorubicin, carboplatin, gemcitabine, doxorubicin, 9-aminocamptothecin, cisplatin, and 5- luorouracil (Paoloni et al. 2002). Intracavitary chemotherapy for carcinomatosis can extend survival time (ST) (Moore et al. 1991a; Charney et al. 2005). Large intestinal: debilitation and hypoproteinemia may complicate treatment, surgical resection with wide margins (4–8 cm), and serosal patching of anastomosis, the colon is more prone to dehiscence than the small intestine. Pubic and/or ischial osteotomy is possible for malignant lesions in the caudal colon (Yoon and Mann 2008), assess/biopsy regional and mesenteric lymph nodes and liver, adjuvant doxorubicin chemotherapy in cats with colonic ADC (Slawienski et al. 1997); intracavitary chemotherapy for carcinomatosis can extend ST (Moore et al. 1991a; Charney et al. 2005); adjuvant doxorubicin chemotherapy in dogs (Paoloni et al. 2002); feline large intestinal ADC more commonly associated with mucosal ulceration and bowel thickening than annular stenosis (Patnaik et al. 1976). Rectal: surgical approaches: rectal eversion, rectal pull-through, or resection and end-to-end anastomosis, fecal incontinence is uncommon if rectal resection 4–6 cm rectum is resected with rectal pull-through surgery,

Neoplasia

Researched Treatment Options and Outcomes however, the size of the dog plays a role in how much rectum can be resected (Nucci et al. 2014). Resection via an anal approach (and rectal prolapse) was reported in 22 dogs (Danova et al. 2006). Thoracoabdominal stapling devices were used to resect masses of the distal third of the rectum (in combination with rectal prolapse), with a minimum of 0.5–1 cm margins. Meantime to veterinarian follow-up was 564 days, and no dog had recurrence of disease during this time (Swiderski and Withrow 2009). Transanal endoscopic resection of benign rectal tumors has been described (Holt and Durdey 1999; Holt 2007; Coleman et al. 2014). In another study, 11 dogs were treated with full-thickness colorectal amputation by either simple transanal or combined abdominal-transanal pull-through technique for colorectal carcinoma, two dogs that had a combined abdominal-transanal approach died within 4 days (Morello et al. 2008). Incontinent endon colostomy has been described in the management of 1 dog with rectal ADC (Kumagai et al. 2003). Piroxicam palliative for rectal tubulopapillary polyps if unresectable or as an alternative to surgery (Knottenbelt et al. 2000). No effective chemotherapy for ADC, but combination of 5- luorouracil and cisplatin may be effective (Stanclift and Gilson 2004). Mean survival time 22 months following surgery, radical surgery associated with high complication rate and poor survival ( 2.5 cm in length had signi icantly shorter survival times; however, tumor length of 27 cm3), bilateral disease, or for gross metastatic disease (Leav et al. 1976; Jeglum et al. 1983; Ogilvie et al. 1991; Post and Mauldin 1992; Hammer et al. 1994; Fineman et al. 1998; Theon et al. 2000). The MST of dogs treated with surgery and chemotherapy was 518 days, which was not statistically different from that of the dogs treated with surgery alone (Nadeau and Kitchell, 2011). A clinical bene it was seen in 12/15 dogs (4 PR and 8 SD) treated with Toceranib phosphate (Palladia®) for thyroid carcinoma ( London et al. 2012 ).. Boron neutron capture therapy is investigational (Pisarev et al. 2006).

Neoplasia

Researched Treatment Options and Outcomes

Hyperthyroid Cats

Multi-nodular adenomatous hyperplasia (majority), malignant carcinomas (1–3%) (Lunn and Page 2013). 131I thyroid ablation is treatment of choice with reported MST 2 years (Petersen and Becker 1995), or 4 years (Milner et al. 2006), compared to 2 years for methimazole treatment (Milner et al. 2006). Treatment options are: oral anti-thyroid medication (Peterson et al. 1988; Mooney 2001; Trepanier et al. 2003; Trepanier 2007; Frenais et al. 2009; Higgs and Hibbert 2012; Daminet et al. 2014), topical methimazole to pinna (Hoffman et al. 2002; Hoffmann et al. 2003; Sartor et al. 2004; Lecuyer et al. 2006; Hill et al. 2011, 2015a, 2015b, 2015c; Boretti et al. 2013, 2014), topical carbimazole to pinna (Buijtels et al. 2006), iodine-restricted food (Melendez et al. 2011a, 2011b; Yu et al. 2011; van der Kooij et al. 2014; Scott-Moncrieff et al. 2015; Hui et al. 2015), thyroidectomy (Flanders et al. 1987; Flanders 1999; Padgett 2002; Birchard 2006; Naan et al. 2006), ultrasound-guided percutaneous ethanol injections (Wells et al. 2001; Goldstein et al. 2001), and ultrasound-guided percutaneous radiofrequency ablation (Mallery et al. 2003). Preoperative scintigraphy is ideal (Lunn and Page 2013).

Table 2.2 Round cell. Neoplasia Researched Treatment Options and Outcomes Mast Cell Tumor

Dogs: The mainstay of treatment is curative intent surgery with 2–3 cm margins laterally and one fascial plane deep depending on the tumor grade (Simpson et al. 2004; Fulcher et al. 2006), or a modi ied lateral margin approach (although 15% dirty margins were seen using this system) (Pratschke et al. 2013). High-grade tumors at greater risk of local recurrence (Donnelly et al. 2015). Smaller margins may be adequate in lower grade tumors and width of complete margins not prognostic for local recurrence (Donnelly et al. 2015). Completeness of excision has been previously shown to be a positive prognostic indicator (Seguin et al. 2001; Weisse et al. 2002b). There was an increased risk of incompleteness of excision (when treated with wide excision with curative intent) when surgery residents performed the surgery, compared with specialist surgeons (Monteiro et al. 2011). Increased tumor size was also a signi icant risk factor for inadequate surgical margins (Monteiro et al. 2011). Grade I tumors may be completely excised with margins of 1 or 2-cm laterally and one fascial plane deep (n = 4 cases), but incomplete lateral excision occurred in 2 of 19 grade II MCTs (10%) using the surgical approach of 2 cm lateral margins and one fascial plane deep (Fulcher et al. 2006). In another study, 15 of 20 cutaneous grade II MCTs were completely excised with 1 cm lateral margins and a deep margin of one fascial plane, and all were completely excised with 2 cm lateral margins and a deep margin of one fascial plane (Simpson et al. 2004). Another approach for local control is marginal surgery with adjuvant radiation, which results in 85–95% 2-year control for stage 0, Patnaik grade I or II (al-Sarraf et al. 1996; Frimberger et al. 1997; LaDue et al. 1998; Turrel et al. 1988). In another study, local cure was achieved in cases with incomplete margins and radiation therapy in 75–96% of dogs (al-Sarraf et al. 1996; Frimberger et al.

Neoplasia Researched Treatment Options and Outcomes 1997; LaDue et al. 1998; Chaf in and Thrall 2002; Dobson et al. 2004; Hahn et al. 2004; Poirier et al. 2006). The rate of local recurrence for grade-II MCT is reported to be as high as 50% if margin status is unknown (al-Sarraf et al. 1996; Macy 1986). In two studies where grade II MCTs were resected with wide margins, the long-term survival igures for dogs with grade II MCTs were substantially improved to approximately 90% with surgery alone (Seguin et al. 2001; Weisse et al. 2002b). If margins are found to be incomplete or close, additional local therapy with primary re-excision or radiation therapy improves survival and local control (Kry and Boston 2014). However, another study found the outcome of dogs with incompletely excised grade II MCTs was not affected by adjuvant treatments (surgery, radiation therapy, chemotherapy, or combination), suggesting attentive monitoring and action upon uncommon recurrence (Vincenti and Findji 2017). Assessing the proliferation activity of incompletely excised grade II MCTs may assist in determining the need for ancillary therapy, however, even those with low proliferation activity can recur (Smith et al. 2017). Using the Patnaik system, 93% with Grade I MCT, 44% with Grade II and 6% with Grade III tumors survived 4 years after surgery (Patnaik et al. 1984). Similarly, 100% of dogs with grade I, 44% with grade II, and 7% with grade III MCT were alive at 24 months after surgery (Abadie et al. 1999). However, in other studies, 5–22% of grade II MCTs metastasized (Seguin et al. 2001; Michels et al. 2002; Weisse et al. 2002b; Cahalane et al. 2004; Murphy et al. 2004). The need for adjuvant chemotherapy for completely excised grade II tumors (when not in a poor prognostic location) is unpredictable; close monitoring is advisable (Seguin et al. 2001); and determining mitotic and Ki67 indices may help identify which subset of grade II MCTs may bene it from chemotherapy (Abadie et al. 1999; Scase et al. 2006; Romansik et al. 2007; Webster et al. 2007;

Neoplasia Researched Treatment Options and Outcomes Maglennon et al. 2008; Elston et al. 2009; Kiupel et al. 2011; Thompson et al. 2011a, 2011b; O'Connell and Thomson 2013; van Lelyveld et al. 2015), with clinical staging being important regardless of histologic grade (Stefanello et al. 2015). Dogs with stage 2 (loco-regional lymph node metastasis) grade II MCT, the use of prednisone, vinblastine, and lomustine after adequate local-regional therapy can provide a median survival in excess of 40 months (Lejeune et al. 2015). In another paper, for dogs with grade 2, stage II MCTs, there was no signi icant difference in survival times between dogs with and without LN metastasis; however, removal of the metastatic LN may prolong survival (Baginski et al. 2014). Vinblastine-prednisolone chemotherapy is given as adjuvant to surgery for high-risk MCT (mucous membrane origin, node-positive, high-grade) (Thamm et al. 2006). Vinblastine-prednisolone chemotherapy increased survival signi icantly compared to the tyrosine kinase inhibitor masitinib as adjuvant to high-risk MCTs in another study (Miller et al. 2014). Another approach is marginal surgery with adjuvant chemotherapy (vinblastine and prednisolone) (Davies et al. 2004). In a study of dogs with a median number of 4 MCTs at presentation, 90% of dogs were treated with surgery, and 40% of dogs were treated with only surgery as the sole form of treatment, and 60% of dogs received chemotherapy. There was no signi icant difference in progression-free survival or MST in those dogs that received chemotherapy compared to those dogs that did not. Incomplete surgical margins were not associated with decreased survival times (O'Connell and Thomson 2013). Chemotherapy may also be used for dogs with multiple cutaneous mast cell tumors or unresectable/metastatic disease. Multiple cutaneous MCTs may represent multiple de novo events rather than metastatic disease, with a disease-free survival time of >5 years in 54 dogs reported (Mullins et al. 2006), and no

Neoplasia Researched Treatment Options and Outcomes difference in outcome compared to stage 1 dogs in another study (Murphy et al. 2006). However in another study, if any one of multiple cutaneous MCTs was identi ied as high grade, then there was a worse prognosis (O'Connell and Thomson 2013), and Kiupel et al.(2005) found that dogs presenting with multiple synchronous MCTs had a signi icant decrease in survival time (Kiupel et al. 2005). In another paper, 23 dogs with MCTs treated with incomplete resection and adjuvant prednisolone and vinblastine chemotherapy, there was a 57% 1- and 2-year disease-free rate, and some of these dogs had multiple MCTs (Thamm et al. 1999). Other chemotherapy agents include lomustine, vincristine, prednisolone/cyclophosphamide/vinblastine, cyclophosphamide/vincristine/prednisolone/hydroxyurea, lomustine/vinblastine, chlorambucil/prednisolone (McCaw et al. 1997; Elmslie 1997; Gerritsen et al. 1998; Rassnick et al. 1999; Thamm et al. 1999; Davies et al. 2004; Taylor et al. 2009; Cooper et al. 2009), vinorelbine (Grant et al. 2008; Wouda et al. 2015), and inhibitors of tyrosine kinase toceranib phosphate which possess both direct antitumor and anti-angiogenic activity (Liao et al. 2002; London et al. 2003). Dogs with grade II or III MCTs treated with the tyrosine kinase inhibitor masitinib had a longer time to disease progression (178 days) vs dogs receiving placebo (75 days), although MST was only improved in dogs with KIT mutations (417 days vs 182 days with placebo) (Hahn et al. 2008). In a subsequent study, the MSTs of dogs treated with masitinib or placebo were not signi icantly different (Hahn et al. 2010). The tyrosine kinase inhibitor Toceranib phosphate (Palladia®) was used to treat bulky (non-resectable) grade II or III MCTs with an overall 43% partial or complete response rate, and 12% stable disease, with 82% of dogs with KIT mutations responding compared to 54% for those without (London et al. 2009). Vinblastine – toceranib phosphate combination showed a 71% objective response rate in one study (Robat

Neoplasia Researched Treatment Options and Outcomes et al. 2012). Water-soluble micellar paclitaxel was safer with 30% biologic response rate compared to lomustine (11% biologic response rate) in the treatment of nonresectable grade II or III MCTs (Vail et al. 2012). In another study of non-resectable MCT, treated with toceranib phosphate-lomustine-prednisone resulted in a response rate of 46% and a median progression-free survival of 53 days (Burton et al. 2015). Non-resectable MCT can also be treated with radiation therapy combined with chemotherapy (toceranib-prednisolone), MST was not reached at a median follow-up of 374 days (Carlsten et al. 2012). Other adjunctive medical therapies include H1 blocker, H2 blocker, omeprazole, sucralfate, and misoprostol. Pretreatment with prednisone prior to surgery (neoadjuvant) can reduce the size of mast cell tumors, facilitating resection with adequate margins in situations where margins cannot be con idently attained because of mass location or size or both (Stanclift and Gilson 2008). ECT with cisplatin administered intratumorally was used to treat 12 cutaneous MCT nodules in dogs. Electrical pulses were delivered to the tumor and surrounding margin. If the tumor did not respond completely to the irst session, additional sessions were performed at 2- to 4-week intervals. The median tumor size was 2.9 cm3, there was a 62.5% complete response with a median follow-up time of 26 months. Tumors >8 cm3 did not respond. Tumor grade prior to treatment was unknown (Kodre et al. 2009). ECT with bleomycin injected into peritumoral tissue has also been reported as adjuvant treatment for incompletely resected MCT in dogs. The overall response rate was 85% with a mean time to recurrence of 53 ± 6.5 months (Spugnini et al. 2006b) Electrogene therapy with IL-12 was used in 11 canine cutaneous MCTs, resulting in a 13–83% reduction (median 50%) of the original tumor volume (Pavlin et al. 2011). ECT with cisplatin and peritumoral IL-12 gene

Neoplasia Researched Treatment Options and Outcomes electrotransfer was used to treat 18 dogs with canine MCT. Eleven of 18 dogs had pre-treatment punch biopsies, and all were grade I or II and the median volume of treated tumors was 2.1 cm3. At a median of 40 months, a complete response was achieved in 72% (Cemezar et al. 2017). Plasma Multiple myeloma treatment modalities include Cell Tumor chemotherapy using melphalan and prednisolone standard, as well as cyclophosphamide, CCNU, chlorambucil, doxorubicin, vincristine (Osborne et al. 1968; MacEwen and Hurvitz 1977; Drazner 1982; Matus et al. 1986; Brunnert et al. 1992; Fan et al. 2002; Hanna 2005; Gentilini et al. 2005; Vail 2007); surgery (stabilization of pathological fractures) (Banks et al. 2003a; Vail 2007) with or without adjuvant radiation therapy, bisphosphonates (Vail 2007); tyrosine kinase–inhibitor therapy (toceranib phosphate) (London et al. 2003), addressing chronic infectious disease/uncontrolled long-term stimulation of the immune system could be important (Geigy et al. 2013). Extramedullary treatment modalities (cutaneous) include conservative surgical resection (can add chemotherapy if local recurrence or incomplete margins) (Kryiazidou et al. 1989; Rusbridge et al. 1999). Radiation alone for stable solitary osseous plasmacytoma (MacEwen et al. 1984; Meis et al. 1987; Rusbridge et al. 1999). Surgery plus radiation for solitary osseous plasmacytoma resulting in an unstable long-bone fracture or surgery with or without radiation for solitary osseous vertebral plasmacytoma resulting in neurological compromise (Vail 2007). Lymphoma Various chemotherapy protocols (MacEwen et al. 1981, 1987; Cotter and Goldstein 1983; Carter et al. 1987; Keller et al. 1993; Postorino et al. 1989; Greenlee et al. 1990; Stone et al. 1991; Page et al. 1992; Myers et al. 1997; Valerius et al. 1997a; Khanna et al. 1998; Zemann et al. 1998; Boyce and Kitchell 2000; Chun et al. 2000; Moore et al. 2001; Garrett et al. 2002; Mutsaers et al. 2002; Rassnick

Neoplasia Researched Treatment Options and Outcomes et al. 2002, 2007, 2014; Morrison-Collister et al. 2003; Saba et al. 2007, 2009; Griessmayr et al. 2007, 2009; Sauerbrey et al. 2007; Dervisis et al. 2007; Flory et al. 2008; Bannink et al. 2008; Brodsky et al. 2009; Chun 2009; Northrup et al. 2009; Zenker et al. 2010; Dervisis and Kitchell 2010; Sorenmo et al. 2010; Daters et al. 2010; Beaver et al. 2010; Lori et al. 2010; Fahey et al. 2011; Rebhun et al. 2011; Flory et al. 2011; Tater et al. 2012; Silver et al. 2012; Higginbotham et al. 2013; Gavazza et al. 2013; Burton et al. 2013; Zandvliet et al. 2013; Meier et al. 2013; Elliott et al. 2013; Barnard et al. 2014; Gillem et al. 2015; Collette et al. 2015; Curran and Thamm 2015; Holtermann et al. 2015; Back et al. 2015; Lucas et al. 2015; Wouda et al. 2015); immunotherapy (investigational) (Crow et al. 1977; MacEwen et al. 1985; Jeglum et al. 1988; Rosales et al. 1988; Steplewski et al. 1990; Jeglum 1996; Sorenmo et al. 2011; O'Connor et al. 2012; Marconato et al. 2014, 2015a, 2015b; O'Connor and Wilson-Robles 2014); radiation therapy for whole body (localize stage I or stage II disease for nasal or CNS or oral lymphoma, palliation of local disease) (Vail and Young 2007; Lurie et al. 2009; Williams et al. 2010; Berlato et al. 2012); bone marrow transplantation and staged half-body radiation after remission with induction of chemotherapy – both investigational ( Gustafson et al. 2004 ; Williams et al. 2004 ) — or surgery for solitary lymphoma (early stage I) or solitary extranodal, or splenectomy for massive splenomegaly due to lymphoma (Moldovanu et al. 1966; Brooks et al. 1987) or surgery for obstructive or ruptured gastrointestinal lymphoma (Marks 2001).

Table 2.3 Mesenchymal. Neoplasia

Researched Treatment Options and Outcomes

Soft Tissue Sarcoma (Schwannoma, Neuro ibroma, Peripheral Nerve Sheath Tumor, etc.)

Surgery, wide margins, with curative intent (Postorino et al. 1988; Kuntz et al. 1997; Dernell et al. 1998b; Banks et al. 2003b, 2004; Baez et al. 2004; Prpich et al. 2014; Bray et al. 2014b), and surgery-marginal resection with adjuvant radiation (Evans 1987; Graves et al. 1988; Forrest et al. 2000; McKnight et al. 2000; Demetriou et al. 2012; Kung et al. 2014) are the current standard of care treatments for canine STS. Systemic chemotherapy of possible bene it for highly anaplastic tumors but as yet unproved for grade III soft tissue carcinomas (Selting et al. 2005). Hypo-fractionated RT for gross STS with or without metronomic chemotherapy also reported (Cancedda et al. 2015a). Marginal resection and localized cisplatin chemotherapy into wound bed (OPLA-Pt/Atrigel) was reported (Banks and Straw 2003; Havlicek et al. 2009). Metronomic chemotherapy (continuous low-dose chemotherapy) with cyclophosphamide and piroxicam signi icantly increased disease-free interval for incompletely resected soft tissue sarcomas compared to control dogs (Elmslie et al. 2008). Re-excision for treatment of soft tissue sarcomas is recommended after recent incomplete resection (Bacon et al. 2007). In one large study, STS removal was performed in general practice, 21% showed local recurrence, and 11% developed metastasis in a median follow-up time of 785 days (Bray et al. 2014a). The time to recurrence was within 1 year for 50%, 2 years for 80%, and in 2 cases

Neoplasia

Researched Treatment Options and Outcomes recurrence occurred >4 years after the original surgery. In this study, only 6% of STS were grade III, completeness of excision was unknown, and 60% were extremity in location (Bray et al. 2014a). Another study showed an 11% recurrence rate for marginally excised, low-grade, extremity STS over a median time of 522 days (Stefanello et al. 2011), and despite the marginal excision, margins were histologically “clean” or “clean but close” in 66%. In several papers, trends suggest that STS located on the limbs may have better prognosis; with longer survival, lower metastasis, and better response to treatment (Brehm et al. 1995; Kuntz et al. 1997; Prpich et al. 2014). Other studies have not found tumor location to be prognostic for survival or local recurrence (Baez et al. 2004; Bacon et al. 2007; Chase et al. 2009). Recurrent STS is more dif icult to control and is associated with reduced overall survival (Bostock and Dye 1980; Postorino et al. 1988; Kuntz et al. 1997; Banks et al. 2004; Ehrhart 2005b; Heller et al. 2005; Liptak and Forrest 2013; Bray et al. 2014a). The chance of a surgical cure is greatest with the irst surgery (Postorino et al. 1988; Graves et al. 1988; Kuntz et al. 1997; MacEwan et al. 2001; Banks et al. 2003b). Both completeness of excision and histological grade predict response to surgery (Kuntz et al. 1997; McSporran 2009; Avallone et al. 2014). Other reported major prognostic factors reported are tumor size, depth of growth, and pathological pro iles (Avallone et al. 2014). Another study reported tumor size ( 3 cm diameter or evidence of ulceration of local invasion

Node (N) N0

No evidence of nodal involvement

N1

Node irm and enlarged

N2

Node irm, enlarged, and ixed to surrounding tissues

N3

Nodal involvement beyond the irst station

Metastasis (M) M0

No evidence of metastasis

M1

Metastasis to one organ system (e.g. pulmonary metastasis)

M2

Metastasis to more than one organ system (e.g. pulmonary and hepatic metastases)

Classification Cutaneous tumors involve the skin or subcutaneous tissues. The World Health Organization (WHO) has a detailed histologic classi ication scheme for mesenchymal and epithelial skin tumors of domestic animals (Goldschmidt and Shofer 1998). Cutaneous tumors can be

broadly classi ied histologically by the tissue of origin into epithelial, adnexal, mesenchymal, round cell, or melanocytic tumors. 1. Epithelial – Epithelial tumors comprise basal cell tumors, papilloma, squamous cell carcinoma, and subungual (nail bed) tumors. 2. Adnexal – Adnexal tumors arise from the adnexal structures of the skin. They include sebaceous gland tumors (adenoma or adenocarcinoma), ceruminous gland adenoma, perianal tumors (adenoma, adenocarcinoma), adenocarcinoma of the apocrine glands of the anal sac, sweat gland tumors, hair follicle tumors, trichoepithelioma, pilomatrixoma, meibomian gland adenoma, and intracutaneous cornifying epithelioma (ICE). 3. Mesenchymal tumors – Mesenchymal tumors originate from connective tissue and are often located within or invade the subcutis and skin. Malignant mesenchymal tumors are referred to as soft tissue sarcomas. Mesenchymal skin tumor types include lipo(sarco)ma, ibro(sarco)ma, hemangio(sarco)ma, myxo(sarcoma)ma, and peripheral nerve sheath tumors (PNSTs) (neuro ibro(sarco)ma and malignant schwannoma). Hemangiopericytomas and feline injection site-associated sarcoma (FISAS) are also included. 4. Round cell – Tumors of round cell populations that are normally resident within the dermis and subcutis. Examples of cutaneous round cell tumors include mast cell tumors, histiocytomas, plasmacytoma, lymphoma, and transmissible venereal tumor. 5. Melanocytic – Most cutaneous melanocytic tumors are benign. Common anatomical sites are the eyelids, face, trunk, and extremities. The biological behavior of melanocytic tumors varies with anatomical location, with those located in the oral cavity and subungual sites are more likely to be malignant and associated with a poorer prognosis. More detailed descriptions of the biological behavior and characteristics of individual tumor types can be found in other veterinary oncology textbooks (Vail et al. 2019; Meuten 2016). Mast cell

tumors (MCTs) and soft tissue sarcomas (STS) are covered later in this chapter. Within individual tumor types, tumors can be classi ied based on biological behavior, histologic grade, and clinical stage. Biological behavior describes the growth characteristics of the tumor, histologic grade, and the degree of tumor differentiation. Clinical stage is described by the WHO Tumor Node Metastasis (TNM) system (Owen 1980) (Table 4.1). Staging is based on the size and invasiveness of the local primary tumor (T), spread to regional lymph nodes (N), and presence or absence of distant metastases (M). The TNM is modi ied with speci ic criteria for different tumor types. The TNM staging system characterizes the pattern and extent of spread from the local tumor which can be correlated to prognosis and can therefore guide appropriate treatment decisions.

General Approach to the Diagnosis and Staging of Skin Tumors Preoperative Assessment History and Physical Examination A thorough history of the clinical course of the skin tumor is essential. Pertinent information gathered should include duration of presence of the mass and the rate of growth, as well as any change in growth rate. Knowledge of any previous aspiration cytology, biopsy, or histology results of the current or other tumors is important and may affect prognosis and treatment decisions. Details of any concurrent diseases are equally important, as they could include signs of paraneoplastic syndromes associated with the skin mass (e.g. gastrointestinal ulceration associated with mast cell tumors). A thorough physical examination is part of a routine clinical examination. A complete blood count, serum biochemistry, and urinalysis are part of a minimum database for many patients with cutaneous masses, who are often middle aged to older, to assess for concurrent pathologies before administration of general anesthesia and surgical intervention. Tumor Staging

Clinical tumor staging determines the extent of the primary tumor and the presence of local or disseminated metastases. The results of accurate staging tests including physical assessment of the mass and ine needle aspiration (FNA) cytology provide information on whether further clinical staging by incisional or excisional biopsy of the mass, regional lymph node evaluation, and diagnostic imaging to assess for metastatic disease are indicated. This is most important for skin tumors that have a high metastatic potential. The tumor type, histologic grade, and clinical TNM stage should ideally be determined before surgical intervention to allow the formation of an appropriate treatment plan and to provide the client with a realistic expectation of prognosis.

Assessment of the Cutaneous Mass The anatomical location of the mass and three-dimensional measurements to determine the tumor volume should be recorded on a tumor map in the medical record. Cutaneous masses should be carefully palpated to determine consistency and the degree of ixation to underlying structures. Diagnostic imaging may be required to assess the degree of tumor invasion into deeper structures.

FNA Cytology All skin and subcutaneous masses should have FNA cytology performed as part of the diagnostic process before surgical intervention. Most skin masses are easily accessible and amenable to this cost-effective procedure, which can provide a rapid diagnosis and differentiate benign from malignant disease in most cases. FNA cytology provides information on tumor type (e.g. round cell vs. epithelial vs. mesenchymal cell types), but often the speci ic cell of origin type or tumor grade cannot be determined because the cytomorphology is not distinctive and no tissue architecture information is available. Round cell and epithelial tumors tend to exfoliate better and are more likely to provide a diagnostic sample compared to mesenchymal tumors. For diagnosing cutaneous neoplasia, FNA cytology had a sensitivity of 89.3%, a speci icity of 97.9%, a positive predictive value of 99.4%, and a negative predictive value of 68.7% compared to histology (Ghisleni et al. 2006). If cytologic evaluation of a cutaneous mass is not diagnostic

or knowledge of the tumor grade will in luence the surgical dose, an incisional or needle core biopsy is indicated to obtain enough tissue to determine the histologic tumor type and grade to determine appropriate treatment options.

Biopsy A pretreatment biopsy is indicated in the following situations: If the type of treatment will be altered by knowledge of tumor type. For example, cutaneous lymphoma (chemotherapy) vs. FSA (surgery) If the extent or surgical dose of treatment would be altered by knowledge of tumor grade, for example, grade III soft tissue sarcoma on an extremity (amputation or wide resection plus or minus adjunctive therapy) vs. grade I soft tissue sarcoma on an extremity (marginal resection) If tumor location is in an anatomical location with dif icult or limited reconstructive options When knowledge of tumor type and grade affects the owner’s willingness to pursue treatment based on prognosis (Ehrhart 2005) Biopsy techniques for skin tumors include needle core, incisional, and excisional biopsies (for technique description see Chapter 1). Needle Core Biopsy Disposable 14- or 16-gauge needle core biopsy needles provide enough tissue for a pathologist to make a histologic diagnosis and, in most cases, provide a grade of skin tumors. Multiple (3–6) biopsy samples should be obtained to maximize the probability of an accurate diagnosis. Generally, the needle core biopsy can be done as an outpatient procedure with only local anesthesia and/or light sedation required. Needle core biopsy is reported to accurately predict surgical biopsy with an overall sensitivity of 95.5%, speci icity of 96.6%, and a positive

predictive value of 95.5% (Aitken and Patnaik 2000). Thus, needle core biopsy performed before surgical excision of cutaneous masses can facilitate surgical planning and reduce the need for multiple surgical procedures. Incisional Biopsy An incisional biopsy will provide a larger tissue sample for histopathological examination compared to a needle core biopsy. Biopsy samples from both the central area of the skin mass, as well as at the margin between tumor and normal skin are recommended to assess local invasiveness. The biopsy tract should be planned so that it is in a location that can be excised with the de initive surgery. Contamination of normal tissues with tumor cells during biopsy can occur and result in local recurrence if the biopsy tract is not removed (Enneking and Maale 1988; Gilson and Stone 1990). Ideally, the surgeon who will perform the de initive surgical procedure will perform the incisional biopsy. A longitudinal biopsy orientation is recommended for extremity skin tumors, as most masses in this region will be excised with incisions parallel to the long axis of the limb. Histologic grade can differ between incisional biopsy and de initive surgical biopsy with incisional biopsy results more frequently underestimating rather than overestimating grade (Perry et al. 2014; Shaw et al. 2018). Based on these indings, grade as determined by pretreatment biopsy should be interpreted with caution. Excisional Biopsy Excisional biopsy involves removal of the skin tumor with a margin of normal tissue in all planes. The potential advantage of an excisional biopsy is that it provides both a diagnosis and de initive treatment in one surgical episode. Excisional biopsy is best suited for small masses with benign or low-grade features of malignancy on FNA cytology in anatomical locations that allow for wide resection. Inappropriate use of excision biopsy can result in incomplete surgical margins compromising the optimal treatment options for a patient. Bacon et al. (2007) reported on 41 cases of unplanned excisional resection of soft tissue sarcoma skin masses that resulted in incomplete resection. Only

41% of cases in that study had preoperative FNA cytology performed, and 59% percent of cases did not have a presurgical biopsy procedure, highlighting the need for appropriate preoperative diagnostic evaluation.

Regional Lymph Node Assessment All regional lymph nodes should be assessed by palpation to assess size, irmness, and adherence to underlying structures and FNA cytology regardless of size as part of the evaluation of a cutaneous mass. The sensitivity and speci icity of FNA cytology for diagnosis of metastatic disease in lymph nodes in solid neoplasms is 91–100% and 91–96%, respectively, compared to histopathology of the entire lymph node (Langenbach et al. 2001; Ku et al. 2017). Factors reported contributing to discrepancies between cytology and histology include focal distribution of metastases and poorly de ined criteria for metastatic mast cell tumors (Ku et al. 2017). False-positives results with cytology were more common with mast cell tumors and melanomas (Ku et al. 2017). Carcinomas are reported to metastasize to regional lymph nodes more frequently than sarcomas (Langenbach et al. 2001). Lymph node size is not predictive for metastatic status. Incisional or excisional biopsy and histologic assessment of the regional lymph node is the optimal approach to lymph node assessment. Identi ication and biopsy of the irst draining regional lymph node, the sentinel lymph node (SLN), is important in the prediction of survival for a variety of cancers in human and veterinary oncology (Tuohy et al. 2009; Beer et al. 2018). The anatomically closest regional LN is not necessarily the SLN, so SLN mapping is recommended. The sentinel lymph node can be identi ied using a variety of techniques including lymphoscintigraphy (Worley 2014), CT lymphography (Brissot and Edery 2017; Grimes et al. 2017; Majeski et al. 2017; Rossi et al. 2018), and methylene blue. SLN mapping and sampling allows identi ication of microscopic metastatic disease that would otherwise have been undetected. In such circumstances, clinical stage changes and consequently additional therapy is recommended that would have otherwise not been offered. This can lead to an improved oncologic outcome (Worley 2014).

Preoperative Diagnostic Imaging Diagnostic imaging is used to evaluate for evidence of metastatic disease as part of the staging process. Three-view thoracic radiographs or CT are used most commonly to evaluate for pulmonary metastases and thoracic lymph node involvement, and abdominal ultrasonography or CT for evaluation of abdominal lymph nodes and intraabdominal metastases. Imaging of the primary cutaneous mass, using ultrasonography, CT, or magnetic resonance imaging, provides detail on the degree of local invasion, particularly at the deep margin that facilitates appropriate surgical anatomical margin planning. This is particularly important when major reconstructive procedures are required to achieve local tumor control. Examples of skin tumors where this is particularly useful are those overlying the thoracic cavity, head and neck or pelvis, and any other area with important anatomical structures (Figure 4.1).

Treatment Options for Skin Tumors Appropriate treatment options in an individual case are based on the tumor type and degree of local tumor disease, the results of staging tests, the presence or absence of metastases, and the overall condition of the patient. Most solid skin and subcutaneous tumors can be treated successfully with surgical resection. Surgery includes tumor removal by means of excision or local ablative therapies, such as cryosurgery, electrosurgery, and surgical lasers. Surgery can be used as the sole treatment modality or in combination with chemotherapy, radiation therapy, or other adjunctive treatments.

Figure 4.1 (a, b) Noncontrast and contrast CT scan imaging of an interscapular vaccine-associated sarcoma in a cat used to plan deep surgical resection margins. Radiation therapy can be used as an effective primary local therapy or as an adjunctive treatment in combination with surgery. Squamous cell carcinoma, basal cell carcinoma, cutaneous lymphoma, and mast cell tumors (MCTs) are the most radiation-sensitive skin tumors. Chemotherapy is the preferred treatment option for some of the round cell tumors, such as lymphoma, transmissible venereal tumor, and some mast cell tumors.

Principles of Surgical Excision The goal of surgical excision of malignant skin tumors is to achieve wide and complete en bloc excision of the primary tumor surrounded by a margin of normal tissue in three dimensions (Figures 4.2a–c). The extent of the surgical margin will depend on the tumor type and location. More conservative margins are appropriate for removal of benign skin tumors. En bloc surgical resection requires removal of any tissue that the tumor is in contact with, which may require removal of fascia, muscle, subcutaneous fat, or even bone. The irst surgery generally provides the best opportunity to achieve local tumor control. Surgical excision of a skin tumor should be done with aseptic surgical techniques and sterile instruments. Gentle tissue handling and maintenance of blood supply with minimization of dead space and tension at the surgery site are important surgical principles to maintain during removal of cutaneous tumors. Any previous biopsy site should

be removed with the resected tissues. Ideally, complete surgical excision of the tumor without entering the tumor capsule should be done to avoid tumor seeding at local or distant sites. Veins should be ligated early in the procedure to prevent hematogenous spread of tumor cells especially in large tumors. Surgical instruments, drapes, and gloves should be changed immediately, and intraoperative lavage should be done, if the tumor is entered inadvertently or if an intracapsular resection is done and the change should be performed routinely after malignant tumor excision. Postoperative surgical drains should be avoided as they can potentially contaminate the normal tissues through which they pass with tumor cells; however, they should be considered if surgery results in a large dead space or is in a high-motion anatomical site that will be predisposed to seroma formation. Most seromas can be managed conservatively and will regress spontaneously.

Surgical Margins The guidelines for surgical margins depend on tumor type, anticipated biological behavior, tumor grade, anatomical location, and adjoining normal tissue types (also see Chapter 1 for further discussion). Surgical resection margins for skin tumors are described as intracapsular, marginal, wide, or radical based on the system developed by Enneking for musculoskeletal tumor excisions (Enneking et al. 1980). Intracapsular resection is de ined as a debulking or cytoreductive procedure that leaves behind clinically evident macroscopic tumor. Local recurrence for malignant tumors is assured unless surgery is followed by radiation therapy or other adjunctive therapies. These surgeries are often performed for palliation of clinical signs. Marginal excision is immediately outside the pseudocapsule of the tumor, leaving behind microscopic tumor in the case of malignant invasive disease. Local recurrence is likely without repeat surgical excision or adjuvant therapies. A common example of this type of excision for skin tumors is “shelling out” soft tissue sarcomas that

appear well encapsulated but are removed through a pseudocapsule of compressed tumor cells, leaving microscopic tumor cell projections in the surgical periphery.

Figure 4.2 (a) Preoperative margins marked on skin with marking pen. (b) En bloc excision of cutaneous mass. Skin incision and excision plane extends at least one fascial plane beyond the deepest layer of tumor. (c) En bloc excision of cutaneous mass. (Images courtesy of Dr. Simon Kudnig).

Wide resection is removal of the tumor with complete margins of normal tissue in all directions. Local recurrence is unlikely after this extent of surgery. For skin tumors, an appropriate example would be the excision of mast cell tumors on the trunk with 2–3 cm lateral margins and at least one fascial plane deep. Radical resection is removal of an entire anatomical structure. Local recurrence is unlikely. An appropriate example for skin tumors where radical resection would be appropriate would be amputation for a stage III soft tissue sarcoma of an extremity. Radical surgical resection requires a thorough knowledge of regional anatomy, concurrent and postoperative side effects, and reconstructive procedures. Any tissue that the tumor touches or invades must be removed with a margin of normal tissue in the curative setting. Fat is a poor barrier to tumor invasion, so wider margins may be required, particularly as a deep margin for skin tumors. Fascia and bone are most often effective barriers to tumor growth, so a deep margin of muscle fascia is preferred. When possible, it is recommended that dissection occurs through normal tissue planes and the tumor could be removed en bloc. Higher-grade tumors generally require a more aggressive approach using larger surgical margins. Surgical margins should be planned with closure of the wound taken into consideration, but completeness of tumor resection and size and quality of surgical margins should not be compromised to facilitate closure. From a surgical oncology perspective, it is preferable in most cases to deal with a large wound rather than an incomplete malignant tumor resection. A wide variety of reconstructive surgical options using skin laps, grafts, or secondary intention wound closure techniques can be used as appropriate for the surgical situation. Mohs micrographic surgery has been described in a pilot study for total margin assessment of cutaneous tumors in veterinary oncology

(Bernstein et al. 2006). This technique requires specialized surgical training in the horizontal sectioning technique and frozen sections to obtain margin evaluation in real time.

Margin Evaluation After local tumor resection, the surgeon has an important role communicating with the pathologist to help identify the specimen margins that are most likely to be close or incomplete. This can be achieved by providing detailed information on the pathology submission form, including pertinent clinical history as well as attempting to maintain normal tissue architecture and using ink and/or sutures to orient the tissues. The surgeon is responsible for interpreting the pathology report in the context of the surgery performed. The pathology report should contain three important pieces of information for the surgeon that will help to dictate whether adjuvant therapy is required: the histologic diagnosis, the tumor grade if appropriate, and the adequacy of surgical margins. If surgical margins are incomplete, the entire surgical scar is assumed to be contaminated with tumor cells and larger surgery or adjunctive treatments such as radiation therapy or chemotherapy are indicated. Because the entire surgical scar is assumed to be contaminated with tumor cells when performing the second surgery where the goal is to remove the residual tumor cells left behind, the entire surgical scar needs to be removed. In one study evaluating the second surgery for soft tissue sarcomas in dogs (Bacon et al. 2007), it was suggested that if wide excision of the previous scar was not possible (because of anatomic location for example), excision of the scar with narrow margins appeared to be bene icial. However, it is not just the scar that is contaminated but the entire previous surgical bed. Therefore, excising the entire surgical bed should be the goal of the second surgery. One study concluded that the extent of the surgical bed is, as expected, proportional to the extent of the irst surgery. The mean maximum lateral extension was 6, 14, 18, and 26 mm for 2-, 4-, 6-, and 8-cm skin defects, respectively. Even so, removing a scar with 3 cm margins around it can lead to an incomplete excision of the surgical bed in some

cases when the skin defect was more than 4 cm (Cunningham and Skinner 2020).

Reconstructive Procedures Reconstructive procedures may be indicated after tumor removal to reconstruct skin de icits, depending on the anatomical location and extent of surgical resection. Reconstructive procedures may include local or pedicle skin laps, delayed primary closure or secondary closure, free skin grafting or free microvascular cutaneous, and muscle or myocutaneous grafts. Detailed descriptions of these reconstructive procedures are beyond the scope of this chapter, and the reader is referred to several texts that describe these procedures in detail (Pavletic 2003, 2018; Swaim 2003; Kirpensteijn et al. 2013). The surgeon should plan the reconstructive procedure before the de initive tumor excision by marking the margins of tumor excision and the proposed lap site with a marking pen prior to surgery (Figures 4.3a–e). Consideration should also be given to the degree of resection required in a circumstance. For example, a grade I MCT located on an extremity could be treated appropriately with a more conservative 1 cm lateral margin resection. An ulcerated grade III MCT with regional lymph node metastasis may be treated with a palliative marginal resection, and a grade II MCT on the pelvic region may require wide excision and an axial pattern lap reconstructive procedure. If a reconstructive procedure is used, the donor site and recipient tumor resection site should be treated as two separate surgical ields, with separate gloves and instruments used for each site to decrease the risk of contaminating the donor site with tumor cells. The donor site should be completely closed before moving to the recipient tumor resection site. Reconstructive lapping procedures can be used successfully in combination with radiation therapy. The severity of complications was reduced when lapping procedures were used as part of the planned therapy as opposed to those used to correct a complication or failure of radiation therapy (Séguin et al. 2005).

Open wound management is an acceptable option after skin tumor resection. Wound healing time is prolonged compared to reconstructive procedures (Prpich et al. 2014).

Adjunctive Therapies for Skin Tumors Radiation therapy and/or chemotherapy are the main treatment modalities used as adjunctive therapies to surgical excision of cutaneous tumors. These therapies may be used for palliative or curative-intent treatment. The indication for adjunctive therapy is based on the speci ic tumor type, biology, histologic grade, clinical stage, and completeness of surgical excision of the primary tumor. Other less-commonly used adjunctive therapies include immunotherapy, photodynamic therapy, cryotherapy, and electrochemotherapy.

Mast Cell Tumors Mast Cell Tumors (MCTs) are the most common malignant cutaneous tumor in dogs and the second most common cutaneous tumor in cats (Miller et al. 1991; Villamil et al. 2011; Shoop et al. 2015; Graf et al. 2018). Cutaneous MCTs arise from the dermis and subcutaneous tissues. MCTs are round cell tumors that have characteristic cytoplasmic granules that contain bioactive substances, including histamine, heparin, proteases, chemotactic factors, and cytokines. There is a large degree of variation in the histologic appearance and biological behavior of MCTs in dogs.

Clinical Presentation Dogs with MCTs are generally middle aged (>5 years) and no sex predisposition is observed (Murphy et al. 2004). Breeds reported to have a high incidence of cutaneous MCTs include Boxers, Boston terriers, Weimaraners, shar-peis, Golden retrievers, Labrador retrievers, Beagles, and Schnauzers (Murphy et al. 2004; Gieger et al. 2003; Hahn et al. 2008, 2004; Kok et al. 2019; Reynolds et al. 2019). Shar-peis have been reported to be the breed most likely to have high-

grade MCTs, whereas the Pug and the Golden Retriever are the least likely breeds to develop high-grade MCTs (Reynolds et al. 2019).

Figure 4.3 Surgical en bloc resection of cutaneous tumor with planned reconstructive skin fold transposition lap. (a) Preoperative skin marking of proposed en bloc tumor excision and axial skin fold transposition lap. (b) En bloc tumor excision. (c) En bloc tumor excision completed with deep margins. (d) Flank fold transposition lap raised to close tumor resection site. (e) Completed tumor resection and reconstructive procedure closure. Source: Images courtesy of Dr. Julius Liptak.

The majority (65–80%) of cutaneous MCTs is solitary. Approximately, 50–60% of canine cutaneous MCTs occur on the trunk, with 25% occurring on the limbs and the remainder on the head and neck areas. All MCTs are locally aggressive but low- and intermediate-grade MCTs have a lower metastatic potential than high-grade MCTs. The gross appearance of cutaneous MCTs is very variable, ranging from raised hairless masses to aggressive, invasive ulcerated lesions (Figure 4.4). Owners may report that MCT masses luctuate in size over a short period of time. Local and paraneoplastic effects can result from release of in lammatory mediators contained within the MCT cytoplasmic granules. MCT palpation or manipulation may cause release of histamine, leading to local redness, swelling, and pruritis. This can progress to degranulation of mast cells, producing erythema, edema, and wheal formation (Darier’s sign) (Figure 4.5). Histamine release can cause gastrointestinal ulceration by stimulating H2 receptors on parietal cells of the stomach and increased secretion of hydrochloric acid.

Diagnosis of MCTs FNA cytology is an inexpensive diagnostic test that can be done inhouse to con irm the diagnosis of cutaneous MCTs in approximately 90% of cases. Cytologically, MCTs consist of large round cells with central nuclei and abundant cytoplasm. The cytoplasm contains intracytoplasmic granules that stain purple with methanolic Romanowsky stains (e.g. May-Grunwald-Giemsa, Wrights) (Figure 4.6).

Figure 4.4 Range of cutaneous mast cell tumor appearances. (a) Ulcerated grade III MCT. (b) Grade II MCT over the mandible area.

Figure 4.5 Darier’s sign secondary to vasoactive substance release of an MCT.

In clinical practice, rapid aqueous Romanowsky stains (e.g. Diff Quik) are commonly used, but these stains may not adequately stain mast cell granules. Other in lammatory cells such as eosinophils and neutrophils are frequently observed mixed with the MCT cells on cytologic examination. Historically, cytology was not able to predict histological grade. Cytological grading systems have now been developed and evaluated to determine if FNA cytology can provide accurate information regarding MCT grade prior to de initive excision (Camus et al. 2016; Hergt et al. 2016; Scarpa et al. 2016). The cytograding system correctly predicted the histological grade with an accuracy of 94%, sensitivity of 84.6–88%, and speci icity of 94–97.3%. Incisional or excisional biopsy is required to provide enough tissue to determine the histologic grade of cutaneous MCTs. An incisional biopsy, obtained via wedge, skin punch, or needle core techniques can be done to establish MCT grade if negative prognostic factors are present or the surgical site is not amenable to wide surgical resection (e.g. distal extremity) to determine if a more conservative marginal excision is appropriate (e.g. for a low-grade tumor) or if or more radical surgery or other adjunctive therapies (e.g. radiation and/or chemotherapy) are indicated for higher grade MCTs. Incisional biopsy grade has been shown to have a high concordance (92–96%) to de initive excisional grade. and are suf iciently accurate for differentiating low-grade from high-grade MCTs (Shaw et al. 2018).

Clinical Staging A modi ied version of the WHO TNM clinical staging scheme is used to stage canine cutaneous MCTs into one of four stages (Table 4.2) (Turrel et al. 1988). Preoperative staging is important to determine prognosis and appropriate treatment options, including surgical dose, radiation, and chemotherapy. A minimum database of a complete blood count, serum biochemistry, and urinalysis is indicated as part of a presurgical workup for any patient with cancer, including MCTs.

Preoperative imaging of the cutaneous MCT mass with ultrasonography, computer tomography, or MRI can facilitate de inition of anatomical margins, especially deep margins, prior to surgery and assist with surgical planning if reconstructive procedures are planned. Assessment of size and shape of intracavitary lymph nodes can also be obtained from CT or MRI imaging. The metastatic pathway for cutaneous MCTs is irst to the sentinel and regional lymph nodes and then to distant sites of spleen, liver, or bone marrow (Pizzoni et al. 2018). Complete staging for cutaneous MCT should include FNA cytology of the sentinel or other regional lymph nodes, abdominal ultrasound and FNA cytology of the spleen and liver and (in some cases) bone marrow cytology (Warland et al. 2014).

Figure 4.6 Cytological appearance of canine cutaneous MCT showing degranulation and intracytoplasmic granules.

Table 4.2 WHO Clinical staging system for canine mast cell tumors. Adapted from: London, C.A. and B. Seguin. 2003. Mast cell tumors in the dog. Vet Clin N Am Small Anim Pract 33(3):473–489.

Clinical Description stage 0 I

Single tumor, incompletely excised from dermis Single tumor con ined to dermis without regional lymph node involvement

II

Single tumor con ined to dermis with regional lymph node involvement

III

Multiple dermal tumors or large in iltrating tumors, with or without regional lymph node involvement

IV

Any tumor with distant metastases or recurrence with metastases (including blood or bone marrow involvement)

Substage a: No systemic signs of disease; Substage b: Signs of systemic disease.

FNA cytologic examination of the regional lymph node should be performed in all cases of cytologically con irmed cutaneous MCT, regardless of whether the lymph node is enlarged or not, to detect early metastasis (Langenbach et al. 2001). Dogs with metastasis to the regional lymph node are classi ied as clinical stage II tumors and have a poorer prognosis (Krick et al. 2009). Lymph node aspirates from normal dogs can contain mast cells (Bookbinder et al. 1992), so diagnosis of lymph node involvement based on FNA cytology should be if greater than 3% of the cell population are mast cells (Dobson et al. 2004). Cytology is a useful method for staging purposes, especially for lymph nodes that are not easily amenable to surgical removal. No standardized cytologic criteria exist for differentiating reactive and metastatic MCT in lymph nodes. The use of methanolic Romanowsky stains rather than rapid aqueous Romanowsky stains should be used for cytology of suspected nodal metastases to increase the identi ication of isolated mast cells (Sabattini et al. 2018). Cytologic criteria for metastatic mast cell disease in lymph nodes have been described and dogs with stage II disease have a signi icantly shorter survival time than dogs with stage I disease independent of grade and

dogs with grade III primary MCTs were more likely to have stage II disease (Krick et al. 2009). Lymph node histology is more accurate than cytology for diagnosis of metastatic MCT disease (Ku et al. 2017; Fournier et al. 2018; Lapsley et al. 2021). Therefore, if cytology is negative for MCT metastasis, extirpation of the regional draining lymph node, regardless of size of the lymph node, should still be performed for staging purposes before or during local MCT treatment as nearly 50% of LNs can show histologically detectable metastatic disease (Ferrari et al. 2018). Furthermore, histology of the lymph node provides a classi ication of the metastasis (HN0-HN3), which is prognostic for outcome (Weishaar 2014). Sampling of lymph nodes in dogs with MCTs that, anatomically, would be expected to be the SLN does not accurately re lect which lymph node is actually the SLN. SLN mapping is recommended to identify the true SLN so that it can be extirpated at the time of surgery to provide the most accurate staging. Identi ication of the sentinel lymph node for canine MCTs has been shown to be reliable with regional lymphoscintigraphy combined with intraoperative lymphoscintigraphy and blue dye (Worley 2014). CT lymphangiography using peritumoral injections of an aqueous contrast solution has also been described to successfully identify sentinel lymph nodes of MCTs and other tumors (Grimes et al. 2017; Lapsley et al. 2021). However, CT lymphangiography was not accurate to assess presence or absence of mast cell tumor metastasis to the sentinel lymph node according to contrast enhancement pattern or attenuation values (Grimes et al. 2020). Abdominal ultrasonography is recommended as part of complete staging to assess the liver, spleen, and abdominal lymph nodes for metastasis (Stefanello et al. 2009; Book et al. 2011; Warland et al. 2014). Dogs with mast cell in iltration of either or both the spleen or liver, have decreased survival times compared to those without in iltration. The routine aspiration cytology of a normal liver and spleen is controversial. One study frequently identi ied mast cells in normal livers and spleens and concluded that routine aspiration cytology could not be recommended (Finora et al. 2006). Later studies found that dogs with cutaneous MCTs that had cytologic evidence of splenic mast cell

metastases, using criteria of clustering of mast cells and atypical mast cell morphology, had a decreased survival time compared to dogs without cytologic evidence of distant disease (Stefanello et al. 2009; Book et al. 2011). All dogs that had cytologic evidence of mast cell metastasis in the liver or spleen had abnormal ultrasonographic indings. The authors concluded that cytology of the liver and spleen regardless of the ultrasonographic appearance of the liver or spleen was indicated as part of clinical staging for dogs with cutaneous MCTs, especially MCT with high biologic behavior (Stefanello et al. 2009). The utility of computed tomography (CT) of the abdomen has been reported for staging of the liver and spleen for MCT disease and was found to be equivocal (Hughes et al. 2019). No consistent imaging pattern was associated with mast cell metastasis for the liver and mast cell metastasis of the spleen coincided with multifocal splenic hypoattenuating lesions. Thoracic radiography is reported to not be useful in the staging of canine cutaneous MCTs as MCTs have not been reported to metastasize to the lungs (Warland et al. 2014; Pizzoni et al. 2018; CartagenaAlbertus et al. 2019). The only rationale for doing thoracic radiographs as part of the staging process is to assess for thoracic lymph node enlargement or evidence of concurrent intrathoracic disease. The routine use of buffy coat smears and bone marrow evaluation are not advocated for routine staging of cutaneous MCTs due to the rarity of bone marrow involvement and the common inding of mastocytemia in dogs with disease other than cutaneous MCTs (McManus 1999; LaDue et al. 1998; Endicott et al. 2007; Warland et al. 2014). The presence of neoplastic mast cell in iltration in the bone marrow seems rare and is generally more common in dogs with grade III primary cutaneous tumors (O’Keefe et al. 1987). Reported indications for bone marrow sampling as part of the clinical staging process of dogs with cutaneous MCTs include abnormal hemogram indings or presentation for tumor regrowth, progression, or new occurrence (Endicott et al. 2007).

Treatment of Canine Cutaneous MCTs

The optimal treatment for an individual patient with MCT disease depends on the tumor grade, anatomical site, clinical stage, and surgical and radiation therapy facilities available. Available treatment options for cutaneous MCTs include surgical excision, radiation therapy, and chemotherapy. Surgery Perioperative Management Perioperative surgical complications may be encountered related to the release of vasoactive substances from mast cell granules secondary to tumor manipulation. MCTs should not be manipulated extensively during the (pre)operative period to avoid the risk of a degranulation reaction. Preoperative treatment with H1 blocker (diphenhydramine) and H2 blockers (cimetidine, ranitidine, or famotidine) and corticosteroids has historically been recommended in dogs with cutaneous MCTs that will be surgically manipulated, including biopsy, and those that show evidence of degranulation, melena, or hemoptysis associated with gastrointestinal ulcerations secondary to histamine release. It has been suggested that hypotension during surgery may be caused by mast cell degranulation and histamine release. A recent study, however, showed that administration of diphenhydramine did not provide any clear bene it in preventing hypotension in dogs undergoing MCT removal (Sanchez et al. 2017). The use of neoadjuvant corticosteroid (prednisone) treatment may facilitate resection of MCT when adequate surgical margins cannot be con idently expected because of location, size, or both (Stanclift and Gilson 2008; Dobson et al. 2004). Mean reduction in MCT volume was 80.6% in 70% of cases treated with neoadjuvant prednisolone. Reduction in tumor size may be related to the anti-in lammatory effect of prednisolone, reducing tumor-related in lammation and edema secondary to tumor cytokine release. There was no difference in response rate between a high dose (2.2 mg/kg) and a low dose (1.0 mg/kg) prednisone protocol. Using neoadjuvant prednisone did not

increase the risk of incomplete margins or local recurrence in one study (Saunders 2020). Margins Surgical Margins Wide surgical excision with adequate lateral and deep margins has historically been the primary treatment of choice for most MCTs. The deep surgical margin is a qualitative margin rather than a quantitative margin. Fascia and collagen-dense tissues are good barriers to tumor in iltration. The deep margin should include at least one fascial plane deep to the tumor that has not been invaded by the tumor. This margin should be removed en bloc with the tumor so that tumor contamination is not encountered during the surgery. The appropriate lateral surgical margin is grade and tumor size dependent. Historically, many MCTs have been treated with ‘surgical dose’ that is greater than required for local control. Simpson et al. (2004) reported that a 2 cm lateral margin and a deep margin of one fascial plane were adequate for complete excision of grade I and II MCTs in dogs. In fact, a 1 cm lateral margin was able to obtain tumor-free margins in 75% of grade II and 100% of grade I cutaneous MCTs. In another study, a 2 cm lateral margin and one deep facial plane excision were successful in completely excising 100% of grade I and 89% of grade II MCTs (Fulcher et al. 2006). A similar local recurrence rate and de novo development rate were observed compared to previous reports with a 3 cm margin. Investigators concluded that excision of grade I and II MCTs with 2 cm margins might minimize complications associated with larger local tumor resection (Fulcher et al. 2006). Wide surgical margins do not appear to be a prerequisite for a successful long-term outcome in dogs with well-differentiated cutaneous MCTs (Murphy et al. 2004). A proportional size model for surgical margins has been proposed where the lateral margins are equivalent to the widest diameter of the MCT, with an upper limit of 2– 4 cm (Pratschke et al. 2013; Chu et al. 2020; Saunders et al. 2020). Using the proportional margins approach, 85–95% of tumors had complete excisional margins and local recurrence of 0–3%.

Complete removal of grade I or II cutaneous MCTs, even with narrow histologic margins, is associated with successful outcome without adjuvant therapy. Narrow (≤3 mm) histologic margins are likely adequate to prevent local recurrence of low-grade MCTs (Schultheiss et al. 2011). In one study, the width of the tumor-free margins on histology was not prognostic for local recurrence for completely excised tumors (Donnelly et al. 2015). High-grade tumors have signi icant risk of local recurrence (36%) regardless of histologic margins width (Donnelly et al. 2015). Adequate margins for grade III MCTs have not yet been determined; thus 3 cm lateral and at least one fascial plane deep margins are recommended. Intraoperative real-time assessment of surgical margins has the strong advantage of allowing the surgeon to know where incomplete margins are and to take appropriate measures to rectify this at the surgery table without necessitating an additional surgery at a later time. Two methods that provide assessment of surgical margins intraoperatively described in veterinary surgery are luorescence-based imaging and optical coherence tomography (see Novel diagnostic imaging techniques in soft tissue sarcomas section). Using a luorescent-based imaging technique, sensitivity and speci icity of the imaging system for identi ication of cancer (soft tissue sarcomas and mast cell tumors) in biopsies have been reported to be 92% for both. Although responsive to antihistamines, hypersensitivity to the luorescent agent was seen in 53% of dogs and the risk needs to be considered in light of the potential bene its of this imaging system in dogs (Bartholf DeWitt et al. 2016). Optical coherence tomography-guided pathology sections of canine mast cell tumors were able to detect incompletely excised MCT near the surgical margin with a sensitivity of 90% and speci icity of 56.2% in one study (Dornbusch et al. 2020). The excised specimen should be submitted in toto and not in sections. The anatomical relationship between the deep fascial plane and lateral margins should be preserved with sutures to help orient the pathologist, and the deep and lateral margins should be inked (ideally with separate colors). There is a signi icant amount of shrinkage artifact that occurs with each step of sample processing (Milovancev et al. 2018). Tissue shrinkage occurs mainly in the skin tissues (24%)

compared to the tumor tissue (4%) (Upchurch et al. 2018). Mean histologic margins have been reported to be 35–42% smaller than the surgical margins (Risselada et al. 2015). Clinicians should take these factors into account when interpreting histologically reported margins relative to surgical margins. Regional Lymph Node Treatment Locoregional control incorporates treatment of the regional lymph node as well as the primary MCT. Approximately, 20% of dogs with cutaneous mast cell tumors will have nodal metastasis at the time of diagnosis. Surgical removal or prophylactic and therapeutic irradiation of the regional lymph nodes is indicated as part of locoregional disease control and is associated with increased survival time (Mendez et al. 2019). Anatomical Site Considerations Appropriate therapy for cutaneous MCTs located on an extremity is dictated by tumor grade. For low- and intermediate-grade MCTs, a combination of a marginal surgical resection with planned external beam radiation therapy (if incomplete margins are achieved) is a rational treatment option. Amputation may be indicated for grade III MCTs to achieve wide surgical margins. Palliative radiation therapy (4 × 8 Gy weekly) in combination with prednisolone has been reported to be useful in the management of measurable MCTs located on a distal extremity (Dobson et al. 2004). Another favorable protocol for measurable MCTs is the combination of prednisone, toceranib, and hypofractionated radiation therapy (Carlsten 2012).

Prognostic Factors Histologic Parameters Grade

There are two grading systems in common use for canine cutaneous MCTs; the Patnaik and Kiupel systems (Patnaik et al. 1984; Kiupel et al. 2011). The grading system developed by Patnaik and colleagues is based on histomorphologic features, including cellularity, cell morphology, invasiveness, mitotic activity, and stromal reaction and is prognostic for survival. Well-differentiated (grade I) MCTs account for 26–55% of all MCTs, intermediate differentiated (grade II) MCTs account for 25–59% of MCTs, and poorly differentiated (grade III) MCTs account for 16–40% of MCTs (Murphy et al. 2006). Tumor grade is the most consistent prognostic indicator for biological behavior and survival time in cutaneous MCTs across multiple studies (Turrel et al. 1988; Patnaik et al. 1984; Thamm et al. 1999). Higher tumor grade is associated with higher risk of metastasis, lower local control rates, and shorter survival times. Grade II MCTs are the most common grade identi ied and have the widest range of biological behavior compared to the other two grades. Most dogs diagnosed with grade II MCT will have a good prognosis; however, there is a subset of these patients that will develop metastases and have decreased survival time. Grade III MCTs have an aggressive clinical behavior and poor survival time compared to grade I or II MCTs, with a reported median survival time for dogs with grade III MCTs of 224–257 days and a metastatic rate of 55–96% (Bostock 1986; Hume et al. 2011). There is signi icant variation in grading of MCTs between pathologists using the Patnaik grading scheme. In one study, 10 veterinary pathologists independently graded the same 60 cutaneous MCTs using the Patnaik grading system (Northrup et al. 2005). Agreement was 62.1% with most variation in classi ication was between grade I and grade II and grade II and grade III tumors. The limitations of the Patnaik grading system prompted development of novel grading systems using mitotic index, argyrophilic nucleolar organizer regions (AgNOR), and Ki67 proliferation markers to help differentiate between grade II MCTs with a poor and good prognosis (Maglennon et al. 2008; Romansik et al. 2007; Scase et al. 2006).

A two-tier grading system for MCTs proposed by Kiupel et al. (2011) has been validated and widely adopted by veterinary pathologists and MCTs are frequently reported with grading according to both these systems. The Kiupel system uses mitotic igures, multinucleated, bizarre nuclei, and karyomegaly for grading criteria. Kiupel graded high-grade MCTs are signi icantly associated with shorter time to metastasis or new tumor development, and shorter survival time. The median survival time was less than four months for high-grade MCTs but more than two years for low-grade MCTs. Dogs with high-grade Kiupel and Grade III Patnaik MCTs were signi icantly more likely to have metastases (mainly lymph node metastases) at the time of initial diagnosis than low-grade or Grade II or I MCTs (Krick et al. 2009; Weishaar et al. 2014). Combining histologic grade with clinical stage information provides a more accurate biological behavior prediction than either parameter alone (Stefanello et al. 2015). Prognosis should not rely solely on histologic grade, regardless of the grading system used, but should also consider the results of clinical staging. Dogs with Stage 1 high-grade tumors treated surgically can have a prolonged survival time (Moore et al. 2020). Mitotic Index Mitotic index (MI) is an indirect measure of cellular proliferation indices and directly correlates with histologic grade; it is a strong predictor for overall survival. Dogs with cutaneous MCTs with a MI of 5 or less had a signi icantly longer survival time than those with a MI greater than 5, regardless of histologic grade (Romansik et al. 2007; Berlato et al. 2015). Mitotic count is also prognostic among dogs with a Kiupel high-grade MCT (Moore et al. 2020). Proliferation Indices Indicators of cellular proliferation can provide prognostic information about the likelihood of MCTs recurring locally and help differentiate the prognosis of grade II MCTs (Séguin et al. 2006). The three most commonly used cellular proliferation indices are AgNORs, proliferating cell nuclear antigen (PCNA), and number of Ki67-positive nuclei.

Increasing AgNOR and PCNA scores were signi icantly associated with a shorter progression free interval (Gill et al. 2007). A Ki67 index of greater than 1.8% is a signi icantly prognostic indicator for poorer survival for grade II MCTs. A higher Ki67 index is also a negative prognostic factor, independent of grade (Scase et al. 2006; Maglennon et al. 2008; Berlato et al. 2015; Smith et al. 2017). The KIT protein is a tyrosine kinase receptor that is a product of the cKIT proto-oncogene. Mutations in c-KIT result in aberrant cytoplasmic expression of KIT in 9–30% of canine MCTs, with high-grade tumors more likely to have a mutation. Immunohistochemistry protocols for the detection of the KIT receptor expression are well established. Increased expression of KIT in the cytoplasm of neoplastic mast cells is a strong indicator of increased risk of local tumor recurrence and a decreased survival time (Kiupel et al. 2004). Histologic panels that employ multiple markers are now available at various veterinary pathology laboratories to facilitate prognostication, especially for grade II MCTs. Clinical Stage The WHO staging system for cutaneous MCT (Table 4.2) has been reported to be prognostic for tumor-free time and survival time with surgical MCT treatment (Turrel et al. 1988). The presence of lymph node metastasis (WHO stage II disease) has been shown in multiple studies to be associated with a poorer prognosis compared to stage I disease (Murphy et al. 2006; Hume et al. 2011; Turrel et al. 1988; Krick et al. 2009). The lymph node metastasis classi ication system (HN0-HN3) is helpful to be more precise regarding the prognostic signi icance (Weishaar et al. 2014). Dogs with grade III primary cutaneous MCTs are more likely to have metastatic MCT in regional lymph nodes (Krick et al. 2009). Dogs with lymph nodes affected by metastatic disease that are treated with either surgery or radiation have prolonged survival time compared to untreated lymph node-positive dogs (Hume et al. 2011; Bae et al. 2020). A different study contradicts this inding for Grade 2 MCTs, showing that positive lymph node status does not adversely affect

survival time (Baginski et al. 2014). Dogs with stage IV disease at presentation have a very poor prognosis (Pizzoni et al. 2018). Size Dogs with MCTs > 3 cm in maximum diameter have a shorter median survival time than dogs with tumors 1500 days) (Thompson 2011; Gill et al. 2020). Survival probabilities are 93–95%, 92–95%, and 86% at one, two, and ive years, respectively (Thompson 2011; Gill et al. 2020). The grading schemes from Patnaik and Kiupel were developed for cutaneous mast cell tumors and may not be appropriate for prognostication. For example, the lowest grade a subcutaneous MCT can be using the Patnaik scale is II, because as soon as the tumor goes into the subcutaneous area, the tumor is de ined as at least a grade II. When these grading schemes were applied to subcutaneous tumors, 98% were grade II on the Patnaik scale and 96% were low grade on the Kiupel scale and this was

not prognostic (Gill et al. 2020). Negative prognostic factors for survival for subcutaneous MCTs are mitotic index, in iltrative growth (i.e. lack of tumor demarcation), and presence of multinucleation (Thompson 2011). Local recurrence is 7–8%. Although incomplete margins are a negative prognostic factor, local recurrence with incomplete margins are low (12–21%) (Thompson 2011; Gill et al. 2020). Mitotic index is a prognostic factor for local recurrence (Thompson 2011).

Postoperative Recommendations Completely Excised MCTs Grade I or II MCTs that are Kiupel low grade excised with complete surgical margins do not require any adjuvant therapy as the risk for local recurrence (5–11%) or metastasis is relatively low (Murphy et al. 2004; Séguin et al. 2001; Weisse et al. 2002; Michels et al. 2002). Patients should be evaluated regularly for signs of local recurrence and any new cutaneous masses should be thoroughly investigated. Grade III MCTs that are completely excised have a low chance for local recurrence but a high chance to develop metastatic disease. As such, these cases should receive adjunctive chemotherapy to delay or prevent metastatic spread. Kiupel high-grade tumors have a local recurrence rate of 18–36%, even when margins are complete (Donnelly et al. 2015; Moore 2020). Incompletely Excised MCTs Incompletely excised grade I or II MCTs have a low chance of local recurrence and low chance of metastatic spread (Séguin et al. 2006). The surgeon has several recommended treatment options in the case of incompletely excised grade I or II MCTs, including monitoring, additional surgery, and adjuvant chemotherapy or radiation therapy. Murphy et al. concluded that dogs with well-differentiated, incompletely excised tumors that did not receive adjuvant treatment did as well as those that did have additional therapy (Murphy et al. 2004). The preferred treatment for incompletely excised MCTs, if possible, is excision of the surgical scar with a larger margin of normal tissue at

least one fascial plane deep. If the anatomical location does not permit extensive resection, a more conservative re-resection and/or adjuvant radiation therapy is indicated (Kry and Boston 2014; Karbe et al. 2021). One study evaluated the excision of surgical scars after 19 incompletely excised mast cell tumors and 4 mast cell tumors with close margins (tumor cells within 3 mm of a surgical margin (Kry and Boston 2014). Local recurrence occurred in 13% of these cases whereas local recurrence occurred in 38% in a group where no further treatment was performed. Tumors where the scar was re-excised had longer median time to local recurrence and dogs with a re-excision had a longer median survival time than dogs and tumors with no further treatment. Presence of microscopic disease was found in 48% of scars and was not prognostic for local recurrence (Kry and Boston 2014). In a more recent study, scar revision (i.e. re-excision) of 86 mast cell tumors that had been excised with tumor cells at the margins (87% of the tumors), margins of 4 mitoses/high-powered ield) is reported as a negative prognostic indicator for feline cutaneous MCT (Lepri et al. 2003; Johnson et al. 2002). A recently proposed grading system for feline cutaneous MCTs classi ied MCTs as high grade if there were >5 mitotic igures in 10 hpfs and at least 2 of the following criteria: tumor diameter >1.5 cm, irregular nuclear shape, and nucleolar prominence/chromatin clusters (Sabattini and Bettini 2019). Further prospective validation of this grading scheme is required. Cats with cutaneous MCTs should be staged with an abdominal ultrasound to evaluate the spleen for evidence of MCTs that may be metastasizing to the cutaneous location.

The prognosis for feline cutaneous MCT with surgical resection is good, with a 16–36% local recurrence rate. Incomplete surgical excision is not associated with a higher rate of tumor recurrence in cats with cutaneous MCTs (Molander-McCrary et al. 1998; Litster and Sorenmo 2006). Radiation therapy using strontium-90 has recently been reported as an effective treatment for feline cutaneous MCT (Turrel et al. 2006). A distinct visceral form of MCT, which affects the spleen without cutaneous involvement, exists in cats and carries a poor prognosis (Litster and Sorenmo 2006). Systemic signs of chronic vomiting, anorexia, and weight loss can be associated with this form of MCT disease. Splenectomy is the recommended treatment for splenic visceral MCT (Kraus et al. 2015) and is associated with improved survival time compared to no splenectomy (Evans et al. 2018). The role of adjuvant chemotherapy for feline splenic MCT is still to be determined. A form of intestinal mast cell tumor also exists in cats (Sabattini et al. 2016; Barrett 2018).

Mesenchymal Tumors and Melanoma Introduction This section will irst evaluate the management of soft tissue sarcomas (STS) and describe general adjunctive therapies. Speci ic types of STS will then be discussed with tumor-speci ic treatment options.

Soft Tissue Sarcomas STS are a heterogenous group of tumors that originate from connective tissues surrounding, supporting, and bridging anatomical structures or tissues. STS have similar biological behaviors, often displaying both benign and malignant characteristics. Although skin and subcutaneous tumors are the most commonly observed STS, these sarcomas can, in principle, arise from any part of the body (Ehrhart 2005; Ettinger 2003; Kuntz et al. 1997). In general, STS are slow-growing and locally invasive tumors, composed mainly of spindle-shaped cells, with a low tendency for metastatic spread. STS are grouped together because of their

comparable biological behavior and clinical characteristics while further histologic classi ication and differentiation are often complicated. The nomenclature follows classi ication of human STS, based on patterns of cellular proliferation and individual cell morphology without conclusive identi ication of the cells of origin and is poorly standardized for animals. Some pathologists, therefore, prefer the term spindle cell tumors of canine soft tissue (Williamson and Middleton 1998). Further differentiation of histologic diagnosis can be achieved using immunohistochemistry (Gaitero et al. 2008; Ettinger et al. 2006; Liptak and Forrest 2013). Canine STS display histological and immunohistochemical features similar to their human equivalents (Milovancev et al. 2015). Tumors typically included in the STS group are FSA, perivascular wall tumors (previously called hemangiopericytoma), liposarcoma, malignant ibrous histiocytoma, mesenchymoma, myxosarcoma, nonplexus derived PNSTs (previously called neuro ibrosarcoma or schwannoma), and undifferentiated sarcoma. There are several mesenchymal tumors that are not considered “soft tissue sarcomas” because their individual biological behavior has a more de ined character and they can usually be identi ied on light microscopy, including hemangiosarcoma, synovial cell sarcoma, gastrointestinal stromal tumors (GISTs), oral FSA, and PNSTs. Rhabdomyosarcoma, lymphangiosarcoma, and leiomyosarcoma are included in this exclusion list by some pathologists, whereas others would group them with STS (Ehrhart 2005; Dennis et al. 2011; Liptak and Forrest 2013). Histiocytic sarcoma is also considered not a typical STS because for one it is not arising from connective tissue and also because it has a differing biologic behavior. The discussion pertaining to the exact histologic differentiation is not one of major clinical importance because the overall biological behavior of STS is similar. Several important features of biological behavior that are common to all STS are listed in Table 4.3.

Table 4.3 Common features of STS (as described by Liptak and Forrest 2013). 1) An ability to arise from any anatomical site in the body 2) STS often have a pseudo-capsule: these tumors seem to be encapsulated macroscopically while histologically tumor margins are usually poorly de ined 3) A tendency to in iltrate along and through fascial planes 4) Local recurrence is common after conservative excision 5) Metastasis through hematogenous route; most common site of metastasis is the lungs 6) A poor response to chemotherapy and radiation therapy in cases where gross tumor is present Incidence and Predisposing Factors STS represent 8–15% of all skin and subcutaneous tumors in dogs and 7–18% in cats (Miller et al. 1991; Mukaratirwa et al. 2005; Theilen and Madewell 1979; Dobson et al. 2002). An STS incidence of 142 per 100 000 dogs per year was reported in the UK (Dobson et al. 2002). Boerkamp et al. (2014) estimated an incidence of 114 STS/100.000 Golden retrievers/year in the Netherlands. Median age of dogs affected with STS is reported to be between 10 and 11 years (range, 5–17 years) (Ettinger et al. 2006; McSporran 2009; Liptak and Forest 2013; Bray et al. 2014). Middle to large breed dogs are commonly affected, with Golden retrievers, Setters, Swiss mountain dogs, Rottweiler, Dobermann, and Boxers reported to be at increased risk for developing certain STS (Boerkamp et al. 2014; Grüntzig et al. 2016). Median age at presentation for STS in cats is 8–11 years (range 1–17 years) (Alberdein et al. 2007; Davidson et al. 1997; Dillon et al. 2005). There are case reports of dogs that developed STS in association with previous trauma, implants, previous injury, and parasitic infection (Spirocera lupi) (Vascellari et al. 2003, 2006; van der Merwe et al. 2008; Rayner et al. 2010). Clinical Signs

STS commonly present as irm, ixed masses (Liptak and Forrest 2013). STS generally grow slowly, and symptoms are related to the site of involvement and the degree of invasion. They can cause dysfunction of an involved organ or signs can be caused by pressure onto surrounding structures. About 60% of STS are found on the limbs, 35% on the trunk, and in 5% the head is involved (Chase et al. 2009; Liptak and Forrest 2013). Large or fast-growing STS can cause skin ulceration. Tumor necrosis can develop due to fast expanding growth (Liptak and Forrest 2013).

Metastasis Higher histologic grades and mitotic counts are factors associated with increased metastatic potential in STS (Dennis et al. 2011). In the case of metastasis, STS usually spread hematogenously, preferably to the lungs (Dernell et al. 1998; Ehrhart 2005; Ettinger 2003; Liptak and Forest 2013). Regional lymph node metastasis is unusual, except for synovial cell sarcoma and histiocytic sarcoma. Reported overall rate of metastasis in dogs is dependent on tumor grade; up to 13% for grades I and II STS compared to 41–44% for grade III STS. (Baker-Gabb et al. 2003; Ettinger et al. 2006; Kuntz et al. 1997; Simon et al. 2007). Rate of pulmonary metastasis at initial presentation is 6% for grades I and II and 38% for grade III. The likelihood of having metastasis at initial presentation is higher when the STS has been present for over three months (Villedieu et al. 2021). Reported overall metastatic rate in cats is 14–20% (Davidson et al. 1997; Dillon et al. 2005). Interestingly, metastases can be slow growing and may not affect survival (Dennis et al. 2011). Diagnostic Strategies and Preoperative Planning Cytology can support a clinical suspicion of STS but rarely con irms the inal diagnosis of the type of STS because they tend not to exfoliate well. A cytological diagnosis of “suspect sarcoma” or “mesenchymal proliferation” is a relatively common inding (Ghisleni et al. 2006; Shelly 2003). A correct diagnosis of STS by cytological examination is generally made in around 60% of cases (Baker-Gabb et al. 2003). The main reason to perform FNA is to rule out benign or nonneoplastic

differential diagnoses including lipoma, seroma, and in lammatory processes, or well-exfoliating tumors such as lymphoma, histiocytoma, carcinoma, and MCTs. A generally accepted shortcoming of cytology is the inability to provide details on the exact diagnosis and the biological aggressiveness (i.e. histological grade) that may be important to plan treatment. A recent study found that in cytologically diagnosed STS, cytological scoring could accurately predict histological grade of these tumors in 60% of the cases in dogs and in 85% in cats (Millanta et al. 2020). Cytology can also be used to investigate enlarged regional lymph nodes for metastasis, albeit rare for STSs. De initive diagnosis of STS is most accurately achieved by histology. Excisional biopsy is only performed when adequate margins can be obtained. Incisional biopsy is preferred if surgical margins cannot be expected and to facilitate the planning of curative surgery. Incisional biopsies can be taken with a scalpel, biopsy punches, needle core biopsy instruments, or trephines (Ettinger 2003; Ehrhart 2005; Liptak and Forrest 2013; Bray 2016). It is however important to bear in mind that preoperative incisional biopsies are not always accurate in terms of predicting histological tumor grade. Tumor grade was overestimated in 12% and underestimated in 29% of preoperative incisional biopsies compared to postexcision whole-tumor specimens of 68 dogs with STS (Perry et al. 2014), stressing the need to always consider all available clinical data such as growth rate and behavior before planning de initive treatment and always perform histological evaluation of the complete excised tumor afterward for de initive diagnosis, grading, and surgical margins evaluation. Tumor seeding from a biopsy is a reported risk in people (Robertson and Baxter 2011), ranging from 1% for human bone neoplasms up to 22% for mesothelioma. By removing the biopsy site at tumor resection this risk can be controlled. The presence of distant metastases is an important prognostic indicator, rendering radiographic or CT evaluation of the thorax a routine diagnostic step before treatment.

STS appear to be encapsulated but often show an invasive growth pattern. The macroscopic capsule is in fact a pseudocapsule, composed of compressed tumor cells and reactive ibrovascular tissue. The tumor can in iltrate along and through fascial planes with inger-like microextensions. Marginal excision will leave microscopic tumor behind, often resulting in local recurrence compromising the optimal treatment plan (Ehrhart 2005). Additionally, measurement of tumor boundaries by physical examination commonly underestimates the actual tumor dimensions (McEntee and Samii 2000); therefore, advanced imaging techniques are recommended for surgical planning. Contrast-enhanced CT and magnetic resonance imaging (MRI) are useful for surgical planning and identi ication of metastatic disease. Considering the limited value of manual determination of subcutaneous tumor size (Ranganathan et al. 2018), advanced imaging is often necessary to properly evaluate tumor extension in surrounding tissues of large STS, STS at locations where wide excision is dif icult due to proximity of critical tissue structures such as in the head and neck, or an STS within a body cavity. In humans, MRI is the preferred modality for assessment of STS in limbs, delineating muscle groups, and separating tumor from adjacent vascular, muscular, and bony structures, while contrast-enhanced CT is indicated in cases of (suspected) bone involvement, intra-abdominal or retroperitoneal tumors, and for screening of pulmonary metastasis (Hanna and Fletcher 1995; López-Pousa et al. 2016; Fuerst et al. 2017; Spoldi et al. 2017; Ranganathan et al. 2018). Novel Diagnostic Imaging Techniques In human STS, speci ic MRI features or combinations of MRI data in multivariable algorithms have been increasingly investigated to build “radiomics” models to predict tumor grade and to assess the integrity of the pseudocapsule. Three-dimensional imaging features from fatsuppressed T2-weighted imaging could be used as candidate biomarkers for preoperative prediction of histopathological grades of soft tissue sarcomas noninvasively (Liu et al. 2008). Accuracy levels of such “radiomics” models currently reach up to 88% (Chhabra et al. 2018; Corino et al. 2018). These indings might have implications for

veterinary patients although they have not been reported to our knowledge. Optical coherence tomography (OCT) is a medical imaging technique that uses light to capture micrometer-resolution, three-dimensional images from within optical scattering media (e.g. biological tissue). Following the generation of an initial set of OCT images correlated with standard hematoxylin and eosin-stained histopathology, over 760 images were subsequently used for automated analysis. Using texturebased image processing metrics, OCT images of sarcoma, muscle, and adipose tissue were all found to be statistically different from one another. This demonstrates the potential use of intraoperative OCT, along with an automated tissue differentiation algorithm, as a guidance tool for soft tissue sarcoma margin delineation in the operating room (Mesa et al. 2017). Fluorescence-based imaging is another technique for real-time intraoperative tumor margin assessment in excision of STS. Fluorescence-based imaging techniques use luorescent agents that are preferentially activated by tumor cells, which can subsequently be measured after excitation by an appropriate wavelength of light (Bartholf DeWitt et al. 2016). Staging and Grading STS are histologically distinguished as low (grade I), intermediate (grade II), and high (grade III) grades, based on the degree of tissue differentiation, cellular pleomorphism, cellularity and matrix formation, mitotic index, and the amount of tumor necrosis (Kuntz et al. 1997). Tumor grade is predictive for distant metastasis, local recurrence, and shorter disease-free intervals. Staging of STS follows a speci ic TNM staging scheme (Table 4.4) (Dennis et al. 2011; Greene 2002; Kotilingam et al. 2006; MacEwan et al. 2001). Despite the low incidence of lymph node involvement, investigation of draining lymph nodes is advised, including biopsy of suspect lymph nodes (Kuntz et al. 1997; Dennis et al. 2011).

Table 4.4 TNM staging and grading system for soft tissue sarcomas. Source: Kotilingam et al. 2006; MacEwan et al. 2001; Greene 2002. The American Joint Committee on Cancer.

T

Primary tumor

TX Primary tumor cannot be assessed T0 No evidence of primary tumor T1 Tumor < 5 cm in greatest dimension T1a Super icial tumor T1b Deep tumor T2 Tumor > 5 cm in greatest dimension T2a Super icial tumor T2b Deep tumor N Regional lymph nodes NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Regional lymph node metastasis M Distant metastasis MX Distant metastasis cannot be assessed M0 No distant metastasis M1 Distant metastasis G

Histologic grade

GX Grade cannot be assessed G1 Low (grade I) G2 Intermediate (grade II) G3 High (grade III) Stage I

Any T

G1–2

N0

M0

T1a-b, T2a

N0

M0

III G3

T2b

N0

M0

IV Any G

Any T

N1

Any M

Any G

Any T

Any N

Any M

II

G3

Serum VEGF and neutrophil counts are positively correlated, and negative between VEGF and hemoglobin content in dogs with sarcoma (De Quieroz et al. 2013). In contrary to primary care practices with predominating low-grade STS (51–84%) (McSporran 2009; Bray et al. 2014), studies from referral practices report high-grade STS are more common (22.7–29%) (Kuntz et al. 1997; Heller et al. 2005). Surgical Aspects Surgical resection is the treatment of choice for most STS. Careful preoperative planning and a wide irst excision, accomplishing 2–3 cm surgical margins around the tumor and one fascial plane deep to the tumor, are considered for surgery with curative intent. If the tumor is attached to a muscle or fascial plane, the entire anatomical layer must be removed. Fat and loose connective tissues do not function as good tumor barriers, necessitating wide margins. If 3 cm tissue is not available in depth, at least a fascial plane underneath the tumor should be obtained. Tumors should not be shelled out of their pseudocapsule due to the high risk of regrowth of tumor cells remaining in and beyond the capsule. In general, wide surgical excision is the preferred therapy for all STS to achieve complete excision. For skin and subcutaneous tumors, this implies either surgical margins of 2–3 cm in all directions or 2–3 cm lateral to the tumor and at least one additional, non-involved tissue plane beneath the tumor. An important rule is that the irst surgery offers the best chance for cure (“the irst cut is the deepest”) (Connery and Bellenger 2002; Dernell et al. 1998; Liptak and Forrest 2013). If the initial surgical excision was incomplete, curative-intent re-excision, if possible at all, will always imply wider

margins and therefore higher morbidity than would have been the case if the initial surgery had been wide enough. Recently, the importance of wide margins has been debated as wide margins were not associated with increased disease-free interval or overall survival (Bray et al. 2014; Chase et al. 2009; McSporran 2009; Stefanello et al. 2008). But in view of patient selection with predominant low-grade STS in primary care practices vs. high-grade STS in referral practices, and current absence of available diagnostic tests to predict required margins for a certain STS, wide surgical margins continue to be the surgeon’s goal in patients treated by surgery only. Incomplete resections increase patient morbidity, treatment costs, risk of further recurrence, and ultimately decreases survival time (Dernell et al. 1998; Kuntz et al. 1997; McKnight et al. 2000). Risk of incomplete excision is increased when the tumor is excised by a surgical resident compared to a board-certi ied surgeon (Monteiro et al. 2011). More experienced oncologic surgeons achieve a signi icantly better outcome, most likely due to a superior ability to use aggressive surgical removal techniques (Rohrborn and Roher 1998). Extensive resections are complicated and may be impossible to close primarily depending on the extent, location, and quality of the surrounding tissue (Prpich et al. 2014). Adequate margins are often not achievable with larger STS located on extremities. Amputation (radical resection) may be an alternative in the absence of major orthopedic or neurological problems, but clearly often meets resistance from the owner. As recurrences after marginal excision of low-grade STS may be less common than expected in high-grade STS (McSporran 2009; Stefanello et al. 2008) smaller margins might be of choice in individual cases. Marginal resection of STS on extremities, either as sole therapy or combined with radiation therapy, may result in a long-term outcome with lower morbidity compared to amputation. Only 11% of marginally excised low-grade STS from extremities of 35 dogs resulted in recurrence, and median disease-free interval and median survival time were not reached after a mean follow-up of more than 1000 days (Stefanello et al. 2008). Another study reported a grade-dependent recurrence after marginal excision of 3 of 41 (7%) grade I tumors, 14 of

41 (34%) grade II tumors, and 3 of 4 grade III tumors. The median time to recurrence was 12 months. In contrast, no recurrences were observed in the 30 tumors treated with complete excision. Thus, histologic grade is a strong predictor for recurrence for marginally excised subcutaneous STS, and clean margins predict nonrecurrence. However, tumor recurrence did not signi icantly reduce survival time, since no signi icant differences in survival time were found between grades treated with marginal excision, between marginal excision and wide excision, or between dogs that died from STS and dogs that died from other causes. This may be explained by the old age of affected dogs and the relatively slow growth of soft tissue sarcomas. Because high-grade STS were not present in adequate numbers, conclusions about grade III tumors in this study could not be made (McSporran 2009). Bacon et al. (2007) reported a recurrence rate of 15% (6/39) after reexcision with margins of 0.5–3.5 cm, with a median follow-up of 816 days. Residual tumor was identi ied in 9 of 41 (22%) resected scars. It was concluded that after incomplete resection of STS, resection of local tissue should be performed, even if excisable tissue margins appear narrow. A long-term favorable prognosis was achievable without radiation therapy or amputation. According to the data in this study, the presence of residual tumor in resected scar tissue should not be used to predict local recurrence (Bacon et al. 2007). Based on these studies therefore marginal excision of low- and intermediate grade-STS may not in luence survival time compared to wide or radical resection. This is most likely caused by the relatively old age (median age of 10 years) of affected dogs and relatively slow growth of low-grade STS. Reported percentages of dogs that died of known STS-related causes after treatment is between 10 and 33% (Baker-Gabb et al. 2003; Ettinger et al. 2006; Kuntz et al. 1997; McSporran 2009; Simon et al. 2007), and many dogs will die of other age-related causes. Radical resection of extremity STS may therefore be considered a last resort treatment for recurrent and high-grade tumors (McSporran 2009; Stefanello et al. 2008). All removed tumors should be submitted for histologic examination. Marking the surgical margins or speci ic areas of questionable margin

status with ink or suture material will guide the pathologist in evaluating the completeness of excision, given the fact that standard histological margin assessment does not evaluate the complete cut edge of the excised tissue specimen but relies on a limited amount of sections through the margin. There are additional methods with the intention to increase reliability of histological margin evaluation, such as intraoperative frozen sections evaluation, and intra- or postoperative margin imprint cytology. By taking a super icial section of tissue from the wound bed after tumor excision, a so-called shaved margin is obtained that can be assessed by the pathologist for remaining tumor cells. It remains to be proven if any of these techniques results in superior surgical margin assessment for speci ic tumor types in dogs and cats (Harris et al. 2014; Milovancev et al. 2017). Using technology for intraoperative real-time assessment of surgical margins is promising to improve the complete excision of canine soft tissue sarcomas. Using a luorescent-based imaging technique, sensitivity and speci icity of the imaging system for identi ication of cancer (soft tissue sarcomas and mast cell tumors) in biopsies have been reported to be 92% for both (Bartholf DeWitt et al. 2016). Using optical coherence tomography, it is possible to differentiate soft tissue sarcoma, muscle, and adipose tissue from one another (Mesa et al. 2017; Selmic et al. 2019). The sensitivity and speci icity of using optical coherence tomography to detect soft tissue sarcoma at the margins in one study were 88.2 and 92.8%, respectively, for within the surgical wound bed (in vivo) and 82.5 and 93.3%, respectively, for the excised tumor specimens (ex vivo). The accurate classi ication for all specimens was 91.4% in vivo and 89.5% ex vivo (Dornbusch et al. 2021). Reconstructive Surgery Many types of reconstructive techniques are available to close defects created by wide removal of skin tumors, and the detailed description of these techniques is beyond the scope of this chapter. Large defects on the head, neck, and body can often be closed using a variety of local and axial pattern skin laps (Kirpensteijn and Ter Haar 2013). Despite the relatively good outcome of axial pattern skin laps in the long term in cats and dogs, short term complication rate was high (90%) and a

second surgery for revision of the reconstruction was performed in 30% of the cases in a recent report (Field et al. 2015). Surgeons and patient-owners, therefore, need to be prepared for the possibility of a prolonged aftercare after surgery for large tumors. Skin reconstruction on the distal limbs is more challenging because local and axial pattern laps are usually not applicable. Options are either aiming for complete excision with narrow margins by excision just outside the tumor pseudocapsule, including underlying muscle fascia, in relatively wellde ined low-intermediate grade STS, sparing part of the skin if it is not attached to the tumor. Depending on speci ic tumor type, margin status, and tumor grade, additional radiation therapy may prevent local recurrence (see speci ic section on radiation therapy). Another option is aiming for a wide excision and thus creating a large skin defect. There are several options to close large distal extremity wounds, including vascularized skin pouch lap, tubed vascularized skin laps, free vascularized skin laps with microvascular anastomosis (Fowler et al. 1998), autologous skin transplant (with or without negative pressure wound therapy augmentation) (Stanley et al. 2013; Miller et al. 2016), or healing by second intention (Prpich et al. 2014). Leaving a wound open can often be preferred over an incomplete tumor excision. Healing by second intention has a relatively good outcome and prognosis, however, wound closure is slow and possible complications include a relatively fragile new skin after epithelization and the risk of developing wound contracture, especially in locations with high degree of motion such as the carpus. In one study evaluating second intention healing after STS removal over an extremity, the average time it took for wounds to heal was approximately two months and over 90% of wounds healed completely by second intention alone. Complications occurred in 23% of wounds during healing and 26% of wounds had complications long-term (Prpich et al. 2014). In some extremity locations, axial pattern laps can be used (Henney and Pavletic 1988), such as the super icial brachial axial pattern lap and the reverse saphenous conduit lap (Elliot 2014; Cavalcanti et al. 2018) for the thoracic and pelvic limb, respectively. Use of the relatively lengthy thoracodorsal axial pattern lap for forelimb wounds was met with a relatively high complication rate of an average of 21% distant lap necrosis in 7/10 dogs and the need for surgical intervention in

6/10 dogs (Aper and Smeak 2003). A phalangeal illet technique provides a sturdy closure of distal metacarpal/metatarsal wounds by sacri icing a digit (Figure 4.7) (Olsen et al. 1997; Demetriou et al. 2007; Cantatore et al. 2013).

Figure 4.7 Excision of STS at distal medial aspect of the metatarsus using a phalangeal illet lap of digit II in a Heidewachtel. (a) Tumor and 1 cm excision margins drawn on the skin. (b) En-bloc excision including metacarpal II and digit II and metacarpal III, metacarpophalangeal joint and proximal part of phalanx I of digit II, preserving the main blood supply of digit III. (c) Removal of the bones and nail of digit III (“ illet”), preserving soft tissues and blood supply. (d) Raising and rotating the phalangeal illet lap into the defect. Note that the digital pad is preserved. This technique is also useful for footpad reconstruction. (e, f) Result after one week. Although elliptical excisions are commonly used for skin tumor removal, several human studies claim to have better results with round excisions. Furthermore, the shape of the tissue to be excised is dictated by the tumor margins, which commonly results in more or less round wounds. In practice, only the lesion and the required margin of surrounding tissue are excised without attempting to design an elliptical skin incision. The resulting wound is closed by opposing the wound edges along the lines of least skin tension, starting in the center of the wound. Such round excisions result in 14–21% shorter sutured wound length and the wound direction differed from the predicted ellipse in 45% of cases (Hudson-Peacock and Lawrence 1995). When using this technique, dog-ears will obviously appear. In general, however, round excision with subsequent dog-ear removal results in better-oriented wounds than those achieved by elliptical excision, minimize tissue excision, decrease wound widening, and may still decrease the inal sutured wound length (Lee et al. 2011). Dog-ear reconstructions are relatively simple and can be performed directly after closure or at a later time (Borges 1982) by removal of the excess skin fold and thus extending the wound length. Techniques to reduce dog-ear folds without removal of skin include suture techniques to anchor the dog-ear to deeper tissues such as the dog-ear tacking suture technique (Kantor 2015) and the three-bite suture technique (Jaber et al. 2015). In the latter technique, a three-bite suture is placed that sequentially pierces the deep fascial plane and each margin of the dogear, thus lattening the dog-ear by anchoring the over-projecting skin to the deep plane. This is a fast, easy, and versatile method of immediate

dog-ear correction without extending the scar while maintaining a full and complete local skin blood supply (Jaber et al. 2015). Another rarely discussed reconstructive technique is the cuticular purse string technique. In a retrospective study by Cohen et al. (2007), the authors reviewed 98 human patients after cuticular purse-string suture placement. These sutures will achieve partial surgical wound closure and the postoperative wound area decreased by 6–90%, with a mean of 60% following purse-string partial closure. The circumferential placement of the cuticular purse-string suture makes it possible to recruit skin from the entire diameter without needing to undermine the wound edges. Generally, the purse string suture is removed three or four weeks after closure to allow the partially closed wound to completely heal by second intention. According to the authors of this study, this closure technique provides uniform tension to the wound, enhances hemostasis at the tissue edge, and signi icantly decreases the size of the defect. The technique has been described in people after surgical removal of skin tumors (Cohen et al. 2007) and is reported to be particularly suitable in older human patients because of their skin laxity (Raposia et al. 2014). Pavletic (2000) described the use of skin stretchers 72–96 hours before excision of large tumors. Skin stretching is an easy way to mobilize skin and is reported to be successful in most cases. Two other techniques for stretching the skin after creating the surgical wound have been studied: staples as anchor points along the edge of each surgical wound margin and a hypodermic needle “skewered” through the skin parallel to each surgical wound margin (needle transpiercing the skin along the length of the margin, going in and out of the skin). Sutures are then placed between the staples or the needles on either side of the wound and tightened over a bandage material covering the open wound (Tsioli 2015). Cryosurgery Cryosurgery is a type of cytoreductive therapy that has been described for super icial skin tumors. Cryosurgery may be used in cases when surgery is not possible because of concurrent debilitating factors that prevent safe anesthesia. Cryosurgical ablation uses tissue freezing to

destroy selected lesions. There are several methods of cryosurgery: open-spray, closed-spray, and cryoprobe method. Liquid nitrogen is sprayed on the tumor from a speci ied distance for 15–60 seconds. For malignant lesions, two to three freeze-thaw cycles are recommended, while for benign lesions, two cycles are recommended. Before application, large vessels feeding the tumor may be ligated to prevent hemorrhage and to improve the freezing effect. Wounds heal by second intention. Patients should be closely monitored following cryosurgery to control the healing of the treated site and to treat possible complications. Reported complications include hemorrhage, pain, edema, depigmentation, tissue retraction, tendon rupture, alopecia, odor, and lameness (De Queiroz et al. 2008). Adjuvant Therapies According to several studies, surgical resection, often described as “aggressive,” “radical,” or “wide,” is the irst or primary treatment of choice with the best overall outcome in STS treatment. The surgical goal should always be removal of the complete tumor. If complete tumor removal is not achievable, for instance where there are important adjacent anatomical structures, cytoreductive surgery can be used as palliative care or in combination with adjunctive therapies. Multimodal therapy including adjuvant radiotherapy and/or chemotherapy may allow reduction in surgical dose without compromising local recurrence rates (Bostock and Dye 1980; Bray 2016; Davidson et al. 1997; Dernell et al. 1998; Ehrhart 2005; Liptak and Forrest 2013). Palliative care can be used to reach an acceptable survival time and, above all, a reasonable quality of living. Radiotherapy External beam radiation sources include X-rays, gamma rays, or electrons delivered by orthovoltage or megavoltage (linear accelerators and cobalt 60) equipment. When X-rays and gamma rays interact with tissue, they transfer their energy, leading to chemical and biologic damage, damaged DNA, and inally cell death. Radiotherapy can be used in a curative or palliative manner before (neoadjuvant) or after (adjuvant) surgical tumor removal. A de initive course of radiotherapy

often involves daily treatments for several days under general anesthesia. Radiation protocols, however, vary based on the tumor type, stage, and site, and from one facility to another. Palliative (coarsely fractioned) radiation therapy has been used for pain relief and improvement of dysfunction in people and in animals suffering from neoplasia. Treatment options for incomplete tumor resections include radiation of the wound bed or re-excision of the wound bed with wider margins (Bacon et al. 2007; Dernell et al. 1998; Forrest et al. 2000; McKnight et al. 2000). A reported 15% recurrence rate after re-excision (Bacon et al. 2007) which is comparable to recurrence after radiation therapy for incompletely resected STS (17–31%) (Forrest et al. 2000; McKnight et al. 2000; Simon et al. 2007). Median survival time after re-excision is also comparable to that after surgery alone (1416 days) (Bacon et al. 2007; Kuntz et al. 1997) and incomplete resection combined with adjuvant radiation therapy (2270 days) (Forrest et al. 2000; McKnight et al. 2000). Grade III STS have signi icantly shorter survival periods, ranging from 236 to 856 days (Kuntz et al. 1997; Selting et al. 2005). Forrest et al. (2000) treated hemangiopericytoma, FSA, and other STS with radiation therapy after tumors were excised to microscopic disease, with a dose that ranged from 42 to 57 Gy given in 3 to 4.2 Gy daily fractions on a Monday through Friday schedule. Median time to local recurrence was more than 798 days. STS tumors at oral sites had a statistically signi icant lower median survival (540 days) as compared to other tumor sites (2270 days). In the same year, McKnight et al. reported a 5-year survival rate of 76% and median disease-free interval of 1082 days after delivery of a total dose of 63 Gy delivered in 3 Gy fractions on alternate days (McKnight et al. 2000). Typical protocols for treating incompletely excised STSs involve curative intent radiation with a total dose more than 50 Gy. Forty-eight dogs with histologically con irmed incomplete or closely excised STSs were treated with a hypofractionated protocol that is typically reserved for palliative radiation therapy (6–8 Gy/weekly fractions to a total dose of 24–32 Gy). In total, 10 dogs (21%) developed local recurrence, 11 dogs (23%) developed metastasis, and 3 dogs developed both (included in each group). The median progression-free survival was 698 days.

The local failure-free probability at one and three years was 81 and 73%. The one- and three-years tumor-speci ic overall survival was 81 and 61%. Long-term local tumor control was achieved in the majority of dogs. This protocol is described by the authors as reasonable to prescribe in older patients or when inancial limitations exist (Kung et al. 2016). Demetriou et al. (2012) reported adjuvant use of hypofractionated radiotherapy after planned marginal canine limb STS resection. Incomplete margins were present in 81–100% of cases. The protocol consisted of four weekly 6–9 Gy doses to a total dose of 24–36 Gy. Local recurrence was reported in 18–21% of cases. Metastases occurred in 2–25% of dogs with follow-up periods of 240–2376 days (median 681–1339 days). Lawrence et al. (2008) reported that coarsely fractionated radiation therapy may be a reasonable palliative option for the management of macroscopic canine STS. The treatment protocol used single parallelopposed ields with a 3 cm margin surrounding the palpable edge of the tumor, if possible, using a cobalt teletherapy unit. CT scans were used, when available, to help estimate ield size and depth of treatment, but true image-based computer planning was not performed. The total dose of radiation applied to the tumor was 32 Gy to the isocenter, delivered as one 8 Gy fraction on days 0, 7, 14, and 21. The overall objective response rate was 50% and included seven partial and one complete response (a cutaneous hemangiosarcoma on the left ventral thorax of a dog that was also treated with chemotherapy). The median progression-free interval was 155 days, with a range of 72–460 days. Radiotherapy in combination with chemotherapy can be used for STS that have metastasized or have a high risk of metastases, such as highgrade STS and feline vaccine-associated sarcoma. Acute side effects of radiation therapy on the skin include moist desquamation and alopecia. Late effects of radiation therapy on the skin include ibrosis, contraction, nonhealing ulcer, and leukotrichia. The higher the dose per fraction, the higher the probability of late effects (Forrest et al. 2000; McEntee 2006; Moore 2002). A 5 × 6 Gy radiation therapy protocol was well tolerated and provided long progression-free interval and overall survival in 50 dogs with macroscopic STS. The addition of metronomic chemotherapy yielded a signi icantly longer overall survival (757 days)

compared with dogs that did not receive systemic treatment (286 days) but did not in luence progression-free interval. Toxicity was low throughout all treatments (Cancedda et al. 2016). Stereotactic body radiation therapy (SBRT) is an emerging type of radiation to treat soft tissue sarcomas in dogs. In one study, 36 and 11% of tumors had a partial or complete response, respectively (Gagnon 2020). The medians for progression-free survival time, time to progression of disease, overall survival time, and disease-speci ic survival time were 521, 705, 713, and 1149 days, respectively. Low histologic grade and extremity locations of STSs were positive prognostic factors for patient survival times (Gagnon 2020). Thermoradiotherapy is a therapeutic process that applies radiation therapy to a tumor while the local temperature of the irradiated tissue has been raised by arti icial means to increase the radiosensitivity of the tissue being treated. Chi et al. identi ied two distinct STS subtypes with signi icant differences in their gene expression and treatment response to thermoradiotherapy, as de ined by changes in diffusionweighted MRI (DWI). The two tumor subtypes could also be readily identi ied by pretreatment gene expression. They performed a gene expression analysis in 22 spontaneous STS before and after the irst hyperthermia treatment combined with radiotherapy. In parallel, DWI was done prior to the treatment course and at the end of therapy. STS with high expression levels of hsp70 and centrosomal proteins are likely to have stronger response to thermoradiotherapy (Chi et al. 2011). Chemotherapy STS are a heterogeneous group of tumors. Because of this heterogeneity, it is hard to obtain suf icient data to set up a solid treatment protocol based on adequately proven clinical trials. The effectiveness of chemotherapy as an adjuvant therapy after resection of STS is thus unclear. Chemotherapy may be bene icial in cases of metastasis, incomplete resection of high-grade tumors, and tumors not treatable with surgery or radiation therapy. Several chemotherapy protocols are used either as single agent or in combination. Metastases are uncommon in STS, however, and are reported to be 13% for low-

grade to 44% for high-grade cutaneous STS. Single-agent doxorubicin, mitoxantrone, or combination protocols using vincristine, doxorubicin, and cyclophosphamide have been reported to have effectiveness for STS (Thornton 2008). One study evaluating adjuvant doxorubicin for high-grade STSs in dogs failed to ind a bene it (Selting et al. 2005). Elmslie et al. (2008) treated 30 dogs after incomplete removal of soft tissue sarcoma by metronomic, continuously low dose, cyclophosphamide (10 mg/m2), and standard-dose piroxicam (0.3 mg/kg) therapy. Disease-free interval (DFI) was 410 days for STS at all sites (trunk, extremities) in treated dogs compared to 211 days for 55 untreated controls. Even though the median DFI was not reached for the treated dogs, it was signi icantly prolonged. It is important to note that a selection bias in the control population may have skewed the conclusions of this study because 100% of the control dogs developed tumor recurrence or were censored from the analysis. Local chemotherapy to prevent the local recurrence of an STS has been evaluated by using intralesional cisplatin-impregnated bead placement following marginal excision of the tumor. About 47% of dogs had local toxicosis and 29% of tumors recurred locally (Bergman et al. 2016). No clinical studies in the dog suggest whether neoadjuvant chemotherapy has any bene icial impact on patient outcome or surgical margins (Bray 2016; Elmslie et al. 2008; Kuntz et al. 1997; Rassnick 2003; Schlieman et al. 2006). In cats, doxorubicin chemotherapy may play a role in extending the disease-free interval in combination with radiotherapy for treatment of incompletely excised soft tissue sarcomas (Hahn et al. 2007). Radiotherapy was performed on an alternate-day schedule, with a total dose of 58.8–63 Gy delivered in 21 fractions. Doxorubicin was administered every 21 days for 3–5 cycles. Median DFI with concurrent radiotherapy and doxorubicin chemotherapy (15.4 months) was signi icantly longer than median DFI with radiotherapy alone (5.7 months). However, survival time was not signi icantly different between groups. Electrochemotherapy uses electroporation to increase cell membrane permeability to cytotoxic drugs. This is done by locally applying electric

ield pulses over the tumor area or tumor excision bed to enhance transmembrane uptake of locally or systemically administered cytotoxic agents. Complete and partial responses have been reported in few cases of macroscopic STS after electrochemotherapy with intravenous bleomycin administration in dogs (Torrigiani et al. 2019). Interesting results have been published of adjuvant electrochemotherapy to treat the scar/wound bed after incomplete excision of STS of different grades with perilesional bleomycin injections (Spugnini et al. 2007a), systemic bleomycin administration (Torrigiani et al. 2019), and a combination of local cisplatin with systemic bleomycin (Spugnini et al. 2019) in dogs. In cats, both intraoperative and postoperative adjuvant electrochemotherapy with local application of bleomycin has been studied (Spugnini et al. 2007b) and remarkable long-term local control has been described for adjuvant electrochemotherapy with local cisplatin injections of the scar/wound bed after incomplete surgical excision of FSAs (Spugnini et al. 2011), and a combination of local cisplatin with systemic bleomycin for incompletely excised FISASs (Spugnini et al. 2020). Immunotherapy The expression of genes encoding for immunostimulatory cytokines or tumor-associated antigens that may negatively in luence tumor viability is being used more frequently. Several attenuated poxvirus vector systems have been developed, for example, NYVAC (Copenhagen vaccinia virus), TROVAC (Fowl pox virus), and ALVAC (Canary pox virus) viral vectors (Paoletti et al. 1995). These recombinant viruses have been administered without any major side effects to animals and humans (Fries et al. 1996). To prevent the recurrence of FSA, ALVAC- or NYVAC-based recombinants expressing feline or human IL2, respectively, were administered to domestic cats. In the absence of immunotherapy, recurrence was observed in 61% of animals within a 12-month follow-up period after treatment with surgery and iridiumbased radiotherapy. Only 39% of the cats receiving NYVAC-human interleukin-2 (IL-2) and 28% of the cats receiving ALVAC-feline IL-2 exhibited tumor recurrences (Jourdier et al. 2003). Additionally, intratumoral administration of histoincompatible cells expressing human IL-2 in spontaneous canine melanoma and feline FSA, in

combination with surgery and radiotherapy, has been shown to increase the disease-free period and survival time (Quintin-Colonna et al. 1996). Haagsman et al. (2013) reported no effect of local interleukin2 therapy on canine PNSTs after marginal surgical excision in a doubleblind randomized placebo-controlled study. Angiogenesis plays an essential role in tumor growth, invasion, and metastasis. Vascular endothelial cell growth factor (VEGF) is one of the key growth factors regulating the process of angiogenesis. In a study of De Queiroz et al. (2013), serum VEGF was measured by enzyme-linked immunosorbent assay quantitative method. Dogs with hemangiopericytoma showed higher serum VEGF levels compared to the patients with malignant PNSTs. Serum VEGF decreases after sarcoma resection. Serum VEGF and neutrophil counts are positively correlated, and negative between VEGF and hemoglobin content in dogs with sarcoma (De Quieroz et al. 2013). Kamstock et al. (2007) evaluated the effect of xenogeneic VEGF vaccination in dogs with cutaneous STS. A total of six immunizations with a human VEGF vaccine were administered intradermally to dogs once every other week for three immunizations, then once every four weeks for three additional immunizations. Eventually, four out of nine dogs remained long enough in the study to receive ive or more immunizations. The ive dogs that failed to receive greater than three immunizations were removed from the study due to progressive tumor growth. A decrease in plasma VEGF concentration was observed in three of the four dogs that received ive or more VEGF immunizations. Tumor microvessel density (MVD) was evaluated in biopsy specimens on weeks 6 and 16 of the study from these four dogs. Two of the four multiply vaccinated dogs demonstrated a signi icant (>50%) decrease in tumor MVD at one or more time points. It should be noted that in one of these dogs, tumor MVD increased at a later time point coincident with progressive growth. In the other two dogs, tumor MVD remained relatively constant after immunization of the tumor. Based on these results, it appeared that repeated VEGF immunization was capable of inhibiting tumor angiogenesis in at least half of the dogs. Palliative Procedures

Surgery, radiotherapy, or chemotherapy (doxorubicin/cyclophosphamide) may be used for palliation: to slow the progression of disease, and to alleviate presumed discomfort (Lawrence et al. 2008). For example, Plavec et al. (2006) treated 15 dogs with unresectable STS with a total tumor radiation dose of 24 Gy, given in three weekly 8 Gy fractions. Tumor responses in 15 dogs included one partial remission (liposarcoma), 13 tumors with stable disease and one progressive disease; median time to progression and median survival time were 263 and 332 days, respectively. None of the treated dogs developed serious complications, even though brachial plexus (in one case) and bones were in the radiation ield. The only side effects of radiation therapy were slowed hair growth rate or change of the color of growing hair. It is important to note, however, and to communicate with the owner, that palliative care aims to improve the quality of life in the short-term (Plavec et al. 2006). Prognosis The prognosis of STS depends on tumor size vs. site, histologic grade, mitotic index, in iltrative growth in surrounding structures, potentially presence of metastasis, and completeness of removal (i.e. the surgical margins) (Ettinger 2003; Kuntz et al. 1997; Dennis et al. 2011). Size is reported to be a prognostic factor for STS (Kuntz et al. 1997), because of the increased dif iculty of achieving wide surgical margins for larger tumors in respect of patient morbidity (Liptak and Forrest 2013). Tumor size was also signi icantly related to survival in feline patients (Dillon et al. 2005). Mitotic index is an important feature determining histological tumor grade and provides information on the proliferative activity of the tumor. Mitotic index is also independently associated with increased and earlier rates of tumor recurrence, higher rates of metastasis, and reduced overall survival (Bray et al. 2014; Dennis et al. 2011; Ettinger et al. 2006; Kuntz et al. 1997; McSporran 2009). The most important prognostic factor for local recurrence is complete surgical margins (Baker-Gabb et al. 2003; Dernell et al. 1998; Kuntz et al. 1997; McSporran 2009; Simon et al. 2007). If complete resection can

be achieved most dogs with STS have in general a good prognosis (Bray et al. 2014; Dennis et al. 2011; McSporran 2009; Kuntz et al. 1997). Following resection, the chance of local tumor recurrence depends on histologic grade and completeness of surgical margins. Most grade I STSs with “close” margins will not recur, but propensity for recurrence increases with grade. Marginal resections lead to recurrence in up to 75% of tumors (in grade III STSs) (McSporran 2009). Further research is needed to determine more precise estimates for recurrence rates and survival as related to completeness of surgical margins and to delineate potential differences in metastatic rate and median survival time between grades. Other potential indicators of prognosis that presently require further investigation include histologic type, tumor dimension, location, invasiveness, stage, markers of cellular proliferation, and cytogenetic pro iles (Bostock and Dye 1980; Bray et al. 2014; Chase et al. 2009; Stefanello et al. 2008).

Specific Soft Tissue Sarcomas Fibrosarcomas FSAs are tumors derived from mesenchymal cells or ibroblasts. FSAs in iltrate surrounding tissues, are locally aggressive, and metastasize hematogenously to distant sites including the lungs, liver, bone, brain, and skin (Powers et al. 1995). Tumor grade is an important determinant in the histologic assessment of soft tissue-origin FSA. Grade I or II FSAs of the skin are unlikely to metastasize. Aggressive and complete surgical excision is the treatment of choice for these FSAs, and long-term control or cure is likely with aggressive surgery with or without radiation therapy. A grade III, or high-grade, FSA is more likely to metastasize, and adjuvant chemotherapy is warranted (Dernell et al. 1998; Davis et al. 2007). Radiation therapy or chemotherapy may also be indicated in the case of unresectable FSA. For microscopic local residual disease, radiation therapy seems to be an effective treatment option (Chun 2005; Forrest et al. 2000; Little and Goldschmidt 2007; Mikaelian and Gross 2002). In contrast to FSAs of the skin, FSAs originating from the oral cavity generally behave in a more malignant

way and carry a poorer prognosis due to an invasive growth pattern (Ciekot et al. 1994). Peripheral Nerve Sheath Tumors PNSTs include a variety of neoplasms including (malignant) schwannoma, neuro ibroma, and neuro ibrosarcoma. Reported incidence is 0.5–2% of all skin tumors in dogs (Goldschmidt and Shofer 1992; Kaldrymidou et al. 2002; Pakhrin et al. 2007), although reported data vary considerably, depending on varying classi ication of these tumors. They are locally aggressive and metastasize rarely (16 vs. 4 months) and survival time (>16 vs. 9 months) than those with incomplete excisions (Davidson et al. 1997). Marginal excision is the major reason that high recurrence rates (up to 70%) have been reported (Davidson et al. 1997; Hershey et al. 2000). Advanced imaging of the tumor is recommended (McEntee and Samii 2000; Morrison and Star 2001) for appropriate treatment planning. Median time to recurrence was signi icantly longer when a cat was operated by a specialist surgeon (274 days) compared to a referring veterinarian (66 days) (Hershey et al. 2000). Other prognostic factors for survival time that are signi icant include local recurrence, presence of distant metastasis, and the number of surgeries (Cohen et al. 2001; Eckstein et al. 2009; Romanelli et al. 2008). Overall

reported median survival time after surgical treatment has been 11.5– 20.3 months (Davidson et al. 1997; Dillon et al. 2005), and median survival time after complete excisions (>16 months) has been signi icantly longer compared to incomplete excisions (9 months) (Davidson et al. 1997).

Figure 4.8 (a) Wide excision of a feline injection-site-associated sarcoma. The skin incision has been performed around the subcutaneous tumor. (b) En bloc resection of tumor mass and surrounding tissue barrier. (c) Visible dorsal spinous processes (arrows) of cervical vertebrae after tumor removal. (d) Closure in layers with simple interrupted suture patterns. Blue nylon skin sutures are visible. The most important prognostic factor for local recurrence, and subsequent survival time, is the achievement of clean surgical margins

(Banerji and Kanjilal 2006; Cronin et al. 1998; Hershey et al. 2000; Kobayashi et al. 2002). Cats undergoing limb amputation for FISAS did better than local excision anywhere else on the body (Hershey et al. 2000). Size of the tumor has been reported to in luence survival time after surgery (Cohen et al. 2001; Dillon et al. 2005; Spugnini et al. 2007b). To achieve wide tumor resection, resection of the dorsal portion of interscapular vertebral spinous processes, partial scapulectomy (Trout et al. 1995), lateral body wall resection (Lidbetter et al. 2002), and hemipelvectomy (Barbur et al. 2015; Straw et al. 1992) may be necessary (Davidson et al. 1997; Davis et al. 2007; Hershey et al. 2000; Romanelli et al. 2008). Some surgeons promote using wider surgical margins than the commonly recommended 2–3 cm lateral margins with one tissue plane in depth, because of the high recurrence rate of FISAS. Fifty-seven cats with FISASs were treated by wide resection using 4–5 cm lateral margins and one fascial plane deep to the tumor, including partial scapulectomy and removal of dorsal spinal processes if indicated. Histologically complete resections were reported for 95% of the tumors; 5% had tumor cells in the margins. Local tumor recurrence developed in 39%, with distant metastasis in 21%. About 51% of the cats were alive at an overall median follow-up period of 366 days (median follow-up period for the alive cats was 600 days) (Romanelli et al. 2008). Phelps et al. (2011) reported in a case series on 91 cats treated by radical excision with ive-centimeter margins including 2 muscle planes or bone deep to the tumor (Figure 4.9). Any anatomic structures that fell within the determined margins were excised, including thoracic wall, abdominal wall, dorsal spinous processes, ilial wing, and scapula. If the tumor was subcutaneous and could be elevated away from underlying structures with 5-cm margins, the underlying structures were not excised. Although excision of FISAS resulted in a metastasis rate similar to rates reported previously, the local recurrence rate appeared to be substantially less than rates reported after less aggressive surgeries. Overall median survival time was 901 days. Out of 91, 13 (14%) cats had local tumor recurrence, 18 (20%) cats had evidence of metastasis after surgery. The median survival time of cats with and without recurrence was 499 and 1461 days, respectively. The MST of cats with and without metastasis was 388 and 1528 days,

respectively. Tumor recurrence and metastasis were signi icantly associated with survival time, whereas other examined variables were not. Major complications occurred in 10 cats, including 7 with incisional dehiscence. The best predictor for the development of wound healing complications after wide excision of FISAS is an increased duration of surgery (Cantatore et al. 2014).

Figure 4.9 Radical excision of a feline injection-site-associated sarcoma. (a) Five cm margins are measured and marked with sterile marker on the skin. (b) The radical excision required abdominal body wall excision and excision of facias in the pelvic limb and over the epaxial muscles, en bloc with the tumor. (c) It was possible to close the skin defect primarily, without the use of reconstructive techniques, which is often the case in cats after radical excision. It is important to consider that the margin size will alter directly after removal of the specimen. Signi icant decreases in surgical margin length in FISASs specimens occur immediately following excision (prior to formalin ixation). Median tumor volume decreases signi icantly between in vivo and ex vivo assessments regardless whether measurements are obtained from 2-D or 3-D CT images. Subgross evaluation of tumor-free margins from on-slide grossly normal surgical margins to pathologist-reported histologic tumor-free margin overestimates the actual (histologic) tumor-free margins (Terry et al. 2016, 2017). Radical surgery is easier with the guidance of advanced imaging in the form of CT or MRI compared to manual palpation. Preoperatively the skin is marked as required for suf icient margins. Available amount of skin for closure has to be assessed preoperatively. If insuf icient, a skin lap can be used (Montinaro et al. 2015), or skin stretcher can help to recruit extra skin in two to three days. Changes in the muscular form according to the forelimb positioning must be appreciated. It is important to have an in-depth anatomical knowledge of the interscapular region of the feline patient to approach the study of any pathology located there and, in particular, to set up an appropriate therapy for the FISASs (Longo et al. 2015). Adjuvant radiation therapy can improve outcomes. Median DFIs after complete resection combined with radiation therapy were 405–1110 days. Survival times after complete resection combined with radiation therapy were 476–1290 days. DFIs after resection with contaminated margins combined with radiation therapy were 112–600 days. Median survival times for contaminated margins combined with radiotherapy were 502–900 days (Cohen et al. 2001; Cronin et al. 1998; Eckstein et al. 2009). According to Eckstein et al. (2009), radiation therapy of

residual microscopic tumor improves median DFI and survival time (20 and 30 months, respectively) compared to residual macroscopic tumor (4 and 7 months, respectively). However, even with neoadjuvant radiation therapy and complete margins after surgical excision, local recurrence has been reported to be 42% (Kobayashi et al. 2002). In a study of 76 cats with vaccine-associated sarcomas, 26 cats were treated with chemotherapy in addition to surgery and radiotherapy. Neither recurrence rates, rate of metastasis, nor survival times were improved in the chemotherapy group (Cohen et al. 2001). Neoadjuvant and adjuvant chemotherapy with epirubicin (25 mg/m2) combined with anatomical resection of FISAS resulted in local tumor recurrence in 3 cats (14%) at days 264, 664, and 1573 after surgery (Bray and Polton 2016), according to the authors these results demonstrate superior rates of tumor-free survival and disease-free interval when compared to historical controls. Of 11 cats treated by stereotactic radiation for FISAS, 8 responded. The median DFI was 242 days, and an MST of 301 days (Nolan et al. 2013). No signi icant effect of chemotherapy only in the treatment of FISAS in clinical settings has been reported yet, although the high metastatic rate is an indication for systemic treatment (Bregazzi et al. 2001; Cohen et al. 2001). Possibly the tyrosine kinase inhibitor, imatinib, will have an effect on FISAS. It inhibited the growth of FISAS in a murine xenograft model (Katayama et al. 2004) and could affect FISAS due to the presence of platelet derived growth factor receptor which is a receptor tyrosine kinase. In one phase 1 clinical trial of imatinib, 4/9 cases trialed had FISAS. In these four cases, a response to treatment was noted and consisted predominantly of short-term tumor stabilization (Lachowicz et al. 2005). In vitro doxorubicin and etoposide alone and in combination differentially alter FISAS cell viability and cycle (Hill et al. 2014). Although masitinib did not directly enhance FISAS cell radiosensitivity under normal in vitro conditions (Turek et al. 2014), combined chemo/radiation therapy has been reported to result in a signi icant reduction in tumor growth compared to the respective mono-therapies with either doxorubicin or radiation. These results support the use of

the concomitant chemo/radiation therapy for adjuvant treatment of FISS, particularly in advanced or recurrent disease where surgery alone is no longer feasible (Petznek et al. 2014). Immunotherapy has been reported successful in xenogeneic cells secreting human interleukin-2 (IL-2). Totally, 16 cats with FISAS were treated, two of which had local recurrence and three had metastatic disease. MST was 16 months in IL-2 treated cats vs. 8 months for nontreated cats (Quintin-Colonna et al. 1996). A second study conducted with human and feline IL-2 resulted in a lower tumor recurrence rate compared to control cats not receiving immunotherapy after surgery and iridium-based radiotherapy (39% and 28% vs. 61% for the controls) (Jourdier et al. 2003). Despite the recommendation for vaccine administration to be on the distal aspect of a limb to facilitate the attainment of clean surgical margins via limb amputation, a high proportion of tumors still developed in the interscapular region in a recent study evaluating the demographics of VAS. For prevention, administration of any irritating substance should be avoided. Vaccination should be performed as often as necessary, but as infrequently as possible. Nonadjuvanted, modi iedlive, or recombinant vaccines should be selected in preference to adjuvanted vaccines. Injections should be given at sites at which surgery would likely lead to a complete cure; the interscapular region should generally be avoided. Postvaccination monitoring should be performed (Hartmann et al. 2015; Shaw et al. 2009). However, these current feline vaccine site recommendations may not be appropriate for cat owners as was concluded by Carwardine et al. (2014) based on an anonymous internet-based cross-sectional study in the UK wherein cat owning respondents would not allow amputation of their cats’ forelimb (20%), hindlimb (15%), or tail (15%).

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5 Head and Neck Tumors Sara A. Ayres and Julius M. Liptak

Lymph Node Staging The regional lymph nodes for head and neck cancers include the mandibular, parotid, and retropharyngeal lymphocentrums. These lymph nodes should be carefully palpated for enlargement or asymmetry. However, this may be inaccurate because lymph node size is not an accurate predictor of metastasis in dogs with oral melanoma (Williams and Packer 2003) and, of the three regional lymphocentrums, only the mandibular lymph nodes are externally palpable (Smith 1995). Furthermore, only 55% of cats and dogs with metastatic oral and maxillofacial tumors have metastasis to the mandibular lymph nodes (Herring 2002). Currently, lymph node aspirates are recommended for all animals with head and neck tumors, regardless of the size or degree of ixation of the lymph nodes (Herring 2002; Williams and Packer 2003). Hopefully, in the near future, sentinel lymph node assessment will become more widely accepted and practiced as this may permit the preoperative diagnosis of metastatic lymph nodes without more aggressive en bloc surgical excisions of the regional lymph nodes. Methods to detect sentinel lymph nodes in people with head and neck cancer include preoperative lymphoscintigraphy, intraoperative blue dyes, and intraoperative gamma probes (Lurie et al. 2006). Lymphoscintigraphy, intraoperative dyes, contrast-enhanced ultrasonography, and intraoperative gamma probes have been described in dogs with various tumors, including head and neck cancer (Nieweg et al. 2001; Nyman et al. 2005; Worley et al. 2014). En bloc resection of the regional lymph nodes has been described, and although the therapeutic bene it of this approach is unknown, it may provide valuable staging information (Smith 1995; Herring 2002). The

skin is incised from the rostral and proximal aspect of the vertical ear canal, ventral to the caudal aspect of the zygomatic arch, to the bifurcation of the external jugular vein (Smith 1995). The platysma and parotidoauricularis muscles are incised to reveal fascia and loose areolar tissue covering the vertical ear canal and masseter muscle. Incision of the areolar tissue over the ventral aspect of the zygomatic arch exposes the parotid lymphocentrum, which has one to three lymph nodes, along the rostral edge of the parotid salivary gland (Smith 1995). The mandibular lymphocentrum, which contains one to ive lymph nodes, is located between the bifurcation of the jugular vein and division of the linguofacial vein into its lingual and facial branches (Smith 1995). The medial retropharyngeal lymphocentrum, which usually consists of one elongated lymph node on the lateral aspect of the thyropharyngeus muscle, is exposed by incising the adventitia along the caudal aspect of the mandibular salivary gland and retracting the mandibular salivary gland rostrally and the brachiocephalicus and sternocephalicus muscles dorsally (Smith 1995). A ventral midline approach has been described for bilateral excision of the mandibular and medial retropharyngeal lymph nodes (Green 2017). The advantages of this approach are that both the left and right lymph nodes can be excised and, if required, the carotid artery can be temporarily occluded for intraoperative hemostasis (can be done in dogs, not cats). The disadvantages include that the parotid lymph node is not excised (however, metastasis to this lymph node is uncommon) and the animal may need to be repositioned for the de initive surgery, following excision of the accessible lymph nodes (Green 2017).

Nasal Planum Tumors Nasal planum tumors are relatively common in cats, but rare in dogs. Squamous cell carcinoma (SCC) is the most common tumor of the nasal planum in both cats and dogs, with SCC originating from the corni ied external surface of the nasal planum in cats and the mucous membrane of the nostril or nasal planum in dogs (Withrow 2007). Other common sites for SCC in cats involve poorly haired regions of the head and neck, such as the eyelids, pinnae, and preauricular areas (Lana et al. 1997;

Thomson 2007). Predisposing causes for the development of head and neck SCC in cats and dogs include light pigmentation (i.e. white hair coat), short hair coat, and chronic exposure to ultraviolet light (Lana et al. 1997; Thomson 2007; Withrow 2007). White-haired cats have 13.4 times the risk of developing head and neck SCC compared to darker colored cats (Dorn et al. 1971). Older animals are typically affected with a mean age at presentation of 8 years for dogs and 12 years for cats (Lana et al. 1997; Ruslander et al. 1997; Withrow 2007). There is no breed predisposition in cats, but there is a high incidence of nasal planum SCC in male golden and Labrador retrievers (Lascelles et al. 2000) (Figure 5.1). Other tumor types include lymphoma, ibrosarcoma, mast cell tumor (MCT), malignant melanoma, hemangioma, and ibroma (Withrow 2007). Eosinophilic granulomas and immune-mediated diseases are non-neoplastic conditions involving the nasal planum which can have a similar erosive (in dogs) to proliferative (in dogs and cats) appearance mimicking benign and malignant tumors (Withrow 2007).

Figure 5.1 Squamous cell carcinoma of the nasal planum in a golden retriever. Note the marked ulceration and erosion combined with some areas of proliferation.

History and Clinical Signs Head and neck SCC are often chronic cancers progressing from actinic changes (crusting and erythema) to carcinoma in situ lesions (noninvasive carcinoma con ined to the epidermis characterized by super icial erosions and ulcers) to invasive carcinomas (deep erosive lesions; Figures 5.1–5.3) (Lana et al. 1997; Thomson 2007; Withrow 2007). Occasionally, nasal planum SCC may have a proliferative appearance (Thomson 2007). The eyelids, preauricular areas, and pinnae should also be examined carefully as up to 30% of cats have SCC in multiple heads and neck locations (Vail and Withrow 2007; Withrow 2007).

Diagnosis and Clinical Staging A deep wedge or incisional biopsy is required for de initive diagnosis of nasal planum tumors (Withrow 2007). Cytologic examination of ine needle aspirates, impression smears, or super icial biopsies is often unrewarding because they usually reveal in lammation, ulceration, and hemorrhage, which can be present in both neoplastic and nonneoplastic lesions (Thomson 2007; Withrow 2007). A deep incisional biopsy is recommended in cats with proliferative lesions and dogs with any nasal planum lesion to determine histology and the depth of invasion (Thomson 2007; Withrow 2007). However, biopsy is rarely required in cats with erosive or ulcerated lesions of the nasal planum, eyelids, preauricular area, and/or pinnae because of the high index of suspicion for SCC (Figure 5.2) (Thomson 2007). Advanced imaging, with either computed tomography (CT) or magnetic resonance imaging (MRI), is recommended for local staging of nasal planum tumors in cats and dogs to determine the caudal extent of the tumor and to assist in determining margins for surgical planning (Withrow 2007). Metastasis to the regional lymph nodes and/or lungs is rare, but it is occasionally noted in cats with advanced or poorly differentiated lesions (Thomson 2007; Withrow 2007). The regional

lymph nodes should be palpated and possibly either aspirated or excised. Three-view radiographs of the thoracic cavity should be considered but invariably show no evidence of pulmonary metastasis (Lana et al. 1997; Withrow 2007).

Figure 5.2 Preoperative appearance of a nasal planum SCC in a cat. The deeply ulcerated and erosive morphology of this lesion is characteristic of SCC of the nasal planum in cats.

Figure 5.3 The typical appearance of an SCC of the pinna in a cat. Note the spectrum of changes typical of feline cutaneous SCC, with regions of erythema (actinic changes), super icial ulceration and erosion (carcinoma in situ), and multifocal areas of deep ulceration and erosion along the apex and medial border of the helix.

Nasal Planum Resection Nasal planum resection is recommended for invasive SCC in cats and dogs (Withrow and Straw 1990; Kirpensteijn et al. 1994; Lana et al. 1997; Lascelles 2004; Thomson 2007; Withrow 2007). Surgery provides excellent local tumor control and has several advantages compared to other treatment options, including ability to examine surgical margins, wide availability as compared to radiation therapy and photodynamic therapy, and affordability with less treatment time and acceptable cosmetic outcome (Lana et al. 1997). For cats with lateral and/or dorsal lesions, partial nosectomy has been described with closure using a lip-to-nose mucocutaneous lap (Massari et al. 2020). It allows retention of a portion of the planum, which is more cosmetically acceptable to owners, and incorporation of buccal mucosa reduces the risk of nasal stenosis and chronic rhinitis. More aggressive surgical procedures have also been described in dogs with more extensive nasal planum tumors (i.e. nasal planum resection combined with either premaxillectomy or bilateral maxillectomy) (Kirpensteijn 1994; Lascelles et al. 2004). These procedures are described in detail in the chapter on oral tumors.

Surgical Technique For resection of the entire nasal planum, animals are positioned in sternal recumbency with their head elevated and symmetrical. Systemic analgesia with perioperative nonsteroidal anti-in lammatory drugs and opioids can be supplemented with bilateral infraorbital nerve blocks using bupivacaine (Thomson 2007). Following surgical preparation and draping, the surgical margins should be indicated with a sterile marker pen. Minimum lateral margins from the visible or palpable extent of the tumor are 5 mm in cats and preferably 2 cm in dogs (Thomson 2007). The deep margin is preferably the junction

between the cartilaginous and bony nasal tissue. A full-thickness incision is performed with a scalpel blade along the marked lateral margins and deeply through the cartilaginous turbinates at the level of the nasal and incisive bones. These incisions will result in brisk hemorrhage which can be controlled with digital pressure and the judicious use of cautery. Following hemostasis, the alar folds can be excised to increase the diameter of the nasal airways and improve the ability to breathe postoperatively. The defect following resection of the nasal planum can be closed with a purse-string suture (Withrow and Straw 1990; Withrow 2007), rolling igure-of-eight suture pattern (Lascelles et al. 2004), or skin-to-nasal mucosa closure using a simple interrupted suture pattern of 4-0 or 5-0 nonabsorbable suture material (Figure 5.4) (Thomson 2007). Skin-to-mucosa closure is preferred because the incidence of postoperative complications, such as stenosis of the nasal aperture, is decreased. The deep and lateral margins of the excised nasal planum should be submitted for histopathological assessment of tumor type and completeness of excision. For partial nosectomy, the tumor is resected with a minimum of 5 mm margins (Massari et al. 2020). New gloves and instruments are used to raise the lap. Two diverging full-thickness incisions are made on the ipsilateral upper lip extending from the lip margin to just below the eye. The cranial edge of the lap is caudolateral to the philtrum. The distance between the cranial and caudal incisions in the lip margin is equal to the width of the defect in the nasal planum. At the tip of the lap (labial portion), the buccal/labial mucosa is divided from the gingival mucosa preserving 1–3 mm of the gingival mucosa. The lap is elevated dorsally by dissecting under the platysma muscle (portion dorsal to lip, ventral to the eye). A bridging incision is made caudolateral to the defect and the mucocutaneous lap is transposed into the defect. At the cranial edge of the lap, the buccal/labial mucosa is sutured to the nasal mucosa in a simple continuous pattern using 4-0 absorbable suture material (e.g. polyglactin 910). The lateral edges are sutured in one layer in a simple continuous pattern. The donor site is closed in two layers in a simple continuous pattern using the same suture material.

Figure 5.4 Immediate postoperative appearance following nasal planum resection in the cat from Figure 5.2. Skin-to-nasal mucosa closure is preferred to purse-string suture closure. Also, note that excision of the alar folds bilaterally results in widening of the nasal airways.

Postoperative Management An Elizabethan collar should be in place until the wound has healed to prevent self-trauma. In the immediate postoperative period, analgesia and intravenous luids should be continued until the animal is eating and drinking voluntarily. Cats will often not want to eat for one to four days after nasal planum resection. The return to voluntary eating can be improved with the perioperative use of infraorbital nerve blocks; use of aromatic, warmed, and/or favorite foods; removal of the scab over the surgery site under sedation; and use of appetite stimulants. Supplemental nutrition through feeding tubes is rarely required. Animals can be discharged when they start to eat voluntarily. A short course of nonsteroidal anti-in lammatory drugs is recommended after

discharge for analgesic purposes. A scab or crust usually forms over the surgical site and this should be removed at suture removal 10–14 days after surgery. Sedation may be required for suture removal.

Complications Complications are uncommon. The most signi icant complication is stenosis of the nasal aperture. This is more common following pursestring closure of the defect. A skin-to-nasal mucosa closure is recommended to minimize the risk of nasal stenosis. If stenosis occurs, then management options include surgical reconstruction with wide skin excision and resection of the rostral nasal septum; laser ablation; insertion of rubber stents; permanent placement of stainless steel intraluminal expansile stents (Withrow 2007); or superior labial mucosal transposition laps (Séguin 2016). The prognosis for normal nasal function in cats that develop nasal stenosis is guarded. Other complications include poor appetite in the initial postoperative period, mild serous nasal discharge, and increased incidence of sneezing (Thomson 2007). The cosmetic appearance is good in cats (Figure 5.5) and fair to good in dogs (Figure 5.6).

Adjunctive Management Adjunctive treatment is rarely required for cats and dogs with completely excised nasal planum SCC, and most of these patients are considered cured (Lascelles et al. 2000; Thomson 2007). Some authors recommend systemic chemotherapy using either carboplatin or doxorubicin for cats with poorly differentiated SCC or SCC lesions with evidence of lymphatic invasion, regardless of whether they have been completely excised (Thomson 2007). Radiation therapy is recommended for incompletely excised nasal planum SCC (Lascelles et al. 2000; Thomson 2007; Withrow 2007).

Figure 5.5 Cosmetic appearance six weeks after nasal planum resection in a cat. Cosmetic results are usually good following nasal planum resection in cats. Note this cat has also had a bilateral pinnectomy for SCC. Up to 30% of cats have multifocal head and neck squamous cell carcinoma. Source: Image courtesy of Dr. Maurine J. Thomson.

Figure 5.6 Cosmetic appearance following nasal planum resection in a golden retriever. Note that the cosmetic appearance is acceptable but not as good as cats following nasal planum resection.

Prognosis The prognosis following nasal planum resection is good to excellent. In cats, local tumor recurrence was reported in two of seven cats (29%) with incompletely excised tumors and no cats with completely resected nasal planum SCC (Lana et al. 1997). In this study, two cats with progressive local disease were euthanized, and the remainder were cured (Lana et al. 1997). In one study, seven cats had complete resection of SCC with partial nosectomy reconstructed using a lip-tonose lap (Massari et al. 2020). There was no recurrence at the end of the study period (follow-up median of 485 days, range of 274–1275 days) (Massari et al. 2020). Local tumor control is also excellent in dogs following nasal planum resection, either alone or in combination with either premaxillectomy or bilateral maxillectomy, with no local tumor recurrence or metastasis in dogs with completely excised SCC (Kirpensteijn et al. 1994; Lascelles et al. 2000, 2004).

Other Treatment Options Prevention of Precancerous (Actinic) Lesions The risk of cutaneous SCC can be minimized in animals with poor pigmentation and hair coats by limiting exposure to sunlight. Topical sunscreens are usually ineffective because animals will quickly lick them off (Withrow 2007). Tattooing has limited ef icacy as it only protects the deeper dermal layers and not the super icial epidermis. Synthetic vitamin A derivatives, such as isotretinoin or etretinate, increase epithelial differentiation and may reverse or limit the progression of precancerous lesions (Evans 1985; Vail and Withrow 2007). However, only 1 of 15 cats with precancerous or SCC lesions responded to isotretinoin therapy (Evans et al. 1985; Vail and Withrow 2007). Cryosurgery

Cryosurgery causes tissue destruction with the controlled use of freezing and thawing. Liquid nitrogen and nitrous oxide are the two most commonly used cryogens. Spray freezing is preferred to contact freezing because colder temperatures can be achieved (Thomson 2007). To maximize tissue destruction, the tumor and a minimum of 5 mm around the tumor should be rapidly frozen to −20 °C and then allowed to thaw slowly and then this process should be repeated three times in total. The response rate to cryosurgery is dependent on tumor size and location. Response rates are better with small, super icial, and noninvasive lesions (less than 5 mm), and tumors involving the eyelids and pinnae (Clarke 1991; Lana et al. 1997). Multiple treatments are often required for nasal planum lesions. Local tumor control can be good with 84% of 90 cats treated with cryosurgery tumor-free at 12 months and 81% tumor-free at 36 months (Clarke 1991). However, other researchers have reported local recurrence in 73% of cats following cryosurgery with a median time to recurrence of 184 days (Lana et al. 1997). Cryosurgery is a readily available and cost-effective treatment modality for small lesions, but disadvantages include margins that cannot be determined and the risk of local recurrence is higher than either nasal planum resection or radiation therapy. Curettage and Diathermy A less aggressive surgical approach has been described for cats with actinic dysplasia and super icial SCC of the nasal planum (Jarrett et al. 2013). Under general anesthesia, the nasal planum lesions are curetted with a 3 mm bone curette to remove all friable tissue and then the curetted tissue bed is treated with diathermy using a 1–2 mm diameter tip at a medium setting (4 on a scale of 1–10) (Jarrett et al. 2013). This process is repeated a further two times under the same general anesthesia. In this study of 34 cats, postoperative complications were uncommon and mild, the cosmetic outcome was very good to excellent, and the local recurrence rate at 12 months was 6% (Jarrett et al. 2013). Radiation Therapy Radiation can be delivered either as local or external beam therapy (Théon 1995; Lana et al. 1997; Fidel et al. 2001; Goodfellow et al. 2006;

Hammond et al. 2007). Local radiation therapy with 90Strontium plesiotherapy is indicated for cats with super icial, but not deep lesions because strontium only penetrates to a depth of 2 mm (Goodfellow et al. 2006; Hammond et al. 2007). Reported 90Strontium protocols include ive fractions of 10 Gy over a 10-day period for a total dose of 50 Gy (Goodfellow et al. 2006) and a single session of one or multiple overlapping applications totaling between 97 and 195 Gy with a median of 128 Gy (Hammond et al. 2007). For appropriate lesions, tumor control is very good with fractionated 90Strontium plesiotherapy with 85% of 15 cats achieving a complete response after either one (11 cats) or two (2 cats) cycles of radiation therapy and none of these cats having evidence of local recurrence after a median follow-up of 652 days (Goodfellow et al. 2006). For 49 cats treated with a single fraction of 90Strontium, 98% of cats responded to treatment and 88% had a complete response, with median progression-free and overall survival times of 1710 and 3076 days, respectively (Hammond et al. 2007). Notably, 20% of cats had local recurrence and 33% of cats developed de novo lesions in other locations (Hammond et al. 2007). Full-course external beam radiation therapy can be used for super icial and deep nasal planum lesions (Théon 1995; Lana et al. 1997; Fidel et al. 2001). Orthovoltage, megavoltage, and proton beam irradiation have been described (Théon et al. 1995; Lana et al. 1997; Fidel et al. 2001). Smaller and super icial lesions are more responsive and can be cured with external beam radiation therapy, but response rates and tumor control are decreased for larger and more invasive lesions (Théon et al. 1995). Cure rates for small lesions are 56%, with median disease-free intervals of 12–16 months and median survival times of 361–946 days (Théon et al. 1995; Lana et al. 1997; Fidel et al. 2001). Photodynamic Therapy Photodynamic therapy involves the local or systemic administration of a photosensitizer that is preferentially retained by tumor tissue. This is followed by irradiation of the tumor with a light of a wavelength which is absorbed by the photosensitizer, resulting in the formation of oxygen-free radicals and tissue death (Roberts et al. 1991; Peaston et al. 1993; Stell et al. 2001; Buchholz et al. 2007; Bex ield et al. 2008;

Ferreira et al. 2009). Similar to other nonsurgical treatment options, photodynamic therapy is only recommended for super icial lesions because the penetration of the wavelength of light used to activate the photosensitizer is limited to 3–4 mm (Buchholz et al. 2007). Complete responses are reported in up to 100% of cats with tumors less than 5 mm, but in less than 30% of cats with larger tumors (Roberts et al. 1991; Peaston et al. 1993; Stell et al. 2001; Buchholz et al. 2007; Bex ield et al. 2008; Ferreira et al. 2009). Complications include local tumor recurrence in up to 64% of cats and facial edema, erythema, and necrosis which resolves slowly over 3–6 weeks (Roberts et al. 1991; Peaston et al. 1993; Stell et al. 2001; Buchholz et al. 2007; Bex ield et al. 2008; Ferreira et al. 2009). Intralesional Chemotherapy Intralesional carboplatin has been investigated in cats with nasal planum SCC. Twenty-three cats with advanced lesions were treated with intralesional carboplatin (100 mg/m2) resulting in a complete response rate of 73%, one-year disease-free survival rate of 55%, and local recurrence rate of 30% (Théon et al. 1996). The combination of carboplatin with puri ied sesame oil reduced systemic absorption and toxicity (Théon et al. 1996). External beam radiation therapy has been combined with intralesional carboplatin in six cats with advanced nasal planum SCC resulting in a complete response in all cats and duration of response for a minimum of eight months in four of these cats (de Vos et al. 2004). Electrochemotherapy has been investigated in nine cats with advanced nasal planum SCC (Spugnini et al. 2009). Electrochemotherapy involved two treatments one week apart of intralesional bleomycin combined with permeabilizing biphasic electric pulses. Adverse effects were minimal and 78% of cats had a complete response of up to three years (Spugnini et al. 2009).

Tumors of the Pinna Tumors of the pinna are uncommon in both cats and dogs. In dogs, tumors involving the pinna are similar to cutaneous and subcutaneous

tumors of other sites, such as MCTs and soft tissue sarcomas (STSs) (Bostock 1986; Vail and Withrow 2007). SCC is the most common tumor of the pinna in cats (Bostock 1986; Vail and Withrow 2007). The gross appearance of these tumors is highly variable, ranging from an ulcerative and erosive appearance of feline SCC lesions (Figure 5.3) to solid masses in many canine pinna tumors (Figure 5.7) (Lana et al. 1997; Ruslander et al. 1997; Vail and Withrow 2007).

Figure 5.7 A MCT along the medial border of the helix of the pinna. Incisional biopsy is recommended for MCTs of the pinna because the extent of surgical margins can be determined by histologic grade. In this case, the tumor was excised with 2 cm margins, as indicated by the sterile marker pen.

Diagnosis and Clinical Staging De initive preoperative diagnosis is often not required for ulcerative or erosive pinna lesions in cats because of the high likelihood of SCC.

However, pinna lesions in dogs should be diagnosed prior to de initive therapy because this will provide valuable information on tumor type, histologic grade, and treatment options. Biopsy options include ine needle aspiration and incisional or wedge biopsy. Excisional biopsy is not recommended in dogs because of the risk of incomplete resection and tumor recurrence. Staging for metastatic disease is dependent on tumor type.

Pinnectomy Partial or total pinnectomy is the recommended treatment for ulcerative and solid tumors affecting the terminal third of the pinna. For tumors affecting the lower two-thirds, the tumor and underlying cartilage can be removed and the wound is closed with a simple skin lap, (Pavletic 2012) as the skin on the outer aspect of the pinna is mobile and the auricular cartilage acts as a natural barrier against tumor spread. Animals are positioned in either sternal or lateral recumbency, depending on tumor location and surgeon preference. The medial and lateral aspects of the pinna are clipped and aseptically prepared. Chlorhexidine preparations should be used with caution, especially in cats, because of the risk of ototoxicity (Igarashi and Suzuki 1985). Following draping, the surgical margins can be marked with a sterile marking pen (see Figure 5.7). The surgical margins are dependent on tumor type and, for canine MCT, histologic grade and tumor size: 1 cm margins are recommended for SCC in cats (Figure 5.8a) and benign tumors in dogs; 3 cm margins for canine STS; and 1 cm margins for grade I canine MCT, 2–3 cm margins for grade II MCT and 3 cm margins for grade III MCT (Lana et al. 1997; Ruslander et al. 1997; Simpson et al. 2004; Vail and Withrow 2007). Proportional margins based on the diameter of the MCT can also be performed (see Chapter 4).

Figure 5.8 (a) Pinnectomy in a cat with multifocal head and neck SCC. Note that preauricular SCC lesions have also been excised. (b) Closure of the pinna involves suturing of the skin over the auricular cartilage. The cartilage should be trimmed if it increases tension on the wound closure. Source: Images courtesy of Dr. Maurine J. Thomson.

For partial and total pinnectomy, the medial and lateral skin and auricular cartilage are incised along the marked margins with a scalpel blade. For tumors involving the apex of the pinna, or both the lateral and medial borders of the helix of the pinna, the pinna is amputated. Partial pinnectomy without amputation is possible for lesions involving either the medial or lateral border of the helix of the pinna. Depending on the location of the tumor and extent of excision, ligation or cauterization of the greater auricular arteries and veins may be required. The auricular cartilage should be trimmed to permit closure of the skin edges over the cartilage without tension. The skin edges are closed in one or two layers with the subcutaneous tissue closed in a simple continuous pattern using absorbable mono ilament suture material and the skin in either a simple interrupted or continuous pattern with nonabsorbable mono ilament suture material (Figure 5.8b). Following partial pinnectomy of tumors involving the lateral or medial borders of the helix of the pinna, reconstruction of the pinna depends on the defect size and location. This reconstruction is often inventive but needs to be planned prior to surgery to ensure suf icient skin has been clipped and prepared to allow reconstruction (Figure 5.9). The margins should be inked and the tumor submitted for histopathologic assessment of tumor type and completeness of surgical excision (Figure 5.10).

Figure 5.9 Immediate postoperative appearance of the reconstructed pinna following MCT resection in Figure 5.7. Pinna reconstruction following partial pinnectomy for tumors involving the medial or lateral borders of the helix of the pinna can be inventive. Cosmetic results are often good.

Figure 5.10 Partial pinnectomy of the affected pinna in Figure 5.3. Minimum margins of 1 cm are recommended to minimize the risk of incomplete excision and tumor recurrence. For owners desiring a more cosmetic result, the pinna defect can be reconstructed using a transposed pedicle lap (Henderson and Horne 2003). The edges of the defect should not be closed but sutured to the donor site in the lateral cervicobuccal area. The pinna is bandaged for two weeks and the lap is then elevated to reconstruct the lateral aspect of the pinna. The medial aspect of the pinna can be reconstructed by folding the lap, creating a second lap, or second intention healing (Henderson and Horne 2003). However, if the original resection was not complete, there is the risk of seeding tumor cells in the donor site. For tumors affecting the distal two-thirds of the pinna, the tumor is removed with appropriate lateral margins, as outlined above, and the underlying auricular cartilage (Figure 5.11a and b). The wound is then closed with a local transposition or advancement lap (Figure 5.11c).

This technique is applicable to tumors on the inner or outer aspect of the pinna (Pavletic 2012). Complications following pinnectomy are uncommon and include hemorrhage, wound dehiscence, and local tumor recurrence. Local tumor control is good following complete excision of feline pinna SCC, with tumor recurrence or de novo tumor development in 23% of cats (Atwater et al. 1991). However, repeat excision or adjunctive treatment is recommended following incomplete resection because local recurrence was reported with incomplete excision (Atwater et al. 1991). Cosmetic results are usually acceptable (Withrow and Straw 1990).

Adjunctive Treatment Adjunctive treatment options for cats with incompletely excised pinna SCC include cryosurgery, photodynamic therapy, 90Strontium plesiotherapy, and external beam radiation therapy (Clarke 1991; Peaston et al. 1993; Lana et al. 1997; Stell et al. 2001; Vail and Withrow 2007). Cryosurgery can also be used as the primary treatment for small and super icial lesions of the feline pinna (Clarke 1991). Adjunctive treatment options in dogs depend on the completeness of excision and tumor type. External beam radiation therapy should be considered for incompletely excised MCT and STS, and systemic chemotherapy is recommended for high-grade or metastatic MCT (Vail and Withrow 2007).

Figure 5.11 (a) A 1.7 × 1.9 × 1 cm luid- illed mass on the convex surface of the pinna of a 7 yo FS Border Collie cross. Histologic diagnosis of benign pigmented basal cell tumor. (b) The basal cell tumor was excised with 0.5–1 cm lateral margins and the underlying auricular cartilage. (c) A 2.5 × 5 cm advancement lap was used to close defect.

Tumors of the External Ear Canal Tumors of the external ear canal are uncommon in the dog and cat. Patients typically present with clinical signs of otitis externa that are poorly responsive to medical management. Clinical signs include otic discharge, head shaking, scratching at the ear, and the presence of a mass. Hemorrhagic discharge can be indicative of trauma or neoplasia (Lanz and Wood 2004). Pain on opening the mouth and the presence of neurologic de icits, including facial nerve paresis, Horner’s syndrome, and vestibular disease (head tilt, ataxia, nystagmus), is consistent with middle ear involvement. Ten percent of dogs with malignant tumors and 25% of cats with either benign polyps or malignant tumors have neurologic de icits (ter Haar 2006). Clinical signs may be present for weeks to years prior to presentation. Otitis externa may develop secondary to obstruction of the ear canal; however, an association has also been found between chronic otitis and the secondary development of neoplastic lesions (Rogers 1988; London

et al. 1996; Moisan and Watson 1996; Zur 2005). If a patient no longer responds to medical management, the presence of a mass (neoplastic, nonneoplastic, or a foreign body) must be considered (Rogers 1988). Bilateral involvement does not exclude the possibility of neoplasia. There are reports of cats and dogs bilaterally affected with ceruminous gland adenocarcinoma or squamous cell carcinoma (Théon et al. 1994; Bacon et al. 2003; Zur 2005). Most patients are middle-aged and older (Rogers 1988; ter Haar 2006). The mean age of dogs with malignant tumors is 9.9 years (range 4–18 years) and of dogs with benign tumors is 9.4 years (range 4–18 years). The mean age of cats with malignant tumors is 11 years (range 3–20 years), and for benign tumors, it is 6.9 years (0.5–15 years) (London et al. 1996). In another study, the mean age for malignant tumors was 9.8 years and for benign tumors was 7.7 years (Bacon et al. 2003). Cocker spaniels are overrepresented for both benign and malignant tumors, likely due to their propensity for otitis externa (London et al. 1996). Historically, it has been reported that the majority of canine tumors are benign and the majority of feline tumors are malignant (Rogers 1988; Théon et al. 1994). However, there have been reports with 50% to the majority of canine tumors also being malignant (London et al. 1996; Moisan and Watson 1996). In dogs, malignant tumors are locally invasive with a low incidence of metastatic disease at the time of presentation (London et al. 1996). There is one report of a dog with an aggressive ceruminous gland carcinoma of the external ear canal with metastases to regional lymph nodes and lungs (Romanucci et al. 2011). Cats tend to have more aggressive malignant tumors than the dog. They may invade the middle ear (Rogers 1988) and often invade the wall of the ear canal extending into the adjacent soft tissue. Metastatic rates of 0–50% have been reported with metastases to regional lymphatics, lungs, and distant viscera (London et al. 1996; Moisan and Watson 1996; Bacon et al. 2003). Most cats die due to tumor recurrence or progression of local disease. Once local disease is better controlled, it is possible that metastatic disease may become more prevalent (London et al. 1996). Ceruminous gland tumors are the most common tumor of the canine and feline external ear canal (Rogers 1988; Carlotti 1991; Bacon et al.

2003). Malignant tumors of dogs and cats include ceruminous gland adenocarcinoma, SCC, and carcinoma of undetermined origin (Figure 5.12). Other malignant tumors affecting dogs include round cell tumor, sarcoma, malignant melanoma, ibrosarcoma, MCT, leiomyosarcoma, plasmacytoma, carcinosarcoma, and hemangiosarcoma. Benign tumors of dogs and cats include in lammatory polyps, ceruminous gland adenoma, sebaceous gland adenoma, multiple follicular cysts, basal cell tumor, and papillomas. Histiocytoma, plasmacytoma, benign melanoma, and ibroma have also been reported in the dog (Lucke 1987; Rogers 1988; London et al. 1996; Bacon et al. 2003; ter Haar 2006, Romanucci et al. 2011; Gatineau et al. 2010). SCC is rare in the external ear canal; however, when present it typically involves the external auditory meatus and has particularly aggressive behavior with local invasion, regional lymph node involvement, and, later, pulmonary metastases (Rogers 1988; Salvadori et al. 2004). Intraorbital and orbital metastases have also been documented (Hayden 1976). In one case report, two cats that had previous bilateral pinnal amputations for SCC developed SCC within the external ear canal and metastatic meningeal carcinomatosis (Salvadori et al. 2004). Although not neoplastic, in lammatory polyps are the most common mass lesion affecting the external ear canal of the cat (Lanz and Wood 2004). They affect the external ear canal by extension from the middle ear (see the section on tumors of the middle ear, below). Ceruminous gland cysts are non-neoplastic masses that can involve the inner pinna and vertical ear canal of the cat (Rogers 1988; Carlotti 1991; Corriveau 2012) (Figure 5.13). Patients are most commonly 2–15 years of age, with multiple masses 1–5 mm in size containing black luid. Both ears may be affected.

Diagnosis Cytology is useful to evaluate concurrent infection with bacteria or yeast; however, it rarely yields neoplastic cells. Tumors do not exfoliate cells readily into the ear canal, and they are masked by in lammatory debris (De Lorenzi et al. 2005; Zur 2005). To look for a mass lesion, the ear is gently lavaged with warm sterile saline and aspirated with a soft,

rubber catheter (De Lorenzi et al. 2005). In severe cases, sedation or general anesthesia may be necessary (Lanz and Wood 2004). Otoscopy is then performed. Video-otoscopy is preferred as there is greater magni ication with better visualization and resolution of the ear canal and tympanic membrane. The instrument port also allows for guided ine needle aspirate or tissue biopsy of the mass. The disadvantage with video-otoscopy is that the patient must be anesthetized and more equipment and staff are needed (Gatineau 2010; Usui et al. 2015).

Figure 5.12 (a) Ceruminous gland adenocarcinoma in the horizontal ear canal of a cat, following total ear canal ablation. (b) Intraoperative picture of concurrent lymph node metastasis.

Figure 5.13 (a) Ceruminous gland cysts affecting the pinna and external ear canal of a 13-year-old spayed domestic short-haired cat. (b) Pinnectomy and total ear canal ablation and lateral bulla osteotomy were performed. Note the extension of the cysts from the vertical ear canal to the pinna with secondary hyperplasia and exudate within the vertical ear canal. The horizontal and vertical ear canals were also resected, but not included in this image. The masses can be irm or friable, pedunculated, or invasive. Pedunculated masses are typically benign, and malignant masses are typically broad based (Rogers 1988; London et al. 1996). A raised or ulcerated appearance does not differentiate benign from malignant (London et al. 1996). Ceruminous adenocarcinoma and SCC are more likely to be invasive, and there may be a hemorrhagic otic discharge. Following identi ication of the mass, a ine needle biopsy (FNB) of the mass should be performed with a 22- or 23-gauge hypodermic or spinal needle (De Lorenzi et al. 2005). In one study, looking at 27 cats with tumors of the external ear canal, cytology from FNB correctly differentiated in lammatory polyps and MCTs from ceruminous gland

adenoma and adenocarcinoma. This differentiation is useful as in lammatory polyps may be treated with traction-avulsion or a ventral bulla osteotomy, whereas the other tumor types would require a total ear canal ablation and lateral bulla osteotomy. The needle is placed into the mass and then withdrawn; syringe aspiration is not necessary. Scraping and impression smears are other techniques for cytologic assessment if the yield is inadequate with FNB alone (Rogers 1988). An alternative is to obtain a small tissue sample (grab biopsy; Bacon et al. 2003) with alligator forceps or a snare (Rogers 1988). For deep masses, an incision into the vertical ear canal can be performed (ter Haar 2006). With this technique, however, there is risk of contaminating adjacent normal tissue, and with the availability of video otoscopes, this technique is rarely necessary. Following de initive mass removal, histopathology should be performed in all cases to con irm the diagnosis and assess invasion into surrounding structures (De Lorenzi et al. 2005). In patients with malignant tumors, evaluation of regional lymph nodes and thoracic radiographs are also recommended (Théon et al. 1994). Historically, bulla radiographs (oblique lateral and open-mouth views) have been performed when there is suspicion of middle or inner ear involvement. However, abnormal indings, such as a soft-tissue density within the tympanic cavity, osseous thickening of the bulla, and sclerosis of the petrous temporal bone, are not speci ic for tumor ingrowth. They could also be consistent with secondary infection or in lammation (Rogers 1988; Marino et al. 1993). In one study, the presence of these radiographic changes in dogs with ceruminous gland adenocarcinoma did not affect the outcome (Marino et al. 1993). CT or MRI is preferred to rule out destruction of the bulla and invasion into adjacent soft tissues, as this negatively affects prognosis and may highlight the need for more aggressive surgery and/or further treatment such as radiation therapy. CT provides excellent images of the bulla, ear canal, and inner ear and has been shown to be more accurate than radiographs in patients with moderate to severe ear disease; however, in patients with milder disease, the accuracy of both CT and bulla radiographs is more variable (Rohleder et al. 2006). MRI is more useful to assess the soft tissue components. When advanced

imaging is not available, ultrasound can be useful to assess subauricular masses, allowing ultrasound-guided ine needle aspirates (Gatineau 2010).

Treatment Surgical excision is the treatment of choice (Rogers 1988). Surgical procedures include lateral ear canal resection, vertical ear canal resection, and total ear canal resection with lateral bulla osteotomy (TECA and LBO). Lateral and vertical ear canal resections have limited application and should be restricted to benign tumors con ined to the lateral or vertical ear canal (Figure 5.14). A CT or MRI should be done to ensure that the horizontal ear canal is not involved (Lanz and Wood 2004). Laser ablation can be considered for some benign tumors (Corriveau 2012; Usui 2015). Historically ceruminous gland cysts have been removed with pinnectomy +/– vertical ear canal ablation. There is one case report of ablation of the cysts using CO2 laser. The vaporization of the masses allows cyst removal with minimal dis igurement of the pinna (Corriveau 2012). TECA and LBO are recommended for any patient with a malignant tumor of the ear canal (Moisan and Watson 1996; ter Haar 2006). In one study of 11 dogs with ceruminous gland adenocarcinoma, four patients with tumors of the vertical ear canal treated with lateral ear canal resection had a 75% recurrence rate compared to no recurrence in the seven patients treated with TECA and LBO (Marino et al. 1993). Similarly, in one study of 22 cats with ceruminous gland adenocarcinoma, cats with tumors involving the lateral aspect of the vertical ear canal had a lateral ear canal resection (Marino et al. 1994). About 66% of the tumors recurred, with only two of the six cats alive at one year. The median disease-free interval was 10 months (range 1– 14). This is compared to cats with a TECA and LBO with a 42-month median survival (range 4–60), 25% recurrence rate, and 12 of 16 alive at 1 year.

Figure 5.14 (a) Vertical ear canal resection for ceruminous adenoma of the vertical ear canal of a dog. (b) Postoperative specimen. Note the focal involvement of the vertical ear canal, allowing this more limited surgical procedure. As there is little indication for a lateral and vertical ear canal resection, the discussion will be limited to TECA and LBO. A complete blood count and biochemical pro ile should be performed prior to surgery. Patients with chronic otitis externa may be hypergammaglobulinemic with a compensatory hypoalbuminemia. In rare cases, fresh-frozen plasma or synthetic colloids, such as pentastarch, may be needed to help support blood pressure. Patients with chronic disease may also have signi icant intraoperative hemorrhage. For patients with bilateral disease, it may be preferable to stage the procedures several days to weeks apart. This reduces the risk of postoperative ventilatory compromise, secondary to edema of the surgery site when both ears have surgery simultaneously. The hematocrit and total solids should be assessed before proceeding with surgery of the second ear. However, in one study there was no signi icant difference in anesthetic and early surgical complication rates between dogs undergoing single-stage bilateral TECA and LBO when compared to dogs undergoing unilateral TECA and LBO (Coleman and Smeak 2016). Patients should have an opiate such as hydromorphone or morphine included in their premedication. It may also be administered during surgery for additional analgesia. The entire pinna and lateral aspect of the head are clipped and prepared for aseptic surgery. Prophylactic intravenous antibiotics are initiated prior to making the skin incision. The patient is placed in lateral recumbency with a towel placed under the head. A circular incision is made with a scalpel blade around the opening of the vertical ear canal encompassing all hypertrophied tissue. Be cautious with the rostral and caudal aspects of the incision to ensure that the blood supply to the pinna is not compromised. The incision is extended through the auricular cartilage. The incised auricular cartilage is grasped with a towel clamp and retracted toward the surgeon, exposing the external wall of the medial aspect of the vertical ear canal. The muscle is closely dissected from the medial aspect of the ear canal down to the level of the horizontal ear canal. Dissection

around the vertical ear canal is then initiated from the exposed medial aspect and continued laterally, alternating in a rostral and caudal direction. Exposure is improved by applying tension on the ear canal away from the area of dissection (Lanz and Wood 2004). The periauricular tissues should be closely dissected, with Metzenbaum and iris scissors, from the perichondrium to prevent trauma to the facial nerve. The facial nerve exits the skull through the stylomastoid foramen, caudal to the external acoustic meatus, and courses caudal and ventral to the horizontal ear canal near its junction with the vertical ear canal. Gentle tissue retraction should be employed, with retractors placed super icial to the facial nerve to prevent iatrogenic trauma, as it may be entrapped in adjacent ibrous tissue (Smeak and Inpanbutr 2005). Bipolar cautery should be used for hemostasis. The ear canal is transected at the junction of the horizontal and osseous external ear canal. Transection can be performed by a stab incision with a scalpel blade, scissors, and by twisting the ear canal. Rongeurs may be needed if the ear canal is ossi ied (Smeak and Inpanbutr 2005). Instruments should be directed in a caudal-to-cranial direction away from the facial nerve. Following removal of the ear canal, the osseous ear canal should be removed with rongeurs. Care is taken to avoid trauma to the branches of the external carotid artery and the retroglenoid vein ventral to the bulla (Lanz and Wood 2004). If hemorrhage occurs, the surgery site should be illed with saline and packed with a gauze square for ive minutes. The alternative is to apply focal pressure to the origin of the bleeding with a cotton-tipped applicator. Bone wax can then be placed (Smeak and Inpanbutr 2005). The tissues on the lateral aspect of the bulla are then gently elevated with a periosteal elevator. The lateral and ventral aspects of the bulla are removed, ensuring good access to the caudal aspect of the tympanic cavity (Smeak and Inpanbutr 2005). When very thickened, this can be facilitated by orienting the rongeurs in a caudodorsal-to-cranioventral direction. Do not use rongeurs on the rostral aspect of the bulla to avoid trauma to the epitympanic recess (Smeak and Inpanbutr 2005). It is imperative that all of the debris and epithelium of the osseous external ear canal and bulla be completely removed to prevent chronic abscessation/ istulation. The lining of the bulla is gently elevated with a curette and, when thickened, can be grasped with a rongeur for

removal. This will expose the white, shiny medial wall of the bulla. The bulla of the cat is divided into a ventromedial and a dorsolateral compartment. It is imperative that both compartments be evaluated. Be careful with dorsal and dorsomedial curettage to avoid damage to the sympathetic trunk and round window. Abnormal tissue hanging dorsally can be gently grasped with a small, curved hemostat (Smeak and Inpanbutr 2005) and teased off. The tympanum may have rolled craniodorsally with the malleus and can be removed by gently grasping craniodorsally into the epitympanic recess (McAnulty et al. 1995). A swab of the epithelium and contents of the bulla should be submitted for aerobic and anaerobic culture and sensitivity. Samples from the bulla and external ear canal are submitted for histopathology. The surgical site is gently lavaged with sterile saline. Some authors indicate that a drain is not necessary if there has been meticulous hemostasis, debridement of devitalized tissue, and good tissue apposition (Devitt et al. 1997). Furthermore, if there is any risk that excision is incomplete, a passive drain is contraindicated as it would allow tumor seeding into adjacent tissue. The subcutaneous tissues are closed with 2-0 or 3-0 absorbable suture in a simple interrupted pattern. Care is taken to ensure that the facial nerve and drain are not entrapped in the closure. The super icial subcutaneous tissues are sutured over the auricular cartilage with 3-0 or 4-0 absorbable suture in a simple continuous pattern. The skin is apposed with nonabsorbable suture (3-0 or 4-0) in a simple interrupted or cruciate pattern. It is important that the cartilage is covered to prevent granulation tissue formation. A soft, padded bandage can be placed following surgery. The affected pinna is placed over the dorsum of the head with several gauze squares placed between the pinna and the head. A secondary layer of gauze roll is applied loosely alternating cranial and caudal to the opposite ear. This is followed with a tertiary layer such as Vetrap. The location of the pinna should be drawn on the bandage to prevent inadvertent trauma during bandage removal. The bandage is changed daily and removed two days after surgery. An Elizabethan collar is indicated if the patient is traumatizing the incision. A modi ication of the above technique is recommended for animals with erect ear carriage. Using new instruments and gloves, an

advancement lap is made rostrolateral to the original circular incision. Two parallel incisions are extended rostrally from the circular incision. The skin is elevated and apposed to the caudal aspect of the circular incision. Following surgery, the ear is bandaged in an erect position with rolled gauze placed on the concave aspect of the pinna.

Postoperative Management Patients should be treated empirically with antibiotics until culture and sensitivity results are obtained. An appropriate antibiotic is then administered for two to four weeks following surgery. Mixed bacterial populations are frequent (Devitt et al. 1997). Common isolates include Staphylococcus intermedius, Pseudomonas aeruginosa, β-hemolytic Streptococcus, Proteus spp., Streptococcus canis, and Escherichia coli (Devitt et al. 1997; Lanz and Wood 2004). Analgesia consists of injectable opiates throughout surgery and immediately postoperatively. Hydromorphone or morphine may be administered every 4–6 hours or as a continuous rate infusion for 24– 48 hours following surgery (Lanz and Wood 2004). A fentanyl patch may be placed 12–24 hours prior to surgery (Lanz and Wood 2004). Nonsteroidal anti-in lammatory medication and tramadol or codeine should be administered for ive days following surgery (Lanz and Wood 2004). Local infusion of anesthetic agents, such as intraoperative splash block, nerve blocks, and continuous infusion into the wound have been investigated. They are inexpensive, reduce the risk of break-through pain, and provide local pain control without systemic side effects such as sedation. Liposomal encapsulated bupivacaine (Nocita) has also been in iltrated into the surgical site (off-label use) but it is more costly. In one study, patients were easier to manage under anesthesia with preoperative local nerve blocks with bupivacaine (Buback et al. 1996); however, their postoperative evaluation did not differ from patients receiving perioperative opiates or opiates and a bupivacaine splash block. In another study, continuous local infusion of lidocaine via an indwelling wound catheter provided comparable pain relief to a morphine constant rate infusion with lower sedation scores. Filters are placed in the line, and the catheter must be handled aseptically to

prevent the introduction of bacteria. Further studies are needed to evaluate acceptable administration rates that would increase the likelihood of analgesia, without risk of systemic toxicity and with minimal wound complications (Wolfe et al. 2006). Bolus injections of bupivacaine through the catheter every six hours may be more successful. There is no evidence that the local administration of anesthetic agents caused an increased incidence of facial nerve de icits or ototoxicity (Wolfe et al. 2006). If there is evidence of postoperative facial nerve paresis or paralysis, eye lubricant should be administered for several days following surgery. This is not typically needed long-term as tear production and third eyelid function are usually unaffected (White and Pomeroy 1990). Patients with concurrent keratoconjunctivitis sicca will require permanent treatment.

Complications In the immediate postoperative period, there can be swelling of the surgery site. This, in combination with the bandage, can cause dif iculty breathing, particularly in brachycephalic patients. Patients should be monitored closely and the bandage should be loosened or removed if there is any concern. Other complications include infection of the surgery site, necrosis of the pinna (Matthiesen and Scavelli 1990; Lanz and Wood 2004), hemorrhage, and neurologic dysfunction, which can include Horner’s syndrome, facial nerve paresis/paralysis, and vestibular disease. Necrosis of the pinna typically occurs along the caudal pinna margin. It is treated with debridement and open wound management (Matthiesen and Scavelli 1990; Lanz and Wood 2004). Preexisting neurologic de icits are often permanent. Following surgery, the incidence of facial nerve paresis/paralysis in dogs is 5–50%, with most cases resolving within four weeks. The cat has a higher incidence of neurologic dysfunction when compared to the dog and a higher incidence of permanent facial nerve de icits despite meticulous dissection (Matthiesen and Scavelli 1990; Bacon et al. 2003; Lanz and Wood 2004). Horner’s syndrome tends to occur only in the feline

patient (Lanz and Wood 2004). It has been reported that in cats undergoing TECA and LBO, 50% developed facial nerve paralysis and 42% developed Horner’s syndrome following surgery of which 28 and 14%, respectively, were permanent. The remainder of the cases resolved within weeks to months (Bacon et al. 2003). Hearing loss is expected in all patients following surgery. Patients with signi icant ear disease may have been deaf prior to surgery. Owners should be warned of this in patients with bilateral disease. When evaluated by brainstem-evoked audiometry (BERA), patients undergoing TECA and LBO had complete hearing loss. The only patients in which hearing was maintained were patients that had the tympanic membrane and ossicles retained (McAnulty et al. 1995). This is rarely clinically acceptable as the retention of the tympanic membrane risks the development of otitis media and the late development of istulous tracts (ter Haar 2006). A signi icant complication following surgery is the development of otitis media and a istulous tract. This has been reported in 5–10% of cases (Lanz and Wood 2004). This may appear 3–12 months after surgery and is attributed to epithelium being left in the bulla or external osseous ear canal (Matthiesen and Scavelli 1990). Other postulated causes include osteomyelitis of the auditory ossicles and inadequate drainage of the middle ear through the auditory tube (Lanz and Wood 2004). Risk is reduced by removing the tympanic membrane and the majority of the lateral and ventral walls of the bulla, allowing ingrowth of vascularized soft tissue (McAnulty et al. 1995). It is the removal of the bony wall of the lateral bulla that is more useful, rather than relying solely on aggressive curettage. There may be transient improvement with long-term antibiotics; however, a lateral or ventral bulla osteotomy to remove the epithelium is preferable.

Prognosis In dogs, most tumors are characterized by local invasion and a low incidence of metastasis. Patients with tumors con ined to the ear canal have a good prognosis with TECA and LBO. A median survival time of greater than 58 months has been reported in dogs with malignant aural tumors (London et al. 1996). In a study of 7 dogs with ceruminous

gland adenocarcinoma, with a median follow-up of 36 months (8–72 months), there were no reports of local recurrence or metastatic disease (Marino et al. 1993). Patients with SCC have a poorer prognosis. In another study, 3 of 23 dogs with ceruminous gland adenocarcinoma died from their tumor, compared to four out of eight with SCC (London et al. 1996). In a third study, local tumor control was obtained with ear canal ablation in six dogs, however, two (one with ceruminous gland adenocarcinoma and one with SCC) developed pulmonary metastases 10 months and 6.5 months, respectively, following surgery (Matthiesen and Scavelli 1990). The mean follow-up time was 18 months (12–44 months). Bulla involvement is a negative prognostic indicator in dogs. Dogs with tumor invasion into the bulla had a signi icantly reduced median survival time of 5.3 months, whereas those with tumors con ined to the vertical or horizontal ear canals survived longer than 30 months (London et al. 1996). Extension into the bulla did not appear to affect outcome in another study, however, histopathology was not done to differentiate secondary infection from tumor ingrowth (Marino et al. 1993). Cats tend to have more aggressive tumors than dogs (London et al. 1996). In one study, cats with malignant aural tumors had a median survival time of 11.7 months (London et al. 1996). Negative prognostic indicators included preexisting neurologic de icits, histologic evidence of invasion, and a histologic diagnosis of SCC or carcinoma of undetermined origin vs. adenocarcinoma (London et al. 1996; Bacon et al. 2003). Cats with neurologic de icits at presentation had a signi icantly shorter median survival time of 1.5 months compared to 15.5 months in cats without neurologic de icits. Cats with histologic evidence of invasion had a median survival time of 4 months vs. 21.7 months for cats that did not have invasion. Cats with ceruminous gland adenocarcinoma lived signi icantly longer than cats with SCC (median of 49 months vs. 3.8 months) and carcinoma of undetermined origin (5.7 months). Cats with ceruminous gland adenocarcinoma, treated with TECA and LBO, had a median disease-free interval of 42 months, survival time of 50 months, and a recurrence rate of 25 with 75% alive at one year (Marino et al. 1994; Bacon et al. 2003). In another study of

15 cats, seven had ceruminous gland adenocarcinoma; of those seven cats, three were dead by six months (Williams and White 1992). The remaining patients had no evidence of recurrence six months after surgery. High mitotic index (≥3 mitotic igures per high-power ield) is a negative prognostic indicator in cats with ceruminous gland adenocarcinoma (Bacon et al. 2003). Histopathologic grade (well, intermediately, and poorly differentiated) did not correlate with outcome.

Adjunctive Treatment In people, total ear canal ablation is most likely to be curative when combined with external beam radiation therapy, particularly with aggressive or very invasive tumors (Zur 2005). There is little information in the veterinary literature regarding outcome from adjuvant therapies. Radiation therapy is recommended for patients where surgical resection is incomplete or where surgical resection is declined (Théon et al. 1994). CT or MRI is recommended for radiation therapy planning (Théon et al. 1994). Megavoltage radiation is recommended in preference to orthovoltage as there is better delivery of radiation to the deeper structures (bulla and vestibular apparatus), reducing the rate of recurrence (Théon et al. 1994). Acute reactions are mild in most patients, and in those with later recurrence, further intervention, including surgery and a second course of radiation therapy, is well-tolerated (Théon et al. 1994). In one study, three patients developed neurologic signs after radiation therapy. This was associated with tumor recurrence in two. In one patient, the development of Horner’s syndrome may have been due to radiation injury; however, the dog had long-term tumor control. Cranial and peripheral nerves are not normally considered major dose-limiting tissues, whereas the brain and spinal cord are. This study used a Monday–Wednesday–Friday schedule (Rogers 1988; Théon et al. 1994). New protocols with more frequent dosing (smaller individual doses) and a higher overall dose may reduce the rate of recurrence. There is little information in the literature regarding chemotherapy. As local control continues to improve, metastatic disease may become

more prevalent.

Tumors of the Middle Ear Primary tumors of the middle ear in small animals are rare, with local extension of tumors from the external ear canal being more common (Rogers 1988; Little et al. 1989; ter Haar 2006). Tumors of the middle ear are typically found in older patients, with some reports supporting a female sex predisposition (Lane and Hall 1992; Lucroy et al. 2004). In one study, the median age was 10.25 years (7–14 years) (Trevor and Martin 1993). Clinical signs include hemorrhagic or serosanguinous otic discharge and pain on opening the mouth (Indrieri and Taylor 1984; Pentlarge 1984; ter Haar 2006). Pain on opening the mouth has been attributed to extension and/or involvement of the temporomandibular joint (Lane and Hall 1992). Neurologic de icits are common, including facial nerve paralysis, Horner’s syndrome, and vestibular syndrome (head tilt, nystagmus, and ataxia) (Wainberg et al. 2019). Patients with tumor extension into the nasopharynx may present with increased chronic nasal discharge, respiratory noise or compromise, dysphagia, and exercise intolerance (Bradley 1984; Trevor and Martin 1993; Lanz and Wood 2004; ter Haar 2006). A similar mass may also be identi ied in the external ear canal. Clinical signs may be present for weeks or months. Para-aural abscessation has also been described. Metastases to the eye, brain, and larynx have been reported (Lane and Hall 1992). Aggressive neoplasia is rare in dogs. Of the malignant tumors of the middle ear of dogs, SCC is the most common (Yoshikawa et al. 2008). Invasion with destruction of the bulla, mandibular condyle, and zygoma have been reported. Papillary adenomas have been documented in the middle ear of dogs (Little et al. 1989). SCC is the most common tumor type in cats (Stone et al. 1983; Rogers 1988; Lane and Hall 1992; Wainberg et al. 2019). Ceruminous gland adenocarcinoma, lymphoma, ibrosarcoma, and osteosarcoma have also been documented in the middle ears of cats (Rogers 1988; Lane and Hall 1992; Trevor and Martin 1993; Wainberg et al. 2019). Benign tumors include ceruminous gland adenoma, cholesteatoma, and

papillary adenoma (Wainberg et al. 2019). In a study which included 13 cats with malignant middle ear tumors treated with ventral bulla osteotomy, 54% of cats presented with a head tilt, 38% presented with Horner’s syndrome, and 31% had facial nerve paralysis (Wainberg et al. 2019). In one review of 11 cats, 54% of the tumors were SCC; 10 of 11 cats had Horner’s syndrome and/or vestibular disease; and 45% had oral signs, including pain on opening their mouths and/or dysphagia (Lucroy et al. 2004). In one report of ive cats, all had facial nerve de icits and most demonstrated pain on opening the mouth. Other clinical signs included ataxia, head tilt, nystagmus, and Horner’s syndrome (Rogers 1988; Trevor and Martin 1993; Wainberg et al. 2019). Nasopharyngeal polyps (NPs) are the most common mass lesion in the feline middle ear (Rogers 1988; Lanz and Wood 2004; Wainberg et al. 2019) and should be differentiated from neoplastic conditions. Cats with NPs are signi icantly younger than cats with other middle ear diseases (Wainberg et al. 2019); the majority of cats are younger than 2 years of age, with a mean age of 1.5 years in one study (Trevor and Martin 1993); however, NPs have been reported in cats up to 15 years of age (Bradley 1984; Lanz and Wood 2004; Wainberg et al. 2019). Patients can be bilaterally affected (Trevor and Martin 1993; Wainberg et al. 2019). It has been proposed that they are secondary to respiratory tract infections with subsequent otitis media (Rogers 1988; Trevor and Martin 1993). Feline calicivirus has been thought to be an inciting agent (Lanz and Wood 2004). A congenital cause has also been postulated in some cases (Lanz and Wood 2004). NPs can arise in the middle ear, auditory tube, or nasopharynx with extension into the nasopharynx and/or external ear canal (Lanz and Wood 2004). Clinical signs include otic discharge, head shaking, head tilt, facial nerve paralysis, or a visible mass (Wainberg et al. 2019). Patients with involvement of the nasopharynx may present with increased chronic nasal discharge, respiratory noise or compromise, dysphagia, and exercise intolerance (Bradley 1984; Trevor and Martin 1993; Lanz and Wood 2004; Wainberg et al. 2019). NPs are typically pedunculated and can be pale gray, white, or pink (Lanz and Wood 2004) (Figure 5.15).

Although less common, in lammatory polyps have also been reported in six dogs (Pratschke 2003; Blutke et al. 2010). All were male and ranged in age from 4 to 13 years. The age of onset in dogs is older than has been reported in cats. Two dogs were bilaterally affected. All dogs had associated otitis externa and media. It is not known if it is primary or secondary. Three had a history of hemorrhage from the external ear canal. Aural epidermoid cyst, or cholesteatoma, is a cystic, nonneoplastic, locally destructive mass within the middle ear that can be misinterpreted as an aggressive tumor. There is an accumulation of keratinized debris in the middle ear that causes subsequent enlargement of the bulla (Hardie et al. 2008; Newman et al. 2015). Cholesteatomas have been reported in dogs and 2 cats. Bilaterally affected dogs have been reported (Harran et al. 2012; Van der Heyden et al. 2013; Ilha and Wisell 2013; Newman et al. 2015; Imai et al. 2019). It is typically associated with chronic otitis externa/media, however, in one study, 2/11 dogs diagnosed with cholesteatoma, presented with nasopharyngeal and/or neurological signs but had no history of chronic otitis externa (Imai et al. 2019). Patients with more advanced disease can present with pain opening their mouth and neurologic signs, including head tilt, facial nerve paresis, and ataxia.

Figure 5.15 Traction-avulsion of a nasopharyngeal polyp extending into the external ear canal of a four-year-old male neutered domestic short-haired cat. A ventral bulla osteotomy was performed to remove the polyp from the middle ear. Nine months previously, a nasopharyngeal polyp had been removed from the pharynx with traction-avulsion. a

Diagnosis Otoscopy may reveal a mass or bulging of the tympanic membrane (Gimmler and Daigle 2012). Myringotomy, under the guidance of videootoscopy, can be used to collect samples from the middle ear for histopathology and culture and sensitivity. Cytology of cholesteatomas reveals a chronic suppurative in lammatory reaction with many

anucleate keratinized squamous epithelial cells (Reidinger et al. 2012; Newman et al. 2015). Skull radiographs have limited use. They may demonstrate a soft-tissue density in the bulla and/or nasopharynx (Bradley 1984; Trevor and Martin 1993; Lanz and Wood 2004). Lateral oblique and open-mouth views are performed to evaluate the bulla (Bradley 1984; Lanz and Wood 2004). The bulla is typically thickened with a luid density within it (Trevor and Martin 1993). Soft-tissue swelling adjacent to the bulla and marked bony destruction of the tympanic bulla, petrous temporal bone, zygomatic arch, and temporomandibular joint have been described (Indrieri and Taylor 1984; Pentlarge 1984; Lane and Hall 1992; Trevor and Martin 1993). CT is superior to MRI in detecting lesions of the inner and middle ear that affect bony structures. It has been considered ideal for diagnosing cholesteatoma, however, in 1 study, MRI was reported to be more useful in early detection (Imai et al. 2019). MRI has better resolution for softtissue lesions (Harran et al. 2012). Advanced imaging is particularly important in patients with neurologic de icits (Horner’s or peripheral vestibular syndrome) to assess invasion into adjacent structures. This allows for appropriate surgical planning. CT or MRI should be interpreted with caution following surgery, as scar tissue has been shown to contrast enhancement and may be misinterpreted as residual disease. In people, follow-up studies to assess completeness of surgical excision are performed within 5–7 days of surgery to reduce this risk (Lucroy et al. 2004). It is important to do a thorough neurologic evaluation prior to surgery and to warn owners that preexisting neurologic de icits may not resolve with surgery. In 13 cats, CT indings most consistent with a NP included a stalk-like structure within the auditory tube, strong rim enhancement, and pathological expansion with thickening of the tympanic bulla (Olivieri et al. 2012). There was no periosteal reaction, however, two cats had mild osteolysis with smooth margins. Eight had enlarged medial retropharyngeal lymph nodes. Cats with malignant nasopharyngeal masses had extension of the mass into another region of the skull including the brain, with severe effacement of the bulla and adjacent structures. Cats with CT evidence of osseous bulla changes are

signi icantly more likely to have a malignant middle ear tumor (Wainberg et al. 2019). In patients with cholesteatoma, otoscopic examination may reveal a pearly white-yellow growth protruding from the middle ear (Newman et al. 2015; Imai et al. 2019). With CT/MRI, a space-occupying, invasive, nonvascular lesion is seen in the tympanic cavity. Some patients will have marked expansion of the bulla and lysis of the squamous or petrosal portions of the temporal bone. Enlargement of the associated lymph nodes has also been documented. Contrast medium enhancement has been observed which can be confused with a neoplastic process. Preoperative biopsies may be obtained with a transcanal endoscopic biopsy or a ventral or transpalatal aspirate from the expanded bulla and submitted for histopathology and culture and sensitivity.

Treatment Ventral bulla osteotomy (VBO) is recommended for diseases con ined to the middle and inner ear. There is good exposure of the tympanic cavity, and gravity assists drainage (Trevor and Martin 1993). A transoral approach to the middle ear has also been described in canine cadavers (Manou et al. 2017). Further investigation is warranted in clinical cases. Total ear canal ablation is recommended in patients with involvement of the external, middle, and inner ear (Trevor and Martin 1993). In patients with middle ear neoplasia that has extended beyond the bulla, surgery can be combined with a rostrotentorial craniectomy, which appears to improve outcome (Lucroy et al. 2004). Mortality in people is typically due to intracranial extension of the tumor (Stone et al. 1983). Follow-up with radiation therapy is recommended, although an increase in survival time is not always achieved (Stone et al. 1983; Rogers 1988). Some patients may also bene it from chemotherapy (ter Haar 2006). For patients with cholesteatoma, conservative management has been described with lushing of the external ear canal, traction and avulsion and/or laser ablation of obstructing masses, and debridement and

lavage of the bulla via the ear canal using a video-otoscope (Imai et al. 2019). Following debridement and lavage, triamcinolone has been placed in the bulla. Treatment is continued with weekly lushing of the ear canal +/− oral steroids, antimicrobials, and oclacitinib. This may be useful in early cases of cholesteatoma or as an alternative to surgery, although long-term medical management is required (Imai et al. 2019). Alternatively, the bulla can be debrided using a VBO, transoral bulla osteotomy, or TECA and LBO (Hardie et al. 2008; Manou et al. 2017). A caudal auricular approach to the tympanic bulla for removal of a cholesteatoma has also been described in a dog, allowing preservation of conduction potentials on BERA response tests (Hardie et al. 2008). Early surgery can be curative; however, recurrence has been reported. Complete removal of the epithelium can be more dif icult in these patients, as the epithelium is adhered to the invaginated bone. Ventral Bulla Osteotomy A rostral-to-caudal incision is made over the bulla, which can be palpated in the cat, caudal and medial to the vertical ramus of the mandible. The platysma muscle is incised, and the linguofacial vein is retracted. The digastricus muscle is dissected from the hyoglossal and styloglossal muscles. The hypoglossal nerve is on the lateral aspect of the hypoglossal muscle and should be protected. The muscles are distracted with self-retaining retractors, exposing the ventral aspect of the bulla. An osteotomy is performed with a Steinmann pin or burr. The opening is enlarged with rongeurs or burr. Samples are removed from the bulla for histopathology, cytology, and culture and sensitivity (aerobic and anaerobic). In one study, four of seven cats with NPs and one of four cats with tumors of the middle ear had positive cultures (Trevor and Martin 1993). The bulla of the cat is divided into a ventromedial and a dorsolateral compartment by an incomplete bone shelf. It is imperative that both compartments be evaluated. It is recommended to be cautious with dorsal and dorsomedial curettage to reduce trauma to the sympathetic nerve ibers as they run along the promontory along the dorsomedial aspect of the bulla and the round window. The bulla is lavaged with warm sterile saline. A drain should not be placed in the case of malignant tumors as it may track neoplastic cells outside of the surgical ield. The subcutaneous tissues and skin are

closed routinely. If a drain is placed, a soft padded bandage should be placed to protect the drain and to qualify and quantify wound drainage. The surgical approach is the same in dogs; however, the bulla cannot be palpated externally. Following surgery, animals should receive hydromorphone or morphine as needed for pain control. Nonsteroidal anti-in lammatory medication may be given for ive days following surgery. From 13 to 83% of patients undergoing VBO have positive middle ear cultures, and antibiotics are administered for one to four weeks based on culture and sensitivity results (Trevor and Martin 1993; Wainberg et al. 2019). The drain is removed one to three days following surgery. Treatment options for NPs include traction-avulsion and VBO (Figure 5.16). Traction-avulsion has historically been associated with a 40– 50% recurrence rate. In one study, there was no recurrence in patients treated with prednisolone following traction-avulsion (Anderson et al. 2000). The patient should be preoxygenated prior to anesthesia. The anesthetist should be prepared for a more dif icult intubation if there is a large mass in the nasopharynx. Although it is preferable to avoid it, a temporary tracheostomy may be performed. Following induction, oxygen may be administered by a small urinary catheter placed into the airway (Figure 5.16). This can also be used as a guide for endotracheal tube placement. Ventral deviation of the soft palate may be noted in patients with a nasopharyngeal mass (Anderson et al. 2000). Pressure can be placed on the soft palate pushing the polyp into view (Anderson et al. 2000). Alternatively, the soft palate can be retracted with a spay hook to expose the polyp. Rarely, the soft palate is incised to expose the mass. The base of the mass is grasped with hemostats (Figure 5.16). Traction and rotation are applied to ensure complete removal of the stalk. Blood should be removed from the nasopharynx with cottontipped applicators. A mirror should be used to ensure that no gross disease is left behind. Following surgery, prednisolone may be administered at 1–2 mg/kg daily for 2 weeks, 0.5–1 mg/kg for 7 days, then every other day for 7–10 days.

Figure 5.16 Traction-avulsion of a large nasopharyngeal polyp in a cat. Note the intratracheal urinary catheter used to insuf late oxygen during polyp removal. The size of the polyp had precluded intubation with an endotracheal tube. Following polyp removal, the cat was intubated and recovered without incident. Masses are removed similarly from the external ear canal (see Figure 5.15). A video-otoscope can facilitate removal of NPs from the middle ear, via the external ear canal (Greci et al. 2014). Under endoscopic visualization, the NP is grasped with hemostats and avulsed with concurrent traction and rotation. Any residual polyp can then be removed from the middle ear under video guidance with small biopsy forceps and Volkmann curettes. When indicated, the septum between the dorsolateral and ventromedial compartments of the bulla should be disrupted to allow more thorough cleaning. In one study, procedure times of 45 minutes to 2.5 hours were recorded. Recurrence rates are comparable to patients treated with VBO alone with fewer neurological complications (13.5%) (Greci et al. 2014). Some authors recommend that a VBO be performed in all patients with NPs that have radiographic changes of the bulla or neurologic de icits.

Excellent results have been reported (Bradley 1984). Complications The patient’s breathing should be monitored closely following surgery, particularly if a bandage was placed. Cats are more likely to be dyspneic following surgery, necessitating bandage removal. In patients with bilateral NPs, staged bilateral VBOs are recommended. In one study, 47% of the cats with single-stage bilateral VBOs had postoperative respiratory complications, including death, compared to 9% with unilateral surgery and 29% with staged bilateral procedures (Wainberg et al. 2019). Cats treated with single-session VBOs had 12.9 times increased odds of developing postoperative respiratory complications and were signi icantly more likely to die as a result of this complication (Wainberg et al. 2019). The reasons for this inding were not identi ied; however, the presence of respiratory signs preoperatively and a positive bacterial culture were also associated with severe upper respiratory signs postoperatively (Wainberg et al. 2019). Horner’s syndrome is the most common neurologic complication following surgery, occurring in up to 80% of cases (Bradley 1984; Trevor and Martin 1993; Lanz and Wood 2004; Wainberg et al. 2019). In one study (Wainberg et al. 2019), Horner’s syndrome was permanent in 28.4% of cats and transient in 71.6% of cats treated with VBO; the median time to resolution in cats with transient Horner’s syndrome was signi icantly quicker in cats where Horner’s syndrome was not present prior to surgery (24 days) compared to cats with preexisting Horner’s syndrome (42 days) (Wainberg et al. 2019). The cause of Horner’s syndrome is trauma to the postganglionic sympathetic axons as they course through the middle ear (Bradley 1984; Trevor and Martin 1993). In one study (Wainberg et al. 2019), 30.1% of cats treated with VBO had postoperative head tilt (26.4% of which were transient and 73.6% were permanent) and 13.5% had facial nerve paralysis (41.0% of which were transient and 59.0% were permanent) (Wainberg et al. 2019). The median times to resolution of these complications were signi icantly quicker when these conditions were not present prior to surgery (head tilt: 55 days vs. 454 days; facial nerve paralysis: 37 days vs. 42 days) (Wainberg et al. 2019). Hypoglossal nerve de icits have also been reported following VBO, due to excessive retraction (Lanz and Wood

2004). The primary non-neurologic complications are recurrent otitis externa and/or media (6%), incisional complications (5%), and local recurrence of the NP (2%) (Lanz and Wood 2004; Wainberg et al. 2019). It is interesting to note that VBO does not appear to have much effect on hearing if the ossicles are intact and the tympanum is preserved. In one study, 11 out of 12 dogs had normal hearing following VBO despite the development of subperiosteal new bone from the inner surface of the bulla with some obliteration of the bulla (ter Haar 2006). Damage to the tympanic membrane does cause conductive hearing impairment, however. This appears to resolve once the tympanic membrane has healed. Fewer complications have been documented with per-endoscopic trans-tympanic traction, performed with a video-otoscope. In one study, 8% of the cats developed Horner’s syndrome which resolved in a few weeks. None had facial nerve paralysis. The percentage of recurrence (13.5%) is less than traction alone and similar to the percentage for VBO (Greci et al. 2014).

Prognosis There are few published reports of outcomes following surgery for neoplasia of the middle ear. A dog with papillary adenoma had a VBO and partial curettage of the middle ear. He was euthanized two years after surgery for chronic otorrhea (Little et al. 1989). There is one report of an eight-year-old Golden retriever with an invasive SCC of the middle ear. A VBO was performed followed by palliative radiation therapy (RT) (800 cGy for three fractions on days 0, 7, 21). Seventy days after the completion of RT, the dog was lethargic and hyporexic. Thoracic radiographs were consistent with metastatic disease. Histopathology was not performed (Yoshikawa et al. 2008). Cats most commonly have aggressive tumors, with the majority being euthanized at the time of diagnosis (Stone et al. 1983; Indrieri and Taylor 1984; Pentlarge 1984; Lane and Hall 1992). In one study of four cats with middle ear neoplasia with tumor types including anaplastic carcinoma, SCC, lymphoma, and ceruminous gland adenocarcinoma, the

mean survival time was 1.25 months (four days to three months), with surgery not improving the clinical course (Trevor and Martin 1993). The patients were euthanized due to progressive or recurrent clinical signs. In a more recent study of 13 cats with malignant tumors and ive cats with benign tumors treated with VBO (Wainberg et al. 2019), cats with malignant tumors had a signi icantly shorter survival time, but their median survival time was still relatively long at 855 days with one- and two-year survival rates of 75 and 50%, respectively. These cats were also signi icantly more likely to have local tumor recurrence (44%) than cats with benign middle ear tumors (15%) (Wainberg et al. 2019). The median survival time for cats with benign middle ear tumors was 1,244 days with one- and two-year survival rates of 60 and 33%, respectively (Wainberg et al. 2019). Survival may be improved with advanced imaging prior to surgery and a more aggressive surgical approach. Follow-up with radiation therapy would be ideal. In patients with extension beyond the bulla, the VBO can be combined with a rostrotentorial craniectomy (Lucroy et al. 2004). In one 15-year-old cat with a papillary adenoma, there was no evidence of recurrence 840 days following surgery (Lucroy et al. 2004). In a 13-year-old cat, an adenocarcinoma was incompletely excised due to irm attachments to the brainstem. Further surgery and radiation therapy were declined. The cat was euthanized 630 days following surgery due to progressive neurologic signs (Lucroy et al. 2004). Cholesteatoma is considered a rare complication of chronic otitis externa. Patients with cholesteatomas have a high recurrence rate following surgery with 50% being recorded in one study (Hardie et al. 2008). Recurrence is more likely in patients with advanced disease, as indicated by inability to open the jaw, neurologic disease, or bone lysis (per CT). Some patients were maintained following surgery with intermittent, systemic antibiotic therapy, based on culture and sensitivity results. The prognosis may be improved if these patients are imaged early in the course of the disease (Hardie et al. 2008; Harran et al. 2012; Newman et al. 2015; Imai et al. 2019). In one report of medical management of cholesteatoma in 11 dogs (13 ears), using videootoscope guided trans-canal debridement and lavage of the bulla, there was a 30% recurrence rate (Imai et al. 2019). These patients required

ongoing medical care (weekly–monthly lavage of the bulla, oral and/or topical steroids, and antimicrobials). In patients with NPs, a decreased recurrence rate is expected with VBO (Lanz and Wood 2004). In one study which included 150 cats with NPs treated with VBO, the local recurrence rate was 2.0% (Wainberg et al. 2019). In contrast, local recurrence was reported in nine cats (41%) after a median of 3.5 months following traction-avulsion (Anderson et al. 2000). Recurrence was more likely when NPs extended into the external ear canal (50% recurred) and in patients where tractionavulsion was performed without prednisolone. Patients with NPs in the nasopharynx and patients treated with prednisolone had no evidence of recurrence. Historically, it has been recommended that any patient with changes on bulla radiographs should have a ventral bulla osteotomy performed. According to Anderson et al. (2000), 30% of the cats with radiographic changes of the bullae had resolution following traction-avulsion. One cat with recurrence had resolution following a second traction-avulsion followed by prednisolone. In one study, 37 cats underwent 39 per-endoscopic trans-tympanic traction of NP and 5 cats had recurrence. Two of these cats had resolution following a second procedure (Greci et al. 2014). Of ive dogs with in lammatory polyps, one had a VBO and four were treated with TECA & LBO (two bilateral) (Pratschke 2003). No recurrence was noted 9–69 months following surgery.

Salivary Gland Tumors The parotid, mandibular, sublingual, and zygomatic salivary glands are major salivary glands. The minor salivary glands are distributed throughout the lips, cheeks, tongue, hard palate, soft palate, pharynx, and esophagus (Clark et al. 2013). Salivary gland tumors are uncommon in the dog and rare in the cat. Most patients are elderly. In a review of the literature, 80 dogs and 78 cats had malignant salivary gland disease (Wells and Robinson 1975; Evans and Thrall 1983; Louw and Van Schouwenburg 1984; Carberry et al. 1987; Brunnert and Altman 1990, 1991; Spangler and Culbertson 1991; Burek et al. 1994; Habin and Else 1995; Thomsen and Myers 1999; Pérez-Martínez et al.

2000; Hammer et al. 2001; Sozmen et al. 2002, 2003; Wiedmeyer 2003; Mazzullo et al. 2005; Militerno et al. 2005; Smrkovski et al. 2006; Faustino and Dias Pereira 2007; Oyamada et al. 2007; Kim et al. 2008; Psalla et al. 2008; Kitshoff et al. 2010; Blackwood et al. 2019). The median age for dogs was 9 years (3–14 years) (Evans and Thrall 1983; Louw and Van Schouwenburg 1984; Carberry et al. 1987; Brunnert and Altman 1990; Habin and Else 1995; Thomsen and Myers 1999; PérezMartínez et al. 2000; Hammer et al. 2001; Sozmen et al. 2003; Militerno et al. 2005; Smrkovski et al. 2006; Faustino and Dias Pereira 2007; Kitshoff et al. 2010), and the median age for cats was 10 years (6–16 years) (Wells and Robinson 1975; Carpenter and Bernstein 1991; Burek et al. 1994; Sozmen et al. 2002, 2003; Mazzullo et al. 2005; Oyamada et al. 2007; Kim et al. 2008; Psalla et al. 2008; Blackwood et al. 2019). In another retrospective study of 24 dogs and 30 cats, the median age for dogs was 10 years (range of 3–14 years), and the median age for cats was 12 years (range 7–22 years) (Hammer et al. 2001). In dogs, there is no breed or sex predilection. In cats, however, Siamese or Siamese-cross cats may be at increased risk, with male cats being affected twice as often as female cats (Hammer et al. 2001). The tumors are typically malignant, locally invasive, and of epithelial origin. Simple adenocarcinoma is the most common tumor type (Carberry et al. 1988; Hammer et al. 2001). Of the 80 dogs reported in the literature with malignant salivary tumors, 66 (82%) were adenocarcinoma (including simple, complex, cyst, and basal cell). The remaining 14 (18%) included malignant mixed tumor (n = 3), acinic cell carcinoma (n = 2), and one of each of the following: mucoepidermoid carcinoma, SCC, carcinoma in a pleomorphic adenoma, solid anaplastic carcinoma, malignant ibrous histiocytoma, malignant myoepithelioma, extraskeletal osteosarcoma, in iltrative angiolipoma, and MCT (Evans and Thrall 1983; Louw and Van Schouwenburg 1984; Carberry et al. 1987; Brunnert and Altman 1990; Spangler and Culbertson 1991; Habin and Else 1995; Thomsen and Myers 1999; Pérez-Martínez et al. 2000; Hammer et al. 2001; Sozmen et al. 2003; Militerno et al. 2005; Smrkovski et al. 2006; Faustino and Dias Pereira 2007; Kitshoff et al. 2010). Of the 78 cats reported in the literature with malignant salivary tumors, 67 (86%) were adenocarcinoma (including simple, complex, basal cell, acinar and ductular). Other tumor types include malignant

mixed (n = 4), acinic cell carcinoma (n = 2), and one each of the following: SCC, solid carcinoma, sebaceous carcinoma, mucoepidermoid carcinoma, and oncocytoma (Wells and Robinson 1975; Carpenter and Bernstein 1991; Spangler and Culbertson 1991; Burek et al. 1994; Hammer et al. 2001; Sozmen et al. 2002, 2003; Mazzullo et al. 2005; Oyamada et al. 2007; Kim et al. 2008; Psalla et al. 2008; Brocks et al. 2008; Blackwood et al. 2019). There was one cat with a histologic diagnosis of carcinoma which was interpreted to be adenocarcinoma, however, tissue was not available for review (Blackwood et al. 2019). Secondary invasion of the salivary glands has been reported with ibrosarcoma and lymphosarcoma (Spangler and Culbertson 1991). Benign tumors are rare. Adenomas and lipomatous in iltration of the mandibular and parotid salivary glands and sialolipoma of the minor salivary glands have been reported in the dog (Carberry et al. 1988; Bindseil and Madsen 1997; Brown et al. 1997; Clark 2013). These masses are not ixed to adjacent tissues and are cured with surgical resection. There is one report of a teratoma associated with the mandibular salivary gland in a boxer (Lambrechts and Pearson 2001). There was no evidence of recurrence seven months following surgery. Adenoma, papillary adenomas, and cystadenoma have been reported in the cat (Carberry et al. 1988; Spangler and Culbertson 1991) (Figure 5.17).

Figure 5.17 (a, b) Salivary adenoma of a minor salivary gland in the lip of a cat that was surgically excised with wide margins. (c) Postoperative appearance. Necrotizing sialometaplasia, a rare disease of the salivary glands, has been described in the dog and the cat (Brooks et al. 1995; Brown et al. 2004). It can be mistaken as a neoplastic condition when evaluated by ine needle aspirate alone. Histopathology is needed to make a de initive diagnosis. In most cases, animals present with unilateral enlargement of the mandibular salivary gland. One case of bilateral involvement has been reported. Terrier breeds are predisposed (six out of seven reported cases) (Brooks et al. 1995). Necrotizing sialometaplasia of the mandibular and sublingual salivary gland of a Maltese and of the parotid gland of a cocker spaniel has been reported (Kim et al. 2010; Nam et al. 2014). Dogs have more dramatic clinical signs with a history of ptyalism, nausea, pain in opening the mouth, frequent vomiting, and anorexia. To our knowledge, these clinical signs have not been reported in the cat. Treatment involves excision of the affected glands and, in dogs, a short course of anticonvulsant medication following surgery. In one study, four dogs treated with surgical excision alone had continued pain and vomiting and were euthanized. The remaining three had phenobarbital initiated following surgery, with resolution or improvement in clinical signs (Brooks et al. 1995). In two reported feline cases treated with surgical excision alone, the patients were disease-free six months and two years following surgery (Brown et al. 2004). Phenobarbital-responsive salivary gland enlargement and hypersialosis have also been reported in dogs with no cytologic or histopathologic evidence of salivary gland pathology (Stonehewer et al. 2000; Alcoverro et al. 2014). The majority present with a sudden onset of retching and gulping with bilateral enlargement of the mandibular salivary glands; unilateral involvement and parotid salivary gland involvement have also been reported. The glands may be painful on palpation. Other clinical signs include ptyalism, lip-smacking, weight loss, and reduced appetite. It has been postulated that the salivary gland enlargement and hypersialosis may be indicative of limbic epilepsy. Three patients in one

report responded well to phenobarbital, and one was also maintained with potassium bromide. None required surgery. Other non-neoplastic conditions include pharyngeal cysts from pharyngeal and cleft remnants near the parotid and mandibular salivary glands and salivary cysts seen in Shibu puppies with GM1 gangliosidosis (Nelson et al. 2012; Rahman et al. 2012). Sialoceles also present with a swelling in the ventral neck, intermandibular space, pharynx, or under the tongue and are not ixed to underlying structures. They have a characteristic clinical appearance with the presence of saliva on cytology and no evidence of neoplasia. With salivary gland neoplasms, the most common presenting complaint is the recent appearance of a mass. In one study, dogs had a median duration of clinical signs of eight weeks and cats had a median duration of four weeks (Hammer et al. 2001). Of the 80 dogs and 78 cats reviewed in the literature, the medical records of 6 dogs and 4 cats had information regarding the duration of clinical signs. The median duration for cats was ive weeks (three weeks to six months), and the median duration for dogs was three weeks (4 days–18 months) (Wells and Robinson 1975; Carberry et al. 1987; Carpenter and Bernstein 1991; Habin and Else 1995; Thomsen and Myers 1999; Pérez-Martínez et al. 2000; Lambrechts and Pearson 2001; Kim et al. 2008; Psalla et al. 2008; Kitshoff et al. 2010; Blackwood et al. 2019). Tumors of the parotid salivary gland are located at the base of the ear, whereas tumors of the mandibular salivary gland involve the upper neck and those of the sublingual salivary gland may extend to the loor of the mouth. Tumors of the zygomatic salivary gland involve the lip and maxilla and may cause ocular signs such as exophthalmos, epiphora, and divergent strabismus (Carberry et al. 1988; Militerno et al. 2005). Other clinical signs include halitosis, dysphagia, weight loss, anorexia, neurologic de icits (facial nerve paresis, Horner’s syndrome), and sneezing (Hammer et al. 2001; Mazzullo et al. 2005). The mass is typically unilateral, irm, nonpainful, and ixed to adjacent structures (Militerno et al. 2005). There have been reports of bilateral involvement (Mazzullo et al. 2005). The mandibular gland, followed by the parotid gland, is the most commonly affected salivary glands (Wells and Robinson 1975; Evans and Thrall 1983; Carberry et al. 1987; Carpenter and Bernstein

1991; Spangler and Culbertson 1991; Habin and Else 1995; Thomsen and Myers 1999; Pérez-Martínez et al. 2000; Hammer et al. 2001; Sozmen et al. 2002, 2003; Mazzullo et al. 2005; Militerno et al. 2005; Smrkovski et al. 2006; Oyamada et al. 2007; Kim et al. 2008; Blackwood et al. 2019). There are reports of tumors affecting the sublingual, zygomatic, and minor salivary glands; however, they are much less common (Louw and Van Schouwenburg 1984; Brunnert and Altman 1990; Spangler and Culbertson 1991; Burek et al. 1994; Hammer et al. 2001; Sozmen et al. 2003; Faustino and Dias Pereira 2007; Psalla et al. 2008; Blackwood et al. 2019). Most tumors are characterized by a rapid in iltrative growth at the time of diagnosis. Metastatic disease typically involves the regional lymph nodes and lungs. In one study, 25% of dogs and 55% of cats had metastasis at the time of diagnosis (Hammer et al. 2001). Seventeen percent of the dogs and 39% of the cats had metastasis to regional lymph nodes, and 8% of dogs and 16% of cats had distant metastatic disease (Hammer et al. 2001). Metastasis to the kidney, bone, eyes, heart, liver, adrenal glands, ribs, spleen, and the brain have been reported (Habin and Else 1995; Park et al. 2009; Tantawet and Banlunara 2010). Cats have more aggressive disease, with a higher incidence of local and distant metastasis at the time of presentation (Hammer et al. 2001). Dogs have a better outcome when diagnosed early, but this has not been demonstrated in the cat.

Diagnosis In most cases, cytology can differentiate neoplastic from non-neoplastic diseases. The cytologic indings consistent with salivary gland adenocarcinoma are well described in the literature (Militerno et al. 2005). Cytology may be dif icult to interpret in cases of necrotizing sialometaplasia (Brooks et al. 1995). Incisional biopsy will yield a more de initive diagnosis. At a minimum, the mass and associated lymph nodes should be evaluated by ine needle aspiration, and thoracic radiographs should be performed. The medial retropharyngeal lymph node has been shown to be a draining lymph node for mandibular salivary adenocarcinoma. Metastases to the mandibular, super icial cervical (prescapular),

axillary, and bronchial lymph nodes have also been reported (Habin and Else 1995; Mazzullo et al. 2005; Blackwood et al. 2019). Radiographs of the cervical region may also be performed to evaluate displacement of structures by a soft tissue mass (the primary tumor and/or lymph nodes) and to evaluate adjacent bone for osseous changes. Ultrasound, CT, or MRI can be used to evaluate tumor and lymph node size and to look for evidence of invasion into adjacent soft tissue or bone. MRI of head and neck lymph nodes, in clinically normal dogs, has been described (Kneissl and Probst 2006). CT images can also be used to evaluate the thorax for metastases. Ocular examination is also recommended as metastases to the eye have been reported. In most cases, there will be other overt signs of metastatic or primary disease; however, patients with choroidal metastases may only have reduced vision. Routine ocular examination may allow earlier detection of metastatic disease (Habin and Else 1995). Diagnostic tests include routine hematology and biochemical pro ile (±T4). Hypoglycemia has been reported in cases of salivary adenocarcinoma (Morrison 2002).

Treatment The primary goal is local tumor control with surgery and/or radiation therapy. A bene it to chemotherapy has not been documented (Blackwood et al. 2019). Surgical resection of the salivary tumor is the treatment of choice. An incision is made over the salivary gland and extracapsular resection is performed. Incisional biopsy tracts and any ixed skin should be excised with the tumor. The gland is exposed and removed with a combination of sharp and blunt dissection. Cautery and hemoclips are useful to provide hemostasis. The patient is placed in dorsolateral recumbency with a rolled towel under the neck. The mandibular salivary gland lies in the bifurcation of the external jugular vein. The skin, subcutaneous tissue, and platysma muscle are incised in a longitudinal direction over the salivary tumor to expose the mass. Dissection is performed around the mass, with excision of adjacent invaded tissue. The proximity to the external

jugular vein, carotid and lingual arteries, and vagosympathetic trunk should be noted. The sublingual salivary gland is closely associated with the mandibular salivary duct, and the caudal portion will be removed concurrently. It should be ligated on the rostral aspect of the mass with a suture or a hemoclip. Following excision, the surgical site is lavaged with sterile saline. Dead space is closed with sutures, and the wound is closed routinely. Passive drains should not be placed because microscopic disease often remains and the drains could track neoplastic cells into adjacent normal tissue. Hemoclips may be placed within the surgical ield to mark the site for radiation therapy. The parotid salivary gland is removed similarly. The patient is placed in lateral recumbency (Dunning 2003). A vertical incision is made over the mass, and the underlying platysma and parotidoauricularis muscles are incised. The tumor is excised from the adjacent tissue. The facial nerve courses ventral to the base of the vertical ear canal with the auriculopalpebral nerve arising from the facial nerve being medial to the parotid salivary gland and should be preserved if possible. For closure, the parotidoauricularis muscle is apposed and the super icial layers closed routinely. If there is signi icant dead space, a light, padded bandage may be placed for 2–5 days following surgery. Advanced imaging is recommended for tumors of the zygomatic salivary gland to determine if the globe can be preserved (Gilger et al. 1994). Invasive tumors of the zygomatic salivary gland are removed via en bloc resection of the affected tissue. Noninvasive tumors can be removed via a lateral orbitotomy with preservation of the globe (Gilger et al. 1994; Hedlund 2002). Generous amounts of lubricant should be placed on the ipsilateral eye and a temporary tarsorrhaphy is performed. The skin is incised over the dorsal rim of the zygomatic arch starting ventral to the lateral canthus and extending caudally to the base of the ear. The palpebral nerve courses in the subcutaneous fat over the temporalis muscle toward the lateral canthus of the eye. It should be isolated and retracted dorsally with moistened umbilical tape. The aponeurosis of the temporalis muscle is incised along the dorsal border of the zygomatic arch. An osteotomy is performed rostral to the orbital ligament and the second site is extended caudally such that it gives maximum exposure to the tumor. If the arch is to be

replaced, holes are predrilled on either side of the proposed osteotomy sites with a 1.0–1.5 mm drill bit or 0.035 inch K-wire. The osteotomy is then performed between the holes with an oscillating or sagittal saw. The orbital ligament is transected midbody, and the arch is re lected ventrally. The lateral canthus and globe are retracted rostrally to expose the orbit. The mass is removed with sharp and blunt dissection. The site should be lavaged with sterile saline. The arch can be replaced and ixed with 22-gauge orthopedic wire. If radiation therapy is planned following surgery, the arch should not be replaced to reduce the risk of the development of a bony sequestrum. The temporalis fascia is sutured to the zygomatic arch. The orbital ligament is sutured with 3-0 absorbable suture, such as polydioxanone (PDS; Ethicon Inc., Cornelia, GA, United States) in a horizontal mattress pattern and the super icial tissues are closed routinely. An Elizabethan collar is indicated following surgery to prevent self-trauma. Complications include seroma formation, infection, facial nerve paresis or paralysis, and tumor recurrence. As most of these tumors are invasive, follow-up with radiation therapy is recommended (Carberry et al. 1988). In one report, six dogs and four cats were treated with a cobalt-60 source and one dog and one cat were treated with a linear accelerator, receiving 32–57 Gy (Hammer et al. 2001). In a separate study, three dogs with parotid gland adenocarcinoma received 10 doses from an orthovoltage unit totaling 45 Gy (Evans and Thrall 1983). In another report, three of six cats received 4 weekly doses of 8 Gy, one cat received 5 weekly doses of 8 Gy and two cats received 12 doses of 4 Gy (Monday–Wednesday–Friday protocol for four consecutive weeks) (Blackwood et al. 2019). Due to the high incidence of local metastasis, the local lymph nodes should also be irradiated (Blackwood et al. 2019). Side effects include transient moist dermatitis, which can be severe in dogs, and permanent hair loss and color change. If the oral cavity is within the ield, the patients may experience transient mucositis. If the eye is in the ield, keratoconjunctivitis sicca, and cataracts may develop months following radiation therapy. Cats have fewer side effects than dogs, typically limited to alopecia and mild erythema of the skin and oral mucosa (Blackwood et al. 2019). Self-trauma has been reported and must be prevented (Blackwood et al. 2019).

Prognosis There are a few reports of prolonged survival following surgical resection with and without radiation therapy. In one study of 24 dogs and 30 cats treated with surgical resection with and without radiation therapy, the median survival was 550 and 516 days, respectively (Hammer et al. 2001). Although follow-up with radiation therapy is preferred, this study documented prolonged survival in patients that had repeat surgical resection of recurrent tumors (Hammer et al. 2001). This is dissimilar from other studies that describe aggressive tumors with the rapid development of metastatic disease. Histologic grade was not prognostic; however, advanced stage was a negative prognostic indicator. Of 80 dogs reported in the literature with malignant salivary tumors, 12 had information regarding treatment and outcome available (Evans and Thrall 1983; Louw and Van Schouwenburg 1984; Carberry et al. 1987; Brunnert and Altman 1990; Habin and Else 1995; Sozmen et al. 2003; Militerno et al. 2005; Smrkovski et al. 2006; Faustino and Dias Pereira 2007). Five were treated with surgery alone (lingual acinic cell carcinoma, extraskeletal osteosarcoma, mandibular adenocarcinoma, carcinoma in an adenoma, and malignant myoepithelioma), three (parotid gland adenocarcinoma) had surgery and radiation therapy, one MCT had surgery and chemotherapy, and four (metastatic parotid adenocarcinoma, invasive solid anaplastic carcinoma, in iltrative angiolipoma, and mandibular basal cell adenocarcinoma) were not treated. Two untreated patients were euthanized at presentation due to extensive disease (Louw and Van Schouwenburg 1984; Habin and Else 1995), one was euthanized 8 months after diagnosis with a massive tumor (Sozmen et al. 2003) and one was doing well 14 months without surgery, although the mass had increased approximately 30% in size. Of the ive patients with surgical excision of the mass, one died shortly after (malignant myoepithelioma) (Faustino and Dias Pereira 2007) and one (osteosarcoma) had recurrence and metastatic disease one month after surgery (Thomsen and Myers 1999). Three (lingual acinic cell carcinoma, mandibular adenocarcinoma, carcinoma in an adenoma) were disease-free 7, 8, and 12 months after surgery (Brunnert and Altman 1990; Militerno et al. 2005; Smrkovski et al.

2006). Of the three patients treated with surgery and radiation therapy (parotid adenocarcinoma), 1 died 40 months after treatment due to a possible abdominal tumor and the other two were disease-free at 12 and 25 months after surgery (Evans and Thrall 1983). Unfortunately, there is little data evaluating the outcome with chemotherapy. An array of protocols has been implemented; however, there are too few numbers to assess outcome. In one study, dogs treated with surgery and chemotherapy had a poorer prognosis than dogs treated with surgery alone and dogs treated with surgery and radiation therapy (Hammer et al. 2001). This may be due to selection bias as patients with more aggressive diseases are more likely to receive chemotherapy. Of the 13 cats reported in the literature, four (mixed tumor, basal cell adenocarcinoma, adenocarcinoma, and nasal acinic cell carcinoma) (Carpenter and Bernstein 1991; Sozmen et al. 2003; Mazzullo et al. 2005; Psalla et al. 2008) were euthanized at presentation, and one (poorly differentiated tumor of the mandibular salivary gland) (Wells and Robinson 1975) was euthanized ive months following presentation. Of the remaining eight cats, only one died with distant metastatic disease. One cat had surgery (adenocarcinoma of a minor salivary gland) (Burek et al. 1994) with tumor recurrence at three months. Two had surgical excision and radiation therapy. One patient had a malignant mixed tumor of the mandibular salivary gland (Kim et al. 2008). The tumor recurred after two doses (4 Gy each). A second surgery was performed and two more doses of RT were administered before pulmonary metastases were documented seven weeks following the initial surgery. The cat died one month later. Another cat with an adenocarcinoma arising from the labial mucosa, presumably from minor salivary gland tissue, received 4 × 9 Gy and was lost to follow-up 766 days following RT (Blackwood et al. 2019). Four cats had surgery, radiation therapy, and chemotherapy (carboplatin, toceranib, and/or metronomic chemotherapy with cyclophosphamide and meloxicam) (Blackwood et al. 2019). Three had adenocarcinoma of the mandibular salivary gland and one had a carcinoma (probable adenocarcinoma) of the labial mucosa. Two received 4 × 8 Gy with one alive at 206 days and the other euthanized at 55 days for presumptive progressive disease.

Two received 12 × 4 Gy with one alive at 549 days and the other euthanized at 570 days due to progressive disease. One cat had RT (4 × 8 Gy) and carboplatin and was euthanized at 258 days due to progressive disease (Blackwood et al. 2019). In people, a correlation with environmental carcinogens and the development of salivary gland tumors has been identi ied. It has been proposed that salivary neoplasia in animals may also have such a relationship, with one author proposing that it may be secondary to exposure to environmental carcinogens during grooming (Hammer et al. 2001).

Tumors of the Lip Any soft tissue tumor can affect the canine lip, with malignant melanoma being the most common (Todoroff and Brodey 1979; Vos and van der Gaag 1987). In one study of 35 lip tumors, 71% were malignant melanoma and the remaining were SCC (20%) and ibrosarcoma (9%) (Todoroff and Brodey 1979). MCT, extramedullary plasmacytoma (with and without amyloid deposits), malignant histiocytosis, and cutaneous lymphoma have also been reported (Lucke 1987; Brunnert and Altman 1991; Rowland et al. 1991; Abraham et al. 2007; Sato et al. 2010). There is one report of four aged dogs with round cell sarcomas of possible myelomonocytic origin. A granular cell tumor of the lip has been reported (Turk et al. 1983). Most patients are older than 10 years of age. Male patients and small breed dogs, particularly cocker spaniels are predisposed to malignant melanoma (Vos and van der Gaag 1987; Ramos-Vara et al. 2000; Schultheiss 2006). Malignant melanoma is characterized by local in iltration and metastasis to regional lymph nodes and less frequently to lungs and other organs (Bostock 1979; Ramos-Vara et al. 2000). The majority of melanomas on the canine lip affect the mucous membrane and have a malignant histologic appearance (Schultheiss 2006). Immunohistochemistry may be indicated to con irm a diagnosis of malignant melanoma as they have a variable degree of pigmentation and may be completely unpigmented (Ramos-Vara et al. 2000).

SCC is the most common tumor affecting the lip of cats (Vos and van der Gaag 1987). Other tumor types include sebaceous adenocarcinoma, apocrine ductal carcinoma, ibrosarcoma, lymphosarcoma, and mastocytoma (Bradley 1984; Vos and van der Gaag 1987; Bradford et al. 2011; Yumuşak et al. 2011). Malignant melanoma is rare (Bradley 1984). Most patients are middle-aged or older (Bradley 1984; Vos and van der Gaag 1987). In cats, basal cell carcinoma of the lip has a benign behavior pattern, with a good prognosis (Karakurum et al. 2009). Fibroma has also been documented (Ulčar et al. 2012).

Treatment Treatment options include surgical resection, cryosurgery, radiation therapy, and chemotherapy. Curative interstitial brachytherapy has been reported in people (Jha et al. 2006). Electrochemotherapy has also been reported (Aminkov and Manov 2004). CT/MRI is useful to assess regional lymph nodes, bony involvement and to plan the extent of resection. Resection of the lip can be combined with a partial maxillectomy/mandibulectomy when there is bony involvement (Salisbury et al. 1986). The upper labial mucosa and cheek are supplied by the lateral nasal artery (a branch of the infraorbital artery) and the angular artery of the mouth and superior labial artery (branches of the facial artery) (Salisbury et al. 1986). The lower lip is supplied by the caudal, middle, and rostral mental arteries (Pavletic 1999). Local reconstruction techniques include simple wedge resection, advancement and buccal rotation laps, and axial pattern laps (Yates et al. 2007). Goals of surgery include separating the nasal from the oral cavity, reconstructing the buccal mucosal surface to prevent excessive scarring, and providing a tension-free closure to the haired skin. Small mucosal defects can heal by second intention; however, large mucosal defects need to be reconstructed. Mucosa is preferred for reconstruction, but when not available, haired skin can be used. Surgical reconstruction can be more challenging in cats as they lack the lip elasticity and abundant adjacent skin of the dog. Axial pattern laps

are particularly useful in the cat (Bradford et al. 2011; Milgram et al. 2011). Small and benign tumors can be removed with simple techniques. Wedge, rectangular, or pentagonal full-thickness skin incisions are made with a scalpel blade to remove the neoplasm, ensuring that adequate margins are obtained (Pavletic 1999) (Figure 5.18). The resection margins can be marked preoperatively with a sterile marker to ensure that the margins are not altered with resection. Moist gauze squares can be placed deep to the lip to apply tension against which to cut. Alternatively, skin hooks, towel clamps, or tension sutures may be placed at the margins to facilitate making the incision (Swaim and Henderson 1997). For closure, the irst suture aligns the labial margins. Starting away from the labial margin, the oral mucosa is apposed with 3-0 simple interrupted sutures and includes the submucosa. The skin is then apposed with simple interrupted 3-0 nonabsorbable sutures. Wedge incisions are closed in a linear fashion, and rectangular incisions are closed in a Y. The mouth should be manipulated to ensure a tension-free closure. When combined with a maxillectomy, the upper mucosal margin is sutured to the palate, closing the oronasal defect. Pavletic has also described the lower labial lift-up and upper labial pulldown techniques for lesions that allow preservation of the lip margin. This is reserved for small or benign tumors to ensure that adequate tissue margins are obtained. This technique is also useful in patients with invasive maxillary or gingival tumors that have focal or more dorsal lip involvement. The primary tumor is removed with fullthickness excision of the labial lesion and preservation of the lip margin. It is important to ensure that adequate tissue margins are obtained. The labial mucosa is then sutured to the gingival margin or hard palate. The skin is closed with simple interrupted sutures. In cases where this causes dorsal deviation of the lip, a V-incision is made at the lip margin. The caudal lip margin is then advanced cranially to close the defect (Figure 5.19).

Figure 5.18 (a) MCT affecting the cheek of a seven-year-old female spayed Beagle mix. (b) Full-thickness resection of the lip. (c) The incision was closed in a Y with no residual disturbance to eyelid or lip function. Appearance two weeks following surgery.

Figure 5.19 (a) Local recurrence of an SCC on the dorsolateral lip of an 11-month-old male neutered Yorkshire terrier. A maxillectomy had been performed seven weeks previously. (b) Full-thickness resection of the mass in (a), including maxilla. (c) The defect is closed with an upper labial pull-down technique. The labial mucosa is sutured to the palatine mucosa to close the oral cavity. The ventral skin margin is then apposed to the dorsal skin margin. To prevent upward deviation of the lip edge, the commissure is advanced rostrally. A strip of lip margin is resected, and the middle of the resected lip becomes the dorsal extent of a vertical suture line. The rostral and caudal portions of the resected lip are then apposed to each other in a vertical incision. For this patient, surgery was followed with radiation therapy and carboplatin. There was no evidence of recurrence three years following surgery. Source: Images courtesy of Dr. Karen Tobias.

A full-thickness advancement lap can be used for larger defects of the rostral one-third of the upper lip and can be combined with a partial maxillectomy for more extensive lesions (Figure 5.20). This technique does not work as well in cats as they have less free lip margin and a smaller commissure. The mass is resected with a rectangular or pentagonal incision (Swaim and Henderson 1997; Pavletic 1999). When possible, a 0.5 cm strip of mucosa should be left along the gingival border to facilitate closure. An incision is made at the dorsal extent of the resection and extended caudally, typically beyond the level of the commissure to allow advancement without tension (Swaim and Henderson 1997). The lap is elevated and advanced rostrally to close the defect. Areas in the lap that are under tension, including the infraorbital nerve, artery, and vein, can be incised (Swaim and Henderson 1997). A small wedge is resected from the dorsorostral aspect of the lap to ensure that the tissue has an adequate blood supply, preventing dehiscence. The mucosal surface is apposed with 3-0 absorbable suture in a simple interrupted pattern. Alternatively, the submucosa is apposed allowing the mucosa to evert into the oral cavity (Swaim and Henderson 1997). When combined with a partial maxillectomy, holes are drilled in the maxilla to anchor the suture and reduce the risk of dehiscence. To ensure alignment, the irst sutures are placed at the rostrodorsal corner and at the labial margin. Sutures are

then continued caudally and ventrally from the rostrodorsal border. The skin is closed with 3-0 nonabsorbable sutures. Jaw mobility should be assessed intraoperatively. Use of this lap may deviate the planum to the side of the surgery; however, this typically resolves within two to three weeks. Bilateral labial advancement laps have also been described for rostral tumors at/near the midline (Taney and Smith 2009). A similar lap can be elevated for rostral lesions of the lower lip (Pavletic 1999). The lower lip is easier to mobilize and can be advanced with a shorter skin incision. The mass is resected, and when possible, a 0.5 cm strip of mucosa is left along the gingival border to facilitate closure. A skin incision is made at the ventral aspect of the wound and extended caudally parallel to the mandible. The skin incision is often shorter than the mucosal incision due to its inherent elasticity. The lap is drawn cranially and sutured into the wound bed. The mucosa is apposed with 3-0 absorbable suture material in a simple interrupted pattern. At the space between the canine tooth and irst premolar, the lip should be attached dorsally to prevent sagging of the lip. The skin is apposed with 3-0 nonabsorbable simple interrupted sutures. For larger defects, a buccal rotation lap may be created (Figure 5.21). The cheek margin is advanced rostrally to ill the defect. The caudal labial margin is brought to the dorsorostral corner of the defect. An appropriate strip of mucosa is removed from the labial margin to allow apposition of the lip to the rostral vertical incision. The mucosal surface is apposed with 3-0 absorbable suture pattern, and the skin is apposed with 3-0 nonabsorbable suture in a simple interrupted suture pattern. Vertical mattress sutures may be placed in any areas under tension. This procedure advances the commissure of the lips rostrally. The commissure can be extended caudally by incising the commissure and suturing the skin to mucosa dorsally and ventrally, however, this is rarely indicated.

Figure 5.20 (a) A MCT involving the rostral lip of an adult mixed breed dog. (b) Following full-thickness resection of the lip. (c) The defect was closed with a full-thickness advancement lap. Note the gingival mucosa left to facilitate closure. An incision was made at the dorsal extent of the resection and extended caudally. The lap was then advanced rostrally to close the defect. Sutures are placed irst at the labial margin and rostrodorsal corner to ensure that the tissues are aligned. (d) The mucosal surface is apposed with simple interrupted absorbable sutures. The skin is then apposed with nonabsorbable sutures. Jaw mobility should be assessed intraoperatively. (e) Postoperative appearance with mild deviation of the planum nasale. This will resolve in two to three weeks.

Figure 5.21 (a) A buccal rotation lap was used to repair the lip of a seven-year-old male neutered schnauzer. The lip was traumatized in a dog ight. The rotation lap is outlined with surgical marker. (b) The lap has been rotated into the defect. Source: Images courtesy of Dr. Geraldine Hunt.

There are several axial pattern laps that can be used in lip reconstruction. The caudal auricular axial pattern lap has been used to reconstruct a chin defect (Aber et al. 2002). The lateral aspect of the wing of the atlas is the base of the lap. The dorsal midline is the dorsal border of the lap, and the ventral border runs parallel to it, originating at the depression between the ear and the wing of the atlas. The incisions are connected with a transverse incision at the level of the scapula. The lap is rotated rostrally below the ear to close the mandibular defect. It can be connected via a tubed lap or a bridging incision. If a tube is used, it is transected three to four weeks after surgery. If there is concern with the integrity of the blood supply, it can be performed in two stages, with an initial incision made halfway between the tube and the donor site and the incision resutured. The tube is then resected two to three days later. A tube lap yields a better cosmetic appearance than a bridging incision; however, there is risk of tube trauma by the patient, and a second procedure is needed for removal. The caudal auricular axial pattern lap is not as robust as other axial pattern laps. Delayed rotation has been recommended to improve integrity of the lap. The lap is precut, through the panniculus, and then resutured. Two weeks later the lap is elevated and rotated into the defect (Dr. Bryden Stanley, personal communication). The super icial temporal artery axial pattern lap (Figure 5.22) can be used to reconstruct the upper lip and can be combined with a maxillectomy if necessary (Fahie and Smith 1997; Lester and Pratschke 2003). The lap is based on the dorsal aspect of the zygomatic arch. The rostral incision extends dorsally from the lateral orbital rim, and the caudal skin incision extends dorsally from the caudal aspect of the zygomatic arch. Parallel skin incisions are continued to the dorsal orbital rim of the contralateral eye. Dissection is performed deep to the frontalis muscle, carefully elevating the lap toward its base. Atraumatic tissue handling is important, and the lap must be kept moist. The lap

can then be rotated into the defect. A closed active suction drain can be placed deep to the lap. In one case report, porcine intestinal submucosa was used to close the mucosal defect (Lester and Pratschke 2003). It was removed six days after surgery but was felt to be a useful scaffold for tissue regeneration. The angularis oris axial pattern cutaneous lap is oriented caudally from the commissure of the mouth (Yates et al. 2007). It is particularly useful to reconstruct mandibular defects in the cat (Bradford et al. 2011) (Figure 5.23a and b). Parallel incisions are extended caudally along the ventral aspect of the zygomatic arch and the ventral aspect of the ramus of the mandible to the horizontal ear canal (Figure 5.23c and d). Dissection to the wing of the atlas has been described, however, there is greater risk of necrosis of the distal tip (Bradford et al. 2011). The lap is elevated from caudal to rostral, deep to the platysma muscle. Careful dissection is performed at the lap base to preserve cutaneous vasculature. Following elevation of the lap, the submandibular lymph nodes can be assessed or resected (Figure 5.23e). The donor site is closed primarily without tension. The lap is rotated into the defect and closed in a single layer (Figure 5.23f and g). The lap can be used to reconstruct both the buccal surface and haired lip when the width of the lap is at least one-half the width of the defect. The lap is lipped 180 degrees into the defect with hair facing the oral cavity. The upper border of the lap is sutured to the mucosal margin with 3-0 absorbable suture in a simple interrupted suture pattern. The lap is folded onto itself and sutured to the skin with 3-0 nonabsorbable suture in a simple interrupted suture pattern.

Figure 5.22 Super icial temporal axial pattern lap. (a) A cutaneous istula developed after radiation therapy for a nasal tumor. (b) The edges of the istula have been debrided. The super icial temporal axial pattern lap has been created. (c) The donor site has been closed and a bridging incision has been created to bring the lap to cover the istula. (d) The lap has been sutured in its heterotopic position. In patients with larger defects, the lap is used to reconstruct the buccal mucosa, and adjacent skin is mobilized over the lap to close the cutaneous defect (Figure 5.24). Lip margin that can be apposed without tension is sutured. The base of the lap is inverted, and the lap is placed into the defect with the haired portion facing the oral cavity. The lap is sutured dorsally to the gingival or hard palate and ventrally to the mandibular gingiva, with 3-0 absorbable sutures in a simple interrupted pattern. The skin is advanced over the lap and inverse tube segment. This leaves a narrow opening to an epithelium-lined skin

tube. In four to six weeks after surgery, once the surgery site has healed and neovascularization has occurred, the short tube segment can be excised. For patients where the upper lip margin is preserved, the buccal mucosa of the lip is sutured to the gingiva or hard palate and the lap is rotated into the defect dorsal to the lip margin via a bridging incision. It can reach the philtrum without tension. With this technique, the redundant skin folds can accumulate food and saliva. Once the lap has healed, redundant tissue can be resected. As an alternative, a tubed lap can be used to reach the lesion in lieu of a bridging incision. The tube can be resected in three to four weeks after the lap has healed. A lap based on a cutaneous branch of the facial artery in cats has been described (Milgram et al. 2011). It is similar to the angularis oris axial pattern lap, however, it is more ventral. The base of the lap is at the rostral border of the masseter muscle. The dorsal border is 1 cm ventral to the zygomatic arch and the ventral border is the ventral midline. In one clinical case, the lap was used to close a defect following exenteration of the eye. The lap was extended to the level of the ear canal (Milgram et al. 2011). In the associated anatomic study performed in cadavers, perfusion of the lap extended to 1 cm caudal to the caudal border of the atlas. Further clinical case studies are needed to assess viability of the longer lap.

Figure 5.23 (a, b) A 3.2 × 1.8 × 1.2 cm squamous cell carcinoma con ined to the soft tissues of the right upper lip of a mature cat. The maxilla and gingiva were not affected. Preoperative cytology of the mandibular lymph nodes was negative. The mass was resected with 3– 5 mm margins. The margins were inked and histology con irmed complete excision. The angularis oris axial pattern lap was used to reconstruct the oral and skin defects. (c, d) The lap was oriented caudally from the commissure of the mouth. Parallel incisions were oriented caudally along the ventral aspect of the zygomatic arch and the ventral aspect of the ramus of the mandible to the level of the horizontal ear canal. (e) The lap was elevated from caudal to rostral deep to the platysma muscle and the mandibular lymph nodes were resected. Histologic assessment con irmed metastasis to the regional lymph nodes. (f) The lap was folded with the skin apposed to the oral mucosa and adjacent skin, such that hair grew on the inner cheek. There was necrosis of distal lap, which was left to heal by second intention. (g) Two months following surgery, the lap has healed with minor deviation of the upper lip. The cat died of metastatic disease 4 months following surgery. There was no evidence of local recurrence. Source: Courtesy of S.A. van Nimwegen.

Figure 5.24 (a) Buccal SCC in an 11-year-old male neutered west highland white terrier. (b) Full-thickness resection of the right cheek, part of the mandible, and part of the maxilla of the patient in (a). (c) The rostral lip margins are apposed. In this patient, a local transposition lap is elevated. Alternatively, the angularis oris axial pattern lap can be mobilized into the defect. The skin lap will be used to reconstruct the buccal surface of the lip. The base of the lap is folded to make an inverse tube (as indicated by the forceps). (d) The skin lap is rotated into the defect with the skin surface facing the mouth. (e) The skin is sutured to the mucosa of the palate. (f) The skin lap is then sutured to the mandible, reconstructing the buccal aspect of the cheek. (g) Intraoral view of the completed reconstruction. (h) Adjacent skin is then advanced over the tubed lap. The triangular-shaped dimple is the opening of the epithelium-lined skin tube. This will become less obvious with hair regrowth. Mild discharge can be treated with clipping and gentle lushing of the tube and possible antimicrobial therapy. This is usually suf icient. However, if the discharge is more frequent, the tube can be resected 4–6 weeks after surgery, once revascularization of the lap has occurred. (i) Intraoral view of the lap 15 days after surgery with hair regrowth. Halitosis was managed with dental mouthwashes, intermittent antimicrobial therapy, and periodic trimming of the hair. The patient was euthanized 15 months after surgery due to renal failure. There was no evidence of local recurrence or overt metastatic disease at that time. Source: Images courtesy of Dr. Doug Huber.

Postoperative Care An Elizabethan collar should be placed for one to two weeks after surgery to prevent trauma to the surgery site. In patients with a caudal auricular axial pattern lap, a lightly padded bandage may be placed over the donor site to prevent irritation from the collar. Moist, cool compresses may be placed over the surgery site for 72 hours after surgery to keep the surgery site clean and reduce swelling (Swaim and Henderson 1997). Soft food should be fed for four weeks after surgery, and playing with hard toys must be prevented. Antibiotics may be given in the

perioperative period.

Complications Billowing of the lap is seen with expiration when the lap is placed over the exposed nasal cavity. This typically resolves within 10 days of surgery. Periodic hair trimming may be needed in patients where the lap extends rostrally to the planum nasale to prevent irritation and sneezing (Yates et al. 2007). Likewise, halitosis may occur when haired skin is used to reconstruct the buccal mucosa. Periodic sedation may be needed to trim the hair in the mouth. Clients should be warned that buccal advancement laps and commissure rotation laps will move the commissure rostrally, changing the shape of the face, and may cause deviation of the planum (Swaim and Henderson 1997). Rotation or axial pattern laps also move hair with different lengths or thicknesses, which will change facial appearance. Ear carriage may also be altered.

Prognosis Outcome for tumors of the lip is often combined with those reported for tumors of the oral cavity (Todoroff and Brodey 1979; Vos and van der Gaag 1987; Ramos-Vara et al. 2000). In one study, no difference was found in outcome between tumors of the lip and oral cavity, when evaluated separately, and the results were combined (Bostock 1979). Melanomas of the lip or oral cavity should be considered behaviorally malignant, despite histologic appearance (Bostock 1979). Death is due to local recurrence and/or metastatic disease. In one study, the median survival time was 15 weeks, with 10% of the dogs alive two years after diagnosis (Bostock 1979). In another study, one-third of the patients with histologically malignant tumors were alive and tumor free more than one year after surgery (Schultheiss 2006). In the third study, dogs with melanoma of the labial mucosa trended toward longer survival (310 days) when compared to oral melanoma at other sites (123 days), however, the difference was not statistically signi icant. In addition, dogs with KIT expression survived 50% longer (Newman et al. 2012). Overall, STSs have a low incidence of metastasis (Vos and van der Gaag 1987). In a report of one dog with an MCT, there was no evidence of recurrence nine months after surgery (Yates et al. 2007).

Plasmacytomas affecting the lip can respond well to surgical excision (Lucke 1987; Brunnert and Altman 1991). In one case report of four dogs, there was no evidence of recurrence 3 and 26 months following surgery, and follow-up was not available for two dogs (Lucke 1987). Of the dogs with round cell sarcoma of possible myelomonocytic origin, patients had local recurrence and metastatic disease (regional lymph node and lung) 10 weeks to one year after resection (Kipar et al. 1995). Granular cell tumors of the lip are behaviorally benign. In one case, there was no evidence of recurrence 28 months after surgical resection (Turk et al. 1983). To our knowledge, there are no case studies that evaluate tumors of the feline lip, exclusively. All are combined with other oral tumors. In general, the majority of oral tumors are described as being malignant with an aggressive course. There is one report of a cat with a welldifferentiated sebaceous adenocarcinoma of the chin reconstructed with a caudal auricular axial pattern lap (Aber et al. 2002). Lymph node evaluation was not performed prior to surgery, and the tumor was removed with 0.25 cm margins. The cat was euthanized ive months after surgery with probable metastatic disease to the regional lymph nodes. There is a report of a cat with sebaceous adenocarcinoma of the rostral chin resected with 0.5–1 cm margins (Bradford et al. 2011). The wound was reconstructed with an angularis oris cutaneous lap. Small clusters of neoplastic cells were identi ied in the submandibular lymph node. Six months following surgery, there was no sign of recurrence and the lymph nodes were normal on palpation. There is a report of a cat with a large periodontal ibromatous epulis involving the upper lip reconstructed with a super icial temporal axial pattern lap (Lester and Pratschke 2003). Seven months after surgery there was no evidence of recurrence. Basal cell carcinoma has been reported to have a good prognosis (Karakurum et al. 2009).

References Aber, S.L., T. Amalsadvala, J. Brown, et al. 2002. Using a caudal auricular axial pattern lap to close a mandibular skin defect in a cat. Vet Med 97:666–671.

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6 Oral Tumors Julius M. Liptak and B. Duncan X. Lascelles

Introduction Oral tumors are common in both cats and dogs with cancers of the oral cavity accounting for 3–12% and 6% of all tumors in these species, respectively (Patnaik et al. 1975; Dorn and Priester 1976; Hoyt and Withrow 1984; Vos and van der Gaag 1987; Stebbins et al. 1989). The surgical oncologist plays a pivotal role in the diagnosis, staging, and treatment of cats and dogs with oral tumors. For instance, an incisional biopsy is often required for de initive diagnosis of an oral tumor and this biopsy needs to be planned appropriately so that the biopsy site will not have a negative impact on the curative-intent treatment plan; clinical staging requires excision of the regional lymph nodes which is important for determining postoperative treatment plans and prognosis; and the most common de initive treatment of oral tumors is surgical excision. For the purposes of this chapter, oral tumors will include tumors involving the mandible, maxilla, palate, and tongue.

Diagnosis and Clinical Staging History and Clinical Signs Most cats and dogs with oral cancer present with a mass in the mouth noticed by the owner. Cancer in the caudal pharynx, however, is rarely seen by the owner, and the animal may present with signs of hypersalivation, exophthalmos or facial swelling, epistaxis, weight loss, halitosis, bloody oral discharge, dysphagia or pain on opening the mouth, or occasionally cervical lymphadenopathy (especially squamous cell carcinoma [SCC] of the tonsil) (Kosovsky et al. 1991; Schwarz et al. 1991a, b; Wallace et al. 1992; Reeves et al. 1993). Loose teeth, especially in an animal with generally good dentition, may be indicative of underlying neoplastic bone lysis, especially in cats (Madewell et al. 1976). A complete examination of the oral cavity during annual health checks is recommended to screen for oropharyngeal masses as this may permit earlier diagnosis, better treatment, and improved prognosis. If a mass is noted during examination of the oral cavity, then accurate notes should be written in the medical records of the size of the mass and anatomic location of the mass in relation to adjacent dentition. Furthermore, a photo of the mass can assist the surgeon in determining the best approach for biopsy and de initive surgery.

Diagnosis and Clinical Staging The diagnosis and clinical staging of animals with oropharyngeal masses are imperative before de initive surgical excision. A biopsy is required for de initive diagnosis, and this will assist the clinician in determining biologic behavior and prognosis. Clinical staging consists of evaluating the extent of the local tumor and the presence of metastatic disease. The regional lymph nodes and lungs are the two most common sites of metastasis in cats and dogs with oral tumors (Liptak 2019). The procedures required for the diagnosis and clinical staging of animals with oral cancer can usually be performed under a short general anesthesia. Diagnosis A large incisional biopsy is often required for a de initive diagnosis. Fine-needle aspirate or impression smear cytology has traditionally been considered unrewarding because many oral tumors are associated with a high degree of necrosis and in lammation; however, one prospective study of 114 cats and dogs with oral masses showed that, in comparison to de initive histopathologic results, ine-needle aspirate cytology had a diagnostic accuracy rate of 98% in dogs and 96% in cats, and impressions smear cytology had a diagnostic accuracy rate of 92% in dogs and 96% in cats (Bonfanti et al. 2015). Dogs with exophytic or ulcerated masses will generally tolerate a deep wedge or core punch biopsy without general anesthesia. Biopsy is recommended in the diagnostic work-up of cats and dogs with an oral mass. Biopsy is

recommended to differentiate benign from malignant disease, for owners basing their treatment options on prognosis, and when other treatment modalities, such as radiation therapy, may be preferable. Oral cancers are commonly infected, in lamed, or necrotic, and it is important to obtain a large specimen. Cautery may distort the specimen and should only be used for hemostasis after blade incision or punch biopsy. Large samples of healthy tissue at the edge and center of the lesion will increase the diagnostic yield, but care must be taken not to contaminate normal tissue, which cannot be removed with surgery or included in the radiation ield. Biopsies should always be performed from within the oral cavity, and not through the lip, to avoid seeding tumor cells in normal skin and compromising curative-intent surgical resection. For small lesions (e.g. epulides, papillomas, or small labial mucosal melanoma), curative-intent resection (excisional biopsy) may be undertaken at the time of initial evaluation. However, accurate notes should be included in the medical records, and/or photographic evidence, to detail the size and anatomic location of the mass if excision is incomplete and further treatment is required. For more extensive disease, waiting for biopsy results is recommended so that appropriate treatment plans can be formulated. Clinical Staging – Local Tumor Tumor size is an important prognostic factor for some types of oral tumors, such as malignant melanoma, SCC, and tongue tumors (Beck et al. 1986; Carpenter et al. 1993; Syrcle et al. 2008; Culp et al. 2013; Fulton et al. 2013; Boston et al. 2014; Burton et al. 2014; Tuohy et al. 2014), and hence an accurate measurement of tumor size should be recorded. Cancers that are adherent to or arising from bones of the mandible, maxilla, or palate should be imaged under general anesthesia to determine the presence of bone lysis and the extent of local disease. Regional radiographs include open mouth, intraoral, oblique lateral, and ventrodorsal or dorsoventral projections (Dhaliwal et al. 1998). Bone lysis is not radiographically evident until 40% or more of the cortex is destroyed and hence apparently normal radiographs do not exclude bone invasion (Liptak 2019). Advanced imaging modalities are now widely available, and these are recommended for imaging of oral tumors, particularly tumors arising from the maxilla, palate, and caudal mandible (Figures 6.1 and 6.2). Computed tomography (CT) scans are generally preferred to magnetic resonance imaging (MRI) because of superior bone detail, but both CT and MRI scans will provide more information on the local extent of the tumor than regional radiographs. In one study, invasion into adjacent structures was noted in only 30% of dogs imaged with radiographs compared to over 90% of dogs imaged with contrast-enhanced CT scans (Ghirelli et al. 2013). This information is important for planning the de initive surgical procedure (or radiation therapy if indicated).

Figure 6.1 Computed tomography scan of a dog with a zygomatic squamous cell carcinoma extending into the inferior orbit and caudal maxilla. Computed tomography scans provide superior detail on the extent of the tumor and tumor invasion and are the preferred imaging modality for planning surgical resection of tumors involving the maxilla, orbit, and hard palate.

Figure 6.2 Computed tomography scan of a dog with a multilobular osteochondrosarcoma arising from the caudal mandible. Computed tomography scans provide superior detail on the extent of the tumor and tumor invasion and are the preferred imaging modality for planning surgical resection of tumors involving the caudal mandible. Clinical Staging – Regional Lymph Nodes Regional lymph nodes should be carefully palpated for enlargement or asymmetry. However, caution should be exercised when making clinical judgments based on palpation alone, as lymph node size is not an accurate predictor of metastasis. In one study of 100 dogs with oral malignant melanoma, 40% of dogs with normal-sized lymph nodes had metastasis and 49% of dogs with enlarged lymph nodes did not have metastasis (Williams and Packer 2003). Furthermore, the regional lymph nodes include the mandibular, parotid, and medial retropharyngeal lymph nodes; however, the parotid and medial retropharyngeal lymph nodes are not externally palpable (Smith 1995). Additionally, only 55% of 31 cats and dogs with metastasis to the regional lymph nodes had metastasis to the mandibular lymph nodes (Herring et al. 2002). Preoperative assessment of the regional lymph nodes is dif icult. CT scans can be useful to determine lymph node enlargement and guide further diagnostics (Gendler et al. 2010); however, in another study, no individual CT indings were predictive of nodal metastasis, and CT scans had a low sensitivity (10.5–12.5%)

and low accuracy (67.5–76.3%) for detection of metastasis to the mandibular and medial retropharyngeal lymph nodes in dogs with oral and nasal tumors (Skinner et al. 2018). Detection of lymph node metastasis using lymphotropic nanoparticles enhanced MRI appears very accurate (Grif in et al. 2020). Lymph node aspirates are recommended for all animals with oral tumors, regardless of the size or degree of ixation of the lymph nodes (Herring et al. 2002; Williams and Packer 2003). The accuracy of lymph node (LN) aspirates for the detection of metastatic cancer in cats and dogs is 77% (Ku et al. 2017). Resection of some or all of the regional LNs has been described and, although the therapeutic bene it of this approach is unknown, this may provide valuable staging information (Smith 1995; Herring et al. 2002). The irst description of extirpation of the regional lymph nodes for cats and dogs with oral tumors was a unilateral approach for removal of the ipsilateral mandibular, medial retropharyngeal, and parotid lymph nodes (Smith 1995; Herring et al. 2002). The skin is incised from the rostral and proximal aspect of the vertical ear canal, ventral to the caudal aspect of the zygomatic arch, to the bifurcation of the external jugular vein (Smith 1995). The platysma and parotidoauricularis muscles are incised to reveal fascia and loose areolar tissue covering the vertical ear canal and masseter muscle. Incision of the areolar tissue over the ventral aspect of the zygomatic arch exposes the parotid lymphocentrum, which has one to three lymph nodes, along the rostral edge of the parotid salivary gland (Smith 1995). The mandibular lymphocentrum, which contains one to ive lymph nodes, is located between the bifurcation of the jugular vein and division of the linguofacial vein into its lingual and facial branches (Smith 1995). The medial retropharyngeal lymphocentrum, which usually consists of one elongated lymph node on the lateral aspect of the thyropharyngeus muscle, is exposed by incising the adventitia along the caudal aspect of the mandibular salivary gland and retracting the mandibular salivary gland rostrally and the brachiocephalicus and sternocephalicus muscles dorsally (Smith 1995). The major disadvantage of this technique is that the contralateral lymph nodes are not removed and metastasis to the contralateral lymph nodes has been documented (Skinner et al. 2017). To address this concern, bilateral extirpation of the mandibular and medial retropharyngeal lymph nodes has been described through both single ventral midline approach (Green and Boston 2017; Skinner et al. 2017) and bilateral paramedian approaches (Wainberg et al. 2018). The single ventral midline approach was preferred by the majority of surgeons in one study because of better visualization of local anatomy and access to the lymph nodes (Wainberg et al. 2018). For this procedure, the animal is positioned in dorsal recumbency, and the skin incision extends through the skin and platysma muscle along the ventral midline from the caudal third of the mandible to the larynx (Green and Boston 2017). The mandibular lymph node is identi ied at the caudal aspect of the vertical ramus of the mandible. The facial vein, which courses over the ventrolateral aspect of the mandibular node, should be preserved. The mandibular lymph node is extirpated using a combination of blunt dissection and electrocautery. The mandibular salivary gland is then identi ied and retracted laterally to expose the medial retropharyngeal lymph node (Green and Boston 2017). This is achieved by bluntly dissecting along the medial aspect of the mandibular salivary gland to expose the medial retropharyngeal lymph node on the caudomedial aspect of the mandibular salivary gland. The medial retropharyngeal lymph node is extirpated using a combination of blunt dissection and electrocautery. These procedures are then repeated on the contralateral side (Green and Boston 2017). The major disadvantage of this technique is that the parotid lymph nodes are not extirpated, and metastasis to the parotid lymph node has been documented (Herring et al. 2002). The major concerns with non-targeted LN resection are the possibility of missing a metastatic lesion and the potential morbidity associated with the excision of multiple lymph nodes. Lymphatic drainage of the oral cavity is highly variable in humans and likely in dogs and cats (Skinner et al. 2017), and the irst draining lymph node can be ipsilateral or contralateral to the tumor and include any one of the mandibular, medial retropharyngeal, parotid, or minor lymph nodes, such as the buccal lymph node (Herring et al. 2002; Skinner et al. 2017). For these reasons, sentinel lymph node mapping and biopsy are becoming the preferred technique for lymph node staging of oral tumors. Sentinel lymph node mapping and biopsy will hopefully become more widely accepted and practiced as this may permit the assessment of nodal metastasis without more aggressive en bloc surgical excisions of the regional lymph nodes (Liptak and Boston 2019). The sentinel lymph node is the irst draining lymph node and the status of this lymph node is representative of the entire lymph node bed. Furthermore, the sentinel lymph node is not necessarily the regional anatomic lymph node. In one study of dogs, the sentinel lymph node was different to the regional anatomic lymph node in 40% of dogs with cutaneous mast cell tumors

(Worley 2014). Methods to detect sentinel lymph nodes in people with head and neck cancer include lymphography using either radiographs, CT, or MRI, contrast-enhanced ultrasound, single-photon emission CT and positron emission tomography, lymphoscintigraphy, intraoperative blue dyes, and intraoperative gamma probes or near-infrared imaging (Balogh et al. 2002; Beer et al. 2018). Indirect lymphography using radiographs or CT, lymphoscintigraphy, intraoperative dyes, and contrast-enhanced ultrasonography have been described in dogs with various tumors, including head and neck cancer (Balogh et al. 2002; Lurie et al. 2006; Brissot and Edery 2017; Grimes et al. 2017; Rossi et al. 2017). The use of lipid-soluble and watersoluble contrast agents have also been reported as methods of detecting the location of the sentinel lymph node preoperatively, and then combining this with methylene blue to aid in the identi ication of the sentinel lymph node intraoperatively (Figure 6.3) (Brissot and Edery 2017; Grimes et al. 2017; Rossi et al. 2017). The advantage of this latter technique is that radioactive materials are not required and hence this is a more widely applicable sentinel lymph node mapping technique. Clinical Staging – Distant Metastasis The inal step in the clinical staging of animals with oral tumors is imaging of the thoracic cavity for metastasis to the lungs. Three-view thoracic radiographs (right and left lateral projections, and either dorsoventral or ventrodorsal projection) are generally recommended. Helical CT scans should be considered for animals with highly metastatic tumor types, such as oral malignant melanoma, as CT scans are signi icantly more sensitive in detecting pulmonary metastatic lesions compared to radiographs (Nemanic et al. 2006). Based on these diagnostic steps, oral tumors are then clinically staged according to the World Health Organization (WHO) staging scheme (Table 6.1) (Owen 1980).

Table 6.1 Clinical staging (TNM) of oral tumors in dogs and cats. Clinical staging system for oral tumors Primary tumor (T) T is Tumor in situ T1 Tumor < 2 cm in diameter at greatest dimension T1a Without evidence of bone invasion T1b With evidence of bone invasion T2 Tumor 2–4 cm in diameter at greatest dimension T2a Without evidence of bone invasion T2b With evidence of bone invasion T3 Tumor > 4 cm in diameter at greatest dimension T3a Without evidence of bone invasion T3b With evidence of bone invasion Regional lymph nodes (N) N0 No regional lymph node metastasis N1 Movable ipsilateral lymph nodes N1a No evidence of lymph node metastasis N1b Evidence of lymph node metastasis N2 Movable contralateral lymph nodes N2a No evidence of lymph node metastasis N2b Evidence of lymph node metastasis N3 Fixed lymph nodes Distant metastasis (M) M0 No distant metastasis M1 Distant metastasis (specify site(s)) Stage grouping Tumor (T) Nodes (N)

Metastasis (M)

I II III

M0 M0 M0 M0 M0 M1

IV

T1 T2 T3 Any T Any T Any T

N0, N1a, N2a N0, N1a, N2a N0, N1a, N2a N1b N2b, N3 Any N

General Surgical Considerations Surgical excision is the most commonly used modality for treatment of the local oral tumor. The surgical approach depends on the type and location of the oral tumor. Except for peripheral odontogenic ibromas

(formally known as ibromatous and ossifying epulides), the majority of tumors involving the mandible, maxilla, and hard palate have some underlying bone involvement and surgical resection of these should include bony margins to increase the likelihood of complete excision. Radical surgeries such as mandibulectomy and maxillectomy are well tolerated by cats and dogs. These procedures are indicated for oral tumors involving the mandible and maxilla, particularly lesions with extensive bone invasion and tumor types that have poor sensitivity to radiation therapy (Withrow and Holmberg 1983; Bradley et al. 1984; White et al. 1985; Withrow et al. 1985; Salisbury et al. 1986; Salisbury and Lantz 1988; Kosovsky et al. 1991; Schwarz et al. 1991a, b; White 1991; Wallace et al. 1992; Kirpensteijn et al. 1994; Lascelles et al. 2003, 2004). Minimum margins of at least 2 cm, and preferably 3 cm, are recommended for malignant cancers such as SCC, malignant melanoma, and ibrosarcoma in the dog. If possible, mandibular SCC in the cat should be treated with surgical margins greater than 2 cm because of high local recurrence rates (Northrup et al. 2006). However, these margins may not be possible without signi icant morbidity because of the extent of the tumor. Moreover, margins required for resection of benign and malignant oral tumors have not been investigated and lesser margins may result in acceptable rates of local tumor control, especially in the maxilla (Syrcle et al. 2008; Liptak et al. 2020). Where 3 cm margins are not possible without signi icant risk of morbidity, 1 cm margins of normal tissue beyond either the grossly visible tumor or the extent of the tumor as determined by imaging, whichever is greater, may be acceptable for malignant oral tumors and 0.5 cm margins for benign tumors (Syrcle et al. 2008). Greater margins are recommended if possible because these guidelines have not been validated and there is little difference in functional and cosmetic outcome with more extensive surgery.

Figure 6.3 Sentinel lymph node mapping and biopsy as described by Brissot and Edery (2017). (a) Fourquadrant peritumoral injection of a lipid-soluble contrast agent is performed under sedation 24 hours prior to surgery in a dog with a maxillary malignant melanoma; (b) Regional radiographs (pictured) or CT scan are performed prior to surgery to identify the sentinel lymph node which, in this case, is the ipsilateral mandibular lymph node; (c) Four-quadrant peritumoral injection of methylene blue is performed intraoperatively to aide in the identi ication of the sentinel lymph node during surgery (d); (e) Regional radiograph of a cat with a malignant melanoma of the lip 24 hours following four-quadrant peritumoral injection of a lipid-soluble contrast agent. The sentinel lymph node in this cat is the minor buccal lymph node. This highlights the importance of sentinel lymph node mapping in the clinical staging of cats and dogs with malignant oral tumors because metastasis only occurs to the palpable mandibular lymph node in 55% of cats and dogs (Herring et al. 2002) and thus assessment of the mandibular lymph node in all cases will result in metastatic lesions being missed in up to 45% of cases. Rostral and segmental bony resections may be suf icient for benign lesions and rostral SCC in dogs. Larger resections, such as total unilateral mandibulectomy, hemimaxillectomy, orbitectomy, and radical maxillectomy, are necessary for more aggressive malignant tumors, especially ibrosarcoma, and any tumor in a more caudal location (Withrow and Holmberg 1983; Bradley et al. 1984; White et al. 1985; Withrow et al. 1985; Salisbury et al. 1986; Salisbury and Lantz 1988; Kosovsky et al. 1991; Salisbury 1991; Schwarz et

al. 1991a, b; White 1991; Wallace et al. 1992; Kirpensteijn et al. 1994; Lascelles et al. 2003, 2004; Verstraete 2005). Reconstruction following mandibular resection has been described, in dogs but is rarely necessary because of good postoperative function and cosmetic appearance (White et al. 1985; Boudrieau et al. 1994, 2004; Bracker and Trout 2000; Spector et al. 2007; Okamura et al. 2017). Furthermore, a high complication rate has been reported following reconstruction and these complications often require revision surgeries for their management (Boudrieau 2015; Sarowitz et al. 2017). In contrast to dogs, cats frequently have a high complication rate following mandibulectomy (Northrup et al. 2006) and hence mandibular reconstruction may improve postoperative functional outcome in cats (Liptak et al. 2017). The surgical techniques for oral tumor resection and postoperative management are described in detail below. A detailed knowledge of the regional anatomy is important for a successful outcome and to minimize the risk of complications. The anatomy should be reviewed prior to surgery, in combination with either CT or MRI images of the patient, to plan the surgical approach, resection, and reconstruction. Cat and dog skulls should be available for intraoperative orientation and planning.

Antibiotics In general, prophylactic antibiotics are usually not necessary for intraoral procedures (i.e. those not involving a skin incision) because the risk of infection is low due to short surgical times and excellent vascular supply to the oral cavity. However, some surgeons prefer the use of prophylactic antibiotics (such as a irst-generation cephalosporin, clavulanate-potentiated amoxicillin, or ampicillin potentiated with sulbactam) administered prior to surgery, every 90 minutes during surgery, and every 6 hours for the irst 24 hours after surgery (Dernell et al. 1998a).

Analgesia Pre-operative regional nerve blocks (Beckman and Legendre 2002; Grubb and Lobprise 2020a, b) systemic non-steroidal anti-in lammatory drugs and opioids are recommended for pre-operative analgesia. Tissue in iltration local anesthetic is recommended at the end of surgery, and the use of non-steroidal antiin lammatory drugs, opioids, ketamine, and alpha-2 adrenoceptor agonists are options for immediate postoperative analgesia while the patient is in the hospital. Appropriate pain relief should be provided following discharge from the hospital, although the options are somewhat limited. Therefore, clinicians are encouraged to manage these oral surgery patients in the hospital until the “at home” options for managing pain are appropriate. Interestingly, emerging research suggests minimizing perioperative pain may help decrease the rate of metastasis following oncologic surgery (Exadaktylos et al. 2006; Bhattacharya et al. 2020), providing additional rationale for carefully considering pain relief. Table 6.2 provides an outline of suggested analgesic options for cats and dogs undergoing maxillofacial resection and reconstruction.

Table 6.2 Suggested analgesic options for oral surgery in cats and dogs. Analgesic Cats optionsa Preoperative Systemic opioid (as part of pre-med and consider additional dose on induction prior to surgery) Loco-regional nerve blocks with bupivacaine. Consider preoperative use of NSAID (or following full recovery if hemorrhage expected).

Dogs Systemic opioid (as part of pre-med and consider additional dose on induction prior to surgery) Loco-regional nerve blocks with bupivacaine. Consider preoperative use of NSAID (or following full recovery if hemorrhage expected).

Intraoperative Continuous rate IV infusion of: hydromorphone (0.005–0.01 mg/kg/h), fentanyl (2–4 mcg/kg/h) or morphine (0.05 mg/kg/h) medetomidine (1–4 mcg/kg/h) ketamine (2 mcg/kg/min)

Injection of bupivacaine liposomal injectable suspension into surgical site tissues (up to 5.3 mg/kg)

Discharge

Oral NSAID for 5–14+ d at recommended perioperative doseb. Do not use if the cat is stressed or has any risk factors for gastrointestinal ulceration. Oral opioid (buprenorphine via the oral transmucosal route, 10–20 mcg/kg q 12 h) for 3–10 d (care with anorexia that may be seen), or use injectable longer-duration action preparation of buprenorphine. Gabapentin (10 mg/kg q 12 h) can be considered.

Continuous rate IV infusion of: hydromorphone (0.005–0.02 mg/kg/h), fentanyl (2–4 mcg/kg/h) or morphine (0.1 mg/kg/h) medetomidine (1–2 mcg/kg/h) ketamine (2 mcg/kg/min)

lidocaine (25–30 mcg/kg/min) Injection of bupivacaine liposomal injectable suspension into surgical site tissues (up to 5.3 mg/kg) Oral NSAID for 10–14+ d at approved preoperative dose. Do not use if the dog is stressed or has any risk factors for gastrointestinal ulceration. Tramadol may be considered. Gabapentin (10 mg/kg q 12 h) can be considered. Amantadine (3–5 mg/kg q 24 h) can be considered.

a These options should be combined as appropriate into individualized protocols. b NSAIDs are generally not approved for extended dosing postoperatively in cats. Recommend either robenacoxib at 1–2 mg/kg daily, or

meloxicam 0.1 mg/kg once on day 1 (perioperative dose), 0.05 mg/kg q 24 h for 4 days, 0.025 mg/kg q 24 h for 4 days, then 0.025 mg/kg q 48 h.

Post-operative analgesia in the hospital should include at least a non-steroidal anti-in lammatory drug (unless contraindicated) and an opioid. Non-steroidal anti-in lammatory drugs are probably safest if administered post-operatively, following recovery from anesthesia, if there is a danger of uncontrolled hypotension occurring during surgery. Non-steroidal anti-in lammatory drugs should either not be administered or their dose decreased in animals with signi icant renal compromise (Mathews 2000;

Lascelles et al. 2007). Opioids, such as fentanyl or morphine, are preferably administered as a continuous rate infusion rather than intermittent injections. Continuous rate infusions of opioids can be combined with ketamine and/or lidocaine for an enhanced analgesic effect; although lidocaine should be used judiciously in cats (Pypendop and Ilkiw 2005). Animals can usually be weaned off continuous rate infusions over a 24 to 48-hour period. Patients should be discharged with at least a non-steroidal anti-in lammatory for an appropriate period of time – one that covers the expected healing time frame. As with the use for chronic pain conditions, non-steroidal anti-in lammatory drugs should be used appropriately, taking care to screen patients for risk factors that may increase the chances of side effects. Non-steroidal anti-in lammatory drugs can be used safely in cats including those with chronic kidney disease (Monteiro et al. 2019) although most of the clinical data comes from their use in cats with chronic pain. In dogs, oral opioids such as codeine and tramadol can be considered for use on discharge, although there is little clinical evidence of an analgesic effect (Davila et al. 2013) probably due to the high irst pass effect on opioids, and the way tramadol is metabolized in dogs. Oral tramadol has the potential to be analgesic in cats, however, cats show a strong aversion to oral tramadol. Injectable tramadol has been shown to be of clinical bene it perioperatively but is not practical for use following discharge. Longer-acting preparations of buprenorphine are available in certain countries for cats and can be useful to provide extended opioid analgesia, although the injection formulation may require daily visits to the hospital. Although there are no data on ef icacy in oral surgery, bupivacaine liposomal injectable suspension (Lascelles et al. 2016) has the potential to address management of early post-operative pain following discharge. The advent of bupivacaine liposomal injectable suspension has provided a much-needed additional option to provide extended analgesia into the “at home” period. Gabapentin and amantadine have been used for the management of chronic pain in both cats and dogs and are options to help manage post-operative pain in the home environment, although there is little evidence to support an analgesic effect in the acute pain setting. That said, often the oral surgery patients are, or have been, chronic pain patients, and so these approaches may be of bene it. Each patient should be managed individually, and frequently re-assessed in the post-operative period and following discharge.

Positioning and Preparation Performing a cross-match test for blood transfusion and having blood products available on-site are highly recommended, particularly for the more extensive surgeries (typically those that involve the caudal aspect of the oral cavity). Animals are placed in the appropriate position and, if necessary, a mouth gag is placed on the lower or non-surgical side. The exact positioning will vary from case to case. The surgeon should evaluate the positioning in each patient to ensure optimal access to tissues at all stages of the procedure. In some procedures (e.g. combined rostral maxillectomy and nasal planum resection), the animal may need to be repositioned during surgery to optimize access for resection and closure. Conforming vacuum packs and tape can be used to assist in positioning and maintaining the position of the head. If necessary, the surgical site is clipped and surgically prepared. No clipping is required for intraoral procedures. For more caudal procedures, the periorbital hair is usually clipped and the eye is included within the surgical ield. The oral cavity is irrigated with 10% povidone-iodine solution which is irst diluted 1-to-10 with tap water (Dernell et al. 1998a). Towel clamps or staples are used to secure the drapes in such a manner to allow for mobilization of the labial tissues. Before performing the incisions, the oropharynx can be packed with gauze in small dogs and cats and laparotomy sponge in large dogs to prevent blood and lavage luid from entering the trachea or esophagus. Counting the number of gauzes or laparotomy sponges that are packed ensures that they are all removed and accounted for at the end of surgery.

Surgical Considerations For excision of malignant oral tumors, minimum margins include 3 cm of bone rostral and caudal to the tumor, based on either gross palpation or preferably imaging indings, and 1 cm of soft tissue (buccal, gingival, or palatine mucosa). Lesser margins can be used for benign oral tumors and marginal excision, possibly combined with cryosurgery, is suitable for peripheral odontogenic ibromas (Dernell et al. 1998a; Liptak 2019). The mandibular symphysis may act as a barrier for tumor invasion. If there is no evidence of rostral mandibular tumors crossing the mandibular symphysis, then excision of the symphysis, including the contralateral middle incisor, should be suf icient for bony margins. Electrocautery should be used

judiciously because of the potential risk of postoperative dehiscence (Withrow et al. 1983; Salisbury et al. 1985). An oscillating saw is preferred for mandibular osteotomies, although pneumatic burrs, Gigli wire, and bone cutters can also be used. Osteotomes should be avoided for all non-symphyseal mandibular osteotomies because of the risk of bone-shattering. In the maxilla and hard palate, osteotomies can be performed with an oscillating saw, pneumatic burr, and/or osteotome and mallet. Osteotomies are performed either between teeth or through teeth. If the chosen margin is over a tooth and the osteotomy is to be done between teeth, the osteotomy is moved away from the tumor such that this particular tooth is removed en bloc with the tumor. If the osteotomy is performed caudal to a canine tooth and part of the canine root is left in the mandible or maxilla remaining in the animal, the root is elevated and extracted. Alternatively, if the osteotomy is performed through the tooth, then the remnants of the tooth roots are elevated and extracted. Mono ilament absorbable suture material (e.g. polydioxanone) is recommended for closure of oral defects because they maintain adequate tensile strength for prolonged periods and are relatively inert which minimizes mucosal irritation and in lammation (Salisbury et al. 1986; Dernell et al. 1998a). A reverse-cutting swaged-on needle is preferred for suturing ibrous soft tissues of the oral cavity because of easier passing of the needle with minimal trauma and better suture purchase (Salisbury et al. 1986). Two-layer closures are preferred to one-layer closure because of a reduced risk of incisional dehiscence (Dernell et al. 1998a). Suture material should be passed through bone tunnels if possible, particularly in the hard palate and maxilla, because of increased holding power compared to soft tissue (Figure 6.4).

Figure 6.4 Bone tunnels have been drilled into the hard palate to provide a secure two-layer closure (hard palate-to-labial submucosa and palatine mucoperiosteum-to-labial mucosa) following partial maxillectomy in a dog.

Surgical Approach to Tumors of the Mandible Anatomy

The lower jaw consists of two mandibles which form a ibrocartilaginous symphysis rostrally and articulate caudally with the skull at the temporomandibular joint (Evans and de Lahunta 2013). Each mandible, left and right, consists of the body and ramus (Figure 6.5). Teeth erupt along the alveolar margin of the mandibular body. The mandibular canal is an important oncologic consideration and extends along the body of the mandible. The inferior alveolar artery, vein, and nerve enter the mandibular canal caudally at the mandibular foramen and the mental nerves innervating the lower lip and chin exit rostrally through three mental foramina (Evans and de Lahunta 2013). Tumors involving the mandibular body can theoretically extend along the mandibular canal and hence the caudal margins for mandibulectomy procedures of these tumors should extend caudal to the mandibular foramen to minimize the risk of incomplete tumor resection.

Figure 6.5 Anatomy of the mandible. The inferior alveolar artery, vein, and nerve course through the mandibular foramen into the mandibular canal. The mandibular canal is an important consideration when resecting mandibular tumors as invasion into the mandibular canal necessitates a more aggressive subtotal or total mandibulectomy. Source: Reproduced with permission from Evans, H.E., and deLahunta, A., ed. 2000. The Head, in Guide to the Dissection of the Dog, 259–321. Philadelphia: Saunders.

The ramus consists of three prominent processes: the coronoid process on the dorsal aspect of the ramus, condylar process on the caudal aspect of the ramus, and the angular process on the caudoventral aspect of the ramus (Figure 6.5) (Evans and de Lahunta 2013). The masseter muscle inserts on the lateral surface of the coronoid and angular processes, the temporal muscle on the medial aspect of the ramus, the pterygoid muscle on the medial and caudal aspects of the ramus and angular process; and the digastricus muscle along the ventral aspect of the mandibular body (Figure 6.6) (Evans and de Lahunta 2013). Mandibulectomy involves en bloc excision of a tumor of the lower jaw. Various mandibulectomy procedures have been described, including unilateral and bilateral rostral mandibulectomy, segmental mandibulectomy, caudal mandibulectomy, and subtotal and total unilateral mandibulectomy.

Rostral Mandibulectomy – Unilateral Unilateral rostral mandibulectomy is recommended for dogs with benign acanthomatous ameloblastoma or SCC lesions which are rostral to the second premolar tooth and do not cross the mandibular symphysis. Bilateral rostral mandibulectomy should be considered for these tumor types which cross the mandibular symphysis and mandibulectomy is recommended for malignant tumors other than SCC in the rostral mandible or acanthomatous ameloblastoma or SCC lesions caudal to the second premolar tooth. For unilateral rostral mandibulectomy, the dog is positioned in lateral recumbency with affected side uppermost (Dernell et al. 1998a). The labial mucosa is incised with a minimum of 1 cm margins around the mass (Figure 6.7a) (Dernell et al. 1998a). This incision is continued rostrally to the mandibular symphysis and caudally to the planned osteotomy site. The labial mucosa is re lected off the mandible with periosteal elevators to preserve the soft tissue of the lip which will be used later for reconstruction of the defect (Figure 6.7b). The sublingual and mandibular salivary gland ducts open at the sublingual caruncle in the frenulum of the tongue (Northrup et al. 2006). This should be preserved if possible (Dernell et al. 1998a), but excisional margins should not be compromised by this anatomic consideration and complications such as ranula formation are uncommon. The rostral osteotomy should include the mandibular symphysis and hence the osteotomy is positioned eccentrically between the contralateral canine tooth and mandibular symphysis (Figure 6.7c). This osteotomy can be performed with either an oscillating saw, biradial saw, or osteotome and mallet (Dernell et al. 1998a). A bone cutter may be suf icient in cats and small dogs. The position of the caudal osteotomy is based on tumor type, tumor dimensions, and imaging evidence of bone invasion. Margins of 1–2 cm for acanthomatous ameloblastoma and 2–3 cm for SCC caudal to the caudal limit of the mass or level of bone invasion should be suf icient. The caudal osteotomy should be performed with an oscillating saw and tapered at the occlusional margin to minimize wound tension during closure (Figure 6.7d and e) (Dernell et al. 1998a). Gigli wire can also be used for the caudal osteotomy, but the mandible can shatter when an osteotome and mallet are used for this osteotomy and hence this should be avoided. Following mandibulectomy, the sublingual mucosa is sutured to the labial mucosa in a single layer of simple interrupted or simple continuous suture pattern using mono ilament absorbable suture material (Figure 6.7f and g) (Dernell et al. 1998a).

Figure 6.6 Anatomy of the mandible showing the muscles of mastication. (a) Pterygoideus medialis and lateralis muscles; (b) Masseter and pterygoideus medialis muscles; (c) Origin of the temporalis and pterygoideus medialis and lateralis muscles; (d) Cut out of the masseter muscle to show the deep portion of the masseter muscle. Source: Reproduced with permission from Evans, H.E., and Christensen, G.C., ed. 1979. Muscles, in Miller’s Anatomy of the Dog, 269–410. Philadelphia: Saunders.

Rostral Mandibulectomy – Bilateral Bilateral rostral mandibulectomy is recommended for dogs with benign acanthomatous ameloblastoma or SCC lesions rostral to the irst premolar tooth and cross the mandibular symphysis. For larger lesions or malignant tumors other than SCC, the caudal osteotomies can be positioned as far caudally as the fourth premolar tooth. However, the risk of complications, particularly dif iculty prehending food, is greater with more caudal osteotomies. For bilateral mandibulectomy, the dog can be positioned in either dorsal, lateral, or sternal recumbency depending on surgeon preference (Dernell et al. 1998a). Dorsal recumbency provides better exposure for dissection of the tumor and performing the osteotomies. Sternal recumbency provides superior exposure for wound closure. The surgical technique for bilateral mandibulectomy is similar to unilateral mandibulectomy. The labial mucosa is incised with a minimum of 1 cm margins around the mass and continued caudally to the planned osteotomy sites. The labial mucosa is re lected off the mandible with periosteal elevators to preserve the soft tissue of the lip which will be used later for reconstruction of the defect (Figure 6.8a and b). The sublingual and mandibular salivary gland ducts open at the sublingual caruncle in the frenulum of the tongue (Northrup et al. 2006). This should be preserved if possible (Dernell

et al. 1998a), but excisional margins should not be compromised by this anatomic consideration. The position of the caudal osteotomy depends on tumor type, tumor dimensions, and imaging evidence of bone invasion. Margins of 1–2 cm for acanthomatous ameloblastoma and 2–3 cm for SCC caudal to the caudal limit of the mass or level of bone invasion should be suf icient. The caudal osteotomy should be performed with an oscillating saw and tapered at the occlusional margin to minimize wound tension during closure (Figure 6.8c) (Dernell et al. 1998a). Stabilization of the remaining portions of the mandible has been described (Boudrieau et al. 1994, 2004; Bracker and Trout 2000; Spector et al. 2007), but is not necessary as function and cosmetic appearance are not improved and the risk of complications is increased. For closure, V-shaped wedges of redundant skin can be removed either laterally or rostrally en bloc with the tumor or after tumor excision to create a soft tissue ridge or dam to minimize drooling and to improve cosmetic appearance (Dernell et al. 1998a). The sublingual mucosa is sutured to the labial mucosa in a single layer of simple interrupted sutures using mono ilament absorbable suture material (Figure 6.8d) (Dernell et al. 1998a).

Figure 6.7 Unilateral rostral mandibulectomy. (a) The labial and gingival mucosa are incised with a minimum of 1 cm margins from an acanthomatous epulis localized to the mandibular canine tooth; (b) The mucosa is then re lected off the underlying mandible (arrows) using periosteal elevators to expose the planned osteotomy sites and protect soft tissues from trauma during osteotomy of the mandible; (c) An eccentric rostral mandibular osteotomy should be performed with either an oscillating saw, osteotome and mallet, or bone cutters to include the mandibular symphysis; (d and e) The caudal osteotomy is performed with an oscillating saw with minimum margins of 1–2 cm for benign tumors, such as this acanthomatous epulis, and 2–3 cm for malignant tumors; (f) The resultant defect following removal of the unilateral rostral mandibular segment; (g) This defect is closed by suturing the sublingual mucosa to the labial mucosa in a single layer of either simple interrupted or simple continuous sutures using mono ilament absorbable suture material.

Figure 6.8 Bilateral rostral mandibulectomy. (a) A malignant melanoma involving the rostral mandible and crossing the symphyseal midline; (b) The labial mucosa is incised with minimum margins of 1 cm and the mucosa is then re lected with periosteal elevators immediately caudal to the planned osteotomy site to protect soft tissues from trauma during osteotomy of the mandible; (c) The mandibular osteotomy is performed with an oscillating saw with minimum caudal margins of 1–2 cm for benign tumors and 2–3 cm for malignant tumors, such as this malignant melanoma; (d) The resultant defect can be closed primarily or V-shaped wedges of lip can be removed either laterally or rostrally to improve cosmetics and function. This defect is closed by suturing the sublingual mucosa to the labial mucosa in a single layer of either simple interrupted or simple continuous sutures using mono ilament absorbable suture material.

Segmental Mandibulectomy Segmental mandibulectomy is recommended for dogs with benign acanthomatous ameloblastoma or lowgrade malignant tumors, such as SCC, located in the mid-mandibular body. Furthermore, these tumors should not penetrate cortical bone. The dog is positioned in lateral recumbency. The labial and lingual mucosa are incised with a minimum of 1 cm margins around the mass (Figure 6.9a). The dissection is continued around the mandibular body with periosteal elevators until the mandibular body is fully exposed. Osteotomies are performed rostral and caudal to the mass with an oscillating saw or Gigli wire (Figure 6.9b). Margins of 1–2 cm for acanthomatous ameloblastoma and 2–3 cm for SCC should be suf icient for complete excision. For closure, the sublingual mucosa is sutured to the labial mucosa in a single layer of simple interrupted or simple continuous sutures using mono ilament absorbable suture material (Figure 6.9c).

Rim Mandibulectomy Rim mandibulectomy is a variation of a segmental mandibulectomy where the ventral cortex of the mandible is preserved with a crescentic osteotomy. Rim mandibulectomy is recommended for surgical excision of benign tumors con ined to the alveolar margin of the mandible (Murray et al. 2010). The approach and technique are similar to those described in the above section on segmental mandibulectomy (Figure 6.10a–d). To create the crescentic osteotomy, a biradial osteotomy blade can be used (Reynolds et al. 2009). In the absence of a biradial blade, right-angled osteotomies can be performed using a pneumatic burr (Linden et al. 2017). The advantage of a rim mandibulectomy, when used for excision of benign mandibular tumors, is that mandibular drift is prevented by preserving the ventral mandibular cortex with no increased risk of incomplete excision and local tumor recurrence (Reynolds et al. 2009; Murray et al. 2010). There is, however, a risk of postoperative fracture through the ventral cortex. In one study, there were no mechanical differences between the crescentic and right-angled osteotomies (Linden et al. 2017), suggesting that the risk of acute fracture would be the similar for both techniques.

Figure 6.9 Segmental mandibulectomy. (a) The labial and gingival mucosa are incised with minimum margins of 2 cm from a ibrosarcoma arising from the alveolar ridge of the third premolar tooth, and the mucosa is then re lected with periosteal elevators immediately rostral and caudal to the planned osteotomy sites to protect soft tissues from trauma during osteotomy of the mandible; (b) The mandibular osteotomies are performed with either an oscillating saw or Gigli wire with minimum margins of 2 cm. (c) The resultant defect is closed by suturing the sublingual mucosa to the labial mucosa in a single layer of either simple interrupted or simple continuous sutures using mono ilament absorbable suture material.

Figure 6.10 Rim mandibulectomy. (a) The labial and gingival mucosa are incised with minimum margins of 1 cm from a recurrent peripheral odontogenic ibroma arising from the alveolar ridge of the rostral-to-mid mandibular body, and the mucosa is then re lected with periosteal elevators immediately rostral and caudal to the planned osteotomy site to protect soft tissues from trauma during osteotomy of the mandible; (b) The mandibular osteotomy is performed with a biradial saw (pictured) or pneumatic burr; (c and d) The resultant defect (c) is closed by suturing the sublingual mucosa to the labial mucosa in a single layer of either simple interrupted or simple continuous sutures using mono ilament absorbable suture material (d).

Subtotal and Total Unilateral Mandibulectomy Total unilateral mandibulectomy is recommended for malignant tumors, particularly those with extensive involvement of the mandibular body. The only difference between subtotal and total unilateral mandibulectomy is the caudal margins. For subtotal unilateral mandibulectomy, the mandible is osteotomized caudal to the mandibular canal and this is primarily indicated for when the tumor can be excised with 3 cm caudal margins without sacri icing the ramus or temporomandibular joint. It should be noted, however, that preservation of these structures does not improve postoperative function or cosmesis and hence subtotal unilateral mandibulectomy should not be performed if caudal margins will be compromised. Total unilateral mandibulectomy includes the temporomandibular joint and ramus. This procedure is more aggressive and is indicated for tumors in which 3 cm caudal margins cannot be attained with subtotal unilateral mandibulectomy. Dogs are positioned in lateral recumbency for subtotal and total unilateral mandibulectomy (Dernell et al. 1998a). To improve exposure for total unilateral mandibulectomy, a full-thickness incision is performed extending from the commissure of the lip to the rostral aspect of the ramus (Dernell et al. 1998a). Branches

of the facial artery and vein should be ligated or cauterized if they are encountered during this incision (Dernell et al. 1998a). The parotid salivary duct is usually dorsal to this incision but should be avoided if possible. This skin incision is not necessary for subtotal unilateral mandibulectomy. For both subtotal and total unilateral mandibulectomy, the labial and buccal mucosa are incised with a minimum of 1 cm margins around the mass (Figure 6.11a) (Dernell et al. 1998a). The mucosal incisions are continued rostrally to the level of the planned osteotomy and caudally to the ramus (Figure 6.11b). The lateral border of the tongue is freed as the medial incision is continued rostrally into the sublingual mucosa (Figure 6.11c). During this dissection, the mandibular and sublingual salivary ducts may be encountered. Some surgeons recommend identi ication and ligation of these ducts, but this is rarely necessary. The dissection is continued around the mandibular body with periosteal elevators until the mandibular body is fully exposed. The genioglossus, geniohyoideus, and mylohyoideus muscles are either transected (if within 1 cm margins of the tumor) or elevated from the medial aspect of the mandible if the tumor does not penetrate the medial cortex (Dernell et al. 1998a). Depending on the location of the tumor, the rostral osteotomy can either be performed through the mandibular symphysis or eccentrically between the contralateral canine tooth and mandibular symphysis. This osteotomy can be performed with either an oscillating saw or osteotome and mallet, while a bone cutter may be suf icient in cats and small dogs (Figure 6.11d). Separation of the mandibular symphysis permits lateral movement of the mandible and better exposure and visualization for caudal dissection. Importantly, the inferior alveolar artery and vein should be identi ied and ligated as they course over the lateral surface of the medial pterygoid muscle before entering the mandibular foramen (Figure 6.11e). For subtotal unilateral mandibulectomy, the caudal osteotomy is positioned at the rostral edge of the insertion of the masseter muscle (Figure 6.11f and g) (Dernell et al. 1998a). This osteotomy should be performed with an oscillating saw. For total unilateral mandibulectomy, the dissection is continued further caudally. Depending on the location of the tumor, the masseter muscle is either incised with 1 cm margins or elevated from the ventrolateral surface and ventral margin of ramus while retracting the mandible in a caudodorsal direction (Figure 6.11h and i); the digastricus muscle is elevated from its insertion along the caudoventral border of the mandibular body (Figure 6.11j); and the pterygoid muscles are elevated from their insertion on the medial aspect of the caudoventral surface of angle of mandible (Figure 6.11k) (Dernell et al. 1998a). The temporomandibular joint capsule is incised laterally and medially and then luxated (Figure 6.11l) (Dernell et al. 1998a). Finally, the temporalis muscle is elevated from its insertion on the coronoid process of the mandibular ramus (Dernell et al. 1998a). The defect is closed in three layers following total unilateral mandibulectomy and two layers following subtotal unilateral mandibulectomy (Dernell et al. 1998a). The deep layer is closed by suturing the pterygoid, masseter, and temporalis muscles. The submucosa is then closed in a simple continuous pattern. The mucosa and skin are closed with either a simple interrupted or simple continuous pattern using mono ilament absorbable suture material. A simple interrupted pattern is recommended for wounds under tension, whereas a simple continuous pattern is suf icient for wounds with minimal or no tension (Figure 6.11m). The commissure of the lip can be advanced rostrally to the level of the irst premolar or canine tooth to minimize hanging of the tongue on the resected side. A stented vertical mattress suture is recommended at the rostral extent of the lip advancement because of high tension at this point when the mouth is opened. While advancement of the commissure of the lip may improve postoperative cosmesis, it may also increase the risk of wound complications.

Ventral Approach for Segmental, Subtotal Unilateral, and Total Unilateral Mandibulectomy The patient is positioned in dorsal recumbency with a sandbag or towel placed under the neck to position the body of the mandible parallel to the surgical table (de Mello Souza et al. 2019). A skin incision is made along the ventral surface of the mandible to the extent required for the mandibulectomy procedure being performed and continued to the angular process of the mandible. The platysma muscle is incised, followed by incision of the insertions of the digastricus muscle, masseter muscle, and mylohyoideus muscle on the ventromedial, ventrolateral, and medial aspects of the mandibular body, respectively (Figure 6.12a) (de Mello Souza et al. 2019). The inferior alveolar artery is identi ied entering the mandibular foramen on the

caudal and medial aspect of the mandible. This vessel is ligated, cauterized, or sealed and transected. The remaining soft tissues are dissected off the medial and lateral aspects of the mandible, and the oral mucosa is incised with a scalpel blade (Figure 6.12b). The mucosal incision is extended rostrally and caudally as necessary for the extent of the mandibulectomy being performed.

Figure 6.11 Subtotal and total hemimandibulectomy. (a) A skin incision may be required extending caudally from the commissure of the lips and then the buccal and labial skin are dissected free from the masseter muscle (m) and mandible following an incision along the labial mucosa; (b) The labial and gingival mucosa are incised with minimum margins of 2 cm in a dog with a mandibular malignant melanoma and the mucosa is re lected with periosteal elevators to protect soft tissues from trauma during osteotomy of the mandible; (c) The sublingual mucosa is incised to expose the medial aspect of the mandibular body and permit identi ication of the inferior alveolar artery and vein; (d) The rostral mandibular symphyseal separation can be performed with an oscillating or sagittal saw (pictured), osteotome and mallet, or bone cutters; (e) The hemimandible is re lected laterally and the inferior alveolar artery and vein are identi ied and ligated (arrow) caudal to their entry into the mandibular foramen (in a cat with a malignant squamous cell carcinoma); (f and g) For subtotal mandibulectomy, which is indicated for rostral malignant tumors invading into the medullary cavity or mandibular canal, the caudal osteotomy is positioned immediately rostral to the rostral attachment of the masseter muscle; (h and i) For total hemimandibulectomy, the dotted lines indicates where the masseter (H) and digastricus (I) muscles are incised from the caudal mandible; (j) The digastricus (D) muscle is re lected off the ventral aspects of the caudal mandible; (k) The pterygoid muscles (P) are re lected from the medial and ventral aspects of the caudal mandible; (l) The masseter muscle is re lected dorsally to expose and incise the temporomandibular joint (dotted line); (m) The resultant defect is closed in two to three layers. The irst layer consists of suturing the master, digastricus, and pterygoid muscles; the submucosa is then closed with a simple continuous pattern; and then the sublingual mucosa is sutured to the labial mucosa using either simple interrupted or simple continuous sutures of mono ilament absorbable suture material. Source: Line diagrams (11A, 11F, 11H and 11I, and 11L) reproduced with permission from Withrow, S.J., and Holmberg, D.L. 1983. Mandibulectomy in the treatment of oral cancer. J Am Anim Hosp Assoc 19:277–278.

Figure 6.12 Ventral approach for segmental mandibulectomy in a dog with a malignant oral melanoma. (a) An incision has been performed along the ventral surface of the mandible and through the platysma muscle; the masseter muscle has been elevated from the body of the mandible laterally and the mylohyoideus muscle from the medial aspect of the mandible. The digastricus muscle on the caudal aspect of the mandible is intact; (b) Following dissection of the muscle attachments, the oral mucosa is incised with a scalpel blade; (c) The segmental mandibulectomy is being performed with an oscillating saw 2 cm rostral to the rostral extent of the malignant melanoma. Note that a string of pearls plate has been preplaced to maintain spatial alignment and occlusion postoperatively; (d) Appearance of the segmental mandibulectomy following resection and removal of the mandibular segment; (e) The oral mucosa is closed through the ventral skin incision using a continuous suture pattern; (f) The ventral skin incision is closed; (g) The ipsilateral mandibular lymph node was extirpated by through caudal extension of the same skin incision without requiring repositioning of the dog. Following preoperative sentinel lymph node mapping which identi ied the mandibular lymph node as the sentinel lymph node, intraoperative sentinel lymph node mapping was performed with four-quadrant peritumoral injection of methylene blue. Note the bluecolored afferent lymphatic vessels and mandibular lymph node. For subtotal and total unilateral mandibulectomy, the symphysiotomy is performed with an oscillating saw and the rostral end of the affected mandible is pulled through the skin incision to allow for easier

identi ication and dissection of the muscles and vessels of the caudal mandibular body and ramus (de Mello Souza et al. 2019). The insertion of the super icial portion of masseter muscle is visualized on the masseteric fossa, on the lateral aspect of the ramus of the mandible, ventral to the zygomatic arch. The insertion of the masseter muscle is severed with the use of periosteal elevators and electrosurgery. The pterygoideus lateralis and medialis muscles can then be visualized. The pterygoideus lateralis inserts on the medial surface of the mandibular condylar process, just ventral the mandibular articular surface; the pterygoideus medialis muscle inserts on the angular process of the mandible; and the temporalis muscle is visualized as it inserts on the coronoid process of the mandible. Manipulation of the cranial aspect of the mandible allows for easy identi ication of the insertions of pterygoideus and temporalis muscles and the temporomandibular joint (de Mello Souza et al. 2019). These muscles are transected adjacent to the temporomandibular joint and the joint is disarticulated by incising the joint capsule with a scalpel blade. Following removal of the mandible (Figure 6.12c and d) and lavage of the surgical site, the wound is closed in the following order: oral mucosa in a simple continuous suture pattern (Figure 6.12e); mylohyoideus, digastricus, and the rostral portion of the masseter muscle are apposed with absorbable suture material in a single continuous pattern; the pterygoideus, temporalis, and caudal portion of the masseter muscles are apposed with absorbable suture material in a simple continuous suture pattern; the subcutaneous layer is closed in a simple continuous suture pattern; and the skin is apposed with non-absorbable suture in an interrupted pattern (Figure 6.12f) (de Mello Souza et al. 2019). The advantages of the ventral approach for segmental, subtotal unilateral, and total unilateral mandibulectomy include easy identi ication of the important regional anatomical structures, including the inferior alveolar artery and temporomandibular joint, avoidance of a zygomatic arch osteotomy for access to the vertical ramus, and dissection of the mandibular (Figure 6.12g) and medial retropharyngeal lymph nodes through extension of the same incision without needing to change patient position (de Mello Souza et al. 2019).

Caudal (Vertical Ramus) Mandibulectomy Caudal mandibulectomy is indicated for benign or low-grade malignant lesions con ined to the mandibular ramus, such as osteoma or multilobular osteochondrosarcoma. More extensive mandibulectomy procedures are recommended for higher-grade malignant tumors. The temporomandibular joint can either be preserved or excised depending on the location of the tumor (Dernell et al. 1998a). Caudal mandibulectomy can also be combined with inferior orbitectomy for tumors with more extensive bony or soft tissue involvement. The dog is positioned in lateral recumbency for caudal mandibulectomy (Dernell et al. 1998a). A curved skin incision is performed over the ventral aspect of the zygomatic arch (Figure 6.13a). The temporalis muscle is elevated off the dorsal aspect of the zygomatic arch with periosteal elevators. The masseter muscle is then elevated off the medial aspect of the zygomatic arch (Figure 6.13b) (Dernell et al. 1998a). During this dissection, the infraorbital artery, vein, and nerve coursing along the medial aspect of the zygomatic arch should be identi ied and preserved. To expose the mandibular ramus, osteotomies of the zygomatic arch should be performed rostrally and caudally with an oscillating saw or Gigli wire (Figure 6.13c). Similar to the mandible, an osteotome and mallet should not be used for these osteotomies, as the hard brittle bone of the zygomatic arch tends to shatter (Dernell et al. 1998a). Following removal of the zygomatic arch, the masseter muscle is elevated from the ventrolateral surface and ventral margin of the ramus, and the temporalis muscle is elevated from its rostromedial insertion on the coronoid process of the mandible (Figure 6.13d) (Dernell et al. 1998a). For caudal mandibulectomies which preserve the temporomandibular joint, the inferior alveolar artery and vein should be identi ied and preserved as it courses over the lateral surface of the medial pterygoid muscle before entering the mandibular foramen (Dernell et al. 1998a). The osteotomy of the mandibular ramus is positioned immediately dorsal to the temporomandibular joint in a coronal direction (Figure 6.13e and 6.13f). This osteotomy should be performed with an oscillating saw or pneumatic burr. When the temporomandibular joint is excised with the caudal mandibulectomy, the inferior alveolar artery and vein are ligated and transected as the medial pterygoid muscle is elevated from the ventromedial aspect of the mandibular angle (Dernell et al. 1998a). The osteotomy is positioned caudal to the irst molar tooth for this more extensive caudal mandibulectomy (Figure 6.13e). This osteotomy should also be performed with an oscillating saw or pneumatic burr.

Figure 6.13 Vertical ramus or caudal mandibulectomy. (a) The dotted line represents the skin incision over the zygomatic arch; (b) The temporalis (T) and masseter (M) muscles are elevated subperiosteally from the zygomatic arch; (c and d) The rostral and caudal aspects of the zygomatic arch are then osteotomized (arrows) (c) to expose the vertical ramus of the mandible (d) following removal of the ostectomized segment of zygomatic arch; (e) The dotted lines represent the two options for osteotomy of the vertical ramus of the mandible. Depending on the location and type of the tumor, the vertical ramus mandibulectomy can preserve (a) or include (b) the temporomandibular joint; (f) In this dog with a multilobular osteochondrosarcoma, the tumor (arrow) has been excised with 2 cm margins (arrowheads) while preserving the temporomandibular joint. Source: Line diagrams (13A and 13E) reproduced with permission from Withrow, S.J., and Holmberg, D.L. 1983. Mandibulectomy in the treatment of oral cancer. J Am Anim Hosp Assoc 19:277–278.

Following caudal mandibulectomy, the defect is closed in three layers with apposition of the fascia of the temporalis and masseter muscles, then subcutaneous tissue, and inally skin (Dernell et al. 1998a).

Surgical Approach to Tumors of the Mandible in Cats

The surgical approach for management of benign and malignant tumors of the mandible is similar to dogs. Mandibulectomy in cats is complicated by the small size of the mandible relative to the size of the oral tumor and the need for 1 cm margins for benign lesions and 3 cm margins for malignant tumors. As a result, less aggressive procedures such as unilateral rostral, segmental and caudal mandibulectomy are rarely possible. Subtotal and total unilateral mandibulectomy are the most commonly indicated and performed procedures for the management of mandibular tumors in cats (Figure 6.11). The surgical technique is the same as dogs, however an esophageal or gastric feeding tube should be inserted as eating can be problematic following mandibulectomy in cats (Figure 6.14) (Northrup et al. 2006).

Postoperative Management Analgesia In the immediate postoperative period, intravenous luids and analgesia are continued and an Elizabethan collar should be placed as soon as the animal is sternally recumbent to prevent self-trauma (Dernell et al. 1998a). See Table 6.2 for suggested perioperative analgesic protocols for cats and dogs undergoing mandibular resections.

Figure 6.14 It is important that a feeding tube be inserted following any mandibulectomy procedure in cats because voluntary intake is often poor for at least two weeks postoperatively.

Nutrition Intravenous luids should be continued until the dog eats voluntarily and is drinking suf icient quantities to maintain hydration. This is rarely a problem and most dogs can be discharged within 24–48 hours. To prevent disruption of intraoral incisions, dogs should only be fed soft canned food and prevented from chewing on hard objects for four weeks (Dernell et al. 1998a). Supplemental nutrition is rarely required in dogs but is important in cats. Following various mandibulectomy procedures in 42 cats, 73% of cats were either dysphagic or inappetent in the immediate postoperative period and ive of these cats never ate voluntarily following surgery (Northrup et al. 2006). An esophageal or gastric feeding tube is strongly recommended in cats because of the high risk of inappetence (Figure 6.14). Supplemental tube feeding is well tolerated in cats and complications associated with feeding tubes are infrequent (Marks 1998). The feeding tube should be removed when the cat begins to eat voluntarily and consistently. Complications Blood loss and hypotension are the most common intraoperative complications (Wallace et al. 1992; Lascelles et al. 2003). Postoperative complications are uncommon and include incisional dehiscence, increased salivation, mandibular drift and malocclusion, and dif iculty prehending food (Withrow and Holmberg 1983; Bradley et al. 1984; Withrow et al. 1985; Salisbury et al. 1986; Salisbury and Lantz 1988; Kosovsky et al. 1991; Schwarz et al. 1991a, b; Hutson et al. 1992; Wallace et al. 1992; Lascelles et al. 2003; Boston et al. 2020). Enteral feeding tubes are not usually required following oral surgery in dogs, but are recommended for cats treated with any type of mandibulectomy as eating can be dif icult for two to four months following surgery (Hutson et al. 1992; Northrup et al. 2006; Boston et al. 2020). Cosmetic Appearance The cosmetic appearance of cats and dogs following mandibulectomy is usually good to excellent. Owner acceptance of postoperative appearance and function is improved with a thorough discussion, including the use of pre and postoperative images of the appropriate procedure, prior to surgery. Owner satisfaction with the cosmetic appearance and functional outcome following mandibulectomy is high with 83% and 85% of owners satis ied following mandibulectomy in cats and dogs, respectively (Fox et al. 1997; Northrup et al. 2006). The cosmetic appearance of dogs is not altered after unilateral rostral, segmental, and caudal mandibulectomy (Figure 6.15a–d). These procedures are rarely performed in cats, although cosmetic appearance is also unchanged following caudal mandibulectomy. Bilateral rostral mandibulectomy results are the most cosmetically challenging of the mandibulectomy procedures in both cats and dogs because of mandibular shortening, excessive drooling and cheilitis, and the tongue hanging out, especially when panting or excited (Figure 6.16). Subtotal and total unilateral mandibulectomy results in a mild concavity on the resected side, which is rarely appreciable, mandibular drift and the tongue hanging out on the resected side (Figure 6.17) (Withrow and Holmberg 1983; Bradley et al. 1984; Salisbury and Lantz 1988; Kosovsky et al. 1991; Schwarz et al. 1991a; White 1991; Dernell et al. 1998a; Northrup et al. 2006). Eating Difficulties Eating dif iculties are reported in 44% of dogs and 73% of cats following mandibulectomy (Withrow and Holmberg 1983; Bradley et al. 1984; Salisbury and Lantz 1988; Kosovsky et al. 1991; White 1991; Dernell et al. 1998a; Northrup et al. 2006). In dogs, this is often related to dif iculty in prehending food. Prehension dif iculties are more common following bilateral rostral mandibulectomy with resection of both canine teeth, particularly the more aggressive bilateral procedures extending caudally to the second premolar teeth (Schwarz et al. 1991a). The majority of dogs with prehension dif iculties adapt within two weeks. Supplemental feeding may be required during this period, such as force-feeding, tube feeding, or feeding soft foods made into a ball. If prehension dif iculties continue beyond two weeks, then other causes should be investigated. Injury to the hypoglossal nerve and mandibular drift can also occasionally result in dif iculties in prehending and eating food (Withrow and Holmberg 1983; Bradley et al. 1984; Salisbury and Lantz 1988; Kosovsky et al. 1991; White 1991; Dernell et al. 1998a; Northrup et al. 2006).

Figure 6.15 (a and b) The typical postoperative appearance of a dog following unilateral rostral mandibulectomy. Note the saliva accumulation rostrally and minimal change in cosmesis; (c and d) The typical postoperative appearance of a dog following vertical ramus (or caudal) mandibulectomy. Note that the cosmetic appearance of the dog is unaltered.

Figure 6.16 The typical postoperative appearance of a dog following bilateral rostral mandibulectomy. Note the shortened mandible and the tongue hanging out. In cats, eating dif iculties are common regardless of the mandibulectomy procedure. In the short-term (≤ 4 weeks), inappetence is reported in 83% of cats following bilateral rostral mandibulectomy, 74% of cats following mandibulectomy, and 83% of cats following resection of more than 50% of the mandible (Northrup et al. 2006). Inappetence is also common in the long-term with 10% of cats with bilateral rostral mandibulectomy, 53% of cats with mandibulectomy, and 83% of cats with resection of greater than 50% of the mandible experiencing eating dif iculties (Northrup et al. 2006). In a study of eight cats treated with radical mandibulectomy, six cats returned to voluntary eating between 1 day and 12 weeks postoperatively with the two remaining cats requiring life-long enteral feeding (Boston et al. 2020). A feeding tube should be inserted at the time of mandibulectomy in cats because of this high risk of inappetence. An esophageal or gastric feeding tube is preferred because of the ability to maintain and use these feeding tubes for a prolonged period. The feeding tube should be removed when the cat begins to eat voluntarily and consistently.

Figure 6.17 The typical postoperative appearance of a dog following subtotal (pictured) or total hemimandibulectomy. The mandible drifts towards the midline and the tongue hangs out on the resected side. In one feline case report, a segmental mandibular defect following partial mandibulectomy for a mandibular osteosarcoma was reconstructed with a customized computer-aided designed and manufactured 3D-printed titanium prosthesis (Figure 6.18a–d) (Liptak et al. 2017). The cat began eating the day following surgery and has experienced no eating dif iculties. While this is only a single case report, this case provides proof-of-principle that reconstruction of the mandible following mandibulectomy may be bene icial in preventing the common complications following mandibulectomy in cats. Incisional Swelling Swelling of the surgical site is common following non-rostral mandibulectomies (i.e. segmental and caudal mandibulectomy, and subtotal and total unilateral mandibulectomy) (Withrow and Holmberg 1983; Bradley et al. 1984; Salisbury and Lantz 1988; Kosovsky et al. 1991; White 1991; Dernell et al. 1998a; Northrup et al. 2006). Swelling resolves spontaneously in ive to seven days. Ice packing every four hours and the administration of non-steroidal anti-in lammatory drugs may assist in decreasing the severity of postoperative swelling. Ranula‐Like Lesions Ranula-like lesions are uncommon and appear as soft, luctuant, non-painful swellings in the frenulum of the tongue ipsilateral to the mandibulectomy procedure (Figure 6.19) (Withrow and Holmberg 1983;

Bradley et al. 1984; Salisbury and Lantz 1988; Kosovsky et al. 1991; White 1991; Dernell et al. 1998a). They are most frequently observed following either subtotal or total unilateral mandibulectomy. Ranula-like lesions may be caused by trauma to the mandibular and sublingual salivary ducts, but hematoma or seroma formation is more likely. Ranula-like lesions will usually spontaneously resolve and treatment is rarely required. Wound Dehiscence Wound dehiscence is reported in 13% of cats and 8–33% of dogs following mandibulectomy (Withrow and Holmberg 1983; Bradley et al. 1984; Salisbury and Lantz 1988; Kosovsky et al. 1991; White 1991; Dernell et al. 1998a; Northrup et al. 2006). Wound dehiscence most commonly occurs three to seven days after surgery. The two most common sites for wound dehiscence are over the rostral end of the osteotomized mandible and at the commissure of the lips (Figure 6.20). Tension at these sites is the most likely cause of dehiscence, although the use of cautery, rapidly absorbing suture material (i.e. catgut or poliglecaprone 25), and poor wound healing capabilities as a result of radiation therapy, chemotherapy, or debilitation may also contribute to wound dehiscence (Withrow and Holmberg 1983; Bradley et al. 1984; Salisbury and Lantz 1988; Kosovsky et al. 1991; White 1991; Dernell et al. 1998a; Northrup et al. 2006). Wound dehiscence can be managed with either second intention healing if the dehisced area is small and granulating, or debridement and resuturing if the defect is large. Dehiscence of the commissure of the lip usually requires surgical revision to improve the cosmetic appearance and the use of tension-relieving sutures, such as a vertical mattress pattern (Dernell et al. 1998a). If the tongue is the cause of tension and dehiscence, then tube feeding may be required for one to two weeks.

Figure 6.18 Reconstruction of a segmental mandibulectomy in a cat with a customized, 3D-printed titanium prosthesis. (a) The computer-aided design and manufactured titanium prosthesis; (b) An intraoperative view of the ixed customized titanium prosthesis following segmental mandibulectomy; (c and d) Lateral and ventrodorsal postoperative radiographs of the segmental mandibular reconstruction with a customized titanium prosthesis. Excessive Drooling Excessive drooling is common, particularly following bilateral rostral mandibulectomy in cats and dogs and resection of more than 50% of the mandible in cats (Withrow and Holmberg 1983; Bradley et al. 1984; Salisbury and Lantz 1988; Kosovsky et al. 1991; White 1991; Dernell et al. 1998a; Northrup et al. 2006). Ptyalism will either resolve spontaneously or signi icantly reduce in volume after several weeks in the majority of animals. However, for cats and dogs with persistent drooling, cheilitis and facial dermatitis are common sequalae. The management options for these complications include daily washing with an antiseptic solution and surgical chelioplasty.

Figure 6.19 A ranula-like lesion (arrow) in a dog one day following subtotal hemimandibulectomy for a malignant melanoma. These may represent either a hematoma or accumulation of saliva. Treatment is rarely required because these lesions often resolve spontaneously. Mandibular Drift and Malocclusion Mandibular drift is common following mandibulectomy, especially the more aggressive mandibulectomy techniques, and is characterized by the mandible drifting towards the contralateral side (Figures 6.16 and 6.21) (Withrow and Holmberg 1983; Bradley et al. 1984; Salisbury and Lantz 1988; Kosovsky et al. 1991; White 1991; Dernell et al. 1998a; Northrup et al. 2006). Mandibular drift is caused by a loss of mandibular support at either the mandibular symphysis or temporomandibular joint. Mandibular drift results in malocclusion and can predispose to osteoarthritis of the temporomandibular joints. Drift of the lower canine tooth towards the midline can cause ulceration and trauma to the overlying hard palate. This is rarely a problem in dogs but has been reported in up to 18% of cats especially following segmental mandibulectomy, mandibulectomy, and resection of more than 50% of the mandible (Withrow and Holmberg 1983; Bradley et al. 1984; Salisbury and Lantz 1988; Kosovsky et al. 1991; White 1991; Dernell et al. 1998a; Northrup et al. 2006). Mandibular drift does not require treatment unless the drift results in complications. For animals with secondary hard palate trauma, the lower canine tooth should either be extracted or shortened with vital pulpotomy (Dernell et al. 1998a). Reconstruction of the mandible with either ulnar or rib autografts and promotion of osseous ingrowth with bone morphogenetic protein-2 have been described to prevent or treat mandibular drift (Boudrieau et al. 1994, 2004; Bracker and Trout 2000; Spector et al. 2007), but this is rarely required and associated with increased expense and risk of complications.

Figure 6.20 Dehiscence of the commissure of the lips and rostral end of the osteotomized mandible in a dog following total hemimandibulectomy for a mandibular osteosarcoma. The dog healed following surgical revision.

Figure 6.21 Mandibular drift following subtotal hemimandibulectomy for a mandibular squamous cell carcinoma. While mandibular drift is typically considered asymptomatic, it will result in malocclusion and possibly palatine trauma and temporomandibular osteoarthritis. Mandibular reconstruction prevents mandibular drift, but this may not be necessary considering that mandibular drift is frequently a cosmetic and not a functional defect. Miscellaneous Complications Other complications reported following mandibulectomy include hemorrhage, infection, pain, dif iculty grooming, and osteoarthritis of the temporomandibular joint (Withrow and Holmberg 1983; Bradley et al. 1984; Salisbury and Lantz 1988; Kosovsky et al. 1991; White 1991; Dernell et al. 1998a; Northrup et al. 2006). Intraoperative hemorrhage can be profuse if the inferior alveolar artery is not ligated prior to subtotal or total unilateral mandibulectomy. To avoid this complication, the inferior alveolar artery should be identi ied on the caudomedial aspect of the mandible as it courses over the temporomandibular joint and pterygoid muscles before entering the mandibular foramen. Hemorrhage can be controlled with ligation, cautery, or a vessel sealing device of the inferior alveolar artery and vein. Alternatively, products which either chemically or physically promote hemostasis, such as Gelfoam or bone wax, can be used if the inferior alveolar vessels cannot be ligated. Hemorrhage from the inferior alveolar artery is rarely severe enough to warrant a whole blood transfusion, but blood loss should be carefully monitored and a cross-matched compatible blood transfusion considered if hematocrit acutely decreases below 15–30%, particularly if this occurs in combination with hypotension, hypoxia and/or clinical, biochemical or echocardiographic evidence of anaerobic metabolism (Jutkowitz 2004). Infection is very rare following mandibulectomy because of the rich vascular supply to the oral cavity (Dernell et al. 1998a). Incisional abscesses are treated with debridement, copious lavage with an isotonic

crystalloid solution, closure of dead space, drainage if possible, and culture-directed antibiotics. Osteoarthritis of the temporomandibular joint is a relatively common radiographic inding, particularly in any animal with mandibular drift, but rarely manifests as a clinical problem (Dernell et al. 1998a). If degenerative joint disease of the temporomandibular joint causes pain on opening of the jaw or eating dif iculties, then non-steroidal anti-in lammatory drugs and chondroprotective agents should be administered. Grooming dif iculties are a speci ic complication in cats, especially following mandibulectomy where 26% of cats have been reported to have long-term grooming problems (Northrup et al. 2006). The cause of these grooming dif iculties may be related to ptyalism, tongue protrusion, mandibular drift, and possibly pain. They are dif icult to manage and, in these cases, owners must groom their cats. Grooming dif iculties are infrequent (18%) but they do have a major impact on the perceived quality of life for affected cats (Northrup et al. 2006; Boston et al. 2020).

Surgical Approach to Tumors of the Maxilla Anatomy For successful maxillofacial surgery, a detailed knowledge of the anatomy is required. This includes a fundamental knowledge of the bones comprising the maxilla and face (frontal, nasal, maxillary, incisive, palatine, and pterygoid) (Figure 6.22a and b), but also a detailed appreciation of the three-dimensional relationship between the bones and various anatomic features of the skull. The best way to appreciate this is to have appropriate skulls (brachycephalic, mesocephalic, and dolichocephalic dog skulls and cat skulls) for review prior to and during surgery. During maxillary surgery, the close proximity of the nasal cavity and cranial cavity needs to be appreciated. A knowledge of the vascular anatomy of the maxilla and orbit is necessary because of the risk of hemorrhage and hypotension during maxillectomy procedures (MacLellan et al. 2018). This includes the major palatine and sphenopalatine arteries for rostral maxillectomies and the infraorbital artery and maxillary artery for caudal maxillectomies (Figure 6.22c and d) (Evans and de Lahunta 2013). Maxillectomy refers to the en bloc excision of a tumor on the upper jaw, which may involve parts of the incisive, palatine, lacrimal, zygomatic, frontal, and vomer bones in addition to the maxilla. The resultant defects are closed using soft tissue laps, particularly vestibular (e.g. alveolar and buccal) mucosalsubmucosal laps with or without palatal mucoperiosteal laps. Various maxillectomy procedures have been described, including incisivectomy (previously known as premaxillectomy), unilateral and bilateral rostral maxillectomy, central maxillectomy, and unilateral and bilateral caudal maxillectomy. Bilateral rostral maxillectomy can be combined with resection of the nasal planum if necessary or continue further caudally for a radical maxillectomy. Caudal maxillectomy can be combined with various orbitectomy procedures if necessary and can be performed either through an intraoral approach or combined intraoral-dorsolateral skin incision approach depending on the tumor location.

Incisivectomy Premaxillectomy is often used in the veterinary literature to describe excisions con ined to the incisive bone (Withrow et al. 1985). Premaxilla is not accepted veterinary anatomic nomenclature and incisivectomy is therefore more appropriate to describe resection of the area rostral to the canines.

Figure 6.22 Anatomy of the maxilla and skull. (a and b) A number of maxillectomy procedures have been described and these involve removal of part or all of the maxilla but may also involve en bloc removal of the incisive, nasal, zygomatic, frontal, and palatine bone. Source: Reproduced with permission from Evans, H.E., and deLahunta, A., ed. 2000. The head, in Guide to the Dissection of the Dog, 259–321. Philadelphia: Saunders.

(c and d) A knowledge of the vascular anatomy of the maxilla and orbit is essential, particularly for caudal maxillectomies, because of the potential for intraoperative hemorrhage. The major palatine and sphenopalatine arteries should be identi ied for rostral maxillectomies and the infraorbital and maxillary arteries for caudal maxillectomies. Source: Reproduced with permission from Evans, H.E., and Christensen, G.C., ed. 1979. Systemic arteries, in Miller’s Anatomy of the Dog, 652– 756. Philadelphia: Saunders.

Incisivectomy is recommended for dogs with benign epulides or small SCC lesions con ined to the incisive bone and associated incisors (Figure 6.23a). More aggressive rostral maxillectomy procedures should be considered for malignant tumors other than SCC and larger acanthomatous ameloblastoma and SCC lesions extending further caudally.

Figure 6.23 (a) A benign acanthomatous ameloblastoma arising from the periodontal ligament of the mandibular incisors. Note that this is a mandibular incisivectomy; (b) The incisivectomy has been performed with an oscillating saw. The labial and oral mucosa are closed in two layers. For incisivectomy, the dog is positioned in dorsal recumbency. The labial mucosa is incised with a minimum of 1 cm margins around the mass. The labial mucosa is re lected off the incisive bone with periosteal elevators to preserve the soft tissue of the lip which will be used later for reconstruction of the defect. The rostral hard palatine mucosa is also incised 1 cm caudal to the mass, but rostral to the canines (Withrow et al. 1985). Larger margins are used if the planned margins will damage existing tooth roots. An osteotomy is performed caudal to the mass along the hard palate mucosal incision. The extent of the bone resection will depend on whether or not, or how much, bone is involved in the neoplastic process. The nasal cavity is not usually entered in this procedure, but the ventrolateral nasal cartilages are exposed (Withrow et al. 1985). Bleeding is generally minor and is controlled by a combination of cautery, ligation, and direct pressure. The defect is closed with a labial mucosal-submucosal lap. The lap is created by undermining the labial mucosa to include the mucosa, submucosa, and as much subcutaneous tissue as possible, using Metzenbaum scissors (Withrow et al. 1985). Vertical releasing incisions are used if necessary. The lap is sutured into position with a two-layer closure, with the irst layer consisting of simple interrupted sutures pre-placed through holes pre-drilled in the bone of the hard palate. The labial and oral mucosa are opposed using simple interrupted sutures (Figure 6.23b) (Withrow et al. 1985).

Rostral Maxillectomy – Unilateral Unilateral rostral maxillectomy is recommended for dogs with benign acanthomatous ameloblastoma or SCC lesions located around the canine tooth and do not extend caudal to the second premolar tooth (Dernell et al. 1998b). Bilateral rostral maxillectomy should be considered for these tumor types which cross the midline and hemimaxillectomy is recommended for unilateral lesions extending caudal to the second premolar tooth. Dogs are positioned in either dorsal or dorsolateral recumbency because the majority of tumors can be resected via an intraoral approach. At this level, the sphenopalatine, major palatine, and infraorbital vessels are larger than at the incisive bone, and bleeding can be more substantial. The surgical technique for unilateral rostral maxillectomy is similar to incisivectomy. The labial and gingival mucosa and palatine mucoperiosteum are incised with a minimum of 1 cm margins around the mass (Figure 6.24a) (Dernell et al. 1998b). Bleeding from the transected major palatine artery can be brisk following the palatine incision, but this can usually be controlled with digital pressure although occasionally ligation or cautery may be required (Dernell et al. 1998b). The mucosa is then re lected off the underlying bone with periosteal elevators to preserve the soft tissues which will be used later for reconstruction of the defect. Osteotomies are performed in the maxilla, incisive bone, and hard palate with either a pneumatic burr, small oscillating saw, biradial saw (Figure 6.24b), or osteotome and mallet (Dernell et al. 1998b). The caudal bone cuts are performed last so bleeding can be quickly controlled after the tumor and bone segment are removed. The

nasal cavity is exposed during unilateral rostral maxillectomy (Figure 6.24c). Bleeding can be signi icant from the turbinates, and a combination of tamponade and ice-cold saline or 0.05% oxymetazoline spray can be used for hemostasis. Cautery is rarely successful for turbinate bleeding. The defect is closed with a labial mucosal-submucosal lap as described for incisivectomy. The lap is created by undermining the labial mucosa to include the mucosa, submucosa, and as much subcutaneous tissue as possible (Figure 6.24d) (Dernell et al. 1998b). It is important to undermine suf icient tissue to prevent the overlying skin from being drawn medially resulting in a poor cosmetic result. The lap is sutured into position with a two-layer closure, with the irst layer consisting of simple interrupted sutures pre-placed through holes pre-drilled in the bone of the hard palate (Figure 6.24e and f). The labial and oral mucosa are opposed using simple interrupted sutures (Figure 6.24g) (Dernell et al. 1998b).

Figure 6.24 Unilateral rostral maxillectomy. (a) The labial and gingival mucosa and palatine mucoperiosteum are incised with minimum margins of 1 cm (dotted lines). Following these incisions, bleeding from the transacted major palatine artery may be brisk and should be controlled with digital pressure; (b) A 30 mm biradial saw is being used to perform a unilateral rostral maxillectomy on a dog with an acanthomatous ameloblastoma. These osteotomies can also be performed with a pneumatic burr, oscillating saw, and an osteotome and mallet. (c) Following elevation of the incised mucosa (M) and lateral (LO), rostral (RO), caudal (C), and medial (MO) osteotomies, the resected segment of maxilla is removed and the nasal cavity (NC) is exposed; (d) The submucosa-mucosa of the adjacent lip is undermined to create a labial mucosal lap for reconstruction of the intraoral defect and also minimize the lip being drawn medially resulting in a poor cosmetic result; (e) The resultant defect is closed in two layers. Holes are predrilled into the bone of the hard palate; (f) The deep layer consists of simple interrupted sutures through these predrilled holes in the bone of the hard palate and labial submucosa; (g) Then the labial and oral mucosa are opposed using simple interrupted or simple continuous sutures of mono ilament absorbable suture material. Source: Line diagram (24A) reproduced with permission from Dernell, W.S., Schwartz, P.D., and Withrow, S.J. 1998. Maxillectomy and premaxillectomy, in Current Techniques in Small Animal Surgery, ed. Bojrab, M.J., Ellison, G.W., and Slocum, B., 124–132. Baltimore: Williams & Wilkins, Baltimore.

Figure 6.25 Bilateral rostral maxillectomy. (a) Bilateral rostral maxillectomy is indicated for dogs with benign invasive tumors, such as this dog with an acanthomatous epulis, or small squamous cell carcinoma lesions rostral to the second premolar tooth and crossing the midline; (b) Following incisions in the labial and gingival mucosa and palatine mucoperiosteum, the mucosa and mucoperiosteum are then re lected with periosteal elevators to protect soft tissues from trauma during maxillectomy; (c) The bilateral rostral maxillectomy is performed with an oscillating saw using minimum caudal margins of 1–2 cm for benign tumors, such as this acanthomatous epulis, and 2–3 cm for malignant tumors. Bleeding can be brisk from the nasal cavity (arrow) and transection of the major palatine arteries (arrowhead); (d) The resultant defect is closed in two layers. The deep layer consists of simple interrupted sutures through predrilled holes in the bone of the hard palate and labial submucosa, and then the labial and mucoperiosteum of the hard palate are opposed, often in a T-shape, using simple interrupted or simple continuous sutures of mono ilament absorbable suture material.

Rostral Maxillectomy – Bilateral Bilateral rostral maxillectomy is recommended for dogs with benign acanthomatous ameloblastoma or SCC lesions located rostral to the second premolar teeth and crossing the midline (Figure 6.25a) (Dernell et al. 1998b). Bilateral rostral maxillectomy can be combined with resection of the nasal planum for tumors

involving both the nasal planum and rostral maxilla (Kirpensteijn et al. 1994). Radical maxillectomy should be considered for SCC lesions extending caudal to the second premolar teeth, malignant tumors other than SCC located rostral to the second premolar teeth and crossing the midline of the palate, and any tumor type invading into the nasal cavity and cartilages (Lascelles et al. 2004). Dogs are positioned in dorsal recumbency for bilateral rostral maxillectomy because resection and reconstruction are performed through an intraoral approach. The surgical technique for bilateral rostral maxillectomy is similar to unilateral rostral maxillectomy. The labial and gingival mucosa and palatine mucoperiosteum are incised with a minimum of 1 cm margins around the mass. Bleeding from the transected major palatine artery can be brisk following the palatine incision, but this can usually be controlled with digital pressure although occasionally ligation or cautery may be required (Dernell et al. 1998b). The mucosa is then re lected off the underlying bone with periosteal elevators to preserve the soft tissues which will be used later for reconstruction of the defect (Figure 6.25b). Osteotomies are performed in the maxilla and hard palate with an oscillating saw, but a pneumatic burr or osteotome and mallet can also be effective. The nasal cavity is exposed during bilateral rostral maxillectomy (Figure 6.25c). Bleeding can be signi icant from the turbinates, and a combination of tamponade and ice-cold saline or 0.05% oxymetazoline spray can be used for hemostasis. Cautery is rarely successful for turbinate bleeding. The defect is closed with bilateral labial mucosal-submucosal laps. The laps are created by undermining the left and right-sided rostral labial mucosa to include the mucosa, submucosa, and as much subcutaneous tissue as possible. The laps are sutured in a T-shape with a two-layer closure, with the irst layer consisting of simple interrupted sutures pre-placed through holes pre-drilled in the bone of the hard palate. The labial and oral mucosa are opposed using simple interrupted sutures (Figure 6.25d) (Dernell et al. 1998b). To minimize drooping of the nose, which is a common postoperative cosmetic defect following bilateral rostral maxillectomy because of loss of ventral support (Figure 6.26a and b), the nasal bone should be preserved at the point where the nasal cartilages attach. Alternatively, a cantilever suture technique has been described in which a buried mattress suture is used to elevate the nasal cartilage (Figures 6.26c–f and 6.27) (Pavletic 2018).

Rostral Maxillectomy – Bilateral Combined with Nasal Planum Resection Bilateral rostral maxillectomy combined with nasal planum resection is indicated for SCC of the nasal planum which has invaded the incisive area or rostral maxilla (Figure 6.28a) (Kirpensteijn et al. 1994). Dogs are positioned in sternal recumbency with the mouth held open using a gag. The head should be elevated to facilitate access to the oral cavity for resection and reconstruction. The nasal planum, labial and gingival mucosa, and palatine mucoperiosteum are incised a minimum of 1 cm caudal to the extent of the tumor (Kirpensteijn et al. 1994). The nasal planum excision usually involves fullthickness incisions through the rostral lips (Figure 6.28b). The mucosal incisions extend transversely across either the incisive region or rostral maxilla to join the full thickness incisions in the left and right rostral lips. The osteotomy is performed from a dorsal approach and preferably with an oscillating saw (Figure 6.28c). The resultant defect is reconstructed by drawing the free edges of the lip to the rostral maxilla so that the left and right lips meet in the midline of the rostral extent of the excised palate thus recreating a continuous rostral lip (Figure 6.28d). The labial submucosa is sutured to bone tunnels drilled in the hard palate and the labial mucosa to the palatine mucosa. Depending on the level of resection, reconstruction of the new nasal ori ice is achieved by suturing the skin to the edge of the nasal cartilages or the nasal bone. Simple continuous purse strings have been described for closure of the nasal opening to an appropriate size (Kirpensteijn et al. 1994), but this approach can result in stenosis of the nasal aperture and respiratory complications. If nasal planum resection has been combined with an incisivectomy, then the skin is sutured to the nasal cartilages in a single layer of simple interrupted sutures. For the combination of nasal planum resection with a bilateral rostral maxillectomy, a two-layer closure is preferred with subcutaneous tissue sutured to bone tunnels drilled in the maxillary bone and skin to the nasal mucosa using a simple interrupted suture pattern (Figure 6.28e and f) (Kirpensteijn et al. 1994). Alternatively, the nasal planum can be cosmetically reconstructed using bilateral rotation-advancement laps of the non-haired margins of the labial mucocutaneous junction (Figure 6.29) (Gallegos et al. 2007; Dickerson et al. 2019).

Radical Maxillectomy Radical bilateral maxillectomy is recommended for tumors of the rostral maxilla extending dorsally into the nasal cavity and malignant tumors other than SCC caudal to the second premolar teeth and extending across the midline (Lascelles et al. 2004).

Figure 6.26 (a and b) Typical drooped nose cosmetic appearance following bilateral rostral maxillectomy in dogs. The severity can vary from mild (a) to more pronounced (b), depending on the level of the maxillectomy caudally); (c) For the cantilever suture technique, a 3–5 cm skin incision is performed along the dorsal midline of the maxilla rostral to the medial canthus of each eye. The skin is undermined and retracted to expose the nasal and maxillary bones and a hole is drilled transversely across the maxilla immediately ventral to the nasal bone with a small Steinmann pin; (d) Large gauge (1 to 1-0) mono ilament suture material is passed through the hole using either a straight swaged-on needle (pictured) or a hypodermic needle as a guide; (e) A 1 cm incision is made through the epithelial surface of each lateral cartilage. The swaged-on needle is passed rostrally deep to the skin and exiting through the lateral cartilage incision on one side of the nasal planum, redirected perpendicularly and passed transversely through the ipsilateral lateral cartilage incision across the nasal planum and exiting through the contralateral lateral cartilage incision, and then redirected perpendicularly through the second lateral cartilage incision and caudally deep to the skin and exiting at the dorsal muzzle incision; (f) The suture material is tightened with a surgeon’s knot to evaluate the appropriate tension for the cantilever suture before completing the knot. Source: (b) Courtesy Bernard Séguin.

Figure 6.27 (a) For the cantilever suture technique, a 3–5 cm skin incision is performed along the dorsal midline of the maxilla rostral to the medial canthus of each eye. The skin is undermined and retracted to expose the nasal and maxillary bones. A hole is drilled transversely across the maxilla immediately ventral to the nasal bone with a small Steinmann pin. (b) A large gauge (1 to 1-0) mono ilament suture material is passed through the hole using either a straight swaged needle or a hypodermic needle as a guide. (c) A 1 cm incision is made through the epithelial surface of each lateral cartilage. The swaged needle is passed rostrally deep to the skin, exits through the lateral cartilage incision on one side of the nasal planum. It is redirected perpendicularly and passed transversely through the ipsilateral lateral cartilage incision across the nasal planum, exits through the contralateral lateral cartilage incision, and then is redirected perpendicularly through the second lateral cartilage incision and caudally deep to the skin. It exits at the dorsal muzzle incision. (d) The cantilever suture is then tightened resulting in elevation of the rostral nose. Source: Illustrations courtesy of Dave Carlson.

The surgical approach is similar to nasal planum resection combined with bilateral maxillectomy with the incisions being made more caudally. Dogs are positioned in sternal recumbency with the mouth held open using a gag. The head should be elevated to facilitate access to the oral cavity for resection and reconstruction.

The irst drape is placed in the mouth over the mandible, tongue, and endotracheal tube, but not pressed tightly against the commissures of the lip because these should be mobile to permit labial advancement for reconstruction of the nasal defect (Lascelles et al. 2004). Additional drapes are placed around the maxilla with the eyelids exposed for orientation. Skin, labial and gingival mucosa, and palatine mucoperiosteum are incised a minimum of 2 cm, and preferably 3 cm, caudal to the extent of the tumor as determined by advanced imaging and intraoperative palpation. The skin incision involves full-thickness incisions through the lips perpendicular to the labial margin and extending dorsally and transversely across the maxilla (Figure 6.30a and b) (Lascelles et al. 2004). As the skin incision is continued deeply through the subcutis tissue and nasolabial muscles, the infraorbital neurovascular bundle should be ligated and transected. The mucosal incisions extend transversely across the alveolar margins and palate to join the full thickness incisions in the left and right lips. The osteotomy is performed from a dorsal approach with an oscillating saw perpendicular to the maxilla and nasal bones. To facilitate reconstruction, the osteotomy should be performed slightly caudal to the level of the skin and mucosal incisions (Figure 6.30c).

Figure 6.28 (a) Bilateral rostral maxillectomy combined with nasal planum resection is indicated in this dog with a nasal planum squamous cell carcinoma invading into the incisive bone; (b) The labial and gingival mucosal and palatine mucoperiosteal incisions are continued along the same sagittal plane through the right and left rostral lips and dorsal to the nasal planum in a cat with an invasive nasal planum squamous cell carcinoma; (c) The nasal planum is resected en bloc with either the incisive bone, as depicted in this intraoperative image, or rostral maxilla; (d) The resultant defect with free lip edges following en bloc removal of the resected nasal planum and incisive bone; (e and f) For closure of the defect, the labial submucosa is sutured to predrilled bone tunnels in the palatine bone and the labial mucosa is sutured to the mucoperiosteum of the hard palate using absorbable mono ilament suture material in either a simple interrupted or continuous suture pattern. The free edges of the lip are sutured in the rostral midline with a standard two-layer closure.

Figure 6.29 An 18-day postoperative image of a dog with a nasal planum resection for treatment of a stage III malignant melanoma reconstructed with bilateral rotation-advancement laps of the non-haired margins of the labial mucocutaneous junction. The resultant defect is reconstructed by drawing the free edges of the lip to the rostral maxilla so that the left and right lips meet in the midline of the rostral extent of the excised palate (Lascelles et al. 2004). This creates a continuous rostral lip and new nasal ori ice and also divides the nasal and oral cavities. Recreation of the rostral lip requires either a unilateral or bilateral labial lap (Lascelles et al. 2004). The labiogingival re lection on each side is incised as necessary to mobilize the labial lap. The mucosa of the labial laps is removed except for a 0.5–1.0 cm width adjacent to the labial margin (Figure 6.30d). This distance is determined by apposing the labial tissues to identify the contact point of the palatine mucosa and labium, and then assessing how much of the reconstructed lip will project ventrally from the palatine mucosa (Lascelles et al. 2004). The lip can interfere with food transfer into the oral cavity if this margin is excessive. Once the mucosa is excised, the labial submucosa is sutured to bone tunnels drilled in the hard palate and the labial mucosa to the palatine mucoperiosteum (Figure 6.30e) (Lascelles et al. 2004). Next, the labial skin margins are sutured together using a igure-of-eight suture pattern (Figure 6.30f). To reconstruct the nasal ori ice, the skin edges are sutured to bone tunnels drilled in the maxillary bone using either a rolling

igure-of-eight or simple interrupted suture pattern (Figure 6.30g). Suture tightening results in the skin covering the rostral edge of the maxilla (Figure 6.30h) (Lascelles et al. 2004).

Caudal Maxillectomy – Intraoral Approach Caudal maxillectomy via an intraoral approach is recommended for unilateral benign and malignant tumors located along the alveolar margins of the mid-to-caudal maxilla (Figure 6.31a) (Dernell et al. 1998b). A combined intraoral and dorsolateral approach is preferred for more extensive tumors, particularly those with involvement of the lateral maxilla and ventral orbit, because of better exposure and ability to achieve hemostasis and superior ability to achieve surgical margins (Dernell et al. 1998b; Lascelles et al. 2003). Advanced imaging is recommended for tumors of the caudal maxilla and orbit to determine the extent of the tumor, resectability of the tumor, and to plan the surgical approach. In some cases, particularly those with more extensive involvement of the orbit, enucleation may be required to improve exposure and likelihood of achieving complete excision of the tumor. The possibility of enucleation and adjuvant radiation therapy if the tumor is incompletely excised should be discussed with the owner prior to surgery.

Figure 6.30 Radical maxillectomy. (a and b) The labial and gingival mucosal and palatine mucoperiosteal incisions are continued along the same sagittal plane through the right and left rostral lips and skin along the dorsal maxilla in a dog with a bilateral rostral oral ibrosarcoma (a, dorsal view) and a dog with an invasive nasal planum squamous cell carcinoma (arrow) (b, lateral view); (c) An osteotomy is performed with an oscillating saw from a dorsal approach perpendicular to the maxilla with a minimum of 2–3 cm margins caudal to the tumor; (d) A portion of the labial mucosa is removed (X) to establish a neolabiopalatine margin of 1 cm wide (A′ to a′ when sutured in place). A′ to a′ is the distance the new lip will hang over the palatine mucosa at the rostral end of the maxilla, and this creates the new palatobuccal recess rostrally. The lap will be transposed and sutured (A′ to A, a′ to a, b′ to b, and c′ to c); (e) Bone tunnels are drilled into the rostral bone of the hard palate so that the deep layer of the intraoral closure can be performed by suturing the labial submucosa to these bone tunnels (arrow). The intraoral closure is completed by suturing the labial mucosa to the mucoperiosteum of the hard palate in either a simple interrupted or simple continuous pattern using absorbable mono ilament suture material; (f) Figure-ofeight suture pattern. The lip margins from the left and right sides are aligned with a igure-of-eight suture pattern (a) and a horizontal mattress suture pattern is used to accurately align the lip margin with the knot tied away from the lip margin. The remainder of the skin is closed with simple interrupted sutures (b); (g) Rolling igure-of-eight sutures are used to roll the skin around the edge of the maxillary bone to hasten mucocutaneous healing and to cover the exposed edges of the maxilla; (h) To reconstruct the nasal ori ice, the skin edges are sutured to bone tunnels in the maxillary bone using either a rolling igure-of-eight (see (g)) or simple interrupted pattern and the lip is reconstructed along the rostral aspect of the maxilla (see (d)). Source: Some images (6.30C-6.30E) and line diagrams (6.30F and 6.30G) reproduced with permission from Lascelles, B.D.X., Henderson, R.A., Seguin, B., et al. 2004. Bilateral rostral maxillectomy and nasal planectomy for large rostral maxillofacial neoplasms in six dogs and one cat. J Am Anim Hosp Assoc 40:137–146.

Dogs are positioned in lateral or dorsolateral recumbency with the mouth held open using a gag. The gingival mucosa and mucoperiosteum of the hard palate are incised with appropriate margins around the mass, depending on whether the tumor is benign or malignant (Figure 6.31b). Bleeding can be brisk following the palatine incision because of transection of the major palatine artery or its branches, but this can usually be controlled with digital pressure, cautery, or ligation (Dernell et al. 1998b). The mucosa and mucoperiosteum are then re lected off the underlying maxillary and palatine bone with periosteal elevators to preserve the soft tissues which will be used later for reconstruction of the defect (Figure 6.31c). Osteotomies are performed in the maxilla and hard palate with either a pneumatic burr, small oscillating saw, or osteotome and mallet. The rostral and lateral osteotomies are performed initially, followed by the palatine and caudal osteotomies (Dernell et al. 1998b). The caudal osteotomy can be dif icult to complete because of poor access and visibility. This is preferably performed with an osteotome and mallet with the osteotome started at the junction between the ventral orbit and caudal maxilla, caudal to the molar teeth, and directed rostrally to connect the lateral maxilla and palatine osteotomies. The palatine and caudal osteotomies are performed last because of the greater potential for hemorrhage from the nasal turbinates and maxillary artery, respectively (Dernell et al. 1998b). If possible, the maxillary artery should be ligated prior to resection, although this can be dif icult from an intraoral approach because of poor exposure and visibility. Following completion of the osteotomies, the free bone segment should be gently elevated and removed (Figure 6.31d). Bleeding from the surgical site is then controlled with either suture or metallic clip ligation or cautery for vessels, and a combination of tamponade and ice-cold saline or 0.05% oxymetazoline spray for bleeding from the turbinates. Cautery is rarely successful for turbinate bleeding. The defect is closed with a labial mucosal-submucosal lap as described for other maxillectomy procedures (Dernell et al. 1998b). The lap is created by undermining the labial mucosa to include the mucosa and submucosa (Figure 6.31e). It is important to undermine suf icient tissue to prevent the overlying skin from being drawn medially resulting in a poor cosmetic result. The lap is sutured into position with a two-layer closure, with the irst layer consisting of simple interrupted sutures pre-placed through holes pre-drilled in the bone of the hard palate. The labial and oral mucosa are opposed using a simple interrupted or continuous suture pattern (Figure 6.31f and g) (Dernell et al. 1998b).

Caudal Maxillectomy – Combined Approach

Caudal maxillectomy via a combined intraoral and dorsolateral approach is recommended for tumors of the mid-to-caudal maxilla which either arise or extend dorsolaterally and/or caudally to the alveolar margin (Figure 6.32a) (Dernell et al. 1998b; Lascelles et al. 2003). The combined approach provides better exposure, and thus improved ability to achieve hemostasis and completely excise the tumor, compared to the intraoral approach for more extensive caudal maxillary tumors (O'Brien et al. 1996; Lascelles et al. 2003); however, excessive intraoperative bleeding is more common with maxillectomies performed via a combined approach (83%) compared to dogs with maxillectomies performed via an intraoral approach (54%) (MacLellan et al. 2018), which may be a re lection of larger tumors being more commonly resected with the combined approach. As discussed previously, advanced imaging is recommended for tumors of the caudal maxilla and orbit to determine the extent of the tumor, resectability of the tumor, and to plan the surgical approach (Figure 6.1). In some cases, particularly those with more extensive involvement of the orbit, enucleation may be required to improve exposure and likelihood of achieving complete excision of the tumor. The possibility of enucleation and adjuvant radiation therapy if the tumor is incompletely excised should be discussed with the owner prior to surgery. Dogs are positioned in lateral recumbency with the mouth held open using a gag. The dorsolateral skin incision is created irst with an incision lateral to midline of the dorsal aspect of the nasal cavity and extending caudally and ventrally to the eye along the zygomatic bone (Figure 6.32b) (Lascelles et al. 2003). This incision is continued through the subcutaneous tissue, between the paired levator nasolabial muscles, and down to bone (Figure 6.32c). Caudally, the ventral aspect of the globe is separated from the dorsal zygoma with a combination of sharp and blunt dissection leaving the conjunctival sac intact, while the masseter muscle is elevated from the ventral aspect of the zygomatic arch using a combination of sharp and blunt dissection (Figure 6.32d) (Lascelles et al. 2003). The most common complication of the combined approach for caudal maxillectomy is blood loss from the maxillary artery (Lascelles et al. 2003). The maxillary artery should be ligated early in the procedure to prevent this complication. The maxillary and palatine arteries are exposed deep within the orbit by carefully retracting the globe dorsally and ligated with either suture material or metallic clips. Exposure may be limited and can be improved by resecting the zygomatic arch rostral to the orbital ligament (Lascelles et al. 2003); however, this is often dif icult and ligation of the maxillary artery is frequently completed at the end of the procedure when the bone segment is freed. The tumor should be excised with appropriate margins depending on whether it is benign or malignant. The dorsal margins are prepared by re lecting the periosteum and associated soft tissues with a periosteal elevator. A second incision is made in the buccal mucosa dorsal to the gingiva and with appropriate margins through an intraoral approach (Figure 6.32e). The mucosal incision is continued down to the bone and undermined with periosteal elevators and scissors to connect the mucosal and dorsal skin incisions and create a bipedicle lap (Lascelles et al. 2003). The infraorbital artery and vein, which will be encountered during this dissection along with the infraorbital nerve, should be individually ligated. The facial vein should also be ligated at the most dorsocaudal aspect of the incision (Figure 6.32f), but the facial vein should be preserved at the level of the dorsal nasal tributary, if possible, to facilitate venous drainage from the muzzle (Lascelles et al. 2003).

Figure 6.31 (a) Caudal maxillectomy through an intraoral approach is recommended for benign and malignant tumors involving alveolar margins of the mid-to-caudal maxilla and not crossing the midline of the hard palate, such as this oral ibrosarcoma in a dog; (b) The labial and gingival mucosa and palatine mucoperiosteum are incised with appropriate margins around the tumor (dotted lines), and a gauze sponge (a) is been placed into the caudal oropharynx to prevent passive aspiration of blood and lavage luid intraoperatively; (c) Following incisions using appropriate margins in the gingival and labial mucosa and palatine mucoperiosteum, the mucosa and mucoperiosteum are re lected off their underlying bone to protect the soft tissues from trauma during osteotomies and preserve these soft tissues for reconstruction of the defect; (d) Rostral, lateral and caudal maxillary and medial palatine osteotomies have been performed and the bone segment is then gently elevated to minimize damage to the underlying nasal turbinates; (e) The submucosa-mucosa of the adjacent lip is undermined to create a labial mucosal lap for reconstruction of the intraoral defect and also minimize the lip being drawn medially resulting in a poor cosmetic result; (f and g) The resultant defect (f) with exposure of the nasal cavity (NC) is closed in two layers. The deep layer consists of simple interrupted sutures through predrilled holes in the bone of the hard palate and labial submucosa, and then the labial and oral mucosa are opposed using simple interrupted or simple continuous sutures of mono ilament absorbable suture material (g). Source: Line diagrams (30B and 30E) reproduced with permission from Dernell, W.S., Schwartz, P.D., and Withrow, S.J. 1998. Maxillectomy and premaxillectomy, in Current Techniques in Small Animal Surgery, ed. Bojrab, M.J., Ellison, G.W., and Slocum, B., 124–132. Baltimore: Williams & Wilkins, Baltimore.

Figure 6.32 (a) A caudal maxillectomy through combined approach is recommended for tumors which arise or extend dorsolaterally from the caudal maxilla or inferior orbit, such as this squamous cell carcinoma arising from the rostral inferior orbit and zygomatic arch; (b) A skin incision is performed along the dorsolateral aspect of the muzzle and extending ventral to the eye and along the zygomatic arch; (c) This incision is then continued through the subcutaneous tissues and to the level of the bone. Note the skin margins around the biopsy site (arrow) which will be excised en bloc with the maxillary bone segment; (d) If required, the masseter (M) and temporalis (T) muscles should be incised and elevated from the zygomatic arch; (e) A second incision is performed intraorally in the buccal mucosa with a minimum of 1 cm margins from the tumor (arrow); (f) During development of the bipedicle lap, the facial vein (FV) may require ligation in the caudal aspect of the skin incision (X) but should be preserved if possible to facilitate venous drainage postoperatively (LNL, super icial levator nasolabialis muscle; DNV, dorsal nasal vein; and LNV, lateral nasal vein); (g) Following periosteal elevation of the muscles and appropriate hemostasis, the bipedicle lap can be retracted dorsally or ventrally to improve exposure for tumor excision (squmaous cell carcinoma, arrow); (h–k) The position of the osteotomies is dependent on the tumor type and location, however, in general, osteotomies are performed with an oscillating saw in the zygomatic arch (1), with either an oscillating saw, osteotome and mallet or pneumatic burr in the dorsolateral (3; i) and rostral (2; j) maxilla, with an oscillating saw or osteotome and mallet in the hard palate (k), and then through the inferior orbit (a) with an osteotome and mallet to connect the dorsolateral maxilla and hard palate osteotomies; (l) The osteotomized bone segment is then gently elevated from the surgical site and removed; (m) The deep layer of the intraoral closure is best performed through the skin incision with simple interrupted sutures between the buccal–labial submucosa and predrilled holes in the bone of the hard palate (arrowheads); (n) The buccal–labial mucosa is sutured to the mucoperiosteum of the hard palate using either a simple interrupted or continuous pattern of absorbable mono ilament suture material; (o) The dorsolateral skin incision is closed routinely. Source: Some images (6.32F and 6.32H) reproduced with permission from Lascelles, B.D.X., Thomson, M.L., Dernell, W.S., et al. 2003. Combined dorsolateral and intraoral approach for the resections of tumors of the maxilla in the dog. J Am Anim Hosp Assoc 39:294–305.

The bipedicle lap can be retracted dorsally and ventrally to allow visualization of the lateral aspect of the maxilla and improve exposure for tumor excision (Figure 6.32g) (Lascelles et al. 2003). The dorsal and rostral maxillary osteotomies are performed at appropriate margins from the tumor with an oscillating saw, pneumatic burr, or osteotome (Figure 6.32h–j). An incision is then made through the mucoperiosteum of the hard palate medial to the alveolar margin or as dictated by the margins of the tumor. The major palatine artery or its branches may be transected during this incision and bleeding from these vessels can be controlled with either digital pressure, cautery, or ligation. The mucoperiosteum is elevated with a periosteal elevator to preserve the soft tissues which will be used later for reconstruction of the defect. An osteotomy is performed in the palatine bone from the ventral aspect of the rostral maxillary osteotomy and extending caudally to the planned caudal extent of the excision (Figure 6.32k). Finally, the caudal osteotomy is completed such that it connects the caudal aspects of the dorsal maxillary and palatine osteotomies (Lascelles et al. 2003). Both the palatine and caudal osteotomies can be performed with either an oscillating saw or osteotome and mallet. If the caudal osteotomy involves the inferior orbit, then this is preferably performed with an osteotome and mallet with the osteotome started at the junction between the ventral orbit and caudal maxilla, caudal to the molar teeth, and directed rostrally to connect the lateral maxillary and palatine osteotomies. The maxillary artery courses deeply through the caudoventral aspect of the ventral orbit. If the maxillary artery has not been previously ligated, then it should be ligated with either suture material or metallic clips at this stage (Lascelles et al. 2003). Following completion of the osteotomies, the free bone segment should be gently elevated and removed (Figure 6.32l). Bleeding from the surgical site is then controlled with either suture or metallic clip ligation or cautery for vessels, and a combination of tamponade and ice-cold saline or 0.05% oxymetazoline spray for bleeding from the turbinates. Cautery is rarely successful for turbinate bleeding. The intraoral incision is closed irst. This is best approached from a dorsal direction through the bipedicle lap (Lascelles et al. 2003). The degree of tension on the lip should be assessed prior to closure. To minimize tension and to prevent the lip from being drawn medially resulting in a poor cosmetic result, particularly following extensive resection of the hard palate, a labial mucosal-submucosal lap may be required. The lap is sutured into position with a two-layer closure (Figure 6.32m and n). If this closure is performed through the dorsal skin incision, then the labial mucosa and mucoperiosteum of the hard palate

are opposed using a simple interrupted or continuous suture pattern. The thick ibrovascular free edge of the lip is sutured to pre-drilled holes in the bone of the hard palate (Lascelles et al. 2003). If this closure is performed through an intraoral approach, which tends to be more awkward, then the lip submucosa to palatine bone closure is performed irst followed by the mucosa–mucoperiosteum closure. Finally, the dorsolateral skin incision is closed routinely (Figure 6.32o). No attempt is made to close the dead space between the oral and lateral nasal incisions. Drains are not required, as the surgical site opens into the nasal cavity and drainage occurs via the nasal ori ice.

Bilateral Caudal Maxillectomy Bilateral caudal maxillectomy is recommended for benign and malignant tumors located in the caudal aspect of the hard palate or tumors located along the alveolar margins of the mid-to-caudal maxilla that extend into the hard palate where the resection needs to cross midline (Tuohy et al. 2019). Advanced imaging is recommended for tumors of the caudal maxilla to determine the extent and resectability of the tumor, and for surgical planning. Dogs are positioned in dorsal recumbency with the mouth held open using a gag (Figure 6.33a). Bilateral buccal mucosal incisions are made, dissecting down to the bone at the proposed level for appropriate margins (Figure 6.33b), which can include removal of infraorbital foramen rostrally, and extending caudally to caudal most molar. The soft tissues are elevated from the bone with periosteal elevators. An incision is made across the mucoperiosteum of the hard palate spanning from left to right, rostral to the tumor. The palatine arteries are transected during the mucoperiosteal incision, and hemorrhage is controlled with pressure, ligation, or metal clips. An incision parallel to the mucoperiosteal incision is made caudally in the soft palate, caudal to the tumor, and hemorrhage is controlled again (Figure 6.33c). A sagittal bone saw is used to perform the osteotomies. The dorsolateral osteotomies are performed in the left and right maxilla, aligned parallel from the buccal side of the proposed resection and into the nasal cavity (Tuohy et al. 2019). The caudal osteotomy is performed into the left and right palatine bones directly caudal to the nasal spine of the palatine bones, into the ventral aspect of the perpendicular lamina. The rostral osteotomy transects the hard palate rostral to the tumor bilaterally. Osteotomes can be used to transect the remaining perpendicular lamina of the palatine bones, rostral to their nasal spine, and residual maxilla. The crest of the vomer bone and the nasal septum is broken by a combination of manually twisting the bone specimen with the tumor and an osteotome. The pterygopalatine portion of the maxillary artery might have to be ligated and transected. Scissors are used to transect any residual soft tissue attachments, such as the nasal mucosa (Tuohy et al. 2019). The maxillary segment is removed (Figure 6.33d). Bleeding from the surgical site is then controlled with either ligatures, metallic clips, or cautery for vessels, and a combination of tamponade and ice-cold saline or 0.05% oxymetazoline spray for bleeding from the turbinates. Cautery is rarely successful for turbinate bleeding.

Figure 6.33 Segmental maxillectomy in a dog with a biologically high-grade, histologically low-grade ibrosarcoma of the hard palate. (a) The dog is positioned in dorsal recumbency with the mouth held open by a gag; (b) Bilateral incisions are made along the buccal mucosa down to the level of the bone; (c) Transverse incisions are made through the mucoperiosteum of the hard palate rostral and caudal to the mass with appropriate surgical margins; (d) Following rostral and caudal osteotomies through the hard palate with an oscillating saw, the segmental maxillectomy segment is removed from the surgical site; (e and f) The segmental maxillectomy site is closed with bilateral labial mucosal-submucosal laps. The defect can be closed using either labial mucosal-submucosal laps (Figure 6.33e and f) or an angularis oris axial pattern lap (Tuohy et al. 2019). Buccal mucosal laps are elevated while preserving the angularis oris vessels bilaterally and the laps are apposed on midline over the hard palate defect. The rostral edges of the buccal mucosal laps are apposed to the mucoperiosteum of the remaining hard palate. Predrilled holes can be created in the palatine process of the maxilla to anchor sutures. The remaining soft palate is apposed to the caudal edges of the bilateral buccal mucosal laps. An interrupted suture pattern is recommended. Alternatively, the angularis oris axial pattern lap is created unilaterally and used to close the hard palate defect. Localized buccal mucosal laps are used to cover any remaining defects around the islandized angularis oris lap. The angularis oris lap donor site can be left uncovered and allowed to heal by second intention.

Surgical Approach to Tumors of the Maxilla in Cats The surgical approach for management of benign and malignant tumors of the maxilla is similar to dogs. Maxillectomy in cats is complicated by the small size of the maxilla relative to the size of the oral tumor and the recommendation for 1 cm margins for benign lesions and 3 cm margins for malignant tumors. As a result, less aggressive procedures such as rostral maxillectomy are rarely possible using these margins, but they are with lesser margins (Liptak et al. 2020). Hemimaxillectomy, either via an intraoral or combined approach (Figure 6.34a–d), is the most commonly indicated and performed procedure for the management of maxillary tumors in cats. Temporary carotid artery occlusion should not be performed in cats to decrease intraoperative blood loss because it can result in fatal cerebral hypoxia (Holmes and Wolstencroft 1959; Gillian 1976; Holmberg 1996). Maxillectomy does not result in the same functional consequences as mandibulectomy in cats; in one study of 60 cats, eating dif iculties were reported in 20% of cats for a median of seven days (Liptak et al. 2020).

Postoperative Management Analgesia In the immediate postoperative period, intravenous luids and analgesia are continued and an Elizabethan collar should be placed as soon as the animal is sternally recumbent to prevent self-trauma (Dernell et al. 1998b). See section “General Surgical Considerations” and Table 6.2 for suggested perioperative analgesic protocols for cats and dogs undergoing mandibular resections. Nutrition Intravenous luids should be continued until the dog eats voluntarily and is drinking suf icient quantities to maintain hydration. This is rarely a problem and most dogs can be discharged within 24–48 hours. Dogs treated with radical maxillectomy may have dif iculty eating dry food and may also require initial assistance in feeding (Lascelles et al. 2003). This includes manual feeding or feeding from an inclined bowl. However, the majority of dogs adapt to unassisted eating within two to three weeks (Lascelles et al. 2003). Supplemental nutrition is rarely required in either dogs or cats following most maxillectomy procedures, but an esophagostomy or gastrostomy feeding tube is recommended in cats following bilateral rostral maxillectomy, with or without nasal planum resection, or radical maxillectomy. To prevent disruption of intraoral incisions, cats and dogs should only be fed soft canned food and prevented from chewing on hard objects or playing with toys for four weeks. Miscellaneous An Elizabethan collar is applied in the immediate postoperative period to minimize self-trauma. Bleeding from the ipsilateral nostril(s) is common for one to three days postoperatively (Figure 6.35a). This rarely requires treatment, but the volume should be monitored.

Figure 6.34 Caudal maxillectomy through a combined approach in a cat with a maxillary osteosarcoma. (a) The dorsolateral skin and intraoral incisions have been performed to create a bipedicle lap; (b) The dorsolateral (arrows) and caudal osteotomies (arrowheads) have been performed with an osteotome and mallet through the skin incision to achieve adequate dorsal and caudal margins; (c) The hard palate osteotomy (arrows) has been performed with an oscillating saw to connect to the rostral and caudal maxillary osteotomies; (d) The osteotomized bone segment is gently removed from the surgical site. Following radical maxillectomy, the surgical site oozes serosanguineous luid and becomes crusty and contaminated with food material and saliva. Topical petrolatum-based antibiotic ointment is initially placed around the nasal ori ice wounds and a topical misting of physiologic saline via a conventional spray bottle can be useful to humidify and cleanse the nasal turbinates. Following discharge, owners should clean and maintain the patency of the new rostral ori ice with saline-soaked cotton balls or Q-tips for approximately four weeks. The surgical site does not tend to be contaminated with food material once healing is complete by eight weeks. However, dogs and cats will continue to have a mild, persistent, clear nasal discharge. This does not bother animals and does not result in dermatitis on the new rostral lip. Rhinitis, a concern because of the exposed turbinates, does not occur. Hair regrowth around the new nasal ori ice does not cause any problems, and we have not seen any cases of self-trauma of the new ori ice from the tongue. Tear staining can be expected due to disruption of the nasolacrimal duct.

Complications Cosmetic Appearance The cosmetic appearance of cats and dogs following various maxillectomy procedures is usually good to excellent. The major exception is radical maxillectomy. As discussed previously, owner acceptance of postoperative appearance and function is improved with a thorough discussion, including the use of pre and postoperative images of the appropriate procedure, prior to surgery. Owner satisfaction with the cosmetic appearance and functional outcome following maxillectomy is high with 85% of dog owners satis ied following partial maxillectomy (Fox et al. 1997).

Figure 6.35 (a) The typical appearance of a dog following caudal maxillectomy through an intraoral approach 24 hours postoperatively (note the epistaxis); (b) The typical appearance of a dog following caudal maxillectomy through a combined approach 24 hours postoperatively; (c) The typical appearance of a cat following caudal maxillectomy through a combined approach 24 hours postoperatively; (d and e) Depending on the degree of resection of the hard palate, the lip may be drawn the midline of the muzzle. While some medialization of the lip is to be expected, this can be minimized by undermining the labial submucosal–mucosal lap. Following unilateral rostral and caudal maxillectomies (Figure 6.35a–e), the skin and lip are often drawn medially towards the midline, and the extent of this will depend on the medial extent of the resection, resulting in a dished in appearance (Fox et al. 1997). Depending on the extent of this medialization of the lip, the ipsilateral mandibular canine tooth may protrude lateral to the upper lip following maxillectomy procedures involving the rostral maxilla (Figure 6.36a and b). Postoperative swelling can also be signi icant, particularly if venous drainage has been compromised during tumor excision, but this usually subsides within 3 weeks resulting in an improved cosmetic appearance. The most common cosmetic defect following bilateral rostral maxillectomy is drooping of the nose because of loss of ventral support (Figure 6.37) (White et al. 1985; Withrow et al. 1985; Salisbury et al. 1986; Schwarz et al. 1991b; White 1991; Wallace et al. 1992; Lascelles et al. 2003). This cosmetic change can be partially corrected by using the cantilever suture (Figure 6.26b–f) (Pavletic 2018). Another common cosmetic defect is protrusion of the mandibular canine teeth rostral to the resected maxilla following bilateral rostral maxillectomy combined with nasal planum resection and radical maxillectomy (Lascelles et al. 2003, 2004).

The cosmetic appearance of dogs following radical maxillectomy is the most challenging of all maxillofacial resections (Figure 6.38a–c) (Lascelles et al. 2004). For owners that have elected to proceed with this procedure, children within the family and uninformed visitors have the greatest dif iculty in accepting the altered cosmetic appearance. Owners should be thoroughly counseled prior to surgery of the expected appearance of their dog. As previously recommended, the use of postoperative images of dogs treated with radical maxillectomy facilitates this discussion. Despite the change in cosmetic appearance, it is important to note that their behavior is unaltered and their function remains good to excellent. The most signi icant functional effects include dif iculty or inability in retrieving or picking up items, dif iculty in eating dry food, and messy eating and drinking. Intraoperative Bleeding Intraoperative bleeding is common during maxillectomy procedures in dogs, occurring in 53.4% of 193 dogs in a recent study (MacLellan et al. 2018), but not cats (Liptak et al. 2020). Intraoperative bleeding is signi icantly more likely in dogs with larger tumors (92% in dogs with tumors > 4 cm compared to 64% in dogs with tumors 2–4 cm and 36% in dogs with tumors < 2 cm), dogs with tumors caudal to the third premolar tooth (69% compared to 32% for tumors rostral to the fourth premolar tooth), dogs treated with caudal or complete maxillectomy (72–77%) compared to other maxillectomy procedures (0–38%), dogs treated with concurrent orbitectomy (83% versus 43%), and dogs with a maxillectomy performed via a combined approach (83%) compared to an intraoral approach (54%) (MacLellan et al. 2018). Intraoperative hemorrhage can be profuse if the major palatine or maxillary artery are not ligated prior to caudal hemimaxillectomy (Dernell et al. 1998b; MacLellan et al. 2018). To avoid this complication, the maxillary artery should be identi ied as it courses along the ventral aspect of the ventral orbit and is ligated. Temporary occlusion of the carotid arteries may be effective in reducing bleeding from the major palatine artery, but this should only be performed in dogs as carotid artery occlusion can be fatal in cats (Holmes and Wolstencroft 1959; Gillian 1976; Hedlund et al. 1983; Holmberg 1996; Holmberg and Pettifer 1997). Hemorrhage from either the maxillary or major palatine artery can be severe enough to warrant a whole blood transfusion (MacLellan et al. 2018), so blood loss should be carefully monitored and a cross-matched compatible blood transfusion considered if hematocrit acutely decreases below 15–30%, particularly if this occurs in combination with hypotension, hypoxia and/or clinical, biochemical or echocardiographic evidence of anaerobic metabolism (Jutkowitz 2004);

Figure 6.36 (a) The postoperative appearance of a dog following unilateral rostral maxillectomy. The lesion was relatively small and the labial mucosal–submucosal lap has been suf iciently undermined to prevent excessive medialization of the lip. (b) For dogs with larger lesions, there may be tension on the labial mucosal-submucosal lap resulting in medialization of the lip such that lip is positioned medial to the ipsilateral mandibular canine tooth. Medialization of the lip can be minimized by undermining the labial submucosal–mucosal lap, but it can be dif icult to prevent this cosmetic result.

Figure 6.37 The typical appearance of a dog following bilateral rostral maxillectomy. Note the mild drooping of the nose as a result of loss of ventral palatine support. Epistaxis Epistaxis is a common postoperative complication in both dogs and cats and was reported in 51.3% of 193 dogs and 11.7% of 60 cats treated with various maxillectomy techniques (MacLellan et al. 2018; Liptak et al. 2020). Epistaxis is often mild and self-limiting, with most cases resolving within ive days of surgery. Eating Difficulties Eating dif iculties are uncommon following the majority of maxillectomy procedures in cats and dogs (White et al. 1985; Withrow et al. 1985; Salisbury et al. 1986; Schwarz et al. 1991b; White 1991; Wallace et al. 1992; Fox et al. 1997; Dernell et al. 1998b; Lascelles et al. 2003; MacLellan et al. 2018; Liptak et al. 2020). Dogs treated with radical maxillectomy may have dif iculty eating dry food and may also require initial assistance in feeding (Lascelles et al. 2004). This includes manual feeding or feeding from an inclined bowl. However, the majority of dogs adapt to unassisted eating within two to three weeks. Supplemental feeding is rarely required in cats with 20.0% of cats having hyporexia for a median of seven days following maxillectomy (Liptak et al. 2020).

Figure 6.38 (a–c) The typical postoperative appearance following radical maxillectomy. Of all the surgical techniques used for resection of oral tumors, radical maxillectomy has the most challenging cosmetic results. Note the shortening of the muzzle and exposure of the mandible and mandibular teeth. Wound Dehiscence and Oronasal Fistula Wound dehiscence is the most common complication following maxillectomy in dogs and cats and is reported in 5–33% of dogs and 20% of cats (White et al. 1985; Withrow et al. 1985; Harvey 1986; Salisbury et al. 1986; Schwarz et al. 1991b; White 1991; Wallace et al. 1992; Fox et al. 1997; Dernell et al. 1998b; Lascelles et al. 2003; MacLellan et al. 2018; Liptak et al. 2020). Wound dehiscence most commonly occurs with three to seven days of surgery and usually caudal to the canines (Harvey 1986; Schwarz et al. 1991b). Tension at these sites is the most likely cause of dehiscence, although the use of cautery, rapidly absorbing suture material (i.e. catgut or poliglecaprone 25), and poor wound healing capabilities as a result of radiation therapy, chemotherapy, or debilitation may also contribute to wound dehiscence (White et al. 1985; Salisbury et al. 1985, 1986; Withrow et al. 1985; Harvey 1986; Schwarz et al. 1991b; White 1991; Wallace et al. 1992; Fox et al. 1997; Dernell et al. 1998b; Lascelles et al. 2003). To minimize the risk of dehiscence, maxillectomy defects should be closed in two layers, preferably using bone tunnels for the irst layer, under minimal tension with long-lasting mono ilament suture material. Tension can be decreased with careful planning and harvesting of the labial mucosal-submucosal lap. Cautery is frequently cited as the cause for dehiscence, however, is rare if the maxillectomy defect is closed with tension-free closure techniques. If dehiscence occurs, then the full extent of dehiscence should be assessed. Dehiscence or failure of the labial mucosa-submucosal lap can result in the development of an oronasal istula (Figure 6.39). A number of techniques have been described for the management of oronasal istulae (Kirby 1990; Smith and Rockhill 1996; Grif iths and Sullivan 2001; Lanz 2001; Niles and Birchard 2001; Bryant et al. 2003; Dundas et al. 2005). However, these may not be possible following maxillectomy because much of the available buccal mucosal or mucoperiosteal tissue typically used for these reconstructions has either been excised or used for reconstruction of the original maxillectomy defect. In these cases, angularis oris axial pattern buccal laps (Bryant et al. 2003), advancement of skin laps into the oral cavity (Figure 6.40) (Dundas et al. 2005; Nakahara et al. 2020), free microvascular grafts of the rectus abdominis muscle (Lanz 2001), free auricular cartilage autograft (Figure 6.41a–e) (Cox et al. 2007; Soukup et al. 2009; Lorrain and Legendre 2012), or insertion of a silicone nasal septal button (Figure 6.42a–c) may be useful (Smith and Rockhill 1996). If the dehiscence does not involve an oronasal istula, then these can be managed with either second intention healing if the dehisced area is small and granulating, or debridement and resuturing if the defect is large.

Figure 6.39 Dehiscence of the intraoral incision following caudal maxillectomy through an intraoral approach with the subsequent development of an oronasal istula.

Figure 6.40 The oronasal istula has been debrided and repaired with a transposition lap of adjacent skin. Mucosal or mucoperiosteal laps are preferred for repair of oronasal defects, but these tissues are often not available because of previous tumor resection.

Figure 6.41 A free auricular cartilage autograft for treatment of a central oronasal istula (a) in a cat following maxillectomy and hard palate resection for a squamous cell carcinoma in situ. (b and c) The free auricular cartilage autograft is harvested using a punch biopsy; (d) The mucoperiosteum is undermined and the free auricular cartilage autograft is inserted dorsal to the oronasal istula and sutured to the mucoperiosteum; (e) Second intention healing has occurred, resulting in correction of the oronasal istula at 33 days postoperatively.

Figure 6.42 (a) A caudal midline oronasal istula following segmental maxillectomy for treatment of a dog with a malignant melanoma of the hard palate; (b) The 3 cm nasal septal button, with two discs, one for the oral side and one for the nasal side of the oronasal istula, separated by a short pillar; (c) The nasal septal button is trimmed to size if necessary and then the dorsal disc is inserted through the oronasal istula to abut the nasal side of the oronasal istula with the ventral disc abutting the oral side of istula. The nasal septal button results in occlusion of the oronasal istula for a duration often > 2 years. Incisional Swelling Swelling of the surgical site is common following caudal maxillectomy, particularly via the combined intraoral–dorsolateral approach, and radical maxillectomy (Lascelles et al. 2003, 2004; MacLellan et al. 2018). In one series of 193 dogs treated with partial maxillectomy, excessive facial swelling was reported in 36.8% of dogs (MacLellan et al. 2018). Swelling usually resolves spontaneously within three weeks. Ice packing every four hours and the administration of non-steroidal anti-in lammatory drugs may assist in decreasing the severity of postoperative swelling. Ulcer Formation Secondary to Trauma by Teeth Ulcer formation due to trauma by teeth is a relatively common complication following maxillectomies involving the rostral maxilla, and is reported in 15% of cats (White et al. 1985; Withrow et al. 1985; Harvey 1986; Salisbury et al. 1986; Schwarz et al. 1991b; White 1991; Wallace et al. 1992; Fox et al. 1997; Dernell et al. 1998b; Lascelles et al. 2003; MacLellan et al. 2018; Liptak et al. 2020). The ulcerated region is usually caused by the ipsilateral mandibular canine tooth (Figure 6.43), although any teeth can cause this trauma, and can occur either inside or outside the lip. Ulceration results from the lip being drawn medially into the occlusal plane of the teeth. Ulcer formation is potentiated by the loss of sensation to the upper lip following severance of the infraorbital nerve. Once the source of the ulceration has been identi ied, options for management include monitoring, cheiloplasty, odontoplasty, crown reduction with vital pulp treatment of the mandibular tooth, or extraction of the mandibular tooth (MacLellan et al. 2018; Liptak et al. 2020). Miscellaneous Complications Other complications reported following maxillectomy include pain, subcutaneous emphysema, infection, nasal discharge secondary to rhinitis, and epiphora. Subcutaneous emphysema, with skin over the surgical site moving with respiration, is occasionally noted in the early postoperative period after maxillectomy procedures involving exposure of the nasal cavity, particularly caudal maxillectomies (Dernell et al. 1998b; MacLellan et al. 2018; Liptak et al. 2020). This is usually mild, non-progressive, and resolves spontaneously within seven days.

Figure 6.43 Ulceration of the upper lip in a cat following unilateral hemimexillectomy. The upper lip has been drawn medially into the occlusal plane of the mandibular canine tooth resulting in ulceration of the lip margin (arrow). In this case, the ulcerated lip resolved following capping of the mandibular canine tooth. Infection is rare following maxillectomy because of the rich vascular supply to the oral cavity (Dernell et al. 1998b) but was recently reported in 7.9% of 164 dogs treated with partial maxillectomy (MacLellan et al. 2018). Incisional abscesses are treated with debridement, copious lavage with an isotonic crystalloid solution, closure of dead space, drainage if possible, and culture-directed antibiotics. Rarely, a mild but persistent nasal discharge is observed following maxillectomy procedures in which the nasal turbinates have been exposed (White et al. 1985; Withrow et al. 1985; Harvey 1986; Salisbury et al. 1986; Schwarz et al. 1991b; White 1991; Wallace et al. 1992; Fox et al. 1997; Dernell et al. 1998b; Lascelles et al. 2003). This discharge is usually clear but can occasionally be mucoid to mucopurulent. Treatment is rarely required, but culture-directed antibiotics may be necessary if an infected rhinitis is suspected.

Mandibular and Maxillary Tumors in Dogs The most common malignant tumors of the mandible and maxilla in dogs are, in descending order, malignant melanoma, SCC, and ibrosarcoma (Todoroff and Brodey 1979; Withrow and Holmberg 1983; Bradley et al. 1984; White et al. 1985; Withrow et al. 1985; Salisbury et al. 1986; Salisbury and Lantz 1988; Kosovsky et al. 1991; Schwarz et al. 1991a, b; White 1991; Wallace et al. 1992; Brønden et al. 2009). Other malignant oral tumors include osteosarcoma, adenocarcinoma, chondrosarcoma, anaplastic sarcoma, multilobular osteochondrosarcoma, intraosseous carcinoma, myxosarcoma, hemangiosarcoma, lymphoma, plasmacytoma, rhabdomyosarcoma, lymphoma, and mast cell tumor (Madewell et al. 1976; Todoroff and Brodey 1979; Withrow and Holmberg 1983; Bradley et al. 1984; White et al. 1985; Withrow et al. 1985; Salisbury et al. 1986; Salisbury and Lantz 1988; Straw et al. 1989; Reeves et al. 1993; Smith 1995;

Holmberg and Pettifer 1997; Dernell et al. 1998c; Dhaliwal et al. 1998; Williams and Packer 2003; Dennis et al. 2006; Wright et al. 2008; Brønden et al. 2009; Hillman et al. 2010; Snyder and Michael 2011; Berlato et al. 2012; Smithson et al. 2012; Elliot et al. 2016; Liptak 2019). SCC is the most common oropharyngeal cancer in cats and the most frequently diagnosed tumor in the tongue of dogs (Madewell et al. 1976; Todoroff and Brodey 1979; Withrow and Holmberg 1983; Bradley et al. 1984; White et al. 1985; Withrow et al. 1985; Salisbury et al. 1986; Salisbury and Lantz 1988; Straw et al. 1989; White 1991; Reeves et al. 1993; Smith 1995; Holmberg and Pettifer 1997; Dernell et al. 1998c; Dhaliwal et al. 1998; Williams and Packer 2003; Dennis et al. 2006; Northrup et al. 2006; Liptak 2019; Liptak et al. 2020). A summary of the common oral tumors is found in Table 6.3.

Oral Tumors in Dogs Malignant Melanoma In comparison to other malignant oral tumors, malignant melanoma tends to occur in smaller body weight dogs, such as cocker spaniel, miniature poodle, Anatolian sheepdog, Gordon Setter, Chow Chow, and Golden Retriever are over-represented breeds (Ramos-Vara et al. 2000). A male predisposition has been reported (Kudnig et al. 2003), but this is not consistent (Ramos-Vara et al. 2000). The mean age at presentation is 11.4 years (Ramos-Vara et al. 2000). Malignant melanoma can be dif icult to diagnose if the tumor or the biopsy section does not contain melanin, especially as amelanotic melanomas represent up to 33% of all oral melanomas in dogs (Figure 6.44a and b) (Liptak 2019). A histopathologic diagnosis of undifferentiated or anaplastic sarcoma or even epithelial cancer should be considered with suspicion for possible underlying melanoma. Melan A is an immunohistochemical stain with a high sensitivity and speci icity for the diagnosis of melanoma in dogs and can be used to differentiate melanoma from other poorly differentiated oral tumors (Ramos-Vara et al. 2000). Melanoma of the oral cavity is a highly malignant tumor with frequent metastasis to the regional lymph nodes and then the lungs (Overley et al. 2001; Kudnig et al. 2003; Williams and Packer 2003; Boston et al. 2014; Tuohy et al. 2014; Skinner et al. 2017). There is a small subset of dogs with well-differentiated oral melanomas and these may have a more benign biological behavior (Tuohy et al. 2014; Esplin 2005). The metastatic rate is site, size, and stage-dependent and reported in up to 80% of dogs (Todoroff and Brodey 1979; Harvey et al. 1981; Brewer and Turrel 1982; MacEwen et al. 1986; Kosovsky et al. 1991; Wallace et al. 1992; Bateman et al. 1994; Blackwood et al. 1996; Théon et al. 1997a; MacEwen et al. 1999; Overley et al. 2001; Freeman et al. 2003; Kudnig et al. 2003; Williams and Packer 2003). The WHO clinical staging system for oral tumors in dogs has prognostic signi icance in dogs with oral melanoma (Table 6.1) (Owen 1980; Hahn et al. 1994; Blackwood et al. 1996; Overley et al. 2001; Kudnig et al. 2003; Proulx et al. 2003; Boston et al. 2014; Tuohy et al. 2014; Kawabe et al. 2015). Malignant melanoma is a highly immunogenic tumors and molecular approaches to treatment, particularly genetic immunotherapy, is an active area of research and treatment (MacEwen et al. 1986; Moore et al. 1991; Elmslie et al. 1994, 1995; Quintin-Colonna et al. 1996; Dow et al. 1998; Hogge et al. 1998; MacEwen et al. 1999; Bergman et al. 2003a, b, 2004; Riccardo et al. 2014; Piras et al. 2017). The biology and molecular mechanisms of canine melanoma development and progression have been reviewed (Modiano et al. 1999; Sulaimon and Kitchell 2003).

Table 6.3 Summary of common oral tumors in the dog and cat. Canine

Frequency Age (years)

Feline

Malignant melanoma

Squamous Fibrosarcoma Acanthomatous Squamous cell ameloblastoma cell carcinoma carcinoma

Fibrosarcoma

30–40% 12

17–25% 8–10

8–25% 7–9

5% 8

70–80% 10–12

13–17% 10

None

Male

None

None

None

None Rostral mandible

– – Tongue, Gingiva pharynx and tonsils

Sex None-Male predisposition Animal size Site predilection

Smaller Larger Gingiva, buccal, Rostral and labial mandible mucosa

Larger Maxillary gingiva and hard palate

Lymph node metastasis

Common (41– 74%)

Occasional (9– None 28%)

Rare

Rare

Distant metastasis

Common (14– 92%)

Occasional (0– None 71%)

Rare

Rare (< 20%)

Gross appearance

Pigmented (67%) or amelanotic (33%), ulcerated Common (57%)

Red, Flat, irm, cauli lower, ulcerated ulcerated

Common (77%)

Common (60– Common (80– 72%) 100%)

Surgery response Local recurrence MST 1-year survival rate

Fair to good 0–59% 5–17 months 21–35%

Good 0–50% 9–26 months 57–91%

Fair to good 31–60% 10–12 months 21–50%

Excellent Poor 0–11% > 28–64 months 45 days 72–100% < 10%

Fair

Radiation response Response rate Local recurrence MST 1-year survival rate

Good 83–94% 11–27% 4–12 months 36–71%

Good – 31–42% 16–36 months 72%

Poor to fair – 32% 7–26 months 76%

Excellent – 8–18% 37 months > 85%

Poor

Poor

Best treatment

Surgery and/or Surgery radiation ± and/or chemotherapy radiation ± immunotherapy

Surgery and/or radiation

Surgery

Surgery and Surgery radiation ± and/or sensitizer radiation

Prognosis MST

Fair to good < 36 months

Good Excellent 18–26 months > 64 months

Bone involvement

Rare (< 40%) Tonsil SCC up to 73% Rare (< 36%)

Goodexcellent 26–36 months

Red, cauli lower, Proliferative, Firm ulcerated ulcerated

Common

Common

90 days

Poor-fair 14 months

Fair

Canine Malignant melanoma

Feline Squamous Fibrosarcoma Acanthomatous Squamous cell ameloblastoma cell carcinoma carcinoma

Cause of death Distant disease Local or distant disease

Local disease

Rarely tumor related

Local disease

Fibrosarcoma

Local disease

Figure 6.44 (a) A melanotic malignant melanoma of the caudal mandible in a dog. De initive diagnosis of malignant melanoma can be dif icult because histopathology can be non-speci ic and up to 33% of malignant melanomas are amelanotic, such as the malignant melanoma depicted in the maxilla of a dog in (b). Squamous Cell Carcinoma SCC is often cited as the second most common oral tumor in dogs but is sometimes cited as the most common canine oral tumor (Figure 6.45a–d) (Hoyt and Withrow 1984; Stebbins et al. 1989; Kosovsky et al. 1991; Schwarz et al. 1991a, b; Wallace et al. 1992; Brønden et al. 2009). There are ive different histologic subtypes of SCC: conventional, papillary, basaloid, adenosquamous, and spindle cell (Nemec et al. 2012). Papillary SCCs typically occur in the rostral oral cavity of dogs less than nine months old, although older dogs have also been reported (Nemec et al. 2012, 2014; Soukup et al. 2013). SCC frequently invades bone. The metastatic rate for non-tonsillar SCC in dogs is 5–29% (Théon et al. 1997a; Fulton et al. 2013; Kühnel and Kessler 2014), but the metastatic risk is site-dependent with the rostral oral cavity having a low metastatic rate and the caudal tongue and tonsil having a high metastatic potential (Liptak 2019). Fibrosarcoma Oral ibrosarcoma is the third most common in dogs (Hoyt and Withrow 1984; Stebbins et al. 1989; Kosovsky et al. 1991; Schwarz et al. 1991a, b; Hutson et al. 1992; Wallace et al. 1992). Oral ibrosarcoma tends to occur in large breed dogs, particularly the Golden and Labrador Retriever. The median age at diagnosis is 7.3–8.6 years and there may be a male predisposition (Liptak 2019). Oral ibrosarcoma may appear surprisingly benign histologically (Figure 6.46) and, even with large biopsy samples, the pathologist will often diagnose ibroma or low-grade ibrosarcoma. This syndrome, which is common on the hard palate and maxillary arcade between the canine and carnassial teeth of large-breed dogs, has been termed “histologically low-grade but biologically high-grade” ibrosarcoma (Ciekot et al. 1994). Even with a biopsy result suggesting ibroma or low-grade ibrosarcoma, the treatment should be aggressive, especially if the cancer is rapidly growing, recurrent, or invading bone. Fibrosarcoma is a locally invasive tumor but metastasizes to the lungs and occasionally regional lymph nodes in less than 30% of dogs (Todoroff and Brodey 1979; Kosovsky et al. 1991; Schwarz et al. 1991a, b; Wallace et al. 1992; Théon et al. 1997a; Frazier et al. 2011; Gardner et al. 2015).

Osteosarcoma Osteosarcoma of axial sites is less common than appendicular osteosarcoma and represents approximately 25% of all cases (Heyman et al. 1992). Of the axial osteosarcomas, the mandible and maxilla are involved in 27% and 16–22% of cases, respectively (Heyman et al. 1992; Hammer et al. 1995). Osteosarcoma is the fourth most common malignant oral tumor in dogs. The prognosis for dogs with oral osteosarcoma is better than appendicular osteosarcoma because of a lower metastatic potential (Heyman et al. 1992; Straw et al. 1996; Selmic et al. 2014; Coyle et al. 2015). A female predisposition has been reported (Heyman et al. 1992). Peripheral Odontogenic Fibroma Peripheral odontogenic ibroma is the preferred term for a group of benign tumors previously known as epulides (Fiani et al. 2011). Four types of epulides have been described in the dog: acanthomatous, ibromatous, ossifying, and giant cell (Dubielzig 1982; Bjorling et al. 1987; Yoshida et al. 1999). Acanthomatous epulis has been renamed acanthomatous ameloblastoma (Figure 6.47), and the ibromatous and ossifying epulides have been renamed peripheral odontogenic ibroma (Figure 6.48). Peripheral odontogenic ibromas are relatively common in dogs. They are benign gingival proliferations arising from the periodontal ligament and appear similar to focal ibrous hyperplasia of the gingiva (Fiani et al. 2011). Unlike acanthomatous ameloblastomas, they do not invade into underlying bone. The mean age at presentation for dogs with peripheral odontogenic ibromas is eight to nine years, and a male predisposition, particularly castrated male dogs, has been reported (Bjorling et al. 1987; Yoshida et al. 1999; Fiani et al. 2011). Peripheral odontogenic ibromas are slow-growing, irm masses and usually are covered by intact epithelium. They have a predilection for the rostral maxilla, rostral to the third premolar teeth (Yoshida et al. 1999; Fiani et al. 2011). Local resection, with or without cryotherapy to the base of the resection, is usually adequate for long-term tumor control, although occasionally mandibulectomy or maxillectomy is required for peripheral odontogenic ibromas with more aggressive local growth or recurrence.

Figure 6.45 Squamous cell carcinoma can have a variable gross appearance. Ulceration and a cauli lowerlike appearance are common (a–c), but they can also appear irm and raised with an intact overlying oral mucosa (d).

Figure 6.46 A ibrosarcoma in the caudal maxilla of a dog. Note the typical appearance of a solid, nonulcerated mass with intact overlying mucosa. Oral ibrosarcomas can appear surprisingly benign in both gross and histologic appearance, but they have an aggressive local behavior and require extensive surgery for complete excision.

Figure 6.47 An acanthomatous ameloblastoma arising from the periodontal ligament of the maxillary canine tooth. These tumors are benign but, unlike peripheral odontogenic ibromas, invade bone and hence require either mandibulectomy or maxillectomy for complete excision. Acanthomatous Ameloblastoma Acanthomatous ameloblastoma is a benign tumor, but with an aggressive local behavior and frequent invasion into bone of the underlying mandible or maxilla. Shetland sheepdogs, old English sheepdogs, and Golden Retrievers are predisposed (White and Gorman 1989; Yoshida et al. 1999, Goldschmidt et al. 2017). The mean age at presentation is 7–10 years; a gender predisposition is unlikely with three studies reporting con licting results (Thrall 1984; Bjorling et al. 1987; White and Gorman 1989; Yoshida et al. 1999). The rostral mandible is the most common site (Figure 6.47) (White and Gorman 1989; Goldschmidt et al. 2017). They do not metastasize. Acanthomatous ameloblastoma is the preferred term, but some pathologists will refer to these tumors by their previous terminology of adamantinoma or acanthomatous epulis (Dubielzig 1982).

Figure 6.48 A peripheral odontogenic ibroma arising from the periodontal ligament of the rostral mandibular incisors. These are benign tumors and can often be managed conservatively. However, in this particular dog, a unilateral rostral mandibulectomy was performed with a biradial saw because the epulis was recurrent and rapidly growing. Eosinophilic Granuloma Canine oral eosinophilic granulomas affect young dogs (one to seven years) and may be heritable in the Siberian Husky and Cavalier King Charles Spaniel (Madewell et al. 1980; Potter et al. 1980; Bredal et al. 1996). The granulomas typically occur on the lateral and ventral aspects of the tongue. They are raised, frequently ulcerated, and may mimic more malignant cancers in gross appearance. Treatment with corticosteroids or surgical excision is generally curative, although spontaneous regression may occur. Local recurrences are uncommon.

Oral Tumors in Cats Squamous Cell Carcinoma SCC is the most common oral tumor in cats (Patnaik et al. 1975; Vos and van der Gaag 1987; Stebbins et al. 1989). Risk factors for the development of oral SCC include lea collars, high intake of either canned food in general or canned tuna ish speci ically, and exposure to household smoke (Bertone et al. 2003). SCC frequently invades bone and bone invasion is usually severe and extensive in the cat (Figure 6.49a and b) (Gendler et al. 2010). Paraneoplastic hypercalcemia has been reported in two cats with oral SCC (Hutson et al. 1992). Control of local disease is the most challenging aspect in cats with oral SCC because of the extent of the local tumor; however, metastasis has been reported to the mandibular lymph node and lungs

in 31% and 10% of cats (Soltero-Rivera et al. 2014), respectively, and hence treatment for this metastatic potential may be warranted for cats in which local tumor control is achieved. Odontogenic Tumors Odontogenic tumors originate from epithelial cells of the dental lamina and account for up to 2.4% of all feline oral tumors (Stebbins et al. 1989). They are broadly classi ied into two groups depending on whether the tumors are able to induce a stromal reaction (Poulet et al. 1992). Inductive odontogenic tumors include ameloblastic ibroma, dentinoma, and ameloblastic, complex, and compound odontomas. Ameloblastomas and calcifying epithelial odontogenic tumors are examples of non-inductive odontogenic tumors (Poulet et al. 1992).

Figure 6.49 (a) A squamous cell carcinoma arising from the alveolar ridge of the maxilla in a cat. The ulcerated appearance is typical for squamous cell carcinoma in cats. (b) Occasionally feline oral SCC will have irm and non-ulcerated appearance. Inductive ibroameloblastoma is the most common odontogenic tumor in cats and usually occur in cats less than 18 months of age and has a predilection for the region of the upper canine teeth and maxilla (Figure 6.50) (Dubielzig et al. 1979; Dubielzig 1982; Stebbins et al. 1989; Poulet et al. 1992; Dernell and Hullinger 1994). Radiographically the tumor site shows variable degrees of bone destruction, production, and expansion of the mandibular or maxillary bones. Teeth deformity is common. Smaller lesions are treated with surgical debulking and cryosurgery or premaxillectomy. Larger lesions will respond to radiation. Local treatment needs to be aggressive, but control rates are good and metastasis has not been reported (Dubielzig 1982; Stebbins et al. 1989).

Figure 6.50 An inductive ibroameloblastoma arising from the rostral maxilla. Note the expansile, noninvasive appearance with displacement of the adjacent canine tooth. This gross appearance is typical of benign oral tumors in cats. Odontomas are benign tumors arising from the dental follicle during the early stages of tooth development (Figueiredo et al. 1974). Odontomas induce both enamel and dentin within the tumor. Odontomas have a similar biologic behavior to ameloblastomas. Eosinophilic Granuloma Eosinophilic granuloma, a condition also known as rodent ulcer or indolent ulcer, occurs more commonly in female cats with a mean age of ive years (McClelland 1954; Scott 1980; MacEwen and Hess 1987; Song 1994). The etiology is unknown. Any oral site is at risk, but it is most common on the upper lip near the midline (Figure 6.51). The history is usually that of a slowly progressive (months to years) erosion of the lip. Biopsies are often necessary to differentiate the condition from true cancers. Various treatments are proposed including oral prednisone at 1–2 mg/kg q 12 h for 30 days or subcutaneous methylprednisolone acetate at 20 mg/cat every 2 weeks; megestrol acetate; hypoallergenic diets; radiation therapy; surgery; immunomodulation; or cryosurgery. The prognosis for complete and permanent recovery is fair, although rare cases may undergo spontaneous regression. Other Tumor Types Oral ibrosarcoma and osteosarcoma are the next most common malignant oral tumor in cats, but very little is reported on its biological behavior (Hoyt and Withrow 1984; Stebbins et al. 1989; Kosovsky et al. 1991; Schwarz et al. 1991a, b; Wallace et al. 1992; Ciekot et al. 1994; Northrup et al. 2006; Liptak et al. 2020). Epulides have also been reported in cats. The most common are the ibromatous and giant cell epulides, of

which the latter may be a more aggressive variant of ibromatous and ossifying epulides (de Bruijn et al. 2007). Acanthomatous ameloblastoma and ossifying epulides are rare in cats (Stebbins et al. 1989; de Bruijn et al. 2007). Other feline oral tumors include osteoma (Fiani et al. 2011) and restrictive orbital myo ibroblastic sarcoma (Bell et al. 2011).

Figure 6.51 An eosinophilic granuloma in a cat. These lesions are non-neoplastic but can be dif icult to treat.

Surgical Approach to Tumors of the Hard Palate Anatomy The hard palate forms the roof of the mouth and separates the oral and nasal cavities. For this reason, reconstruction of the hard palate is important following tumor excision to prevent the formation of oronasal istula. The other major anatomic consideration is the vasculature of the hard palate which consists of the paired minor palatine artery and common trunk of the major palatine and sphenopalatine arteries (Evans and de Lahunta 2013). The major palatine artery arises from this common trunk, passes through the caudal palatine foramen, and then courses rostrally deep to the mucoperiosteum of the hard

palate and along the palatine groove midway between the alveolar margin and midline of the palate (Evans and de Lahunta 2013). Knowledge of the location of the caudal palatine foramen and course of the major palatine artery is important because tumor excision at the level of the caudal palatine foramen can cause the transected artery to retract into the foramen and dif iculty in controlling the resultant hemorrhage. The sphenopalatine artery enters the nasal cavity and courses rostrally along the nasal side of the maxillary portion of the hard palate (Evans and de Lahunta 2013).

Hard Palate Resection Full-thickness resection of the hard palate is indicated for excision of malignant tumors of the hard palate (Figure 6.52a) or in combination with maxillectomy procedures for maxillary tumors extending into the hard palate. The surgical approach is planned from either preoperative CT or MRI scans and evaluation of skull. Hard palate tumors are excised via an intraoral approach. Dogs and cats are positioned in dorsal recumbency with the rostral maxilla taped down to the surgical table and the mandible held in an open mouth position by being taped caudally. Exposure may be improved with bilateral full-thickness incisions in the commissure of the lips, but this is rarely necessary or effective. Temporary occlusion of the carotid arteries can be effective in reducing bleeding from the major palatine artery, but this should only be performed in dogs as carotid artery occlusion can be fatal in cats (Holmes and Wolstencroft 1959; Gillian 1976; Hedlund et al. 1983; Holmberg 1996; Holmberg and Pettifer 1997). A full-thickness incision is made through the mucoperiosteum of the hard palate to the bone with a scalpel blade using appropriate margins around the tumor. The mucoperiosteum is re lected off the bone with periosteal elevators to preserve the soft tissues which will be used later for reconstruction of the defect. Hemostasis is achieved using cautery, digital pressure, and ligation of larger vessels. Resection of the hard palate can be combined with maxillectomy if required. Osteotomies are performed in the bone along the same line as the mucoperiosteal incisions with either a high-speed burr, oscillating saw, or osteotome and mallet. The excised tumor is then removed en bloc (Figure 6.52b). A number of techniques have been described for reconstruction of the hard palate defect with uni- or bilateral buccal mucosal laps most common (Kirby 1990; Niles et al. 2001; Banks and Straw 2004). The size of the lap is determined by cutting a piece of drape material to the size of the defect and then rotating it out onto the buccal mucosa allowing for additional tissue to account for the pedicle. Any teeth between the palate defect and the lap need to be extracted and the underlying maxillary bone rasped to ensure no sharp edges remain. The lap is raised with as much underlying tissue as possible (Figure 6.52c). The lap should be sutured into the hard palate defect using a two-layer closure with the irst layer consisting of preplaced sutures anchored through holes drilled in the hard palate bone (Figure 6.52d). The second layer consists of simple interrupted sutures opposing the lap mucosa and mucoperiosteum of the hard palate. The donor site is closed by simple apposition (Figure 6.52e). Although the use of bilateral overlapping mucosal single-pedicle laps has been described for correction of soft palate defects (Grif iths and Sullivan 2001), single layer laps are preferred to overlapping laps to minimize tension at the suture lines. Care should be taken to ensure that the lap will not be traumatized by remaining teeth. If this is possible, then these teeth should be extracted. Other techniques described for reconstruction of palate defects include the combination of a hard palate mucoperiosteal rotational lap combined with a soft palate hinge lap (Beck and Strizek 1999), and the angularis oris axial pattern lap, either as a mucosal or full-thickness skin lap (Bryant et al. 2003; Dicks and Boston 2010; Cook and Thomson 2014; Tuohy et al. 2019; Nakahara et al. 2020).

Figure 6.52 (a) Full-thickness excision of the hard palate is indicated for malignant tumors of the hard palate, such as this oral ibrosarcoma, or in combination with maxillectomy procedures for maxillary tumors extending into the hard palate; (b) The mucoperiosteum and bone of the hard palate are incised and osteotomized, respectively, with appropriate margins around the tumor; (c) A unilateral buccal mucosal lap has been raised to reconstruct the defect in the hard palate; (d) The buccal mucosal lap is sutured into the defect in two layers with the deep layer consisting of simple interrupted sutures between the submucosa of the buccal lap and predrilled holes in the hard palate; (e) The mucosa of the buccal lap is then sutured to the mucoperiosteum of the hard palate using simple interrupted sutures of absorbable mono ilament suture material.

Postoperative Management and Complications The postoperative management and potential complications are the same as described for maxillectomy. To minimize the risk of dehiscence and oronasal istula formation, esophagostomy or gastrostomy tube feeding is recommended for two weeks to bypass the oral cavity.

Surgical Approach to Tumors of the Tongue

Diagnosis and Clinical Staging An incisional biopsy, such as a punch or wedge biopsy, is recommended for the diagnosis of tongue lesions in cats and dogs. A biopsy is recommended because knowledge of the type of lesion may change treatment options (i.e. surgical dose or multimodality therapy with either radiation therapy and/or chemotherapy) or the willingness of the owner to pursue curative-intent treatment. Ultrasonography may be helpful in delineating the margins of tongue masses in dogs to assist in surgical planning (Solano and Penninck 1996). Similar to tumors of the mandible and maxilla, the regional lymph nodes should be assessed by palpation, ine-needle aspirate cytology, or tissue samples collected by surgical excision. Palpation of lymph node size and degree of ixation are unreliable indicators of metastasis (Williams and Packer 2003). Ideally, sentinel lymph node mapping and biopsy should be performed to histologically assess the irst draining lymph node from the tongue tumor. Surgical excision of the bilateral mandibular and medial retropharyngeal lymph nodes (Green and Boston 2017; Skinner et al. 2017; Wainberg et al. 2018), or surgical excision of the mandibular, parotid, and medial retropharyngeal lymph nodes (Smith 1995; Herring et al. 2002) are alternative approaches, but each of these techniques have disadvantages such as being non-selective, failing to completely sample all the lymph nodes of the head and neck and thus potentially missing metastatic nodes (Smith 1995; Herring et al. 2002; Skinner et al. 2017), and possibly being associated with a higher complication rate than targeted, single sentinel lymph node extirpation. Three-view thoracic radiographs or CT scans are recommended for evaluation of pulmonary metastasis in cats and dogs with malignant tongue tumors.

Anatomy The tongue is primarily composed of skeletal muscle and is divided into the body and root. The body accounts for the rostral two-thirds of the tongue and represents the free portion of the tongue. The midline of the body of the tongue is indicated by the median groove. The margin of the tongue separates the tongue into its dorsal and ventral surfaces. The ventral surface of the body of the tongue is attached to the loor of the oral cavity by the lingual frenulum (Chibuzo 1979). The paired lingual arteries are the principal blood supply of the tongue. These cross the medial surface of the hypoglossal muscle at the root of the tongue and then course rostrally as secondary branches to the intrinsic and extrinsic muscles of the root and body of the tongue (Chibuzo 1979).

Glossectomy Glossectomy is de ined as partial, subtotal, near-total, or total depending on the location of the excised segment of tongue and the degree of excision (Dvorak et al. 2004). Partial glossectomy involves excision of part or all of the body of the tongue rostral to the frenulum. Subtotal glossectomy involves the entire free portion of the tongue and a portion of the genioglossus and/or geniohyoid muscles caudal to the frenulum. Near-total glossectomy is de ined as resection of ≥ 75% of the tongue. Total glossectomy is amputation of the entire tongue (Dvorak et al. 2004). In people, partial glossectomies are considered minor glossectomies whereas subtotal, near-total, and total glossectomies are de ined as major glossectomies (Dvorak et al. 2004). The vast majority of reports in dogs refer to minor or partial glossectomy as more aggressive procedures are often not performed because of the potential for poor postoperative function (Beck et al. 1986; Carpenter et al. 1993; Dvorak et al. 2004). Surgical excision of tongue tumors is recommended if the tumor is con ined to rostral (partial glossectomy) or lateral (subtotal glossectomy) half of the tongue (Beck et al. 1986; Carpenter et al. 1993; Dvorak et al. 2004). Using these guidelines, the majority of dogs are not candidates for surgical excision of tongue tumors as 54% of canine tongue tumors are either located in the midline or are bilaterally symmetrical (Beck et al. 1986). However, more aggressive (or major) glossectomies are possible because minimal complications were reported in ive dogs treated with subtotal to total glossectomy for non-neoplastic diseases (Dvorak et al. 2004). Major glossectomy is not recommended in cats because of the high risk of severe and permanent functional complications, including inability to eat, drink and groom (Dvorak et al. 2004). For glossectomy, the tumor is excised with the appropriate margins (i.e. 1 cm margins for benign lesions and carcinomas, and 1–3 cm margins for melanomas and soft tissue sarcomas) (Syrcle et al. 2008). This will

involve excision of the tongue (Figure 6.53a) and perhaps portions of the frenulum and genioglossus and geniohyoid muscles (Figure 6.53b and c). These tissues are highly vascular and hemostasis with cautery, ligatures, and/or ligaclips is important to minimize the risk of blood loss and wound complications. If possible, at least one of the lingual arteries should be preserved as they course through the frenulum because ligation of both lingual arteries may result in vascular compromise to the remaining tongue (Dvorak et al. 2004). Following resection of the mass, the tongue can be closed in one or two layers using mono ilament absorbable suture material in either a simple interrupted (Figure 6.53d) or continuous suture pattern (Figure 6.53e). The submucosa or muscular tissue can be sutured to minimize tension on the mucosal closure and also assist in hemostasis. The dorsal tongue epithelium is then sutured to the ventral mucosa. An esophagostomy or gastrostomy tube should be inserted if greater than 50% of the tongue has been resected to supplement feeding in the postoperative period (Dvorak et al. 2004). Wedge Glossectomy A full-thickness wedge-shaped incision is performed around the tumor (Figures 6.54a–c and 6.55a and b). The defect can be closed by apposing the ventral mucosa to the dorsal mucosa therefore closing it longitudinally, which will cause a narrowing of the tongue (Figure 6.55c); or it can be closed transversely by suturing the dorsal mucosa together (Figures 6.54d and 6.55) and the ventral mucosa together (Figure 6.54e), which will cause a deviation of the tip of the tongue to the side of the excision. Transverse Glossectomy A full-thickness incision is made transversely across the tongue caudal to the tumor (Figures 6.56a, b, and 6.57a). The defect is closed by apposing the dorsal mucosa with the ventral mucosa (Figures 6.56c and 6.57b). Depending on the shape of the tumor, it may be possible to create a V-shaped incision with the apex of the “V” directly caudally on midline (Figure 6.57c and d). This defect is closed by apposing the dorsal mucosa on either side together and the ventral mucosa as well (Figure 6.57e). Longitudinal Glossectomy A full-thickness longitudinal incision is made along the midline from the tip of the tongue to the caudal extent of the tumor (Figure 6.58a). The incision is then brought to the lateral edge of the tongue providing an adequate margin of normal tissue (Figure 6.58a). The defect is closed by apposing the ventral and dorsal mucosal layers together along the length of the incision (Figure 6.58b). An alternative closure method is to rotate the remaining tip of the tongue and suture the cut edges of the mucosa dorsally together and ventrally together (Figure 6.58c) (Montinaro and Boston 2013). Benign tumors can be removed with a marginal excision (Figure 6.59).

Postoperative Management Nutrition is the most important aspect of postoperative management following glossectomy in cats and dogs. Intravenous luids should be continued until the animal is either eating voluntarily or drinking suf icient quantities to maintain hydration. This is rarely a problem following partial glossectomy and most cats and dogs can be discharged within 24–48 hours. To prevent disruption of intraoral incisions, animals should only be fed soft canned food and prevented from chewing on hard objects for four weeks. Supplemental nutrition via either an esophagostomy or gastrostomy tube is recommended in dogs treated with subtotal to total glossectomy. Dogs can be trained to eat following major glossectomy procedures by manually dropping chilled canned food meatballs into the back of the oral cavity while the muzzle is held in an elevated position (Dvorak et al. 2004). Once dogs are able to pick up and swallow a meatball without assistance, the meatball should be placed in a bowl of water to encourage drinking (Dvorak et al. 2004). The majority of dogs will begin to eat and drink unassisted within four weeks of surgery. This initial period can be very intensive and require a signi icant investment in both time and effort for the owners (Dvorak et al. 2004). Feeding tubes can be removed when dogs are able to consistently eat and drink voluntarily and without assistance. Analgesia is also important in the postoperative period. However, in people, glossectomy offers substantial palliation of pain associated with lingual tumors and the majority of patients do not require postoperative

analgesics (Dvorak et al. 2004). A similar inding has not been reported in animals, so postoperative analgesia should at least include a non-steroidal anti-in lammatory drug.

Figure 6.53 (a) A ibrosarcoma on the free portion of the tongue of a dog has been excised with 2 cm margins; (b) A squamous cell carcinoma arising from the lateral frenulum of dog; (c) Following excision of this squamous cell carcinoma, hemorrhage is common and, in this case, the lingual artery has been ligaclipped (arrow); (d) Following excision of the ibrosarcoma from the free portion of the tongue (a), the defect has been closed in a single layer of simple interrupted sutures using absorbable mono ilament suture material; (e) Following excision of the squamous cell carcinoma (b–d), the defect has been closed in two layers of simple continuous suture patterns.

Figure 6.54 (a) A primary glossal soft tissue sarcoma in a dog; (b) The soft tissue sarcoma is resected using a wedge-shaped excision; (c) Appearance of the tongue following wedge-shaped resection of the soft tissue sarcoma. In this case, the wedge-shaped excision was closed transversely by suturing the dorsal mucosa together (d) and ventral mucosa together (e).

Figure 6.55 (a and b). The tumor is removed with a wedge of the tongue. The defect can be closed by apposition of the dorsal and ventral mucosa together (c) or by apposition of the dorsal mucosa together and ventral mucosa together (d). Source: Illustrated by Molly Borman.

Radiation therapy should be considered for tongue tumors which are incompletely excised, considered inoperable, or metastatic to the regional lymph nodes.

Complications Complications of glossectomy include intraoperative hemorrhage and postoperative dehiscence, prehension dif iculties, ptyalism, tongue necrosis, heat stress, local tumor recurrence, and, particularly in cats, dif iculty grooming (Beck et al. 1986; Carpenter et al. 1993; Dvorak et al. 2004; Syrcle et al. 2008). Hemorrhage is common because of the rich vasculature of the tongue. However, bleeding during glossectomy is usually easily controlled with cautery and ligatures. Temporary occlusion of the carotid arteries may decrease the risk of hemorrhage and blood loss in dogs but is rarely required (Hedlund et al. 1983; Holmberg and Pettifer 1997). Carotid artery occlusion should not be performed in cats (Holmes and Wolstencroft 1959; Gillian 1976; Holmberg 1996).

Postoperatively, dehiscence has been reported but is usually minor and heals rapidly by second intention because of the vascularity of the tongue (Dvorak et al. 2004; Syrcle et al. 2008). Necrosis of the free portion of the tongue has been reported following minor glossectomy, presumably because of compromise to both of the paired lingual arteries (Dvorak et al. 2004). For this reason, one of these paired arteries should be preserved during partial or subtotal lateral glossectomy procedures.

Figure 6.56 (a) A benign extramedullary plasmacytoma of the tongue in a dog; (b) The plasmacytoma has been excised with a transverse glossectomy caudal to the tumor; (c) The transverse glossectomy is closed by suturing the dorsal and ventral mucosa.

Figure 6.57 (a and b) A full-thickness incision is made transversely across the tongue caudal to the tumor. (c) The defect is closed by apposing the dorsal mucosa with the ventral mucosa. (c and d) Alternatively, a Vshaped incision with the apex of the “V” directly caudally on midline. (e) This defect is closed by apposing the dorsal mucosa on either side together and the ventral mucosa as well. Source: Illustrated by Molly Borman.

Figure 6.58 (a) A full-thickness longitudinal incision is made along the midline from the tip of the tongue to the caudal extent of the tumor. The incision is then brought to the lateral edge of the tongue providing an adequate margin of normal tissue. (b) The defect is closed by apposing the ventral and dorsal mucosal layers together along the length of the incision. (c) An alternative closure method is to rotate the remaining tip of the tongue and suture the cut edges of the mucosa dorsally together and ventrally together. Source: Illustrated by Molly Borman.

Ptyalism is most commonly reported following major glossectomy (Dvorak et al. 2004) but is uncommon following partial and subtotal glossectomies. Various techniques have been proposed to treat ptyalism, including oral glycopyrrolate, sialoadenectomy, salivary duct ligation, and salivary duct diversion, but these have either been unsuccessful, partially successful, or inconsistent (Dvorak et al. 2004). Heat stress is a possible complication following major glossectomy (Dvorak et al. 2004). The dorsal surface of the canine tongue contains numerous arteriovenous anastomoses which are necessary for thermoregulation (Chibuzo 1979). The tongue is also important for heat dissipation through panting. Major glossectomy removes these arteriovenous anastomoses and reduces the effectiveness of panting. The risk of heat stress can be minimized by avoiding hot environments, minimizing activity during warmer periods of the day, and immediate cooling if the dog becomes hot through excessive activity or excitation. The tongue plays an important role in food prehension and swallowing. Eating is rarely affected following minor glossectomies, even in cats, but major glossectomy in both cats and dogs can prevent normal eating

as the tongue is integral for the oral phase and also initiates the pharyngeal phase of swallowing. As described above, this effect is usually temporary in dogs but permanent in cats. Supplemental nutrition is required in dogs until they are able to be trained to eat and drink unassisted (Dvorak et al. 2004). Major glossectomy is not recommended in cats because of poor ability to eat, drink and groom.

Figure 6.59 (a) A benign extramedullary plasmacytoma of the tongue in a dog; (b) The plasmacytoma has been resected with a longitudinal glossectomy, using an elliptical incision around the tumor with appropriate margins; (c) The longitudinal glossectomy is closed by suturing the dorsal mucosa.

Tongue Tumors in Dogs Tongue tumors are uncommon in cats and dogs. In dogs, tongue tumors account for up to 4% of all oropharyngeal neoplasms (Dennis et al. 2006). In one study, neoplasia was reported to account for 54% of canine lingual lesions with 64% of these being malignant tumors (Beck et al. 1986; Syrcle et al. 2008). The majority of these tumors are located on the dorsal surface of the tongue but are evenly distributed between the rostral, mid, and caudal portions of the tongue (Beck et al. 1986). For unknown reasons, 16% of dogs and up to 29% of people with tongue tumors have a second primary tumor (Dvorak et al. 2004). Hence, thorough physical examination and clinical staging are important in animals with tongue tumors. Melanoma and SCC are the most common malignant tongue tumors, followed by lymphoma, adenocarcinoma, salivary gland carcinoma, hemangiosarcoma, ibrosarcoma, mast cell tumor, and then a variety of soft tissue sarcoma subtypes such as liposarcoma, myxosarcoma, and rhabdomyosarcoma (Dennis et al. 2006; Syrcle et al. 2008; Culp et al. 2013; Burton et al. 2014). The odds of melanoma are signi icantly greater in large breed dogs such as Chow Chows and Chinese Shar Peis (Dennis et al. 2006). Lingual SCC is more common in female dogs and white-coated breeds, particularly Poodles, Labrador Retrievers, and Samoyeds (Carpenter et al. 1993; Dennis et al. 2006). A grading scheme for lingual SCC in dogs has prognostic signi icance (Carpenter et al. 1993). Common benign tumors include squamous papilloma, plasma cell tumor, granular cell tumor (or myoblastoma), rhabdomyoma, ibroma, and lipoma (Dennis et al. 2006; Syrcle et al. 2008). Non-neoplastic tongue lesions include glossitis, eosinophilic granuloma, and calcinosis circumscripta (Dennis et al. 2006).

Tongue Tumors in Cats The most common tongue tumor in cats is SCC and this is most frequently located on the ventral surface of the tongue and frenulum (Liptak 2019). Other malignant tumors are rare but include melanoma and ibrosarcoma. Non-neoplastic lesions include eosinophilic granuloma and calcinosis circumscripta (Liptak 2019).

Multimodal Management of Oral Tumors Radiation Therapy Radiation therapy can be effective for locoregional control of oral tumors. Radiation therapy can be used as primary treatment, with either palliative or curative-intent, or as an adjunct for incompletely resected tumors or tumors with an aggressive local behavior, such as oral ibrosarcoma. Malignant melanoma, canine oral SCC, and some benign tumors, such as the epulides, are known to be radiation responsive and radiation therapy should be considered in the primary treatment of these tumors (MacEwen et al. 1986; Blackwood and Dobson 1996; Théon et al. 1997a, b; Kawabe et al. 2015). For canine oral SCC, dental tumors, and ibrosarcoma, daily and alternate day protocols have been described consisting of 2.7–4.2 Gy per fraction with a total dose ranging from 48 to 57 Gy (Théon et al. 1997a; Forrest et al. 2000). Tumor control is better for smaller benign and malignant lesions (T1 and T2 tumors) treated with radiation alone (Blackwood and Dobson 1996; Théon et al. 1997a, b; Kawabe et al. 2015). Local tumor control and survival time can be improved by combining radiation therapy with radiation sensitizers, surgery, and/or chemotherapy, especially for tumors considered radiation-resistant, such as canine oral ibrosarcoma and feline oral SCC (Thrall 1981; Evans et al. 1991; LaRue et al. 1991; Hutson et al. 1992; Ogilvie et al. 1993; Jones et al. 2003). Radiation sensitizers, such as etanidazole and gemcitabine, have improved response rates in cats with oral SCC and platinum drugs have been used as radiation sensitizers in dogs with oral melanoma (Evans et al. 1991; Freeman et al. 2003; Jones et al. 2003; Proulx et al. 2003). Oral melanoma is responsive to coarse fractionation protocols. Four different hypofractionated radiation protocols have been described: (i) three weekly 8–10 Gy fractions for a total dose of 24–30 Gy (Bateman et al. 1994; Proulx et al. 2003), (ii) four weekly fractions of 9 Gy for a total dose of 36 Gy (Blackwood and Dobson 1996; Proulx et al. 2003), (iii) six weekly 6 Gy fractions for a total dose of 36 Gy (Freeman et al. 2003), and (iv) eight weekly 6 Gy fractions for a total dose of 48 Gy (Turrel 1987). In humans, the effect of total radiation dose is controversial, but fraction dose does have an impact on response rates. Doses greater than 4 Gy per fraction are recommended as response rates are signi icantly better with fractions greater than 8 Gy compared to less than 4 Gy (Overgaard et al. 1986). However, in one study of dogs with oral melanoma comparing two hypofractionated protocols of 9–10 Gy per fraction to a fully fractionated protocol of 2–4 Gy per fraction, there were no signi icant differences in either local recurrence rates or survival time (Proulx et al. 2003). Signi icantly longer survival times were reported overall (median survival times of 233 days compared to 122 days) and for dogs with stage III disease (median survival times of 210 days compared to 99 days) following treatment with megavoltage radiation in one study of 111 dogs comparing hypofractionated orthovoltage (6.3–10Gy/fraction for 4–6 fractions for a total dose of 38–40Gy) and megavoltage (6–10Gy/fraction for 4–8 fractions for a total dose of 40–50Gy) irradiation of oral melanomas (Kawabe et al. 2015). Coarse fractionation of oral melanoma has also been described in ive cats with limited success, including one complete response and two partial responses (Farrelly et al. 2004). Acute effects are common but self-limiting. These include alopecia and moist desquamation, oral mucositis, dysphagia, and ocular changes, such as blepharitis, conjunctivitis, keratitis, and uveitis (Roberts et al. 1987; Jamieson et al. 1991; Théon et al. 1997a, b; LaRue and Gillette 2007; Kawabe et al. 2015). The acute effects of coarse fractionation are less than experienced with the full-course protocols used for oral SCC and dental tumors and usually resolve rapidly (Blackwood and Dobson 1996). Late complications are rare, occurring in less than 5% of cases, but can include permanent alopecia, skin ibrosis, bone necrosis, and oronasal istula formation, development of a second malignancy within the radiation ield, keratoconjunctivitis sicca, cataract formation, and ocular atrophy (Thrall et al. 1981; Thrall 1984; Théon et al. 1997a, b). Orthovoltage radiation is associated with a higher incidence of second malignancies and bone necrosis than megavoltage irradiation (Thrall 1984; Théon et al. 1997a, b).

Chemotherapy The major problem with most oral tumors is control of local disease. However, chemotherapy is indicated for some tumors because of their high metastatic potential, especially oral melanoma in dogs and tonsillar SCC in cats and dogs. Over-expression of COX-2 has been noted in feline oral SCC (Hayes et al. 2006) and canine oral malignant melanoma (Pires et al. 2010; Martínez et al. 2011), however non-steroidal antiin lammatory drugs such as piroxicam have not been effective in the management of this disease in cats in

preliminary studies (DiBernardi et al. 2007). In vitro research has shown that celecoxib does have inhibitory effects on canine melanoma cell lines over-expressing COX-2 (Seo et al. 2014), but this has not been investigated clinically. Piroxicam does have some effect against oral SCC in dogs (Schmidt et al. 2001) and this response rate is improved when piroxicam is combined with either cisplatin or carboplatin (Boria et al. 2004; de Vos et al. 2004). Liposome-encapsulated cisplatin is not effective in cats with oral SCC (Fox et al. 2000), but mitoxantrone, in combination with radiation therapy, has shown some potential in a limited number of cats with good local responses and durable remission (LaRue et al. 1991; Ogilvie et al. 1993). The platinum drugs show the most promise in treating dogs with oral melanoma, including intralesional cisplatin (Kitchell et al. 1994) and systemic carboplatin (Rassnick et al. 2001; Dank et al. 2012). Measurable responses to intralesional bleomycin and systemic melphalan have also been reported (Page et al. 1991; Spugnini et al. 2006).

Immunotherapy Malignant melanoma is a highly immunogenic tumor. The use of immunotherapy agents and biologic response modi iers is an emerging and exciting approach for the adjunctive management of dogs with oral melanoma. Biologic response modi iers, such as Corynebacterium parvum and liposome muramyl tripeptide phosphatidylethanolamine (L-MTP-PE), have shown encouraging results compared to control groups in controlled clinical studies (MacEwen et al. 1986; MacEwen et al. 1999). Others, however, have failed to improve survival times in dogs with malignant melanoma, such as bacillus Calmette-Guérin (BCG) and levamisole. Genetic immunotherapy is an active area of research and current approaches have resulted in signi icant improvements in local control rates and survival times. These approaches include systemic administration of interleukin-2 (IL-2) and tumor necrosis factor (Moore et al. 1991); intratumoral injection of xenogeneic histoincompatible human Vero cells genetically modi ied to produce human recombinant IL2, a potent proin lammatory cytokine (Quintin-Colonna et al. 1996); autologous vaccines from irradiated tumor cells transfected with human recombinant (hr) granulocyte-macrophage colony-stimulating factor (GM-CSF), a potent hematopoietic and proin lammatory cytokine (Hogge et al. 1998); direct injection of DNA into tumors to induce expression of staphylococcal enterotoxin B (a superantigen) in combination with either GM-CSF or IL-2 (Elmslie et al. 1994, 1995; Dow et al. 1998); DNA vaccination with either murine or human tyrosinase, which can result in cytotoxic and T-cell responses, with or without human recombinant GM-CSF (Bergman et al. 2003a, b, 2004; Grosenbaugh et al. 2011); and human-recombinant chondroitin sulfate proteoglycan-4 DNA-based electrovaccination (Riccardo et al. 2014; Piras et al. 2017). Immunotherapeutic approaches, in combination with either surgery and/or radiation therapy, are promising in the management of oral melanoma. A DNA vaccine with human tyrosinase is now commercially available for the adjunctive treatment of dogs with completely excised oral malignant melanoma.

Prognosis Clinical series of over 500 dogs with various oral malignancies treated with either mandibulectomy or maxillectomy have been reported (Withrow and Holmberg 1983; Bradley et al. 1984; White et al. 1985; Withrow et al. 1985; Salisbury et al. 1986; Salisbury and Lantz 1988; Kosovsky et al. 1991; Schwarz et al. 1991a, b; White 1991; Wallace et al. 1992; Kirpenstein et al. 1994; Lascelles et al. 2003, 2004). The majority of cases were treated with surgery alone. Unfortunately, the methods of reporting and end results vary with each paper. Overall, the lowest rates of local tumor recurrence and best survival times are reported in dogs with acanthomatous ameloblastoma and SCC, while the ibrosarcoma and malignant melanoma are associated with the poorest results (Withrow and Holmberg 1983; Bradley et al. 1984; White et al. 1985; Withrow et al. 1985; Salisbury et al. 1986; Salisbury and Lantz 1988; Kosovsky et al. 1991; Schwarz et al. 1991a, b; White 1991; Wallace et al. 1992). Most of these reports suggest that histologically complete resection and rostral location are favorable prognostic factors. In two studies of 142 dogs treated with either mandibulectomy or maxillectomy, tumor-related deaths were 10- to 21-times more likely with malignant tumors, up to 5 times more likely with tumors located caudal to the canine teeth, and 2- to 4times more likely following incomplete resection (Schwarz et al. 1991a, 1991b). Rostral locations are usually detected at an earlier stage and are more likely to be resected with complete surgical margins. Local tumor recurrence is more frequent following incomplete resection, with 15–22% and 62–65% of tumors

recurring following complete and incomplete excision respectively (Schwarz et al. 1991a, b), and recurrent disease negatively impacts survival time as further treatment is more dif icult and the response to treatment is poorer (Overley et al. 2001). Fibrosarcoma continues to have an unacceptable local recurrence rate and needs to be addressed with wider resections or other adjuvant therapies, such as postoperative radiation (Forrest et al. 2000). On the other hand, melanoma is controlled locally in 75% of cases, but metastatic disease requires more effective adjuvant therapy, such as radiation therapy, chemotherapy, or immunotherapy. For dogs treated with megavoltage radiation, tumor size is the most important factor in local tumor control for both benign and malignant oral tumors. Local recurrence is reported in up to 30% of cases and, compared to T1 tumors (< 2 cm diameter), recurrence is three-times more likely in T2 tumors (2–4 cm diameter) and up to eight-times more likely in T3 tumors (> 4 cm diameter) (Théon et al. 1997a, 1997b). Tumor size is also associated with survival in dogs with malignant oral tumors, with three-year progression-free survival rates of 55%, 32%, and 20% for T1, T2, and T3 tumors, respectively (Théon et al. 1997a).

Malignant Melanoma The prognosis for dogs with oral melanoma is guarded. Metastatic disease, particularly to the lungs, is the most common cause of death with metastasis to the lungs reported in 14–67% of dogs (Todoroff and Brodey 1979; Harvey et al. 1981; Brewer and Turrel 1982; MacEwen et al. 1986; Kosovsky et al. 1991; Wallace et al. 1992; Bateman et al. 1994; Blackwood and Dobson 1996; Théon et al. 1997a; MacEwen et al. 1999; Overley et al. 2001; Freeman et al. 2003; Kudnig et al. 2003; Proulx et al. 2003; Williams and Packer 2003; Boston et al. 2014; Tuohy et al. 2014). Surgery and radiation therapy can provide good control of local disease, but strategies to manage the high metastatic potential of malignant melanoma, such as immunotherapy, are required for better disease control and longer survival times. Surgery is the most common treatment for management of the local tumor. The local tumor recurrence rates vary from 22% following mandibulectomy to 48% after maxillectomy in earlier reports (Kosovsky et al. 1991; Wallace et al. 1992; Kudnig et al. 2003), but 16–17% overall in more recent studies (Boston et al. 2014; Tuohy et al. 2014). The median survival time for dogs with malignant melanoma treated with surgery alone varies from 150 to 874 days with 1-year survival rates less than 35% (Harvey et al. 1981; Kosovsky et al. 1991; Schwarz et al. 1991a, b; Wallace et al. 1992.; MacEwen et al. 1999; Ramos-Vara et al. 2000; Overley et al. 2001; Freeman et al. 2003; Kudnig et al. 2003; Boston et al. 2014; Tuohy et al. 2014). In a recent study, the median progression-free interval and survival time following surgery alone for oral malignant melanoma were > 567 days and 874 days, respectively (Tuohy et al. 2014). Tumor control and survival time are signi icantly better when surgery is included in the treatment plan (Hahn et al. 1994). In comparison, the median survival time for untreated dogs with oral melanoma is 65 days (Harvey et al. 1981). Variables which are known to have prognostic signi icance in dogs treated with surgery alone or in combination with other modalities include age, tumor size, clinical stage, the ability of the irst treatment to achieve local control, and histologic and immunohistochemical criteria such as the degree of differentiation, mitotic index, nuclear atypia score, pigment quanti ication, COX-2 expression, Ki-67 expression, and c-kit expression (Harvey et al. 1981; Brewer and Turrel 1982; MacEwen et al. 1986, 1999; Bateman et al. 1994; Blackwood and Dobson 1996; Théon et al. 1997a; Overley et al. 2001; Freeman et al. 2003; Kudnig et al. 2003; Sánchez et al. 2007; Bergin et al. 2011; Martínez et al. 2011; Newman et al. 2012; Boston et al. 2014; Tuohy et al. 2014). Prognostic information for melanocytic tumors in dogs has been reviewed (Smedley et al. 2011). Age at presentation was prognostic in one study with dogs (≥ 12 years having a 2.0 greater hazard of tumor-related death than younger dogs and a median survival time of 224 days compared to 630 dogs for dogs < 12 years (Boston et al. 2014)). Intact female dogs had a signi icantly worse prognosis compared to spayed female dogs in another study (Tuohy et al. 2014). Dogs with tumors less than 2 cm diameter have a median survival time of 511 days compared to 164 days for dogs with tumors greater than 2 cm diameter or lymph node metastasis (MacEwen et al. 1986), and dogs with melanomas 2–4 cm and > 4 cm in diameter had 1.7 and 3.8 greater hazards of tumor-related death, respectively, compared to tumors < 2 cm (Boston et al. 2014). In another study, tumor size > 3cm was prognostic with a median survival time of 874 days for melanomas < 3 cm 396 days for melanomas > 3 cm (Tuohy et al. 2014). The reported median survival times for dogs with stage I, II, and III melanomas are 630–874, 240–818, and 173–207 days, respectively (Boston et al. 2014; Tuohy et al. 2014). Median survival times are signi icantly shorter for dogs

with recurrent oral malignant melanomas compared to dogs with previously untreated oral melanomas (Harvey et al. 1981; Overley et al. 2001). In some studies, tumor location also has prognostic importance with rostral mandibular and caudal maxillary sites having a better prognosis than other sites (Hahn et al. 1994; Kitchell et al. 1994; Martínez et al. 2011). Breed, degree of pigmentation, microscopic appearance, and DNA ploidy are not prognostic. In one study, dogs treated with adjunctive radiation therapy had signi icantly longer survival times, but this result may have been confounded by age, which was also prognostic in this study (Boston et al. 2014). In one study of 64 dogs with surgically treated welldifferentiated melanomas of the lips and oral cavity, 95% of dogs were either alive or had died of unrelated causes at the end of the study period (Esplin 2008). Dogs with COX-2 over-expression have a 2.8 greater hazard of tumor-related death than dogs with no COX-2 over-expression, with distant metastasis reported in 35% of dogs with COX-2 over-expression and 5% of dogs with mild or absent COX-2 immunolabelling (Martínez et al. 2011). Furthermore, the 12-month survival rates for dogs with high, moderate, low, and no COX-2 expression were signi icantly different at 33%, 64%, 75%, and 100%, respectively (Martínez et al. 2011). Oral melanoma is responsive to hypofractionated radiation therapy protocols. Response rates are excellent with 83–100% of tumors responding and a complete response observed in up to 70% of melanomas (Turrel 1987; Bateman et al. 1994; Blackwood and Dobson 1996; Théon et al. 1997a; Freeman et al. 2003; Kawabe et al. 2015). Local recurrence is reported in 15–26% of dogs with a complete response with a median time to local recurrence of 139 days (Bateman et al. 1994; Blackwood and Dobson 1996; Théon et al. 1997a; Freeman et al. 2003). Progressive local disease was observed in all dogs that did not achieve a complete response in one study (Bateman et al. 1994). The most common cause of death is metastasis, and this is reported in 58% of dogs with a median time to metastasis of 311 days (Freeman et al. 2003). The median survival time for dogs treated with radiation therapy is 171–363 days with a 1-year survival rate of 23–48% and a 2-year survival rate of 21% (Bateman et al. 1994; Blackwood and Dobson 1996; Théon et al. 1997a; Freeman et al. 2003; Proulx et al. 2003; Kawabe et al. 2015). Local tumor control and survival time are signi icantly improved with rostral tumor location, smaller tumor volume, no radiographic evidence of bone lysis, postoperative irradiation of microscopic disease, and megavoltage irradiation (Blackwood and Dobson 1996; Théon et al. 1997a; Proulx et al. 2003; Kawabe et al. 2015). When considering the risk factors of a non-rostral location, bone lysis, and macroscopic disease in one series of 140 dogs with oral melanoma, the median survival time was 21 months and signi icantly better if none of these risk factors were present compared to a median survival time of 11 months with one risk factor, 5 months with two risk factors, and 3 months with all three risk factors (Proulx et al. 2003). Tumor size is important with the median progression-free survival for dogs with T1 oral melanomas is 19 months compared to less than 7 months for T2 and T3 tumors (Théon et al. 1997a). In one study of 111 dogs treated with either orthovoltage or megavoltage hypofractionated protocols, tumor size and clinical stage had a signi icant effect on outcome with median survival times for dogs with stage I, II, III, and IV oral malignant melanoma of 758, 278, 163, and 80 days, respectively (Kawabe et al. 2015). In this study, there was a greater risk of death and decreased survival times overall and for dogs with stage III melanoma when treated with orthovoltage radiation therapy (Kawabe et al. 2015). Hypofractionated radiation therapy has also been described in ive cats with oral melanoma resulting in a 60% response rate and median survival time of 146 days (range 66– 224 days) (Farrelly et al. 2004). Adjunctive management is indicated in dogs with oral melanoma because of the high metastatic risk. These can be administered either intralesionally or systemically. Intralesional implants which release cisplatin signi icantly improve survival time compared to control dogs, with a median survival time of 51 weeks compared to 10 weeks, but implant-related complications were common (Kitchell et al. 1994). The platinum drugs are preferred for both radiation sensitization (Freeman et al. 2003; Proulx et al. 2003) and systemic chemotherapy (Overley et al. 2001; Rassnick et al. 2001). Both melphalan and carboplatin result in similar outcomes with an overall response rate of less than 30% and a median duration of response of approximately four months (Page et al. 1991; Rassnick et al. 2001). Cisplatin and piroxicam have been investigated, but this treatment regimen, despite a response rate of 18%, should be used with caution because of a high rate of renal toxicosis (Boria et al. 2004). In one study, multimodality therapy with surgery and adjunctive chemotherapy improved the survival time from 318 days for surgery alone to 1120 days, but this result was not signi icant because of low case numbers (Overley et al. 2001). In another study of 17 dogs treated with surgery and adjuvant carboplatin, the median progression-free survival was 259 days (with 41% of dogs developing local tumor recurrence and 41% of dogs developing metastasis) and the

median survival time was 440 days (Dank et al. 2012). Two recent studies have shown no bene it in survival times with the use of adjunctive chemotherapy (Boston et al. 2014; Tuohy et al. 2014), with overall median survival times of 335 days and 352 days in dogs that were and were not treated with systemic adjuvant therapy (Boston et al. 2014). Immunotherapy is preferred to chemotherapy for the adjunctive management of dogs with malignant oral melanoma. Immunotherapy is commonly used for the adjuvant treatment of dogs with oral melanomas. The use of DNA vaccinations with either murine or human tyrosinase in dogs with advanced stages of oral melanoma (clinical stages II–IV) results in median survival times of 224–389 days (Bergman et al. 2003a, b, 2004; Grosenbaugh et al. 2011). In one study of nine dogs treated with DNA vaccine encoded for human tyrosinase, complete response was observed in one dog with lung metastasis, two dogs with stage IV disease and bulky metastasis lived for greater than 400 days, and two dogs with stage II or III disease died of other causes approximately 500 days after treatment with no evidence of tumor at necropsy (Bergman et al. 2003b). The median survival time is signi icantly improved to 589 days when the primary oral site and regional lymph nodes are controlled with surgery or radiation therapy (Bergman et al. 2003a). In a prospective study of dogs with surgically excised stage II or III oral melanoma which compared 58 dogs treated with DNA vaccine encoded for human tyrosinase to a historical control of 53 unvaccinated dogs, the median survival time was signi icantly longer for dogs in the vaccinated group (not reached compared to 324 days) with tumor-related deaths in only 26% of vaccinated dogs compared to 64% of unvaccinated dogs (Grosenbaugh et al. 2011). In two prospective studies investigating human recombinant chondroitin sulfate proteoglycan-4 DNA-based electrovaccination following surgical resection in dogs with stage II or III oral MMs, the survival outcomes were signi icantly longer in vaccinated dogs (Riccardo et al. 2014; Piras et al. 2017). For vaccinated and unvaccinated dogs, respectively, the local recurrence rates were 21–35% and 39–42%; the metastatic rates were less than 36% and 79–90%; the 6-month survival rates were 96–100% and 63–69%; the 12-month survival rates were 64–74% and 15–26%; the 24-month survival rates were 30% and 5%; the median DFIs were 477 days and 180 days; and the MSTs were 653–684 days and 200– 220 days (Riccardo et al. 2014; Piras et al. 2017). For vaccinated dogs, outcomes were signi icantly better for dogs weighing less than 20 kg (Piras et al. 2017). While two retrospective papers have been published which question the ef icacy of using the melanoma vaccine in the adjunctive setting (Ottnod et al. 2013; Boston et al. 2014), both papers are retrospective with small case numbers and hence the evidence for the melanoma vaccine remains much more convincing than the evidence against the melanoma vaccine. The location of malignant melanoma may also have some prognostic signi icance. Melanomas of the lip and tongue may have a lower metastatic rate with survival more dependent on local control of the tumor. In one series of 60 dogs with oral melanomas at various sites treated with combinations of surgery, radiation therapy, chemotherapy, and immunotherapy, the median survival time for dogs with lip melanomas was 580 days and was not reached and greater than 551 days for dogs with tongue melanomas (Kudnig et al. 2003). In comparison, the median survival time was 319 days for maxillary melanomas and 330 days for melanomas of the hard palate (Kudnig et al. 2003). In another study, the median survival time was signi icantly longer for dogs with labial mucosal melanomas (310 days) than mandibular and maxillary melanomas (123 days) (Newman et al. 2012).

Squamous Cell Carcinoma Canine Oral Squamous Cell Carcinoma The prognosis for dogs with oral SCC is good, particularly for rostral tumor locations. Local tumor control is usually the most important challenge, although metastasis to the regional lymph nodes is reported in up to 10% of dogs and to the lungs in 3–36% of dogs (Théon et al. 1997a). In contrast, SCC of the tonsils and base of the tongue are highly metastatic, with metastasis reported in up to 73% of dogs, and local or regional recurrence is common (MacMillan et al. 1982; Beck et al. 1986; Brooks et al. 1988). Surgery and radiation therapy can both be used for locoregional control of oral SCC in dogs. Photodynamic therapy has also been reported with good results in 11 dogs with oral SCC (McCaw et al. 2000). Surgery is the most common treatment for management of non-tonsillar SCC (Withrow and Holmberg 1983). Following mandibulectomy, the local recurrence rate is 0–10% and the median survival time varies from 19 to 43 months with 88–100%, 79%, and 58% 1-, 2-, and 3-year survival times, respectively (Kosovsky et al. 1991; Fulton et al. 2013; Soukup et al. 2013; Kühnel and Kessler 2014). In comparison, the

local recurrence rate is 14–29% after maxillectomy with a median survival time of 10–39 months and a 1-, 2- and 3-year survival rates of 57–94%, 69%, and 38%, respectively (Wallace et al. 1992; Fulton et al. 2013; Kühnel and Kessler 2014). The higher local control and survival rates with mandibular resections are probably because the rostral mandible is the most common location for oral SCC in dogs and complete surgical resection is more likely for these rostral tumors. However, tumor location (both mandibular versus maxillary and location within the oral cavity) was not prognostic following surgical excision in three recent studies (Fulton et al. 2013; Kühnel and Kessler 2014; Mestrinho et al. 2017a). In one study, the median survival time for untreated dogs was 54 days with a 0% 1-year survival rate (Fulton et al. 2013). In comparison, the 1-year survival rate for dogs with surgically excised oral SCC was 94%, with median survival times not reached for dogs with stage I oral SCC and 420, 365, and 50 days for dogs with stage II, III, and IV oral SCC, respectively (Fulton et al. 2013). The presence of tumor-associated in lammation and risk score of 2 or ≥ 3 (combination of tumor-associated in lammation, lymphatic or vascular invasion, and peripheral nerve invasion) were associated with a signi icantly worse prognosis (Fulton et al. 2013). Dogs with tumor-associated in lammation had a two times greater hazard of tumor-related death than dogs without tumor-associated in lammation. Dogs with a risk score of ≥ 2 had a 1.7-times greater hazard of tumor-related death, with a median survival time of 365 days and 1-year survival rate of 36%, compared to dogs with a risk score of 0 or 1, in which the median survival time was not reached and the 1-year survival rate was 80% (Fulton et al. 2013). In two studies of dogs with surgically resected mandibular and maxillary SCC, overall median disease-free survival times were not reached with one- and two-year disease-free survival rates of 75–79% and 61–76%, respectively (Mestrinho et al. 2017b; Riggs et al. 2018). The median disease-free survival was signi icantly shorter for dogs with grade III SCCs (138 days) and SCCs with a proliferating cell nuclear antigen expression greater than 65% (155 days) compared to dogs with grade II SCCs and SCCs with a proliferating cell nuclear antigen expression ≤ 65% (not reached) (Mestrinho et al. 2017a). In one study, incomplete histologic margins were associated with a signi icantly worse outcome (median survival time was 1140 days compared to not reached for dogs with complete histologic excision), but dogs with incomplete histologic margins treated with adjuvant hypofractionated radiation therapy were signi icantly less likely to die of tumor-related reasons than dogs not treated with adjuvant radiation therapy (Riggs et al. 2018). Full-course radiation therapy, either alone or as an adjunct following incomplete surgical resection, is also a successful treatment modality for the management of oral SCC in dogs (Evans and Shofer 1988; LaDueMiller et al. 1996; Théon et al. 1997a). The local tumor recurrence rate is 31%. The median survival time for radiation therapy alone is 14–16 months and increases to 34 months when combined with surgery (Evans and Shofer 1988; LaDue-Miller et al. 1996). In one series of 39 dogs with oral SCC, the overall median progression-free survival time was 36 months with 1- and 3-year progression-free survival rates of 72% and 55%, respectively (Théon et al. 1997a). Local tumor control was better with smaller lesions as the median progression-free survival time and 1-year progression-free survival rates for T1 tumors (< 2 cm diameter) was not reached and greater than 68 months and 89%, respectively, compared to 28 months and 83% for T2 tumors (2–4 cm diameter), respectively, and 8 months and 41% for dogs with T3 tumors (> 4 cm diameter), respectively (Théon et al. 1997a). Other favorable prognostic factors include rostral tumor location, maxillary SCC, and young age (Evans and Shofer 1988). Rostral tumors (median survival time of 28 months compared to 2–10 months for caudal to extensive tumors), non-recurrent tumors (median survival time 29 months compared to 7 months for recurrent SCC), portal size less than 100 cm2/m2 (median survival time 24 months compared to 7 months), and age less than 6 years (median survival time of 39 months compared to 10 months) are good prognostic factors for dogs treated with orthovoltage radiation therapy (Evans and Shofer 1988). Younger age is also prognostic for dogs treated with megavoltage radiation as the median survival time of 315 days for dogs with oral SCC and older than 9 years is signi icantly shorter than the 1080 days reported for dogs less than 9 years (LaDue-Miller et al. 1996). Chemotherapy is indicated for dogs with metastatic disease, bulky disease, and when owners decline surgery and radiation therapy. However, as the metastatic potential of oral SCC in dogs is relatively low, the role of chemotherapy in minimizing the risk of metastatic disease is unknown. In one series of 17 dogs treated with piroxicam alone, the response rate was 17%, with one complete response and two partial responses (Schmidt et al. 2001). The median progression-free interval for dogs responding to piroxicam was 180 days and signi icantly longer than the 102 days for dogs with stable disease (Schmidt et al. 2001).

The outcome is better when piroxicam is combined with either cisplatin or carboplatin. In a series of nine dogs treated with piroxicam and cisplatin, the overall median survival time was 237 days with 56% of dogs responding to this chemotherapy protocol having a signi icantly better outcome than non-responders with a median survival time of 272 days compared to 116 days (Boria et al. 2004). However, renal toxicity was reported in 41% of dogs in this study, and such toxicities limit the clinical effect of this protocol. In another small series of seven dogs with T3 oral SCC treated with piroxicam and carboplatin, a complete response was observed in 57% of dogs and this response was sustained in all dogs at the median follow-up time of 335 days (de Vos et al. 2004). Feline Oral Squamous Cell Carcinoma The prognosis for cats with oral SCC is often perceived as being poor (Bostock 1972; Cotter 1981; Bradley et al. 1984; Reeves et al. 1993; Hayes et al. 2007); however, surgical resection does provide the potential for surprisingly good outcomes in many cats (Northrup et al. 2006; Boston et al. 2020; Liptak et al. 2020). Local control is the most challenging problem. In one series of 52 cats, the one-year survival rate was less than 10% with median survival times of three months or less for surgery alone, surgery and radiation therapy, radiation therapy and low-dose chemotherapy, or radiation therapy and hyperthermia (Reeves et al. 1993). However, 42% of these cats had SCC involving the tongue, pharynx, or tonsils. The oncologic outcome may be better for cats with mandibular or maxillary SCC. The median survival time for seven cats treated with a combination of mandibulectomy and radiation therapy was 14 months with a 1-year survival rate of 57% (Hutson et al. 1992). Local recurrence was the cause of failure in 86% of these cats between 3 and 36 months after therapy. In another series of 22 cats treated with mandibulectomy alone, the median disease-free interval was 340 days with a 38% local tumor recurrence rate (Northrup et al. 2006). The majority of cats developed local tumor recurrence within the irst year with one-, two-, and three-year progression-free survival rates of 51%, 34%, and 34%, respectively (Northrup et al. 2006); interestingly, this suggests that long-term, disease-free survival is possible for the majority of cats living to one year without local recurrence or metastasis. Tumor location and extent of resection had prognostic importance with a median survival time of 911 days for rostral tumors, 217 days following mandibulectomy, and 192 days when greater than 50% of the mandible was resected (Northrup et al. 2006). In a series of 13 cats with maxillary SCC treated with maxillectomy, the median survival time was not reached with 83% of cats alive at two years postoperatively; only one cat developed local tumor recurrence (Liptak et al. 2020). Radiation therapy alone is generally considered ineffective in the management of cats with oral SCC. In seven cats treated with a palliative radiation protocol (three fractions of 8 Gy on days 0, 7, and 21), the overall median survival time was 60 days; three cats did not complete the protocol and six cats had either progressive disease or radiation complications (Bregazzi et al. 2001). In nine cats treated with an accelerated radiation protocol (14 fractions of 3.5 Gy delivered twice daily for nine days), the overall median survival time was 86 days and, although not signi icant, the median survival time for cats with a complete response was 298 days (Fidel et al. 2007). In 13 cats treated with intratumoral injection of radioactive holmium microspheres, the overall median survival time was 113 days, but this was signi icantly better (296 days) in the 55% of cats with a local response (van Nimwegen et al. 2018). The combination of radiation therapy with radiation sensitizers or chemotherapy improves response rates and survival times. Using the same accelerated radiation protocol with carboplatin resulted in a 52% complete and 22% partial response rate at 30 days with a median survival time of 163 days in 31 cats (Fidel et al. 2011). Intratumoral etanidazole, a hypoxic cell sensitizer, resulted in a 100% partial response rate in nine cats completing the radiation therapy course with a median decrease in tumor size of 70% and a median survival time of 116 days (Evans et al. 1991). Gemcitabine was used at low doses as a radiation sensitizer in eight cats with oral SCC with an overall response rate of 75%, including two cats with complete responses, for a median duration of 43 days and a median survival time of 112 days (Jones et al. 2003). However, gemcitabine is not recommended as a radiosensitizer in cats because of signi icant hematologic and local tissue toxicities (LeBlanc et al. 2004). The combination of radiation therapy with mitoxantrone holds some promise; in two series of 18 cats, a complete response was observed in 73% with a median duration of response of 138–170 days and a median survival time of 184 days (LaRue et al. 1991; Ogilvie et al. 1993). Tumor location, clinical stage, and the completeness of response are reported prognostic factors (Fidel et al. 2011; Poirier et al. 2013). Location was a prognostic factor with signi icantly longer median survival times in cats with SCC of the tonsils (not reached, mean 724 days) and cheek (not reached) than other locations

(Fidel et al. 2011). A complete response at 30 days was also associated with a signi icantly longer survival time (379 days) than non- or partial responders (115 days) (Fidel et al. 2011). Hypofractionated radiation therapy has also been reported in cats with oral SCC. An overall response rate of 81%, with a median survival time of 174 days, was reported in 21 cats treated with an accelerated hypofractionated radiation therapy protocol consisting of 10 daily fractions of 4.8 Gy for a total dose of 48 Gy (Poirier et al. 2013). In 54 cats treated with 8–10 Gy weekly fractions for a total dose of 24–40 Gy, the radiation-induced adverse effects were considered mild with the majority of owners reporting a subjectively improved quality of life (Sabhlok and Ayl 2014). The overall median survival time was 92 days and cats with sublingual SCCs had a longer median survival time (135 days) than cats with mandibular SCC (80 days) (Sabhlok and Ayl 2014). Palliative stereotactic radiation therapy (SRT) has been investigated in 20 cats with a 39% overall response rate and a median progression-free interval and median survival time of 87 and 106 days, respectively; however, there was a high complication rate with mandibular fracture in 55% of 11 cats, ibrosis in 50% of 6 cats with lingual SCC, and oronasal istula in 33% of 3 cats with maxillary SCC (Yoshikawa et al. 2016a, b). In this study, cats with a low Bmi-1 percentage, which is an oncogene responsible for suppression of cellcycle inhibitors and confers resistance to both chemotherapy and radiation therapy, had a signi icantly better outcome with longer median progression-free interval than cats with a higher Bmi-1 percentage (Yoshikawa et al. 2016a). Other prognostic factors for cats with oral SCC treated with stereotactic RT include gender, tumor microvascular density, and degree of keratinization (Yoshikawa et al. 2016b). Chemotherapy appears to be largely ineffective in the management of cats with oral SCC. No responses were observed in 18 cats treated with liposome-encapsulated cisplatin (Fox et al. 2000) or 13 cats treated with piroxicam (DiBernardi et al. 2007). However, non-steroidal anti-in lammatory drugs and toceranib phosphate have been shown to signi icantly improve outcomes in cats with measurable oral SCC (Hayes et al. 2007; Wiles et al. 2017). In one study of 23 cats with oral SCC with no previous treatments, toceranib phosphate and/or a non-steroidal anti-in lammatory drug resulted in a biologic response rate of 57%, with a complete response in 4%, partial response in 9%, and stable disease in 43% of cats (Wiles et al. 2017). The median survival time of cats treated with toceranib phosphate and/or a non-steroidal antiin lammatory drug (123 days) was signi icantly longer than the 45-day median survival time for cats not treated with toceranib phosphate (Wiles et al. 2017). Cats with a biologic response to treatment with toceranib phosphate and/or a non-steroidal anti-in lammatory drug had signi icantly better median progression-free survival (112 days) and overall median survival time (202 days) than cats that did not respond to treatment (29 days and 73 days, respectively) (Wiles et al. 2017). Cats treated with a nonsteroidal anti-in lammatory drug also had a signi icantly improved median survival time (169 days) than cats not treated with a non-steroidal anti-in lammatory drug (55 days) (Wiles et al. 2017). As most of these small case series are retrospective in nature, caveats as to the true ef icacy of these therapeutic approaches await con irmation in controlled, randomized trial settings. Pamidronate, a bisphosphonate drug with anti-osteoclastic activity, has been shown to reduce proliferation of feline cancer cells and palliate cats with bone-invasive tumors, including oral SCC (Wypij and Heller 2014). In a pilot study of ive cats with oral SCC treated with pamidronate, some of which were treated with other modalities including non-steroidal anti-in lammatory drugs, the median progression-free and overall survival times were 71 days and 170 days, respectively (Wypij and Heller 2014).

Fibrosarcoma The prognosis for dogs with oral ibrosarcoma is guarded. These are locally aggressive tumors and local control is more problematic than metastasis. Metastasis is reported to the regional lymph nodes in 19–22% of dogs and to the lungs in up to 27% of dogs (Kosovsky et al. 1991; Wallace et al. 1992; Théon et al. 1997a; Frazier et al. 2011). Multimodality treatment of the local disease may improve prognosis (Brewer and Turrel 1982; Forrest et al. 2000; Gardner et al. 2013), but results are con licting. Surgery is the most common treatment for oral ibrosarcoma. The median disease-free interval for ive cats treated with mandibulectomy was 859 days (Northrup et al. 2006), and the median survival time was not reached in 18 cats treated with maxillectomy with an 89% 2-year survival rate (Liptak et al. 2020). Local recurrence has been reported in up to 59% of dogs following mandibulectomy (Kosovsky et al. 1991) and 40% following maxillectomy (Wallace et al. 1992). However, a retrospective series reported local

recurrence in 24% of 29 dogs with mandibular and maxillary FSA (Frazier et al. 2011). Local tumor recurrence was signi icantly associated with incomplete excision and breed (Golden Retriever or Golden Retriever mixed breed dogs). Two of the seven dogs with local tumor recurrence developed recurrent disease after incomplete excision and adjunctive radiation therapy (Frazier et al. 2011). In older reports, the 1-year survival rates rarely exceed 50% with surgery alone (Withrow and Holmberg 1983; Bradley et al. 1984; White et al. 1985; Withrow et al. 1985; Salisbury et al. 1986; Salisbury and Lantz 1988; Kosovsky et al. 1991; Schwarz et al. 1991a, b; White 1991; Wallace et al. 1992); however, the median survival time in a recent retrospective series was 743 days with a median progression-free interval of > 653 days and oneand two-year survival rates of 88% and 58%, respectively (Frazier et al. 2011). Oral ibrosarcomas are considered radiation resistant (Hilmas and Gillette 1976; Thrall 1981; Creasey et al. 1982). The mean survival time of 17 dogs treated with radiation therapy alone was only 7 months (Thrall 1981). Radiation therapy combined with regional hyperthermia improved local control rates to 50% at one year in a series of 10 cases (Brewer and Turrel 1982). When radiation therapy is used as an adjunct to surgical resection, local tumor recurrence was reported in 32% of dogs overall and the median survival time increased to 18–26 months with a 1-year progression-free survival rate of 76% (Théon et al. 1997a; Forrest et al. 2000). In one study, 17 of 48 dogs with oral ibrosarcomas were treated with adjuvant hypofractionated radiation therapy; radiation therapy did not provide a protective effect with signi icantly poorer survival times in dogs treated with radiation therapy (Riggs et al. 2018). However, in another study, the addition of radiation therapy to surgery resulted in signi icantly longer median progression-free (301 days compared to 138 days) and overall survival times (505 days compared to 220 days) than mandibulectomy or maxillectomy alone (Gardner et al. 2013). A smaller tumor size improves the outcome following radiation therapy, with the median progression-free survival time of 45 months for dogs with T1 tumors compared to 31 months and 7 months for T2 and T3 tumors, respectively (Théon et al. 1997a).

Osteosarcoma Osteosarcoma of axial sites is less common than appendicular osteosarcoma and represents approximately 25% of all cases (Heyman et al. 1992). Of the axial osteosarcomas, the mandible and maxilla are involved in 27% and 16–22% of cases, respectively (Heyman et al. 1992; Hammer et al. 1995). In one study, only 3.8% of 183 dogs with maxillary, mandibular, or calvarial osteosarcoma had evidence of metastasis at the time of diagnosis, with distant metastasis reported in 32–46% of dogs following de initive treatment (Selmic et al. 2014). The outcome following mandibulectomy alone is variable with median survival times of 14–18 months and 1-year survival rates of 35–71% (Kosovsky et al. 1991; Heyman et al. 1992; Straw et al. 1996). Following mandibulectomy, local recurrence and metastasis have been reported in 15–28% and 35–58% of dogs, respectively (Kosovsky et al. 1991; Selmic et al. 2014; Coyle et al. 2015). The median metastasis-free interval and median survival time were 627 days and 525 days, respectively, in one study of 50 dogs (Coyle et al. 2015). Following maxillectomy, in a recent study of 69 dogs, local recurrence and metastasis were reported in 58% and 32% of dogs, respectively (Selmic et al. 2014). The median survival time for dogs with maxillary osteosarcoma varies from 5 to 10 months with a 1-year survival rate of 17–27% with local tumor recurrence rather than distant metastasis being the most common cause of death (Heyman et al. 1992; Wallace et al. 1992; Hammer et al. 1995; Selmic et al. 2014). Local tumor control is the most challenging problem and resecting oral osteosarcomas with complete surgical margins is imperative. The completeness of excision was prognostic for both local tumor recurrence and survival in multivariate analyses in one study (Selmic et al. 2014). The combination of surgery with either radiation therapy or chemotherapy did not improve the outcome in dogs with incompletely resected tumors, highlighting the necessity for an aggressive surgical approach (Kazmierski et al. 2002; Selmic et al. 2014). These results are supported by another study of 45 dogs with axial osteosarcoma in which favorable prognostic factors included complete surgical excision, mandibular location, and smaller body weight dogs (Hammer et al. 1995). Other poor prognostic factors for dogs with mandibular, maxillary, and/or calvarial osteosarcoma include serum alkaline phosphatase levels > 140 U/L, increased monocyte counts, telangiectatic histologic subtype, mitotic index, histologic grade, and local tumor recurrence (Selmic et al. 2014; Coyle et al. 2015). Dogs with grade II/III mandibular osteosarcoma have a 2.8-times greater hazard of tumor-related death than dogs with grade I mandibular osteosarcoma; with median survival times and 1-year survival rates 648 days and 77%, respectively, for dogs with grade I

mandibular osteosarcoma, and 306 days and 24%, respectively, for dogs with grade II/III mandibular osteosarcoma (Coyle et al. 2015). The role of chemotherapy in the management of dogs with oral osteosarcoma was considered controversial because local tumor recurrence was the most common cause of tumor-related deaths; however, adjuvant chemotherapy results in signi icantly longer metastasis-free intervals and survival times in dogs with mandibular osteosarcoma (Coyle et al. 2015). Dogs not treated with chemotherapy had a 2.8-times greater hazard of tumor-related death than dogs treated with chemotherapy; with median survival times of 1023 days and 525 days for dogs with mandibular osteosarcoma treated and not treated with adjuvant chemotherapy, respectively (Coyle et al. 2015). The prognosis for cats with either mandibular or maxillary osteosarcoma is very good following surgery alone. In six cats with mandibular osteosarcoma, one cat died of local tumor recurrence and the remaining ive cats (83%) were alive and disease-free at three years post-mandibulectomy (Northrup et al. 2006). In ive cats with maxillary osteosarcoma, one cat died of local tumor recurrence and the remaining four cats (80%) were alive and disease-free at two years post-maxillectomy (Liptak et al. 2020).

Multilobular Osteochondrosarcoma Multilobular osteochondrosarcoma is an infrequently diagnosed bony and cartilaginous tumor which usually arises from the canine skull, including the mandible, maxilla, and hard palate (Straw et al. 1989; Dernell et al. 1998c). Surgery is recommended for management of the local tumor. The overall rate of local recurrence following surgical resection is 47–58% and is dependent on completeness of surgical resection and histologic grade (Straw et al. 1989; Dernell et al. 1998c). The median disease-free interval for completely resected multilobular osteochondrosarcoma is 1332 days and signi icantly better than the 330 days reported for incompletely excised tumors (Dernell et al. 1998c). In terms of tumor grade, the local recurrence rate for grade III tumors is 78% and signi icantly worse than the recurrence rates of 30% and 47% for grade I and II multilobular osteochondrosarcoma, respectively (Dernell et al. 1998c). The tumor has a moderate metastatic potential, particularly to the lungs, which is grade-dependent but usually late in the course of disease. Metastasis is reported in up to 58% of dogs with the median time to metastasis of 426–542 days (Straw et al. 1989; Dernell et al. 1998c). Metastasis is signi icantly more likely following incomplete surgical resection, with a 25% metastatic rate in completely excised tumors and 75% following incomplete resection (Dernell et al. 1998c). Tumor grade also has a signi icant impact on metastatic rate with metastasis reported in 78% of grade III multilobular osteochondrosarcoma compared to 30% of grade I and 60% of grade II tumors (Dernell et al. 1998c). There is no known effective chemotherapy treatment for metastatic disease, but survival times greater than 12 months have been reported with pulmonary metastasectomy because of the slow-growing nature of this tumor (Dernell et al. 1998c). The overall median survival time is 21 months and is grade-dependent, with reported median survival times of 50 months, 22 months, and 11 months for grade I, II, and III tumors, respectively (Straw et al. 1989; Dernell et al. 1998c). Tumor location also has prognostic signi icance as the outcome for dogs with mandibular multilobular osteochondrosarcoma is signi icantly better with a median survival time of 1487 days compared to 587 days for these tumors at other sites (Dernell et al. 1998c). SRT has been described for the treatment of eight dogs with multilobular osteochondrosarcoma (Sweet et al. 2020). The dogs were treated with 10 Gy on three consecutive days. CT scans done 3–9 months after SRT in ive dogs showed a reduction in tumor volume by 26–87% in four dogs and an increase in tumor volume by 32% in one dog. Three dogs had local disease progression and metastasis was suspected in two dogs, 90–315 days after SRT. The median progression-free survival time was 223 days and the median overall survival time was 329 days (Sweet et al. 2020).

Acanthomatous Ameloblastoma Surgery or radiation therapy is also used in the management of dogs with acanthomatous ameloblastoma. Mandibulectomy or maxillectomy is required for surgical resection of acanthomatous ameloblastomas because of frequent bone invasion by this benign tumor. Local recurrence rates following bone-removing surgery are less than 5% (Withrow and Holmberg 1983; White et al. 1985; Bjorling et al. 1987; White and Gorman 1989; Kosovsky et al. 1991; Wallace et al. 1992; Yoshida et al. 1999; Goldschmidt et al. 2017). The impact of surgical and histologic margins was investigated in 23 dogs with acanthomatous ameloblastoma (Goldschmidt et al. 2017). Resections were incomplete in 21.7% of dogs overall, including 33.3% of dogs with 1.0 cm surgical margins, 25.0% of dogs with 1.5 cm surgical margins, and no dog with 2.0 cm surgical

margins; despite this, local tumor recurrence was not reported in any dog. This inding raises questions about the ideal surgical margins for resection of acanthomatous ameloblastomas in dogs and whether further local therapy is required following incomplete excision. Megavoltage radiation therapy, consisting of an alternate day protocol of 4 Gy per fraction to a total of 48 Gy, results in a three-year progression-free survival rate of 80% in dogs with acanthomatous ameloblastomas (Théon et al. 1997b). The overall local recurrence rate varies from 8 to 18% in two studies of 39 dogs and recurrence was eight times more likely with T3 tumors compared to T1 and T2 tumors (Thrall 1984; Théon et al. 1997b). The majority of tumors recur within the radiation ield, which suggests a higher radiation dose may be required to achieve higher rates of local tumor control, particularly for tumors greater than 4 cm in diameter (Théon et al. 1997b). Other complications associated with radiation therapy include malignant transformation in 5–18% of dogs and bone necrosis in 6% of dogs (Thrall 1984; Théon et al. 1997b). Intralesional bleomycin has been reported in two studies of dogs with acanthomatous ameloblastoma (Yoshida et al. 1998; Kelly et al. 2010). In total, 10 dogs were treated with curative-intent intralesional bleomycin, and all had complete responses. In one study of six dogs (Kelly et al. 2010), one to sixteen (median, ive) intralesional injections were administered prior to achieving a complete response. The median time to complete response was 1.5 months. There was no evidence of recurrence at one year in one study (Yoshida et al. 1998) and after a median follow-up time of 842 days in another study (Kelly et al. 2010).

Peripheral Odontogenic Fibroma The prognosis for dogs with peripheral odontogenic ibromas is excellent following treatment with either surgery or radiation therapy. These are benign tumors, and metastasis has not been reported, hence local tumor control is the principal goal of therapy. The local tumor recurrence rate following surgical resection without bone removal varies from 0 to 17% (Bjorling et al. 1987; Bostock and White 1987). Radiation therapy is also effective with a three-year progression-free survival rate of 86% (Théon et al. 1997b). However, full-course radiation therapy is usually not required as these tumors can be adequately managed with simple surgical resection (Yoshida et al. 1999). Local recurrence is common in cats with multiple peripheral odontogenic ibromas and is reported in 73% of 11 cats three months to eight years after surgical resection (Colgin et al. 2001).

Tongue The prognosis for tongue tumors depends on the site, size, type, and grade of cancer, completeness of excision, and local tumor recurrence (Carpenter et al. 1993; Syrcle et al. 2008; Culp et al. 2013). Cancer in the rostral tongue has a better prognosis possibly because rostral lesions are detected at an earlier stage, the caudal tongue may have richer lymphatic and vascular channels to allow metastasis, and rostral tumors are easier to resect with wide margins (Carpenter et al. 1993). Tumor size was also prognostic in one study: dogs with tongue tumors > 4 cm2 were 9.6-times more likely to develop local recurrence and/or distant metastasis and up to 18.5-times more likely to die of their tongue tumor than dogs with tumors ranging from 1 to 4 cm2 (Syrcle et al. 2008). Complete surgical excision was signi icantly more likely with smaller tumors and tumors located in the rostral free portion of the tongue (Carpenter et al. 1993; Syrcle et al. 2008). Furthermore, complete surgical excision was signi icantly associated with increased survival times and dogs with incomplete histologic margins were signi icantly more likely to develop local recurrence and/or distant metastasis and die of their tumor (Carpenter et al. 1993; Syrcle et al. 2008). Dogs with local tumor recurrence, which was reported in 26% of 31 dogs following glossectomy and is more likely with large and malignant tumors, were 33.3-times more likely to die as a result of their tumor than dogs without local recurrence (Syrcle et al. 2008). Dogs with benign tongue tumors have a signi icantly longer disease-free interval and median survival time than dogs with malignant tongue tumors (Syrcle et al. 2008). In one study, the median survival time for dogs with benign tongue tumors was not reached and > 1607 days compared to 286 days for dogs with malignant tongue tumors (Syrcle et al. 2008). Dogs with malignant tongue tumors were 7.6-times more likely to have local recurrence and/or distant metastasis and 14.7-times more likely to die of their tumor than dogs with benign tongue tumors (Syrcle et al. 2008).

Tongue SCC in dogs are graded from I (least malignant) to III (most malignant) based on histologic features such as degree of differentiation and keratinization, mitotic rate, tissue and vascular invasion, nuclear pleomorphism, and scirrhous reaction (Carpenter et al. 1993). The overall median survival time for dogs with tongue SCC was 301 days in one study (Syrcle et al. 2008). The median survival time for dogs with grade I tongue SCC was 16 months following surgical resection and this was signi icantly better than the median survival times of 4 and 3 months reported for grade II and III SCC, respectively (Carpenter et al. 1993). The 1-year survival rate was 50% following complete surgical resection and approached 80% with complete histologic resection of low-grade SCC (Carpenter et al. 1993). In another study, median survival for dogs with lingual SCC was 216 days (Culp et al. 2013). Long-term control of feline tongue tumors is rarely reported with one-year survival rates for tongue SCC less than 25% (Liptak 2019). The median survival time for dogs with tongue melanoma was 222 days in one study with 45% diagnosed with distant metastasis to the lungs (Syrcle et al. 2008). In one small series, local control was obtained by surgery in four of ive tongue melanomas, and the metastatic rate was less than 50% (Bostock 1972). In another series of dogs with tongue melanoma, the median survival time was not reached and was greater than 551 days (Kudnig et al. 2003). However, in a more recent study, the medial survival time for dogs with lingual melanoma was 241 days (Culp et al. 2013). Dogs with hemangiosarcoma of the tongue may have a better prognosis compared with hemangiosarcoma in other organs. In one study, median progression-free survival was 524 days and the median overall survival time was 553 days (Burton et al. 2014). Prognostic factors signi icantly associated with increased survival included small tumor size and absence of clinical signs of an oral mass at the time of diagnosis (Burton et al. 2014). Granular cell myoblastoma is curable cancer (Turk et al. 1983). These cancers may look large and invasive but are almost always removable by conservative and close margins (Syrcle et al. 2008). Permanent local control rates exceed 80%. They may recur late but serial surgeries are usually possible. The majority of benign tongue tumors are cured with surgical resection, even with incomplete surgical margins (Syrcle et al. 2008). The biologic behavior of other malignant tongue cancers is generally unknown due to the rarity of these conditions (Syrcle et al. 2008).

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7 Alimentary Tract William T.N. Culp, Ryan P. Cavanaugh, Earl F. Calfee III, Paolo Buracco, and Tania A. Banks

Esophagus Surgical Anatomy and Potential Procedures The esophageal anatomy from a surgical standpoint is fairly simple; however, an understanding of particular intricacies is essential to ensuring a successful outcome with surgery. The wall of the esophagus is unique among gastrointestinal organs in that while it does have four coats, three of these are similar to other gastrointestinal organs (mucosa, submucosa, and muscularis) whereas the fourth or outermost coat is adventitia as opposed to serosa (Evans 1993). The adventitia is a ibrous layer that blends into the organs adjacent to the esophagus (Evans 1993). The muscular composition of the esophageal wall varies between dogs and cats; the entire length of the dog esophagus is striated muscle whereas the distal one-third of the cat esophagus is smooth muscle (Dyce et al. 1996; Glazer and Walters 2008). The esophagus has three major sections and a few important landmarks (Evans 1993; Shamir et al. 1999). The three major sections of the esophagus, including cervical, thoracic, and abdominal regions, are clearly delineated by their location. Two esophageal sphincters exist based on studies evaluating function; the upper esophageal sphincter consists of ibers from the cricopharyngeus muscle and cranial wall of the esophagus, and the lower esophageal sphincter consists of muscle layers around the esophagus and diaphragmatic crura (Dyce et al. 1996; Shamir et al. 1999; Glazer and Walters 2008). The esophagus starts dorsal to the trachea but then takes on a slightly left-sided orientation in the cervical region. During passage through the thoracic cavity, the esophagus again relocates to a more symmetrically dorsal position (Evans 1993; Dyce et al. 1996).

The esophageal blood supply is considered to be segmental. The cervical portion receives blood from the cranial and caudal thyroid arteries, the thoracic portion receives blood from the bronchoesophageal and dorsal intercostal arteries as well as from esophageal branches of the aorta. The abdominal esophagus receives blood from the left gastric artery (Evans 1993). Additionally, a collateral blood supply that exists within the esophageal wall has been identi ied (Macmanus et al. 1950). This blood supply allows the esophagus to maintain perfusion if the thoracic blood supply is compromised; however, necrosis will occur if the esophagus loses both the cervical and thoracic blood supply (Macmanus et al. 1950). Venous drainage is via satellite vessels of the arteries that supply the esophagus (Evans 1993; Evans 2010). Similar to the vasculature, several nerves supply the esophagus and vary based on the section of esophagus evaluated. The paired pharyngoesophageal and paired pararecurrent laryngeal nerves supply the cervical region, the left pararecurrent nerve and vagal trunks supply the thoracic region, and the vagal trunks supply the abdominal region. Lymph node drainage is via the medial retropharyngeal, deep cervical, cranial mediastinal, bronchial, portal, splenic, and gastric lymph nodes (Evans 1993). Esophageal neoplasia is rare, and surgery of the esophagus is technically demanding and generally considered dif icult (Withrow 2007a). When treating esophageal neoplasia, resection of the tumor and subsequent anastomosis is recommended when possible. In very rare cases of small benign esophageal masses (e.g. adenomatous polyps), a local resection via esophagotomy may be considered.

Aspiration and Biopsy Principles Samples from the esophageal tumor may be obtained prior to surgery by ine needle aspiration (FNA) or a pretreatment biopsy. These techniques can be performed percutaneously by ultrasound or computed tomography (CT) guidance. Ultrasound may be an excellent tool to guide esophageal aspiration in the cervical region; however, the dif iculty of obtaining a sample by FNA is increased when the tumor is

located in the thoracic cavity. In large dogs, FNA of an intrathoracic esophageal tumor may not be possible. If esophagoscopy is being performed, aspirates or biopsies can be obtained simultaneously (Gualtieri 2001; Withrow 2007a). Esophagoscopy is often recommended in these patients to assess the esophageal mucosa and lumen and obtaining a sample from the luminal surface of the esophagus is advantageous as this may decrease the chance of tumor seeding when a percutaneous technique is performed. When performing a biopsy from the esophageal lumen, a deep tissue sample is desirable, and multiple biopsies should be obtained (Parker and Caywood 1987; Withrow 2007a). Devices that can be used include biopsy forceps passed alongside or through the working channel of the esophagoscope and cautery loops, which have been successfully employed to obtain a sample of an esophageal plasmacytoma (Parker and Caywood 1987; Hamilton and Carpenter 1994; Gualtieri 2001). Biopsies obtained under esophagoscopic guidance can be frustrating as the results are often nondiagnostic and tumors may not penetrate the mucosa (Parker and Caywood 1987; Farese et al. 2008). In one study of four dogs with esophageal leiomyosarcoma, all underwent esophagoscopy and three were noted to have no mucosal abnormality (Farese et al. 2008). A biopsy obtained in the fourth case (with mucosal penetration) was nondiagnostic (Farese et al. 2008). In a study of spirocercosis-induced sarcomas, 15 of 15 dogs that underwent esophagoscopy had masses noted during the exam (Ranen et al. 2004b). In the six cases in which an endoscopic biopsy was performed, a diagnosis of sarcoma was obtained in three (Ranen et al. 2004b). Open approaches can also be used to obtain pretreatment biopsies. A standard ventral midline cervical approach is generally suf icient for esophageal neoplasia in this region. An intercostal lateral thoracotomy will allow suf icient exposure to obtain a biopsy of an esophageal tumor in the thorax.

Clinical Signs Patients with an esophageal tumor will often present for signs such as ptyalism, dysphagia, odynophagia, regurgitation, hematemesis, and

weight loss (Ridgway and Suter 1979; Parker and Caywood 1987; Gualtieri 2001; Farese et al. 2008). These signs are usually progressive, but an acute exacerbation of signs is possible once the tumor reaches a certain size. If perforation of the esophagus occurs prior to diagnosis, signs of sepsis such as cardiovascular collapse, vomiting, diarrhea, lethargy, and anorexia may also occur. Upon leakage into the thoracic cavity or mediastinum, respiratory distress secondary to pleural effusion or mediastinitis may also be seen. Additionally, respiratory signs (e.g. dyspnea, cough) may be noted in association with aspiration pneumonia or pulmonary metastasis (Ridgway and Suter 1979; Parker and Caywood 1987). Hypertrophic osteopathy has been described as a paraneoplastic condition associated with spirocercosis-induced sarcomas and lameness may be noted during the physical examination (Ranen et al. 2004a, 2004b).

Diagnostic Tests Clinical Laboratory Testing Blood work is essential in the overall assessment of a patient with suspected esophageal neoplasia. More advanced diagnostics such as CT and magnetic resonance imaging (MRI), as well as surgical treatments, will require general anesthesia, and being aware of systemic illness is essential. Additionally, signs of esophageal perforation secondary to an esophageal tumor may manifest as blood work abnormalities consistent with sepsis, including neutrophilia/neutropenia, hypoglycemia, liver enzyme increases, hyperbilirubinemia, and azotemia. If an esophageal neoplasm has been progressively bleeding intraluminally, anemia may also be noted. A fecal smear should be performed in dogs with esophageal neoplasia. Eggs can be detected on the smear and con irm the presence of Spirocerca lupi (Ranen et al. 2004b). This test does not always demonstrate eggs, however, as only two of eight cases in one study exhibited a positive fecal smear (Ranen et al. 2004b). Radiography

Cervical and thoracic radiography is essential for any patient presenting with clinical signs consistent with an esophageal disorder. Cervical and thoracic radiographs have several bene its in that a soft tissue mass in the region of the esophagus can be diagnosed, a mass effect secondary to an esophageal tumor may be noted, and the patient can be evaluated for pulmonary metastatic disease or cardiac/pulmonary pathology that may compromise the patient during anesthesia (Figure 7.1) (Ridgway and Suter 1979; Ranen et al. 2004, 2008; Farese et al. 2008). Esophageal neoplasia will often appear as a soft tissue mass, and in one study, 27 of 28 malignant esophageal masses were visible on radiographs (Ranen et al. 2004; Dvir et al. 2008; Farese et al. 2008). In cases of esophageal sarcomas that develop secondary to spirocercosis, spondylitis may also be diagnosed on radiographs (Ranen et al. 2004).

Figure 7.1 (a) Lateral and (b) ventrodorsal radiograph of a dog with an esophageal leiomyosarcoma. Source: Images courtesy of Dr. Julius Liptak.

Caudodorsal mediastinal disease causing a mass effect visible on radiographs is most likely to occur from an esophageal abnormality (Kirberger et al. 2009). Caudal mediastinal masses are more commonly

diagnosed from a dorsoventral or ventrodorsal radiographic view (86%) as opposed to a lateral view (50%) (Kirberger et al. 2009). The right lateral view, however, allows for the most accurate quanti ication of mass dimensions (Kirberger et al. 2009). Contrast radiography is a valuable tool in the diagnosis of esophageal neoplasia. Signs such as an irregular mucosal surface, smaller lumen size, and a decreased ability to pass contrast through the esophageal lumen may suggest that a mass is present (Ridgway and Suter 1979). Additionally, altered peristalsis in the region of the neoplastic stricture may also be noted (Ridgway and Suter 1979). Ultrasound Cervical and thoracic ultrasound can be used for assessing esophageal tumors. Visualization of masses is likely easier in the cervical region; however, ultrasound provides a noninvasive option that may improve the assessment of a particular tumor in any region of the esophagus. Furthermore, ultrasound may be used as a method of aiding FNA of a mass that is in an accessible location. Recently, a procedure for endoscopic ultrasonography of the esophagus was described (Baloi et al. 2013). In these healthy dogs, ultrasound was shown to be useful in the assessment of esophageal wall integrity, although evaluation of all esophageal layers was not possible in all dogs. Over time, the clinical utility of this procedure will become more clear. CT and MRI CT is readily available at many veterinary clinics and has been shown to be an excellent imaging modality for intrathoracic structures (Figure 7.2) (Prather et al. 2005). Data concerning CT evaluation of esophageal tumors are limited in the veterinary literature, but CT adds diagnostic information such as size and shape of the mass, changes in adjacent organs, and pulmonary metastases (Dvir et al. 2001). In one study, CT was not helpful in determining tumor esophageal wall attachment (differentiating sessile from pedunculated masses) (Dvir et al. 2001). In a separate study, a triple-phase dynamic CT technique was used to compare nonneoplastic and neoplastic esophageal nodules that developed secondary to spirocercosis in dogs (Kirberger et al. 2015).

That study determined that neoplastic lesions were more likely to demonstrate mineralization (93%) and tended to have an irregular surface and less perfusion than nonneoplastic counterparts.

Figure 7.2 CT of an esophageal tumor located in the region of the cardia. Source: Image courtesy of Dr. Laurent Findji.

While veterinary literature describing the MRI changes associated with esophageal neoplasia is lacking, MRI has been used in a limited role in human medicine to assess esophageal disease (Jamil et al. 2008;

Sakurada et al. 2009). Further investigation is necessary before the usefulness of this imaging modality in the assessment of esophageal tumors is fully known. Esophagoscopy Esophagoscopy is an excellent diagnostic modality to assess esophageal neoplasia (Figures 7.3 and 7.4) (Dvir et al. 2001; Gualtieri 2001). Using esophagoscopy, a clinician can determine the extent of tumor involvement and potential surgical resectability as well as obtain a pretreatment biopsy. A critical assessment of thoracic radiographs should be performed to evaluate the patient for a potential esophageal perforation prior to esophagoscopy. If an esophageal perforation exists, insuf lation during esophagoscopy may cause a tension pneumothorax with resultant respiratory compromise (Gualtieri 2001). Common indings during esophagoscopy in patients with esophageal neoplasia may include pedunculated or cauli lower-like masses, bleeding, necrosis, and mucosal discoloration (Ranen et al. 2004). Some cases may have complete esophageal obstruction that can manifest as a irm, irregular annular growth (Gualtieri 2001).

Surgery Approach The surgical approach to an esophageal tumor is dependent on the location. The cervical esophagus is approached via a ventral midline incision with the patient in dorsal recumbency. The subcutaneous tissues are bluntly and sharply dissected to expose the paired sternohyoideus muscles. As the esophagus is more left-sided in the cervical region, the trachea is gently retracted to the right to allow for esophageal exposure. Other important structures to be avoided in this region include the carotid sheath, recurrent laryngeal nerves, thyroid glands, and parathyroid glands. If further exposure of the caudal cervical esophagus is needed, the cervical incision can be extended caudally to allow for a cranial median sternotomy. Access to the cranial thoracic esophagus is attained through either a right or left intercostal thoracotomy approach. The left-sided approach

is accomplished through either a third or fourth intercostal incision. Following incision of the intercostal musculature and entry into the thoracic cavity, the brachiocephalic trunk and subclavian vasculature must be retracted. The right side of the cranial thoracic esophagus is approached through either a third, fourth, or ifth intercostal thoracotomy. Adequate esophageal exposure on the right side requires retraction or ligation of the azygous vein and retraction of the trachea ventrally. Tumors located at the level of the base of the heart might be best approached from the right side because of the aortic arch passing to the left side of the esophagus and the inability to retract the aortic arch. A surgical approach to the caudal esophagus is performed through a left-sided seventh, eighth, or ninth intercostal thoracotomy. It is important to be aware of the location of the vagus nerve to prevent inadvertent damage during tissue dissection or surgical resection. Approaches to the most caudal aspects of the thoracic esophagus can be performed through a ventral midline celiotomy combined with diaphragmatic incision and caudal median sternotomy if necessary (Figure 7.5).

Figure 7.3 Esophagoscopy of a carcinoma diagnosed by endoscopicassisted biopsy.

Figure 7.4 Endoscopic view of an esophageal leiomyosarcoma. Source: Image courtesy of Dr. Jim Farese.

Techniques Evidence-based recommendations for surgical margins during esophageal resection and anastomosis in veterinary patients do not exist. Recommendations for other gastrointestinal organs have been made; however, these are highly variable, with margins of 1–8 cm being described depending on the study and tumor type (White and Gorman 1987; Aronson 2003; Morello et al. 2008). As a general guideline in humans undergoing esophageal resection, removal of 4–10 cm of tissue beyond the palpable tumor is recommended (Kato et al. 1998; Mariette et al. 2002). In experimental dogs, resection and anastomosis of 14– 70% of the esophagus has been performed successfully; the cases with 40–70% resection generally included a myotomy to relieve tension on the anastomosis site (Saint and Mann 1929; Attum et al. 1979). In a

study of dogs undergoing esophageal resection and anastomosis to treat esophageal perforation, mortality was noted in 33% of dogs after one-third of the esophagus was resected (Parker and Caywood 1987). For low-grade leiomyosarcoma, a marginal resection with incomplete excision can lead to adequate local control for over a year based on only four dogs (Farese 2008).

Figure 7.5 An abdominal approach has been used for a leiomyoma involving the caudal esophagus. Source: Image courtesy of Dr. Laurent Findji.

Once the affected region of esophagus has been approached, the area of interest is isolated by the placement of sterile laparotomy sponges to prevent contamination of adjacent tissues. The region to be resected is clamped orad and aborad to the tumor to prevent spillage of esophageal contents, and the tumor is removed, preferably with a wide margin for malignant tumors. The esophageal sections that are to be

anastomosed are clamped with noncrushing forceps or held by an assistant’s ingers. The esophageal ends are then apposed and sutured. Several esophageal anastomosis techniques have been described, and controversy exists as to the appropriate suture type, pattern, and amount. Some authors suggest the use of nonabsorbable sutures such as polypropylene; however, absorbable sutures (e.g. polydioxanone) can also be used successfully (Parker and Caywood 1987; Flanders 1989; Schunk 1990; Oakes et al. 1993). In a study evaluating bursting strength and histopathology of esophageal anastomoses, a double-layer, simple interrupted closure resulted in the greatest immediate wound strength as well as best tissue apposition and healing; however, this type of closure was the longest to perform (Oakes et al. 1993). The authors did recommend a single-layer, simple interrupted suture pattern in cases where time was limited (Oakes et al. 1993). Singlelayer, simple continuous suture patterns are not recommended (Oakes et al. 1993). The submucosa has been shown to be the holding layer, and it is essential that this layer be included in the closure regardless of the technique that is employed (Dallman 1988). In general, it is recommended to suture the far esophageal wall irst (Kyles 2003). When performing a double-layer closure, the knots of the inner layer are generally placed within the esophageal lumen, and the mucosa and submucosa are incorporated. The knots of the sutures in the outer layer are placed extraluminally (Oakes et al. 1993). Sutures should be positioned 2–3 mm apart as well as 2 mm from the cut edge of the esophagus (Rosin 1975) (Figure 7.6).

Figure 7.6 (a) Resection and anastomosis of an esophageal leiomyoma depicted in Figure 7.5. (b) Specimen after resection. Source: Images courtesy of Dr. Laurent Findji.

Stapling during esophageal surgery has been proposed as an alternative to suturing (Pavletic 1994). The use of circular and linear stapling instrumentation has been described for veterinary patients, and proposed bene its of stapling over sutured anastomoses include simpli ication of the procedure, decreased surgical time, and reduced surgical ield contamination (Pavletic 1994). For end-to-end esophageal anastomoses (as performed for esophageal tumors), the stapling device can be entered orad to the tumor through the mouth or pharynx or aborad to the tumor through the stomach (Pavletic 1994). Techniques for massive esophageal resection exist in the human literature, and sporadic reports of experimental animals undergoing esophageal substitution can be found (Pavletic 1990). Some of the described techniques include small intestinal substitution, skin substitution, and gastric advancement (Parker and Caywood 1987; Straw et al. 1987; Gregory et al. 1988; Kuzma et al. 1989; Pavletic 1990). Long-term outcome data of clinical cases that have undergone these techniques is minimal. Other measures that may be considered to support a patient undergoing esophageal surgery include esophageal myotomy, esophageal patching, and nutritional support. A myotomy can be performed orad or aborad, or both, to the anastomosis; however, as the

procedure is being performed to remove neoplasia, seeding of additional surgical sites is possible. To perform a myotomy, a 2–3 cm incision is made in the external muscular sheath of the esophageal wall 3 cm from the divided end without incising through the internal muscular sheath. The incision is allowed to heal by second intention. In an experimental study evaluating large esophageal resections, six of eight dogs with a 60% esophageal resection that had a single myotomy survived. Furthermore, 8 of 10 dogs with 60% esophageal resection and 4 of 8 with 70% esophageal resection survived when resection was combined with an orad and aborad esophageal myotomy. Patches may be used as support structures for an esophageal wound. Patches can be made from surrounding structures such as pericardium and muscle or more distant organs such as small intestine and omentum; alternatively, synthetic materials may also be used (Parker and Caywood 1987; Kyles 2003; Hayari et al. 2004). Omentum is the most readily available vascularized tissue for support of esophageal closures (Hayari et al. 2004). The creation of an omental pedicle lap lengthens the functional distance that the omentum can be advanced (Ross and Pardo 1993). Following lap creation, the omentum is advanced into the thoracic cavity through a created diaphragmatic defect. Care is taken to avoid twisting or kinking of the vascular pedicle. The omentum is then tacked over the surgical site, and the diaphragmatic defect is closed with enough tension to prevent herniation of other abdominal viscera but not to cause occlusion of the omental lap blood supply (Williams and Niles 1999). A gastrostomy tube may be indicated after esophageal surgery, and this can be placed at the same time as the esophageal surgery via a laparoscopic-assisted or open approach. For the laparoscopic-assisted approach, a subumbilical camera port is placed irst. A ventrolateral left-sided abdominal port is then established (with laparoscopic guidance), and a laparoscopic Babcock forceps is introduced into the port to grasp the fundus of the stomach. The stomach is pulled to the abdominal wall, and a stay suture is placed into the stomach to hold it in close proximity to the abdominal wall. The ventrolateral port is enlarged to allow exteriorization of a 2–3 cm section of stomach wall. A 1 cm gastrotomy is performed, and the gastrostomy tube is introduced

into the stomach. A purse-string suture is placed in the stomach wall to secure the gastrostomy tube to the stomach, and then box sutures are placed from the stomach wall to the transversus abdominis muscle to secure the entire complex (stomach, gastrostomy tube, abdominal wall) together. The body wall incision is closed routinely, and the gastrostomy tube is secured to the skin with a inger trap pattern. For placement of a gastrostomy tube using an open approach, a ventral midline celiotomy is performed. An incision is created on the ventrolateral abdominal wall that allows a gastrostomy tube to be introduced through the skin and into the abdomen. A gastrotomy is performed, and the tube is placed into the stomach. A purse-string suture pattern is used to secure the tube to the stomach, and a box suture pattern secures the stomach to the abdominal wall. The celiotomy is closed routinely, and the gastrostomy tube is secured to the skin with a inger trap pattern. Healing and Complications Esophageal surgery has been associated with a high rate of complications, and several factors may account for this reputation. The esophagus lacks a serosa, and therefore an immediate ibrin seal does not form over an esophageal incision as is seen in other regions of the gastrointestinal tract (Flanders 1989; Schunk 1990; Shamir et al. 1999). Due to the absence of this seal, leakage is potentially a higher risk after esophageal surgery, and exact apposition of the divided ends of the esophagus is essential (Schunk 1990). As the esophagus is tethered at two ends, tension on the anastomotic site is greater than in other regions of the gastrointestinal tract. During each respiration, as the diaphragm contracts, the esophagus is being pulled, and tension on the anastomosis site increases (Schunk 1990; Shamir et al. 1999). As the esophagus has a segmental blood supply, meticulous attention should be paid to preserving these vessels during esophageal surgery; as stated previously, loss of both the cervical and thoracic blood supplies results in esophageal necrosis (Macmanus et al. 1950). Other factors that may increase postoperative complications include the lack of omentum, the peristaltic contractions that the esophagus undergoes,

and the continual bathing of the incision with food and/or saliva (Flanders 1989; Schunk 1990; Shamir et al. 1999). Complications Major postoperative complications can include dehiscence and stricture (Parker and Caywood 1987; Schunk 1990). Adherence to meticulous surgical principles such as gentle tissue handling, proper suture technique, and esophageal rest as well as being cognizant of the factors that may compromise esophageal healing, will improve the success rate and decrease the likelihood of dehiscence. If an esophageal stricture occurs, techniques such as bougienage and balloon dilation may need to be considered (Leib et al. 2001; Glazer and Walters 2008). Alternative Techniques The use of transendoscopic esophageal mass ablation of esophageal sarcomas that developed secondary to spirocercosis was recently described in two reports (Yas et al. 2013; Shipov et al. 2015). Different techniques for ablation were utilized successfully in those cases including neodymium: yttrium-aluminum-garnet laser iber ablation and cautery snare polypectomy. In one study, the procedures were deemed successful in 12/15 dogs, and overall, were considered to have low morbidity and short hospitalization times (Shipov et al. 2015). Esophageal stenting to palliate the clinical signs associated with a primary esophageal squamous cell carcinoma in a dog has also been described (Hansen et al. 2012). In that dog, a self-expanding metallic stent was placed using luoroscopic guidance. The clinical signs improved over the next 12 weeks until euthanasia was performed for unrelated disease (Hansen et al. 2012).

Histologic Tumor Types Esophageal neoplasia generally occurs in three scenarios: Primary neoplasia of the esophagus, neoplasia metastatic to or invading the esophagus from another organ, or neoplasia that occurs in conjunction with S. lupi infection. Primary tumors that have been reported in the esophagus of companion animals include osteosarcoma, ibrosarcoma, undifferentiated sarcoma, squamous cell carcinoma, scirrhous

carcinoma, undifferentiated carcinoma, adenocarcinoma, leiomyoma, leiomyosarcoma, plasmacytoma, and adenomatous polyp (Ribelin and Bailey 1958; Campbell and Pirie 1965; Parthasarathy and Chandrasekharan 1966; Ridgway and Suter 1979; McCaw et al. 1980; Culbertson et al. 1983; Parker and Caywood 1987; Hamilton and Carpenter 1994; Rolfe et al. 1994; Takiguchi et al. 1997; Ranen et al. 2004a, 2008; Farese et al. 2008; Gibson et al. 2010). Thyroid tumors are the most likely tumors to secondarily invade the esophagus; however, respiratory tract tumors and stomach tumors have also been reported (Ridgway and Suter 1979). Dogs are the de initive hosts of S. lupi, which is a nematode capable of being released into the stomach and migrating to the thoracic aorta after ingestion (Dvir et al. 2008). Once located within the thoracic aorta, these organisms can penetrate into the esophageal wall (Dvir et al. 2008). S. lupi infestation causes nodules to form within the esophagus, and these nodules can undergo malignant transformation to form a sarcoma. The earliest report of this disease described ive osteosarcomas and two ibrosarcomas; however, undifferentiated sarcomas have also been identi ied (Seibold et al. 1955; Ranen et al. 2004a).

Adjuvant Therapies and Outcome The prognosis in dogs and cats with esophageal neoplasia that is surgically resected is poorly described. In cases of benign esophageal tumors, such as leiomyomas and plasmacytomas, early and aggressive surgical resection may be curative (Hamilton and Carpenter 1994). In a recent report of four dogs undergoing esophageal resection of lowgrade leiomyosarcomas, outcomes were favorable as two dogs died of unrelated conditions (one at approximately 3.5 years and the other at 65 days after surgery). Of the other two dogs, one developed megaesophagus, but was still alive at 388 days postoperatively (lost to follow-up) and the other was still alive at 405 days postoperatively (study conclusion) (Farese et al. 2008). In that study, despite large tumor size and incomplete excision, surgical removal of low-grade leiomyosarcomas resulted in long-term resolution of clinical signs (Farese et al. 2008).

In a study of esophageal sarcomas that developed secondary to spirocercosis, 19 dogs underwent surgery and 10 survived the perioperative period (Ranen et al. 2008). The median disease-free interval and survival time of those 10 dogs were 260 and 278 days, respectively (Ranen et al. 2008). Chemotherapy was pursued in six cases of that report and included doxorubicin in ive dogs and a combination of doxorubicin and carboplatin in one dog (Ranen et al. 2008). The histological score of the metastatic disease was signi icantly lower in the dogs that received chemotherapy as compared to the histological score of the primary tumor that was resected (Ranen et al. 2008). Of 19 dogs that underwent necropsy, 10 were diagnosed with metastatic disease. While the ability to identify cases of esophageal neoplasia in veterinary patients is improving with the use of diagnostics such as esophagoscopy and CT, long-term success is often not achieved due to progression of the disease at the time of diagnosis, the highly metastatic nature of many of the esophageal neoplasms, and inherent challenges associated with esophageal surgery. The use of adjuvant treatments such as chemotherapy and radiation therapy are minimally described; however, these options should be considered when esophageal tumors are encountered. The rarity of esophageal tumors likely accounts for the paucity of literature dedicated to the topic, but surgical advances that allow for more aggressive resection options should continue to be pursued.

Stomach Diagnostic Workup and Biopsy Techniques Comprehensive staging is essential for the successful management of the canine or feline patient with a suspected gastric neoplasm. Local imaging techniques that are commonly used for gastric tumor evaluation include radiography, ultrasound, CT, and endoscopy (Easton 2001). Radiographs generally have limited diagnostic value but can be useful in detecting gross abnormalities within the stomach as well as lymphadenopathy or ascites (Easton 2001). Contrast radiography is a

highly sensitive modality for identifying gastric mural abnormalities associated with neoplastic conditions (Swann and Holt 2002). Despite the relatively low incidence of thoracic metastasis for the commonly diagnosed gastric neoplasms, three-view radiography of the thorax should always be performed as a component of patient staging prior to moving forward with more expensive and advanced diagnostic testing (Swann and Holt 2002). Abdominal ultrasound allows visualization of changes associated with gastric wall thickening and also can be used to screen for intraabdominal metastatic disease (Penninck et al. 1998; Lamb and Grierson 1999; Easton 2001). Ideally, gastric ultrasonography should be performed in the fasted animal when the stomach is illed with water; however, adequate evaluation can be accomplished in incompletely fasted patients (Lamb and Grierson 1999). In general, correlation between ultrasonographic abnormalities and de initive tumor pathology is inconsistent (Penninck et al. 1998; Lamb and Grierson 1999; Easton 2001). In the study by Lamb and Grierson (1999), commonalities in the shape of the lesion, the type of mural layers affected, and the presence or absence of extension through the gastric serosa allowed for accurate prediction of the histopathological tumor type in greater than 80% of cases (Lamb and Grierson 1999). In that study, thickening of the muscular layer of the gastric wall, involvement of the gastric antrum, and the presence of a focal mass were consistent with a tentative diagnosis of leiomyoma or leiomyosarcoma, whereas evidence of extension of the mass beyond the serosal surface of the gastric wall was suggestive of carcinoma since none of the other tumor types displayed this behavior (Lamb and Grierson 1999). Ultrasonographic factors that were not useful in predicting tumor type included the following: Degree of thickening of the gastric wall, presence of lymphadenopathy or ulceration, and lesion echogenicity (Lamb and Grierson 1999). Ultrasound-guided ine needle biopsy is commonly employed as an initial step to con irm a tissue diagnosis when a gastric mass has been identi ied. This technique may also prove useful when poor condition of the patient precludes the use of endoscopic biopsy or when lesions appear to be located in a region (i.e. submucosally) of the gastric wall that cannot be accessed via endoscopy (Bonfanti et al. 2006). In the study by Bonfanti and

colleagues (2006), FNA of gastric masses resulted in agreement between the results of cytological assessment and the de initive histological diagnosis in only 50% (7 of 14) of cases. It is suspected that concomitant peritumoral gastric in lammation or intratumoral necrosis contributes to the poor diagnostic accuracy of FNA and cytology of gastric tumors (Bonfanti et al. 2006). Thus caution should be exercised when interpreting the results of cytological examination of ine needle aspirates from gastric masses; however, this should not necessarily preclude the clinician from performing this test because certain gastric neoplasms (i.e. lymphoma) can be readily diagnosed using this modality (Bonfanti et al. 2006). Endoscopic biopsies are the mainstay for diagnosis of gastric neoplastic conditions. Endoscopy allows direct visualization and tissue procurement through minimally invasive measures. Endoscopy can also be very helpful in de ining the extent of disease for lesions with mucosal involvement. The limitations of endoscopy will be encountered when tumor in iltration into the mucosal layer of the stomach is not present or when extension into this layer is incomplete (i.e. focal mucosal invasion with secondary mucosal in lammation mimicking diffuse involvement). A 2015 study by Marlof and colleagues compared the sonographic and endoscopic indings in a group of dogs (n = 17) and cats (n = 5) with histologically con irmed gastric neoplasia (Marlof et al. 2015). In their patient population, abdominal ultrasonography correctly identi ied 50% of the gastric tumors while endoscopy identi ied 95% and there was sonographic and endoscopic tumor location agreement in only 36% of cases. Of the cases missed by sonography, lymphoma was found to be the most common tumor (Marlof et al. 2015). This study further validates the utility of endoscopy for the diagnosis and staging of gastric neoplasms. Advanced imaging with CT and MRI is invariably useful in imaging of gastric neoplastic conditions in animals; however, our experience with these modalities is still relatively limited. The normal anatomy of both the canine and feline abdominal cavities has been previously described (Collins et al. 1989; Smallwood and George 1993a, 1993b; Samii 1998, 2005). A 2012 report by Terragni and colleagues examined the utility of helical hydro-CT to identify and characterize gastric wall pathology in a

population of 14 dogs and four cats with gastric neoplasia. With this approach, water (30 ml/kg) is used as a neutral luminal contrast medium which is then coupled with IV contrast administration, thereby improving enhancement of the gastric wall. The technique allowed for excellent visualization and assessment of the stomach in this clinical patient population and was deemed a simple and useful technique to better characterize the extent of in iltrative gastric disease in animals (Terragni et al. 2012). A recent study by Tanaka and colleagues demonstrated the usefulness of contrast-enhanced CT for diagnosing and staging dogs with gastric tumors. Mean CT attenudation values in early- and delayed-phase postcontrast images were lower for lymphoma than for the mean attenudation values of other gastric tumors. Additionally, dogs with lymphoma were more likely to have widespread, bulky, and rounded lymphadenopathy compared to other tumor types (Tanaka et al. 2019). It is likely that as our collective experience with these imaging modalities increases, the use of CT and/or MRI for staging and treatment planning of gastric neoplasms will become the mainstay (Figure 7.7). Laparoscopy is gaining increased availability and application in veterinary medicine. Laparoscopic exploration of the abdomen is useful in further de ining the extent of disease in animals with gastric neoplasia. Lymph nodes or hepatic tissue suspected of containing metastatic disease can be biopsied using laparoscopic techniques or with keyhole abdominal incisions. Gastric biopsies are obtained with laparoscopic-assisted techniques through limited ventral midline incisions (Barnes et al. 2006). Incorporation of wound retractor devices such as the Alexis wound retractor has facilitated minimally invasive laparoscopic gastric and small intestinal exploration with targeted organ biopsy (Shamir et al. 2019).

Figure 7.7 Precontrast helical CT image of a dog with a midbody gastric neoplasm. The pylorus is clearly visualized (white arrow), allowing for margin assessment and to help determine the planned surgical procedure (i.e. gastroduodenostomy vs. pyloric sparing procedure). This tumor is seen to be extending full thickness through the lumen from the lesser curvature (black arrowheads) to the greater curve (white arrowheads) of the stomach. Intraoperatively, gastric resection and anastomosis were used to effectively excise the neoplasm. During open surgical exploration of a gastric tumor, diagnostic and therapeutic dilemmas can be encountered when the orientation or extent of the gastric mass is different from that which was anticipated based on preoperative staging. A similar situation can arise when a gastric mass is encountered as an incidental inding during exploratory laparotomy. In these situations, excisional biopsy techniques (i.e. partial gastrectomy or gastroduodenostomy, see below) are generally preferred so long as they do not interfere with a subsequent resection, should one be necessary based on the results of histopathological tumor assessment. Intraoperative FNA and cytology may be bene icial when unplanned gastric lesions are encountered during routine exploratory laparotomy. For example, in the case of an extensive gastric neoplasm or one that is located in a region of the stomach that is less amenable to excisional biopsy (i.e. cardia or pylorus), intraoperative cytology may con irm gastric lymphoma, whereby excisional biopsy may not be warranted. A 2014 study by Riondato and colleagues evaluated the utility of this approach in a clinical population of dogs with gastric neoplasia and validated its ef icacy (Riondato et al. 2014). Regardless, decisions should be made based on a comprehensive understanding of the likely risk factors for the patient (i.e. morbidity rate of procedure) and the anticipated short- and long-term outcome based on the expected tumor biology of common gastric neoplasms.

Technical Aspects of Surgical Procedure Anatomy The canine and feline stomachs are divided into four separate regions: Fundus, body, antrum, and pylorus. Gastric blood low is derived from

the branches of the celiac artery that originates from the descending aorta just cranial to the cranial mesenteric artery. The right and left gastric arteries arise from the celiac artery and supply tissues adjacent to the lesser curvature (Grandage 2003). The right and left gastroepiploic arteries arise from branches of the celiac and supply the tissues along the greater curvature of the stomach. The branches of these four vessels continue along the dorsal and ventral surfaces of the stomach, with areas of relative hypovascularity in the regions between the two vascular ields, i.e. between the lesser and greater curvatures. About 80% of the blood low is directed to the mucosa and 20% allocated to the serosa, muscularis, and submucosa (Grandage 2003). Gastric innervation is supplied by branches of the vagus nerves (parasympathetic) as they traverse the diaphragm adjacent to the esophagus and from the splanchnic nerves (sympathetic) coursing through the celiacomesenteric ganglion accompanying the celiac artery. Gastric lymph nodules are present throughout the mucosal layer and primarily drain into the surrounding hepatic regional lymphocenters (Grandage 2003). Several essential anatomic structures exist in the region of the gastric pylorus, including the bile duct, pancreatic duct(s), hepatic artery, and portal vein. The portal vein must be protected with any surgical procedure involving resection of the pylorus. Preservation of the hepatic artery is preferred; however, if this structure is compromised, administration of large doses of penicillin may be suf icient to prevent decompensation of the patient (Markovitz et al. 1949). Sacri ice of the bile duct, however, is sometimes necessary during surgical procedures. If the bile duct is transected, then a biliary diversion procedure (e.g. cholecystoduodenostomy) is necessary. The major duodenal papilla is located 2–3 cm aborad to the pylorus in the dog and the cat. The bile duct empties into the major duodenal papilla. The pancreatic duct also empties into the major duodenal papilla in dogs and cats. In 80% of cats, this is the sole pathway for exocrine pancreatic secretions to enter the intestinal tract (Grandage 2003). In dogs, the accessory pancreatic duct, which empties into the duodenum at the minor duodenal papilla (aborad to the major duodenal papilla), is frequently the major source of exocrine pancreatic secretions.

General surgical recommendations for gastrointestinal surgery are applied during gastric resection procedures for neoplasia. These include gentle tissue handling and regular moistening of tissues to decrease postoperative in lammation and adhesion formation. Simple interrupted and continuous suture patterns have both been deemed acceptable for gastric closure. Likewise, both single-layer and two-layer closures have been deemed appropriate for gastric closure (Rasmussen 2003). Two-layer closures offer the bene it of improved hemostasis and greater security against incision line dehiscence. Disadvantages of twolayer gastric closures include luminal compromise and disruption of surrounding relevant anatomic structures. This is generally not a concern during closure of routine gastrotomy incisions; however, during complex gastric reconstructions (i.e. gastroduodenostomy), both two-layer and simple continuous closures should be avoided because they can contribute to luminal narrowing (Rasmussen 2003). Synthetic, mono ilament absorbable suture material is preferred for gastric surgery. Acceptable options include polydioxanone (PDS), poliglecaprone 25 (Monocryl), and polyglyconate (Maxon). Multi ilament absorbable suture materials such as polyglactin 910 (Vicryl) and polyglycolic acid (Dexon) can also be used for gastric resection and reconstruction. The degradation properties of these materials should be able to withstand the harsh environment of the stomach for the two-week period needed for the stomach wall to return to normal strength (Rasmussen 2003). Chromic gut suture material is not recommended based on the rapid degradative properties demonstrated during in vivo testing (Rasmussen 2003).

Surgical Procedures Submucosal Resection Several surgical procedures are applicable to neoplastic conditions of the stomach. The most conservative of these is the gastric submucosal resection (Rasmussen 2003). This procedure is indicated only for benign gastric lesions such as mucosal or submucosal polypoid adenomas. Prior to application of this surgical technique, advanced imaging with ultrasound and/or CT/MRI in combination with

endoscopy and tissue sampling with endoscopic biopsy or FNA is performed to rule out malignant disease. A gastrotomy incision is made opposite the mass. Stay sutures are placed into the mass to facilitate traction. An incision is then made through mucosa and submucosa, 1 cm from the periphery of the lesion. Scissor dissection is performed around the periphery of the mass until it is completely detached from its tissue bed. Submucosa and mucosa are then closed with a simple interrupted or continuous pattern using absorbable suture material (Kerpsack and Birchard 1994; Rasmussen 2003). Closure of the gastrotomy incision is performed in either one or two layers, depending on the integrity of the surrounding stomach and the tension placed on the wound. Leak testing is not performed for the gastrotomy incision. In people, endoscopic removal of gastric mucosal polyps is commonly employed. A recent report describes the successful use of endocautery for endoscopic removal of gastric polypoid lesions in a dog and cat (Foy and Bach 2010). An additional clinical report describes the use of argon plasma coagulation to facilitate endoscopic removal of a broad-based gastric polyp (Teshima et al. 2013). As widespread access to endoscopic equipment increases, this technique will likely gain in popularity; however, currently, its application is limited to relatively wellcircumscribed, pedunculated gastric lesions (Foy and Bach 2010). Partial Gastrectomy Partial gastrectomy can be performed for malignant conditions of the stomach. The anatomy of the in low tract makes partial gastric resections dif icult in the area of the gastroesophageal junction. Because of the aggressive and diffuse nature of most gastric neoplasms, partial resections are often not feasible. The speci ics of the surgical technique applied in an individual patient are dependent upon the exact location of the mass. Masses con ined to the greater curvature are most easily excised because of signi icant distances between the location of the mass and essential anatomic features (i.e. gastroesophageal junction, vagal innervation, bile duct, celiac artery). Excisions along the greater curvature can be hand sewn in one or two layers. The margins of the resection are initially de ined, and noncrushing clamps placed on either

side of the area to be resected. Preplacement of stay sutures into the tissues to be closed facilitates closure and tissue control (Figure 7.8a). Tissue transection is then performed in increments followed by either simple continuous or interrupted closure that incorporates all layers of the gastric wall (Figure 7.8b and c). Prior to closure, authors advocate for aseptic surgical glove change by the primary surgeon and any assistant that handled the excised tissue block as well as the introduction of clean surgical instruments so that cross contamination is not introduced. A second layer inverting closure can be performed at the discretion of the attending surgeon based on the amount of remaining stomach (i.e. an inverting pattern should not be performed if additional luminal compromise will result in limited gastric retention capacity), tension on the closure, and integrity of the surrounding tissue (Figure 7.8d) (Kerpsack and Birchard 1994; Rasmussen 2003). Alternatively, resection of masses associated with the greater curvature can be facilitated with stapling devices such as thoracoabdominal (TA) or gastrointestinal anastomosis (GIA) tissue staplers. GIA staplers minimize potential contamination of the abdominal cavity by placing double rows of staples on both sides of the surgical resection incision. This effectively creates two closed tissue cavities at the completion of the staple placement (Rasmussen 2003; Tobias 2007). Tissue clamps such as Doyens or Rochester-Carmalts are used in conjunction with TA stapling devices to minimize abdominal contamination. TA stapling devices used for gastric closures place two rows of staggered B-shaped staples. Following placement and iring of the stapler, tissue is transected between the stapler and the tissue clamp. Necrosis along gastric resection staple lines has been associated with leakage; therefore, if a stapling device is used for a partial gastrectomy, the staple line should be oversewn with a simple continuous inverting suture pattern (Clark 1994; Tobias 2007). For lesions that are either between the greater and lesser curvature or on the lesser curvature, partial gastrectomy is possible only if the peripheral margins of the lesion are clearly de ined and do not extend to the gastroesophageal junction. The most commonly performed partial gastrectomy procedure involves excision of tissues adjacent to the pylorus in the antrum. This

procedure requires complete excision of the pylorus as well as a portion of the gastric antrum and proximal duodenum and is commonly referred to as a Billroth procedure. Two types of Billroth procedures are described.

Figure 7.8 (a) Intraoperative image of the initial dissection for a gastric leiomyosarcoma. The extent of the gastric mass was identi ied using palpation, and stay sutures were placed such that approximately 1 cm margins would be obtained. Initially, the gastric lumen was breached well away from the palpable extent of the mass, and direct visualization was then used to guide the remainder of the dissection. (b) The mass has been completely excised leaving the pyloric antrum (oriented to the left of the image and identi ied with the black arrow) and remainder of the gastric body. The tissue is manipulated to plan the gastric anastomosis such that minimal tension and luminal disparity are created. (c) The dorsal aspect of the anastomosis is completed irst with placement of full-thickness simple interrupted sutures with the knots tied intraluminally. Circumferential progression of the anastomosis is then completed. Intermittent manipulation of the tissue should be performed to ensure that the two ends of the anastomosis will have symmetrical apposition. (d) Intraoperative image of the completed gastric resection and anastomosis. The pylorus is again located to the left of the image. This dog recovered without complication and did not suffer from volume retention issues secondary to gastric luminal narrowing. Billroth I (Pylorectomy and Gastroduodenostomy) Several essential anatomic structures exist in the region of the pylorus, including the bile duct, pancreatic duct(s), hepatic artery, and portal vein. Because of this, care is taken to prevent iatrogenic damage to any one of these structures. If the resection necessitates excision of the major duodenal papilla, then a biliary diversion (i.e. cholecystoduodenostomy or cholecystojejunostomy) procedure is required. If a biliary diversion procedure is not performed, then at least 1 cm of normal tissue is maintained orad to the major duodenal papilla at the time of tissue resection. Wide surgical margins are rarely possible with neoplastic conditions in the pyloric region. However, at least 1–2 cm of grossly normal tissue is ideally excised with any neoplastic mass (Rasmussen 2003). Mobilization of antral and pyloric regions of the stomach is initiated with transection of gastrohepatic ligaments and paraduodenal

peritoneum. Transection of the hepatogastric ligament results in increased gastric mobility and improved exposure to the dorsal aspect of the gastric surface. Identi ication and ligation of the branches of the gastric and gastroepiploic vessels supplying the tissue in the region to be resected are then performed. This allows full circumferential exposure of the pylorus (Rasmussen 2003). Stay sutures are placed 1–2 cm orad and aborad from transection site and 3–5 cm apart. Atraumatic clamps are placed orad and aborad to the line of transection, and the tissues are incised adjacent to these clamps. If any question exists about the proximity of the bile duct to the area of resection, the major duodenal papilla is catheterized. At least 1 cm of normal tissue is maintained between the line of the resection and the major duodenal papilla in order to minimize postoperative bile duct obstruction associated with surgical edema. Two primary options exist for the anastomosis of the stomach and duodenum. Traditionally, an end-to-end anastomosis is performed. Because of predictable size discrepancies between the duodenal and gastric openings, the gastric opening is partially closed using a simple interrupted or continuous (one- or two-layer) closure (Rasmussen 2003). Because of the need to maintain proper tissue alignment for the inal anastomotic procedure, a double-layer closure is often not feasible (Rasmussen 2003). It is essential to incorporate the holding layer of the stomach (i.e. submucosal layer) to prevent suture pull through and dehiscence. Following partial gastric closure, the remaining gastric and duodenal ori ices are opposed using a simple interrupted, single-layer pattern. Sutures are placed 2–3 mm apart and 2–3 mm from the tissue edge. The initial sutures are placed at the free edge of the previously performed partial gastric closure as this is the area of greatest potential leakage. The anastomotic procedure is then completed by placing the dorsal sutures, followed by the ventral sutures (Rasmussen 2003). Depending on the amount of stomach excised, leak testing to assess and verify the security of the anastomosis, may or may not be feasible. If concern exists about the possibility of postoperative edema causing temporary bile duct obstruction, a bile duct stent can be placed at the time of the surgical repair (Mayhew et al. 2006; Mayhew and Weisse 2008). The choledochal stenting procedure is accomplished by inserting an approximately 5- to 10-cm section of the distal end of a red

rubber catheter through the major duodenal papilla into the common bile duct. Approximately half the length of the stent should reside within the common bile duct, with the other half of the stent residing in the duodenum. The portion of the stent remaining in the duodenum is secured by passing one or two sutures (mono ilament absorbable suture material) through the stent wall and then through the submucosa of the duodenal wall just aborad to the major duodenal papilla. The most common-sized red rubber catheters used to complete the stenting procedure are 5 and 8 F (Mayhew et al. 2006; Mayhew and Weisse 2008). As an alternative to the end-to-end anastomosis, an end-to-side anastomosis can be performed. The end-to-side technique is more ideally suited when signi icant sections of the stomach are excised and large discrepancies exist between the created gastric and duodenal ori ices. Following tissue excision, the gastric opening is closed completely in one or two layers. Alternatively, an appropriately sized TA stapling device can be used to close the gastric lumen at the time of the gastric excision (Rasmussen 2003). A full-thickness incision can then be made in the stomach, a certain distance from the completed gastrectomy closure, and a hand-sutured gastroduodenostomy performed using a simple interrupted or a simple continuous suture pattern. Alternatively, a stapled gastroduodenostomy is performed whereby a gastrotomy incision is then performed a distance away from the proposed stoma site in an area that will allow triangulation of an endto-end anastomosis (EEA) stapling device. The EEA is advanced through the gastrotomy and pressed against the mucosa of the proposed end-to-side anastomosis. An additional stoma is then created in the stomach at a location that minimizes tension for the duodenal anastomosis. A purse-string suture is placed prior to advancement of the EEA stapler through the gastric wall. The instrument anvil is attached to the stapler and advanced through a previously placed duodenal purse-string suture. The instrument is then ired, completing the inverting anastomosis, and removed through the gastrotomy incision. The gastrotomy incision is then either handsewn in two layers or closed with a TA stapling device (Rasmussen 2003).

Billroth II (Gastrojejunostomy) Gastrojejunostomy (GJ) procedures are performed when there is removal or compromise of the major duodenal papilla or extensive removal of the antrum of the stomach resulting in excessive tension, thereby precluding reapproximation of the duodenum to the stomach during attempted reconstruction. Some type of biliary rerouting procedure (i.e. cholecystoduodenostomy or cholecystojejunostomy) is therefore necessitated. These procedures are rarely performed for gastric or pancreatic neoplastic conditions because of the perceived high morbidity and mortality rates associated with them or because of the presumed poor prognosis for patient recovery based on the extent or type of neoplastic disease (Rasmussen 2003). Because of the high morbidity and poor quality of life anecdotally reported with Billroth II, Roux-en-Y procedures have been advocated instead (Monnet 2020). There are no published data regarding clinical outcome in small animals regarding the Roux-en-Y procedure. The Billroth II procedure begins with gastric resection in a manner identical to the Billroth I procedure. Care must be taken during resection of the duodenum not to damage the pancreatic blood supply (pancreaticoduodenal artery and vein). Individual duodenal vessels are ligated up to the level of the duodenal transection. The duodenal lumen is closed using either sutures or a stapling device (TA stapler). If both the major and minor duodenal papilla are compromised, then permanent pancreatic enzyme supplementation will be necessary; however, endocrine function of the pancreas will remain intact (Rasmussen 2003). A GJ can be performed using any one of several techniques, including end-to-side (suture or stapling techniques), side-to-side linear (sutured or stapled; TA and GIA), and side-to-side circular (sutured or stapled; EEA) (Rasmussen 2003). There is no evidence present in the veterinary literature to support application of one technique over the other. The anastomosis should, however, be performed using the most orad section of jejunum possible that minimizes tension on the surgical site. Complete Gastrectomy

Long-term survival following complete gastrectomy is described in a single case report in the veterinary literature (Sellon et al. 1996). In that study, the gastrectomy was performed on a West Highland terrier with diffuse gastric adenocarcinoma (gastric ACA) and consisted of removal of the stomach from the esophageal hiatus to pylorus with no creation of a reservoir. The esophagus was anastomosed to a remnant of the antrum, leaving the pylorus intact. Postoperatively, a jejunostomy tube was placed for nutritional management; however, persistent hypoalbuminemia and intermittent abdominal pain associated with eating were still noted (Sellon et al. 1996). If signi icant disparities exist between the orad and aborad apertures, then similar techniques used for gastroduodenostomy are necessary to facilitate closure. Technically, this procedure is signi icantly less complicated than other described procedures for gastric neoplasia (i.e. Billroth II GJ). Excision of the stomach requires placement of a jejunostomy tube at the time of surgery for supplementation of feeding. Complete gastrectomy is associated with signi icant dif iculty maintaining adequate long-term nutrition because of absent reserve capacity (Sellon et al. 1996). In people, common complications of complete gastrectomy include dehiscence of the esophagojejunostomy anastomosis, stricture of the anastomosis, and jejunoesophageal re lux causing alkaline re lux esophagitis (Levine et al. 1991). Gastric Lymph Node Dissection The standard of care for gastric lymph node dissection in veterinary patients with gastric neoplasia has not been established. Studies evaluating gastric neoplasia in people have demonstrated that the stage of disease is a strong prognostic variable, with depth of tumor invasion into the gastric wall, lymph node metastasis, and presence of distant metastasis serving as negative correlates for survival (Ozmen et al. 2008). Despite this, the role and extent of lymphadenectomy in gastric cancer is controversial, with con licting data surrounding the bene it of aggressive lymph node dissection (Ozmen et al. 2008). Currently, sentinel node navigation surgery is being used in an attempt to minimize the morbidity seen with indiscriminant node dissection. This is accomplished using either peritumoral blue dye injection (isosulfan

blue and patent blue violet) techniques and/or technetium-99m tin colloid injection followed by lymph node detection using a handheld gamma probe. Traditionally, it was recommended that a minimum of 15 lymph nodes be examined in order to accurately stage a human patient using conventional tumor-node-metastasis (TNM) categories because the absolute number of metastatic locoregional lymph nodes is considered the most reliable prognostic indicator for patients with radically resected gastric cancer. Detection of the sentinel node(s) with subsequent histopathological evaluation assists the surgeon in taking a personalized approach to the extent of node dissection in each patient, potentially sparing them from unnecessary surgery (Ozmen et al. 2008).

Aftercare The postoperative provision of enteral nutrition is of paramount importance in patients recovering from resections for gastric neoplasia. Many patients will already be nutritionally de icient (due to their underlying gastric disease) leading into surgery, and in people, malnutrition and preoperative weight loss have been shown to be signi icant risk factors for postoperative complications and mortality rate (Fourtanier et al. 1987; Yamanaka et al. 1989; Pacelli et al. 1991). Recently, similar indings were identi ied in dogs undergoing Billroth I procedures (Eisele et al. 2010). In the study by Eisele et al. (2010), dogs without preoperative weight loss enjoyed signi icantly longer survival times compared with those dogs that had preoperative weight loss (Eisele et al. 2010). Oral feeding with an easily digestible, low-fat, high carbohydrate diet is initiated 12–24 h after surgery. Indications for immediate assisted (enteral) feeding because of malnutrition include prolonged anorexia (i.e. more than 48 h), weight loss of greater than 10% of body weight, inadequate muscle mass, and low albumin concentration (i.e. less than 2.5 g/dL in cats or less than 2.1 g/dL in dogs) (Rasmussen 2003). Early enteral feeding mitigates the early postoperative hypercatabolic state and stimulates gastrointestinal healing through mucosal cell nutrition. Early and aggressive enteral nutritional supplementation also preserves function of the gastrointestinal mucosal barrier, thus

augmenting host immune defense mechanisms and decreasing rates of infection resulting from bacterial translocation (Moss et al. 1980; Zaloga et al. 1992; Marik and Zaloga 2001; Cavanaugh et al. 2008). Jejunostomy (J tube) or GJ tube feeding tubes are preferred in dogs undergoing gastric resection procedures. J tubes can be placed through the right ventrolateral body wall (Crowe and Devey 1997; Daye et al. 1999; Yagil-Kelmer et al. 2006). A stab incision is made through the body wall caudal to the umbilicus and 2–4 cm to the right of ventral midline. An 8 French pediatric feeding tube is placed through the body wall. A stab incision is then made through the antimesenteric surface of a loop of jejunum approximately 10 cm aborad to the duodenocolic ligament. The feeding tube is then inserted through the stab incision and advanced aborally for 10–12 cm. A jejunal purse-string suture is then placed around the tube as it exits the jejunum using 3-0 or 4-0 mono ilament absorbable suture material. A jejunopexy is then performed with four to six interrupted sutures between the jejunum and the body wall around the jejunostomy tube. Alternatively, a locking box suture can be used for the jejunopexy. This involves placement of two circumferential sutures using absorbable suture material between the jejunum and the body wall around the jejunostomy tube. The sutures are placed in concentric rings with two bites into the body wall and jejunum, respectively. Both sutures involve alternating bites between jejunum and body wall (Crowe and Devey 1997; Daye et al. 1999; Yagil-Kelmer et al. 2006). GJ tubes are placed through the left ventrolateral body wall, ideally incorporating a 2–3 cm region of the remaining greater curvature/gastric body (Cavanaugh et al. 2008). Similar to J-tube placement, the GJ tube is inserted through the body wall into the peritoneum in a region where minimal tension will be placed on the stomach once the tube is secured by a gastropexy. The desired region of the stomach for tube insertion is selected, and the GJ tube is introduced into the stomach through a stab incision. The tube is then secured with a preplaced purse-string suture of 2-0 or 3-0 polydioxanone. A leftsided body wall-tube gastropexy is then completed by placement of four simple interrupted mattress sutures (from the stomach to the transversus abdominis muscle) surrounding the tube, with 2-0 or 3-0

polydioxanone. The jejunostomy component of the GJ tube set is then advanced through the inner lumen of the gastrostomy tube and is inserted through the pyloric antrum into the proximal portion of the duodenum. Using a combination of manual traction and manipulation, the jejunostomy component is then advanced such that the tip of the tube is positioned within the proximal third of the jejunum. The tube is then secured to the outside skin using a purse-string or inger-trap suture. The author prefers to use a commercially available GJ tube set (Ponsky Pull PEG kit with soft silicone retention dome, standard kit 20.0 Fr and Jejunal feeding/decompression tube, 9.0 Fr, 35-inch length; Bard Endoscopic Technologies, Billerica, MA) since the components of the tube interface well with each other, decreasing the risk of migration of the J tube out of the inner lumen of the gastrostomy tube. A major bene it of the GJ tube is that access to both the stomach and the small intestine is achieved without the need for an additional enterotomy. Since gastroparesis, vomiting, and inappetence are common after radical gastrectomy procedures, the dual lumen access of the GJ tube will allow for gastric decompression without interfering with the ability to provide nutrition into the small intestine. Complications associated with GJ tube usage are minimal, and although the use of these tubes in gastrectomy procedures has not been speci ically assessed, this author generally prefers their use to J tubes (Cavanaugh et al. 2008). As with any laparotomy procedure involving the gastrointestinal tract, postoperative pain is controlled by injectable opioids, either with intermittent injections or constant-rate infusions. Peri-incisional infusion of an extended-release liposomal formulation of bupivacaine (Nocita, Aratana Therapeutics, Leawood, KS) has been shown to provide incisional anesthesia for up to 72 hours postoperatively. A recent randomized clinical trial showed that dogs recovering from elective sti le surgery required less rescue analgesia and lower amounts of opioids compared to dogs receiving nonliposomal 0.5% bupivacaine hydrochloride (Reader 2020). Although currently not labeled for softtissue procedures, off-label use of liposomal bupivacaine is commonly performed in veterinary medicine, and application in gastrointestinal surgical procedures has the bene it of reducing narcotic requirements.

Likewise, epidural analgesia can be applied perioperatively to augment parenterally prescribed analgesic regimens and to facilitate dose reductions of these protocols, thus minimizing their effect on intestinal motility (Rasmussen 2003). Continuous-rate infusions (CRI) of lowdose lidocaine (1 mg/kg IV bolus followed by 10–50 mcg/kg/min CRI) and ketamine (0.5 mg/kg IV bolus followed by 2–10 mcg/kg/min CRI) are routinely used for their adjunctive analgesic properties, and minimal side effects of this regimen are reported (Gaynor 2002). Perioperative antibiotics (i.e. cefazolin: 22 mg/kg IV at 2-h intervals) are administered prior to the surgical incision and can be continued up to 24 hours after surgery. Gastrointestinal protectants such as histamine blockers, synthetic prostaglandins, or proton pump inhibitors can be administered to decrease the caustic nature of gastric contents (Henderson and Webster 2006). Promotility agents such as metoclopramide should be considered to help eliminate postoperative gastroparesis and nausea. The centrally acting antiemetics maropitant (Cerenia) and ondansetron (Anzemet) are also useful in combating these signs, especially since their administration can be achieved through nonenteral routes. Nonsteroidal anti-in lammatories are best avoided. Early ambulation improves gastrointestinal motility and should be encouraged in postsurgical patients (Rasmussen 2003). Maintenance of appropriate blood low is essential to intestinal healing, and this should be promoted through the judicious use of luid therapy (crystalloids and colloids), adequate blood pressure support, and optimization of pain control using multimodal analgesic regimens (Rasmussen 2003). If the major and minor duodenal papilla are compromised during the surgical procedure, then supplementation of pancreatic enzymes (Viokase) should be initiated during the early postoperative period.

Cosmetic and Functional Outcome Functional outcome is greatly affected by complete gastrectomy because of the loss of reserve capacity. Partial gastrectomy has potential effects on the reserve capacity, depending on the total amount removed. Published percentages for the amount of stomach that can safely be excised without concern for postoperative morbidity have not

been established. Factors that in luence this decision include the lesion size and location, the margin size necessary to achieve complete excision of the tumor, the duration of clinical signs, and the presumed distensibility of the remaining segment of stomach. In general, dogs tolerate gastric resection well with minimal long-term morbidity. Dogs that have undergone pylorectomy, such as Billroth I and Billroth II, do not have a sphincter separating the stomach and small intestines and are therefore at risk for biliary re lux, which can cause gastritis and the dumping syndrome. The clinical signs are vomiting and nausea and may be worse with a Billroth II.

Potential Complications There is limited information available on complication rates and types of complications after radical gastric surgery (Billroth I and II and total gastrectomy) in dogs and cats. In people, major complications of gastric cancer surgery include anastomotic leakage or stenosis, pleural effusion, intraoperative hemorrhage, wound dehiscence, pancreatitis, and functional problems (Yasuda et al. 2001; Park et al. 2005). Differences in complication rates and risk factors for operative morbidity vary widely throughout the human medical literature. However, extent of surgery is consistently identi ied as a risk factor, with total gastrectomy patients having greater complication rates than gastroduodenostomy patients (Yasuda et al. 2001; Park et al. 2005). This should be taken into consideration when communicating riskbene it scenarios with owners of dogs and cats prior to aggressive gastric resections. A retrospective study evaluating 24 dogs undergoing Billroth I procedures de ined risk factors for morbidity and mortality after this procedure (Eisele et al. 2010). Major postoperative complications (anastomotic dehiscence) occurred in 8.3% (2 of 24) of the dogs in the study group. Both of these dogs were treated successfully with revision procedures and ultimately enjoyed prolonged survival times (Eisele et al. 2010). Postoperative hypoalbuminemia occurred in 62.5% (15 of 24) and anemia in 58.3% (14 of 24) of dogs, of which 33% (8 of 24) required the additional supportive intervention of blood product transfusion. Other commonly reported postoperative complications

included hypotension, hypoglycemia, aspiration pneumonia, and ultrasonographic evidence of pancreatitis (Eisele et al. 2010). The short-term mortality rate in the study was not negligible, with 75% (18 of 24) of dogs surviving more than 14 days postoperatively. Preoperative weight loss and a diagnosis of malignant neoplasia were associated with signi icantly shortened survival times. Dogs with malignant neoplasia had an overall median survival time (MST) of 33 days, which reinforces the need for comprehensive preprocedural diagnostic planning and client communication based on the most likely biological malignancies that occur within the stomach (Eisele et al. 2010). In another study, two dogs out of nine had intraoperative complications and 33% of dogs had pancreatitis following a Billroth I (Abrams 2019). The long-term quality of life with a Billroth I appears good overall with postprandial discomfort, vomiting, and diarrhea being reported as complications in less than 30% of dogs (Gualtieri 1999). A study evaluating the outcome of gastrectomy to resect gastric carcinoma in 40 dogs reported minor intraoperative complications in six dogs and major intraoperative complications in three. All three dogs that experienced major intraoperative complications developed septic peritonitis. Major postoperative complications were reported in eight dogs, including septic peritonitis secondary to dehiscence in four dogs (Abrams 2019).

Common Tumors for Which This Procedure is Performed Gastric tumors are uncommon in the dog and cat, comprising approximately 1% of all malignant neoplasms in these species (Withrow 2007c). The most common gastric malignancies reported in the dog include adenocarcinoma, leiomyosarcoma, and lymphoma. In cats, lymphoma is the most common malignant gastric neoplasm; however, adenocarcinoma has been reported, with a breed predisposition in Siamese cats (Rossmeisl et al. 2002; Swann and Holt 2002; Withrow 2007c). Other reported primary gastric malignancies include mast cell tumors, extramedullary plasmacytomas, carcinoids, and ibrosarcomas. Benign tumors of the stomach include ibromas, leiomyomas, or proliferative mucosal lesions from congenital or

acquired antral pyloric hypertrophy. Benign tumors are generally cured with appropriately applied gastric resections. Gastric ACA accounts for between 42 and 72% of all malignant gastric neoplasms, with older dogs and male dogs being predisposed (Swann and Holt 2002; Withrow 2007c). Breed predispositions in the Belgian shepherd, chow chow, rough-coated collie, Bouvier des Flandres, Groenendael, standard poodle, Norwegian elkhound, and Staffordshire bull terrier have been reported, suggesting a potential genetic component to the development of this neoplasm (Swann and Holt 2002; Withrow 2007c; Seim-Wikse 2013). ACAs have a predilection for developing within the pyloric antrum or along the lesser curvature of the stomach, thereby complicating surgical intervention. Three morphologic forms of gastric ACA are described: (i) the diffuse form also known as “leather bottle stomach” (linitis plastica), which creates signi icant gastric wall thickening; (ii) a discrete, polyploid form; and (iii) a form with ulcerated, mucosal plaques (Swann and Holt 2002; Withrow 2007c). A histological classi ication scheme (diffuse type vs. intestinal type [similar to those seen in humans]) has been developed for gastric ACAs; however, this system does not afford any prognostic value to the clinical patient (Patnaik et al. 1978). Immunohistochemical evaluation of canine gastric ACA’s revealed expression of CDX-2 and HER-3 both of which are found in human intestinal adenocarcinoma and have been correlated with negative prognostic indices when overexpressed (Doster et al. 2011). The development of metastatic disease is common in dogs with gastric ACA. A comprehensive literature review of canine ACA determined a 76% (100 of 132) metastasis rate, with the most common sites of metastasis including regional lymph nodes (n = 81), peritoneum (n = 27), liver (n = 19), spleen (n = 15), lungs (n = 13), adrenal glands (n = 6), pancreas (n = 5) as well as structures within the urogenital tract and long bones (Swann and Holt 2002). In another study, evidence of metastatic disease at the time of surgery was histologically con irmed in 45% of the dogs with gastric carcinoma. The location of metastatic spread included regional lymph node, mesentery, and liver (Abrams 2019).

Surgical treatment of gastric ACAs does not generally yield long-term survival results, as many dogs will ultimately suffer from either recurrent or metastatic disease. Survival times are usually less than three months after the onset of clinical signs in untreated dogs; however, with surgical treatment, survival times may be increased to less than eight months (Swann and Holt 2002; Abrams 2019). Retrospective analysis of the veterinary literature revealed survival times ranging from two hours to ive years, with an MST of two months (only 17 of 140 dogs reported on in the literature had available information regarding survival data). In a more recent study of dogs with gastric carcinoma treated with a type of gastrectomy, median survival was 178 days with a one-year survival rate of 17.5% (Abrams 2019). Leiomyosarcomas are the second most common gastric tumor in dogs but tend to occur much less frequently than ACAs. A retrospective study evaluating gastric tumors from a single institution over a 13-year time period identi ied only two patients with histologically con irmed gastric leiomyosarcomas (Swann and Holt 2002). Both of these dogs underwent treatment of their tumor via a Billroth I procedure, and both were con irmed to have metastatic disease to the liver at the time of surgery. One dog died four weeks after surgery due to progression of the liver metastasis, and the other was lost to follow-up 2.5 months after surgery. Another study evaluating gastrointestinal leiomyosarcoma (GILM) in dogs found that the MST was one year for dogs surviving the immediate postoperative period (Kapatkin et al. 1992). Paraneoplastic hypoglycemia has been reported in dogs with gastric leiomyosarcomas and is usually reversible with resection of the tumor. The precise mechanism of action is unclear but is likely a combination of secretion of an insulin-like substance by the tumor, tumor-mediated glucose metabolism, or tumoral-based interference with the liver’s ability to produce or store glucose (Beaudry et al. 1995; Bagley et al. 1996; Bellah and Ginn 1996). Recently, the true incidence of GILMs has been called into question since many of these tumors are being reclassi ied as gastrointestinal stromal tumors (GISTs). A study by Russel et al. (2007) found that out of 42 previously diagnosed GILMs, 28 were reclassi ied as GISTs based

on immunohistochemical con irmation of c-kit (CD-117) expression. Leiomyosarcomas do not express the c-kit protein and can therefore be distinguished from GISTs based on immunohistochemical staining properties (Russel et al. 2007). In people, GISTs have a predilection for developing within the stomach; however, this tendency is not replicated in veterinary patients whereby the cecum and large intestine are reported as the most common sites for GIST development. Regardless, if a smooth muscle-based gastric tumor has been diagnosed, immunohistochemical con irmation of tumor type is recommended. Although survival time comparison between GISTs and GILMs did not reveal statistically signi icant differences (MST of 11.6 months for GISTs vs. 7.8 months for GILMs treated with surgery alone), it does appear that GISTs may behave less aggressively than GILMs (Russel et al. 2007). Additionally, since GISTs express the c-kit protein, which is a transmembrane receptor with a tyrosine kinase component, adjunctive therapy options may be available. Tyrosine kinase receptor inhibition therapy in people with GISTs has resulted in improved survival when compared to conventional adjunctive treatments (Russel et al. 2007). Toceranib has been reported to have biological activity against GISTs in dogs (see adjuvant therapies section) (Berger 2018).

Adjuvant Therapies Adjuvant therapy with either chemotherapy or external beam radiation has not been extensively investigated for any of the commonly diagnosed gastric neoplasms in animals. In people, gastric cancer is a devastating disease, with ive-year survival rates of less than 20%. Despite potentially curative resection of stomach cancer, 50–90% of patients ultimately succumb to the disease because of tumor recurrence. Despite numerous randomized clinical trials comparing surgery alone with adjuvant chemotherapy, de initive evidence of the ef icacy of adjuvant chemotherapy is lacking (Paoletti et al. 2010). A meta-analysis of 17 clinical trials evaluating the ef icacy of adjunctive chemotherapy in humans revealed an improvement in overall survival in patients receiving a luorouracil-based chemotherapy regimen (Paoletti et al. 2010). Based on this meta-analysis, it is now recommended that patients undergo adjuvant chemotherapy after complete resection of their gastric cancer (Paoletti et al. 2010).

Chemotherapy has been attempted both as single-agent therapy and as an adjunct to surgery in dogs. Unfortunately, no large-scale studies are available to help establish a consensus regarding the ef icacy of any given chemotherapeutic regimen. Generally, it is believed that chemotherapy is not effective for gastric ACA by itself (Swann and Holt 2002; Withrow 2007c). In a recent study, chemotherapy prolonged the survival of dogs with gastric carcinoma following gastrectomy (Abrams 2019). Toceranib (Palladia) has been shown to have biological activity against GISTs in dogs. In one study, ive of seven dogs with gross disease experienced a clinical bene it (three complete responses, one partial response, one stable disease). Median progression-free interval (PFI) in dogs with gross disease was 110 weeks (Berger 2018).

Liver and Gallbladder General Operative Considerations Surgical procedures indicated in the treatment of neoplastic liver disease include partial or complete liver lobectomy. A limited number of nonsurgical, palliative techniques have also been described (Weisse et al. 2002) and this area continues to be a source of active clinical research. Therapeutic strategies are largely based on the morphologic distribution of the neoplastic disease within the liver.

Morphological Classification of Liver Tumors Three morphologic types of primary liver tumors have been described: (i) massive, (ii) nodular, and (iii) diffuse. These morphologies are based on the geographic distribution of disease within the liver. Massive tumors are de ined as single, large masses, which are located within only one lobe of the liver. Nodular tumors are multifocal in origin and are located within more than one lobe of the liver. A diffuse morphological distribution indicates global effacement of the hepatic parenchyma or multifocal nodules present within all of the liver lobes (Liptak et al. 2004b). Conventional, curative-intent surgical therapy (complete lobectomy) for liver tumors is generally reserved for those

with a massive morphological distribution. Partial or complete liver lobectomy can be considered for nodular lesions if their distribution is compatible with these procedures. Benign and incidentally discovered nodular liver disease is common in the dog. In one study, focal hyperplastic nodules were detected in up to 70% of dogs older than six years of age and in all dogs older than 14 years of age (Bergman 1985). It is not uncommon to ind small nodules within liver lobes at surgery, that were not detected during preoperative abdominal imaging. This presents the surgeon with a diagnostic and therapeutic dilemma which requires careful consideration prior to implementing a surgical treatment. It is our opinion that if these nodules are few in number (fewer than two nodules) and located on the periphery of a lobe, excisional biopsy should be considered using one of the described partial lobectomy techniques (see below). If more than two nodules are detected, or if the nodules are centrally located within the affected lobe, an incisional biopsy should be considered. If the gross appearance of the nodules is similar, a single representative incisional biopsy is usually suf icient.

Diagnostic Workup and Biopsy Techniques In neoplastic liver disease, the necessity of and type of liver biopsy performed is dictated by a multitude of clinical and individual patient variables. Of paramount importance is the associated risk of the procedure for each patient. Comprehensive, preprocedure imaging is essential to help formulate risk-bene it ratios based on lesion location, distribution, and appearance. Abdominal ultrasonography is currently the preferred method for identifying and characterizing hepatobiliary tumors in dogs and cats (Liptak et al. 2004b). Ultrasonographic evaluation of liver tumors involves two essential elements: Detection of the lesion (assessing presence and number of lesions) and characterization of the lesion (assessing echogenic characteristics, size, and location of lesions) (Haers and Saunders 2009). Surgical planning is then based on the size and location of the mass and its relationship to adjacent anatomical structures such as the caudal vena cava and gallbladder. Despite its utility, conventional ultrasonography lacks the ability to differentiate

between benign or malignant lesions and histological tumor types (Liptak et al. 2004b; O’Brien et al. 2004). Development of contrast-enhanced ultrasonography (CEU) has improved the capacity of this tool for use in the characterization of liver tumors and in the differentiation of benign vs. malignant disease (Haers and Saunders 2009). With this technology, intravenous injection of gas microbubbles (tiny, inert, gas- illed microspheres stabilized by an outer shell) allows an enhanced appreciation of organ perfusion and tissue vascularity, similar to contrast enhancement seen with other advancedimaging modalities (O’Brien et al. 2004). CEU is particularly useful for detecting small and ill-de ined malignant lesions, which are often invisible in conventional ultrasound (Haers and Saunders 2009). In human patients, contrast harmonic ultrasound improves the conspicuity of nodules, can improve detection of the number of nodules, and improves the accuracy of a diagnosis of malignancy (O’Brien et al. 2004). In people with in iltrative liver disease, one study demonstrated that usage of CEU allowed for the detection of 40–45% more nodules when compared to conventional ultrasound techniques (Dietrich et al. 2004). Although relatively untested in animals, smallscale clinical studies have yielded promising results. In a study of 32 dogs with naturally occurring liver nodules, CEU was able to differentiate benign from malignant disease with sensitivity, speci icity, and diagnostic accuracy rates of 100%, 94.1%, and 96.9%, respectively (O’Brien et al. 2004). In another clinical study of 20 dogs with splenic tumors, CEU was able to correctly differentiate benign vs. metastatic liver lesions with a sensitivity and speci icity of 100% (Ivancić et al. 2009). Most conventional ultrasound units are not adequately equipped with the low-frequency transducers and computer software necessary to perform CEU. The promising results in the studies to date suggest that the bene its associated with CEU may foster the more routine integration of this modality, despite the substantial initial costs to upgrade preexisting ultrasound units. In humans, the limitations of ultrasound are well recognized, and therefore advanced imaging modalities are routinely used for the diagnosis, staging, and posttreatment monitoring of patients with liver tumors. MRI is currently the modality of choice for characterizing

primary hepatic lesions in human patients (Clifford et al. 2004). Using MRI, characterization of lesions as malignant or benign can be completed with an overall accuracy approaching 95% and a sensitivity and speci icity of approximately 90%. Often, the signal intensity and morphology of hepatic lesions are deemed so characteristic for certain neoplasms that histological con irmation is deemed unnecessary (Clifford et al. 2004). A pilot study using MRI to characterize focal hepatic lesions in dogs has been performed (Clifford et al. 2004). In this study, MRI was able to accurately differentiate benign from malignant lesions in 25 of 27 dogs, with a sensitivity of 100% and a speci icity of 86% (Clifford et al. 2004). Comprehensive descriptions of the morphological MRI changes observed within their study population were provided (Table 7.1). In humans, hepatobiliary-speci ic contrast agents are utilized with MRI in order to augment the ability to detect pathologic lesions in the liver. The contrast agent gadobenate dimeglumine has been evaluated in dogs with liver metastases from primary liver tumors and this agent holds promise to increase the ability of MRI to detect small or inconspicuous lesions (Louvet et al. 2015).

Table 7.1 Hepatic lesion characterization relative to normal liver using MRI. Source: Reprinted with permission from Clifford et al. (2004).

T1

T2

Post-Gd

Other

Malignant HCC

Isointense Isointense ↑↑↑ to liver to mildly ↑a

Capsule; abnormal hepatic architecture

Hemangiosarcoma ↑↑b

↑↑

↑↑

Multiplicity; continuous rim enhancement, progressive enhancement in delayed phase

Metastatic disease ↑↑

↑

↑

Multiplicity; continuous rim enhancement

Benign: Regenerative nodules

Isointense Isointense Isointense Nodular contour to liver

Pseudolesion

Isointense Isointense Isointense No lesion present

Gd, gadolinium; HCC, hepatocellular carcinoma a Up arrows represent hyperintense. b Down arrows represent hypointense.

In people, CT remains as one of the principal imaging methods used for diagnostic examination of the liver and biliary system (Saini 1997) and its usage in dogs and cats for this purpose has also become relatively commonplace. In particular, contrast-enhanced CT is a routinely used staging modality in people with suspected metastatic liver disease. An added bene it to CT is that comprehensive staging of the patient can be completed by examining the thorax and other extra-abdominal

structures for metastasis at the same time as the examination of the liver. One potential concern with the use of helical CT for liver cancer staging is its relative insensitivity for detecting small, isolated lesions (especially if lesions are less than 2 cm in diameter). Studies show that about one in three lesions can be missed, with a sensitivity of less than 60% for detecting small lesions (Saini 1997). The CT characteristics of primary liver tumors have been retrospectively evaluated in a population of 33 dogs who underwent CT imaging followed by surgical excision and then histopathological examination of the affected liver tissue. Common tumor characteristics in dogs with con irmed hepatocellular carcinoma (HCC) included the presence of a capsule around the tumor, cyst-like lesions within the tumor, hypoattenuation during the equilibrium phase of contrast administration, and marginal enhancement, all of which were observed in 93% of the cases. Benign nodular hyperplasia was found to be signi icantly less likely to have a capsule and was more commonly smaller and isoattenuating in the equilibrium phase of contrast clearance (Fukushima, et al. 2012). Helical CT angiography (CTA) can also be useful for surgical planning. Dual-phase CTA with 3D reformatting allows a detailed appreciation of tumor size, location, and vascularity (Figure 7.9). Vascular invasion into surrounding anatomic structures (i.e. vena cava) can also be elucidated, allowing for more complete intraoperative preparedness and improved patient selection. A retrospective study evaluating triple-phase helical CT usage in 70 dogs with hepatic tumors characterized the differences between HCC, nodular hyperplasia, and metastatic lesions and found that this imaging modality was very useful in differentiating between the different pathological subtypes (Kutara et al. 2014). Ultrasonographic-assisted biopsy is the most common modality used for procuring tissue samples of neoplastic liver lesions in dogs and cats (Liptak et al. 2004a). The diagnostic accuracy and safety of various abdominal ultrasound-guided liver biopsy techniques have been extensively evaluated. In one report, major complications were observed in 0.9% (2 of 117) of animals undergoing tissue core liver biopsies using an 18-gauge (1.2 mm, 20 cm long) automated biopsy device (Leveille et al. 1993). Both of these patients were cats and both sustained traumatic laceration of the bile duct resulting in the need for

exploratory surgery to repair the defect and to treat for bile peritonitis. Minor complications, consisting of focal hemorrhage or hematoma formation at the biopsy site was detected in 5.6% (7 of 126) of animals undergoing either tissue core liver biopsies or FNAs using a syringe attached to a 20-to 25-gauge, 1- to 1.5-inch (2.5–3.81 cm) needle. All minor complications were considered self-limiting (Leveille et al. 1993). Contraindications for an ultrasound-guided ine needle or core biopsy procedure include blood coagulation abnormalities, ascites (large-volume), microhepatica, a suspected hepatic cyst or abscess, vascular tumor, or a lesion that is adjacent to large bile ducts or hepatic vessels (Rawlings and Howerth 2004). In a study of 434 dogs (n = 310) and cats (n = 124) undergoing ultrasound-guided biopsy procedures, signi icant bleeding complications, de ined as a relative hematocrit decrease of greater than 10% with the necessity of therapeutic intervention (transfusion of blood products or resuscitative luids because of hemodynamic instability), were observed in thrombocytopenic animals (platelet count less than 80 × 103/μl). Additionally, dogs with a prolonged one-stage prothrombin time (>9.1 seconds) and cats with prolonged activated partial thromboplastin time (>21.9 seconds) were more likely to have complications than patients with normal values. It is therefore recommended that routine prebiopsy coagulation pro iles (i.e. one-stage prothrombin time, activated partial thromboplastin time, and platelet count) be performed prior to ultrasound-guided biopsy procedures (Bigge et al. 2001; Rawlings and Howerth 2004).

Figure 7.9 Postcontrast helical CT image of a dog with a multilobular, cavitated mass within the papillary process of the caudate liver lobe (white arrows). The mass was compressing and displacing the stomach. A nodule (black arrow) was identi ied within the right lateral liver lobe, however, the owner requested attempts at surgery since the CT suggested that complete resection of the caudate liver lobe mass was feasible. Both the nodule and the mass were consistent with a leiomyosarcoma (grade III).

A greater concern with ultrasound-guided tissue procurement of neoplastic lesions is the accuracy of these tests when compared to open surgical tissue biopsy. In one study, agreement between ine needle liver aspirates and surgical wedge biopsies was found in only 30.3% (17 of 56) of canine cases and 51.2% (21 of 41) of feline cases, respectively (Wang et al. 2004). In that study, the sensitivity of cytology to diagnose neoplasia was 14% in dogs and 33% in cats (Wang, 2004). In a later study of ultrasound-guided liver aspirates, cytology had a sensitivity of 52% and a positive predictive value of 86.7% for neoplasia in dogs (Bahr 2013). A study evaluating the morphological histologic diagnosis assigned to a needle biopsy specimen demonstrated agreement with the de initive histological diagnosis in only 48% (59 of 124) of dogs and cats with hepatic disease, but needle biopsies were 70% accurate for the diagnosis of neoplasia (Cole et al. 2002). These discrepancies should serve as a caution to clinicians considering a ine needle aspirate or needle biopsy to be a de initive diagnostic tool when characterizing in iltrative or neoplastic liver disease (Rawlings and Howerth 2004). Attempts at improving the correlation between cytology and histopathology have been investigated through the application of the immunohistochemical proliferation marker, Ki-67, to cytological liver specimens. In this study, it was identi ied that cytological specimens of dogs with liver tumors (n = 9) showed greater than 50% Ki-67-positive cells when compared to dogs (n = 21) with nonneoplastic liver disease having little or no Ki-67 positive cells (Neumann and Kaup 2005). Using Ki-67 proliferation indices, it was determined that the diagnostic accuracy of cytological evaluation was increased from 78 to 100% for malignant neoplasia (Neumann and Kaup 2005). Serological quanti ication of alphafetoprotein (AFP) is another novel technique that has been investigated as a means to con irm a diagnosis of malignant liver neoplasia in dogs. In people, abnormally high levels of circulating AFP have been demonstrated in 70–80% of human hepatic tumors (Lowseth et al. 1991). A single canine study demonstrated signi icantly higher serum levels of AFP in dogs with HCC and cholangiocarcinoma when compared to dogs with other types of liver neoplasia, nonneoplastic liver disease, and no liver disease (Lowseth et al. 1991). It should be noted that these techniques have not gained

widespread acceptance, and additional large-scale studies are needed before their clinical utility is validated.

Laparoscopic Biopsy Techniques Laparoscopy has become a routinely used adjunct to preoperative imaging examinations in humans with hepatic neoplasia (Lo et al. 2000; Montorsi et al. 2002). In particular, laparoscopy is an effective tool for staging the local extent of disease and for determining ideal candidate selection in patients that will subsequently undergo laparotomy for hepatic resection. Importantly, the use of laparoscopy can help avoid unnecessary laparotomy in patients with unresectable disease (Lo et al. 2000). In dogs, laparoscopic biopsy of the liver using clamshell laparoscopic biopsy forceps has been shown to produce minimal immediate hemorrhage and results in adequate tissue samples for accurate histological evaluation (Vananjee et al. 2006). Samples can be obtained from regions of the liver (adjacent to biliary structures and large vessels) that are generally inaccessible with percutaneous techniques, and laparoscopy is not strictly contraindicated in patients with ascites or coagulation defects (Rawlings and Howerth 2004; McDevitt et al. 2016). Additionally, the 2D imaging achieved with laparoscopy is superior to that of traditional laparotomy, as images are magni ied by the laparoscope (Rawlings and Howerth 2004). Laparoscopy is routinely used as an adjunct staging tool when preoperative imaging analysis has failed to instill con idence that the liver tumor is resectable or when primary hepatic origin of the tumor cannot be established. Detailed descriptions of operative laparoscopic biopsy techniques have been published and may be found elsewhere (Mayhew 2009).

Incisional Biopsy and Partial Lobectomy Liver biopsy via laparotomy is considered the gold standard technique for procuring representative tissue suf icient to achieve a de initive histological diagnosis. In humans, a biopsied liver sample must contain a minimum of six to eight portal triads in order to be considered adequate for an accurate histological diagnosis. In one veterinary study, 19% of 4 mm punch-biopsy samples and 42% of needle-biopsy (16-

gauge needle) samples contained less than six to eight portal triads (Vananjee et al. 2006). Direct translation from human studies regarding the ideal number of portal triads necessary for an adequate tissue diagnosis cannot be made; however, concern exists over the small sample size obtained through minimally invasive techniques. Liver biopsy samples measuring 1 × 1 × 1 cm consistently result in the suf icient number of portal triads required for accurate histological assessment. Therefore, open surgical biopsies of the liver should result in procurement of at least this volume of tissue (Vananjee et al. 2006). Nodules that are centrally located within a liver lobe may preclude the removal of an ideal volume of liver tissue for biopsy. In general, use of a 6-mm (or larger) Baker or Keyes skin biopsy punch to procure tissue from a portion of the nodule is suf icient for accurate histological assessment. When performing this technique, it is important to avoid penetration of more than half the thickness of the liver lobe so as to prevent traumatic laceration of the large hepatic veins situated along the concave surface of the lobe (Martin et al. 2003). Once the biopsy tissue has been removed from the liver, hemorrhage from the biopsy defect can be controlled through placement of a premeasured (cut to it) piece of Gelfoam dressing within the defect, followed by several minutes of gentle tamponade (Martin et al. 2003). With extremely vascular tumors (i.e. metastatic or primary hemangiosarcoma), uncontrolled hemorrhage may occur from the biopsy site despite tamponade with a hemostatic agent. Gentle placement of a mattress suture (the author prefers a small diameter, mono ilament absorbable suture such as 3-0 to 4-0 polydioxanone) across the defect may aid in further controlling hemorrhage; however, the friable nature of the liver in these situations may result in tearing once the suture is tightened. As a failsafe mechanism, the surgeon should be prepared to perform a partial lobectomy to gain control of the hemorrhaging biopsy tract. This reiterates the need for careful planning of a proposed biopsy site. When multiple representative nodules are present, preferential selection of a peripherally located nodule in the left division may facilitate “damage control,” if a biopsy-related complication occurs. Incisional biopsy and partial liver lobectomy techniques can be categorized based on the location of the tumor within the liver lobe. Wedge resections or encircling ligature (guillotine) placement

techniques are used for peripherally located tumors, whereas midbody lobe dissection and ligation techniques are used for more centralized lesions. The encircling ligature technique is applicable for small nodules that are located at the extreme periphery of a liver lobe or for attainment of a section of diffusely in iltrated liver that is to be removed for staging purposes. Wedge resections can be used for larger lesions and for those that are not located at the extreme periphery of the lobe. With either procedure, a single crushing (guillotine) ligature (Figure 7.10a) or multiple overlapping mattress ligatures (wedge) (Figure 7.10b) are placed such that the liver parenchyma is compressed suf iciently to prevent the leakage of blood and bile (Rawlings and Howerth 2004). For partial lobectomy of tumors located more centrally within the liver lobe, a moderate amount of hepatic parenchymal dissection will be necessary. Initially, the proposed section of liver to be resected is outlined by sharply (scalpel blade or electrocautery) dividing the liver capsule along the ventral or convex surface of the lobe (Blass and Seim 1985). Following this, blunt dissection of the hepatic parenchyma can be accomplished through either digital compression ( inger fracture technique) or separation using the blunt end of a Bard scalpel handle. This blunt dissection will allow isolation and ligation of vessels located within the hepatic parenchyma. As an alternative to blunt dissection with a scalpel handle or inger fracture, the inner component of a Poole suction tip can be used for intrahepatic dissection. This technique is particularly useful when dissecting through deeper or hard-to-access regions of the liver lobe since visualization is enhanced when the suction tip removes hemorrhage and portions of the crushed parenchyma (Martin et al. 2003). Once adequate dissection has been achieved, ligation of the remaining parenchyma and its associated vasculature may be achieved through application of an appropriately sized linear stapling device (see total lobectomy next) or by placement of an encircling ligature. When compared to other techniques for liver biopsy, the skeletonization and clip technique has been shown to result in larger quantities of blood loss, however, since the quanti ied volume of loss has been shown to be typically 1836 days) compared to those in the incomplete group (median 765 days) (Matsuyama 2017). In the study by Kosovsky et al. (1989), local recurrence was only detected in 1 of 18 dogs after partial liver lobectomy for HCC. Overall, the data suggest that lobectomy should be considered in dogs with massive HCC even if excision is not likely to be complete. Likewise, a poor prognosis should not necessarily be assigned to dogs when postoperative tumor margin assessment reveals that the HCC was incompletely excised. In two comprehensive, retrospective studies evaluating nonhematopoietic hepatobiliary neoplasms in cats, HCC was identi ied in only 4% (3 of 62) of the study population (Post and Patnaik 1992; Lawrence et al. 1994). Therefore, speci ic prognostic criteria and expected outcome statistics for feline HCC are not readily available. It is generally assumed that cats treated with complete liver lobectomy for solitary, massive HCCs without evidence of metastatic disease will enjoy prolonged survival times, similar to dogs in this predicament. HCCs in cats with nodular or diffuse distributions would be expected to respond

less favorably to surgical therapy; however, this has yet to be substantiated with large-scale scienti ic studies. Bile Duct Carcinoma of the bile duct is the most common primary malignant liver tumor in the cat and the second most common in dogs (Patnaik et al. 1980, 1981b; Post and Patnaik 1992; Lawrence et al. 1994; Liptak et al. 2004a; Liptak 2007). Benign adenomas represent the second type of bile duct tumor identi ied in dogs and cats. Bile duct adenomas, also termed hepatobiliary cystadenomas (based on their gross cystic appearance), are common in cats, representing more than 50% of all feline hepatobiliary tumors (Figure 7.16a, b). Hepatobiliary cystadenomas are relatively uncommon in dogs (Post and Patnaik 1992; Lawrence et al. 1994; Adler and Wilson 1995; Trout et al. 1995; Liptak et al. 2004b). Anatomically, bile duct tumors can be found within any of the three segments of the biliary system: Intrahepatic ducts, gallbladder, or extrahepatic ducts. Intrahepatic tumors tend to predominate in dogs with bile duct carcinoma, whereas in cats, a relatively equal distribution of intrahepatic and extrahepatic tumors has been reported. Bile duct carcinoma of the gallbladder is considered rare in both species, accounting for less than 5% of cases (Patnaik et al. 1980, 1981b; Patnaik 1992; Post and Patnaik 1992; Lawrence et al. 1994; Liptak et al. 2004b). Bile duct carcinomas are biologically aggressive tumors with high rates of systemic metastasis. In one study of dogs with bile duct carcinoma, systemic metastasis was found in 21 of 24 (87.5%) cases, with lymph nodes, lungs, and peritoneum representing the most common sites for metastasis (Patnaik et al. 1981b; Liptak et al. 2004b). Diffuse intraperitoneal metastasis and carcinomatosis are frequently reported in cats with bile duct carcinoma, representing 67–80% of cases (Figure 7.17) (Patnaik 1992; Post and Patnaik 1992; Lawrence et al. 1994; Liptak et al. 2004b). In dogs with bile duct carcinoma, massive and nodular morphological distribution subtypes tend to predominate, representing 37–46% and

54%, respectively. Diffuse disease tends to occur less commonly with a reported incidence of 17–54% (Table 7.3) (Patnaik et al. 1980, 1981b; Liptak et al. 2004b). Liver lobectomy for treatment of massive bile duct carcinoma has been recommended in dogs and cats. Unfortunately, large-scale clinical studies are not available, and no prognostic factors have been identi ied. Clients should be cautioned, however, that most animals treated for bile duct carcinoma tend to succumb to the disease within six months of therapy secondary to local recurrence or distant metastasis (Liptak et al. 2004b).

Figure 7.16 (a, b) Postmortem images of a cat with a massive cystadenoma originating from the left division of the liver. Note the characteristic luid- illed cystic component of the mass.

Figure 7.17 Intraoperative image of a cat with bile duct carcinoma and secondary carcinomatosis. Hepatobiliary cystadenomas are slow-growing, benign tumors that tend to occur in older cats and are often discovered incidentally. When present, clinical signs are usually nonspeci ic and are related to the mass effect created by the tumor compressing surrounding abdominal organs (i.e. vomiting from gastric compression). Treatments for cystadenomas in people include percutaneous aspiration and drainage, marsupialization, and partial or total excision. Malignant transformation from cystadenoma to carcinoma has been reported in cats, and therefore total excision via lobectomy has been recommended as the treatment of choice (Adler and Wilson 1995; Trout et al. 1995; Liptak et al. 2004b). The morphological distribution of the tumor should be considered prior to lobectomy as multicentric disease has been reported with a frequency equal to massive, solitary lesions (Adler and Wilson 1995). Generally, cats with solitary lesions that are treated with lobectomy enjoy prolonged survival times. In a study of ive cats undergoing lobectomy for treatment of hepatobiliary cystadenomas, surgical complications were not observed and tumor recurrence or tumor-related mortality was not observed (Trout et al. 1995). Table 7.3 Literature summary of the frequency of morphologic classi ications of malignant primary liver tumors in dogs. Source: Reproduced with permission from Liptak et al. (2004).

Tumor type

Massive Nodular Diffuse

Hepatocellular carcinoma 53–84% 16–25% 0–9% Bile duct carcinoma

37–46% 0–46%

17–54%

Neuroendocrine tumor

0%

33%

67%

64%

0%

Sarcoma (mesenchymal) 36% Carcinoid (Neuroendocrine)

Hepatic carcinoid tumors, derived from neuroectodermal tissue or from amine precursor uptake and decarboxylation (APUD) cells, are rarely reported in dogs and cats (Patnaik et al. 1981c; Liptak et al. 2004b). In

a necropsy study of 12 245 dogs seen over a 15-year period, hepatic carcinoids represented only 14% (15 of 110) of all the primary liver tumors identi ied (Patnaik et al. 1980). More commonly, carcinoids develop as primary pancreatic or gastrointestinal tract tumors and metastasize to the liver (Patnaik et al. 1980). Since these tumors arise from dispersed cells of the neuroendocrine system, they can be functional in origin. Low-molecular-weight polypeptide or protein hormones such as secretin, cholecystokinin, and chromogranin can be synthesized from the tumors, and when derived from APUD cells, the tumors can secrete serotonin or adrenocorticotrophic hormone (Morrell et al. 2002). In dogs, hepatic carcinoids tend to affect younger animals, compared to other primary hepatic neoplasms. In one study, the median age was eight years, with 71% of dogs being less than 10 years of age at the time of diagnosis (Patnaik et al. 1980). Although primary hepatic carcinoids have been reported in the gallbladder, they more commonly have intrahepatic origin in the dog (Patnaik et al. 1981c; Willard et al. 1988; Morrell et al. 2002; Liptak et al. 2004b). Unfortunately, due to the typical morphological distribution of these tumors within the liver, surgical therapy is not usually considered bene icial. A diffuse distribution is observed in 67% of cases, and nodular patterns are seen in 33% of cases. The massive morphological distribution (i.e. solitary lobe involvement) is generally not seen (Patnaik et al. 1980, 1981c; Liptak et al. 2004b). Additionally, metastatic disease is identi ied in 93% of dogs, with locoregional lymph nodes, lungs, and the peritoneum representing the most common sites of extrahepatic spread (Patnaik et al. 1980, 1981c; Liptak et al. 2004b). Mesenchymal Commonly reported types of primary hepatic sarcomas include leiomyosarcoma, hemangiosarcoma, and ibrosarcoma, representing 9%, 3%, and 1% of all primary hepatic malignancies, respectively. Other types of primary hepatic sarcomas include liposarcoma, rhabdomyosarcoma, osteosarcoma, and malignant mesenchymal. In general, however, malignant primary and nonhematopoietic sarcomas are rare in dogs and cats (Patnaik et al. 1980, 1981b; Patnaik 1992;

Post and Patnaik 1992; Lawrence et al. 1994; Liptak et al. 2004b). Benign primary hepatic mesenchymal tumors, such as hemangioma, have been reported; however, these are also uncommon. Large-scale veterinary studies evaluating prognostic criteria for the surgical management of hepatic sarcomas have not been performed. These tumors usually demonstrate an aggressive biological behavior, with metastasis being identi ied in 86–100% of cases (Patnaik et al. 1980; Kapatkin et al. 1992; Liptak et al. 2004b). Likewise, a nodular morphological distribution is seen in 64% of cases, making candidacy for surgery unpredictable. A massive distribution is seen in 36% of cases, and fortunately, diffuse disease is not commonly observed (Patnaik et al. 1980; Liptak et al. 2004b). Surgical treatment for solitary massive hepatic sarcomas has been recommended; however, prognosis is usually poor unless metastatic disease is not a factor.

Adjuvant and Other Therapies Large-scale prospective controlled studies evaluating the ef icacy of speci ic chemotherapeutic regimens for animals with malignant hepatic neoplasia have not been performed (Liptak 2007). A retrospective study evaluating adjunctive or primary treatment with gemcitabine chemotherapy in 18 dogs with HCC found no signi icant survival advantage with its use (Elpiner et al. 2011). It is unlikely for conventionally fractionated radiation to be ef icacious based on the fact that the canine liver is unable to tolerate cumulative doses beyond 30 Gy (Liptak 2007). One study reported six dogs with massive HCC treated with 3D conformal radiation therapy (3D-CRT) (Mori et al. 2015). Five dogs had a partial response and one dog had stable disease and the median survival was 567 days (Mori 2015). In human medicine, stereotactic body radiation therapy (SBRT) is used, which allows the administration of large doses of radiation focally to the tumor while sparing the surrounding tissues. SBRT is effective because the radiation is delivered with absolute precision, thereby achieving maximum treatment ef icacy with minimal toxicity to nearby unaffected liver tissue. SBRT is of particular value in patient populations deemed to have nonresectable liver tumors and a review article by Doi and colleagues reported similar ef icacy to that seen with other standards of

care palliative treatments such as transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) (Doi et al. 2018). Anecdotally, stereotactic radiation therapy has been used in the treatment of dogs with liver tumors and fair responses have been observed, however, more research into this area is still necessary. In humans with metastatic liver tumors or with persistent recurrent disease, chemotherapy is usually recommended; however, no single drug or combination of drugs given systemically leads to a reproducible response rate of more than 25% or adds any survival bene it (Kokudo et al. 2010). A recent study was conducted to evaluate the gene expression of growth factors and growth factor receptors in dogs with HCC with the hope that these data could be used for the development of targeted therapies (Iida et al. 2014). In the 18 HCC’s evaluated, plateletderived growth factor-beta (PDGF-B), transforming growth factoralpha, epidermal growth factor receptor, epidermal growth factor, and hepatocyte growth factor were found to be differentially expressed as compared to normal control and benign liver tissue samples. It was concluded that PDGF-B is suggested to have the potential to become a valuable ancillary target for the treatment of canine HCC (Iida et al. 2014). Another avenue of active research is the harnessing of pharmaceutical agents that help prevent aberrant DNA methylation within tumors which has been shown to be a major player in the early and late stages of tumorigenesis. A 2015 study evaluating the effects of Zebularine, a DNA methyltransferase inhibitor, found that the drug was effective at inducing apoptosis of cholangiocarcinoma cells and previous work of the authors found a similar effect against HCC (Nakamura et al. 2015). Clinical application of these treatments is not widespread but with ongoing work the hope is that these novel therapies will prove durable in their ef icacy, allowing for expansion of the medical therapies available for liver neoplasia. TACE is commonly employed in the treatment of people with advancedstage or nonresectable liver tumors (primarily HCC) (Liapi et al. 2007). TACE involves selective, percutaneous catheterization (using luoroscopy) of the desired hepatic artery branch based on tumor location. Angiography is used to de ine the affected region, and once identi ied, the vessel targeting the speci ic tumor bed is accessed. A combination of cisplatin, doxorubicin, and mitomycin C mixed with

ethiodol is injected until stasis of blood low to the region is achieved. Mechanistically, TACE is effective based on the understanding that most malignant hepatic lesions receive their blood supply by the hepatic artery, thereby delivering highly concentrated doses of chemotherapy to the tumor bed and sparing the surrounding hepatic parenchyma (Liapi et al. 2007). A meta-analysis that included seven randomized trials of arterial embolization for unresectable HCC in people showed a statistically signi icant improvement in two-year survival compared with control (either conservative treatment or less favorable therapy, such as intravenous 5- luorouracil). TACE-treated patients showed a median survival of more than two years compared to a median survival of four to seven months in patients with inoperable HCC (Llovet et al. 2003; Liapi et al. 2007). The potential for therapeutic application of TACE in veterinary medicine is vast, and success in the palliation of eight dogs with HCC has been reported (Weisse et al. 2002; Oishi et al. 2019). Additionally, a single case report of successful utilization of TACE for palliation of a cat with HCC has been reported in the veterinary literature (Iwai et al. 2015). Microwave ablation (MWA) or RFA are other locoregional treatments that have been developed for managing human patients with nonresectable or metastatic hepatic neoplasia. With these treatments, a small antenna is deployed (often in a minimally invasive fashion) to a focal area of affected liver tissue and a predetermined alloquat of thermal energy is delivered in a controlled manner, resulting in cell death of the tumor tissue. MWA relies on the rapid oscillation of an electromagnetic ield for generation of heat whereas, RFA requires an electrical current which may result in a less predictable ablation zone (Yang et al. 2017). A case series demonstrating the effective use of MWA in ive dogs with primary or metastatic hepatic neoplasia has been published, establishing the framework for continued development of this technology for use as an effective treatment in animals (Yang et al. 2017).

Pancreas Pancreatic Anatomy

The pancreas is divided into right and left lobes. The right lobe is located in the mesoduodenum between the duodenum and ascending colon. The left lobe is contained within the deep leaf of greater omentum between the left kidney, stomach, and transverse colon. Where the two limbs meet, close to the pylorus, the pancreas parenchyma is thicker and referred to as the body of the pancreas. The anatomy of the pancreatic duct system differs signi icantly between the cat and the dog. Digestive secretions enter the duodenum as follows. 1. The accessory pancreatic duct (largest one in dogs; opens at the minor duodenal papilla). Only 20% of cats have an accessory pancreatic duct (Figure 7.18). 2. The pancreatic duct (relatively small and may be absent in dogs but is the main or only duct in cats; opens at the major duodenal papilla) (Figure 7.18). About 68% of dogs have both an accessory pancreatic duct and a pancreatic duct (Cornell and Fischer 2003). A third duct is present in 8% of dogs. Interlobular ducts converge and enter the duodenum at right angles to the duodenal wall without tunneling. The minor duodenal papilla opens approximately 2 cm aborad to the major duodenal papilla, and the common bile duct enters the duodenum at the major duodenal papilla. Extrahepatic biliary obstruction may occur secondary to pancreatic swelling or masses due to impingement of the common bile duct as it enters the major duodenal papilla. When multiple pancreatic ducts exist in the dog, they all communicate with the parenchyma of the gland. It is therefore possible to maintain exocrine secretion from the entire gland with ligation of a single duct.

Pancreatic Vasculature Celiac arterial vasculature is generally the primary blood supply, with two to three direct branches from the celiac artery to the pancreas commonly found (Figure 7.18). Branches of the splenic artery enter the left limb. The celiac artery branches into the hepatic artery to supply the body of the pancreas. The hepatic artery sends blood to the right

gastric artery and continues as the gastroduodenal artery, also supplying the body and the cranial right limb. The gastroduodenal artery divides into the right gastroepiploic and the cranial pancreaticoduodenal arteries, supplying the cranial half of the right limb of the pancreas. The cranial mesenteric artery supplies only the caudal portion of the right limb, through the caudal pancreaticoduodenal artery. Damage to the cranial and caudal pancreaticoduodenal arteries may lead to duodenal devitalization because these vessels also supply the duodenum.

Imaging of Pancreatic Neoplasia Speci ic indications for the examination of the pancreas include, but are not limited to, vomiting, anorexia, weight loss, abdominal pain, icterus, therapy-resistant diabetes mellitus, and hypoglycemia (Hecht and Henry 2007).

Figure 7.18 Anatomy of the canine pancreatic duct system and vascular system. Source: Illustration courtesy of Dave Carlson.

Ultrasonographic Examination of the Pancreas Abdominal ultrasound does not always provide a clear image of the pancreas, for example, due to gas or other contents in the stomach, duodenum, or colon (Robben et al. 2005; Garden et al. 2005). Pancreatic tumors may also be small and poorly delineated from the surrounding parenchyma (Iseri et al. 2007). A neoplastic pancreas may appear to be normal on abdominal ultrasound or may mimic or be

associated with abscessation, pancreatic necrosis, or pancreatitis (Hecht and Henry 2007). When a pancreatic tumor is identi ied, it generally appears as a pancreatic or peripancreatic nodule or mass lesion of variable size and echogenicity (Lamb et al. 1995; Bennett et al. 2001; Seaman 2004; Hecht et al. 2007). However, ultrasonographic features in feline pancreatic nodular hyperplasia include pancreatic nodules of up to 1 cm diameter, and there is signi icant overlap between the ultrasonographic indings for pancreatitis, pancreatic neoplasia, nodular hyperplasia (Hecht and Henry 2007), and multiple cystic adenomas. In a study of 19 cats, a pancreatic mass was detected using either radiography or ultrasonography in 50% of cats with pancreatic neoplasia. In the same study, a single pancreatic nodule or mass exceeding 2 cm in at least one dimension was the only imaging inding unique to pancreatic malignant neoplasms but was only encountered in 4 of 14 cats (Hecht et al. 2007). Pancreatic ultrasound should also include an evaluation of the entire peritoneal cavity (Hecht and Henry 2007), to identify abdominal effusion, extrahepatic biliary obstruction, and possible metastatic disease. There are numerous differential diagnoses for hepatic nodules, and cytology or histopathology is required before hepatic metastasis is assumed. In cats with primary pancreatic neoplasia, metastatic liver lesions tend to be single and large, whereas multiple smaller lesions tend to be hepatic nodular hyperplasia (Hecht et al. 2007). Lamb et al. (1995) reported that abdominal ultrasound identi ied 12 of 16 (75%) pancreatic neoplasms and 6 of 11 (55%) abdominal metastases in dogs. Radiographic Examination of the Pancreas Abdominal mass effect and poor serosal detail can be observed in 78% of cats with malignant pancreatic tumors (Hecht et al. 2007) and in 100% of cats with pancreatic adenocarcinoma (Seaman 2004). Barium studies may reveal delayed transit time, duodenal narrowing, or duodenal invasion in cases of pancreatic carcinoma (Withrow 2007a). There are no reports of abdominal radiographs detecting abdominal metastasis of insulinomas (Steiner and Bruyette 1996).

Imaging of Endocrine Pancreatic Tumors Insulinoma If the clinical signs and serum glucose and insulin pair support a diagnosis of insulinoma, a transabdominal ultrasound is commonly performed preoperatively to (i) identify pancreatic mass(es) and (ii) assess the liver and regional lymph nodes for any evidence of metastasis. Findings should not be overinterpreted, as multiple suspicious masses seen on abdominal ultrasound correlate poorly with metastatic disease at the time of exploratory surgery (Tobin et al. 1999). Abdominal ultrasound visualized a pancreatic nodule in only one of ive dogs with insulinoma (due to gas in surrounding bowel), whereas CT diagnosed a pancreatic mass in two of three dogs (Garden et al. 2005). Ultrasound detected 5 of 14 (36%) primary insulinomas, CT detected 10 of 14 (71%) primary insulinomas, and single-photon emission computed tomography (SPECT) with radiolabeled octreotide (a speci ic form of somatostatin receptor scintigraphy) detected 6 of 14 (43%) primary insulinomas (Robben et al. 2005). Although conventional preand postcontrast CT was more sensitive than ultrasound or SPECT in this study, it signi icantly overestimated metastases (28 false-positive lesions) (Robben et al. 2005). Despite the low sensitivity of abdominal ultrasound for detecting insulinomas, it is still useful as an initial screening test in the assessment of dogs with hypoglycemia and for the exclusion of differential diagnoses such as insulin-like growth factor II-like peptideproducing extrapancreatic tumors (Boari et al. 1995) (see Table 7.4).

Table 7.4 Differential diagnosis for hypoglycemia in dogs. Source: Adapted from Feldman and Nelson (2004); Cornell and Fischer (2003).

Insulin (iatrogenic overdose, insulinoma – insulin-secreting tumor of pancreatic islet B cells—or other neoplasm secreting insulin-like factor, for example, leiomyosarcoma or lymphoma) Hunting dog hypoglycemia Idiopathic hypoglycemia of neonates and toy breeds Endocrinopathies (e.g. hypoadrenocorticism, growth hormone de iciency, glucagon de iciency (pancreatic disease) Hepatic disease (e.g. portosystemic shunts, necrosis due to toxins and infectious agents, cirrhosis, storage diseases) Chronic renal failure Starvation Pregnancy Sepsis Severe polycythemia Laboratory error Dynamic CT (with contrast medium injection and images taken in arterial and pancreatic phases) clearly identi ied a pancreatic nodule in one dog with insulinoma, and tumor size and location on CT correlated with surgical indings. The difference between the CT values of the pancreatic mass and those of the normal pancreatic parenchyma was the highest at the arterial phase, similar to humans (Iseri et al. 2007). Dual-phase CTA has been reported in three dogs with histopathologically con irmed pancreatic insulinoma. In all three dogs, there was agreement between the dual-phase CTA indings and the surgical indings, and dual-phase CTA indings identi ied lesions not seen with abdominal ultrasonography. The arterial and portal phases of the dual-phase study were critical for complete identi ication of all lesions present (Mai and Caceres 2008). Later studies have shown triple-phase CT may be preferable for the preoperative detection of canine insulinoma. Pancreatic masses were detected in the arterial

phase in six out of nine cases, and in the pancreatic or later phase in three out of nine cases (Fukushima K et al 2016). In another study, 26/27 canine insulinomas were successfully detected using contrastenhanced CT; however, the location of the mass was accurate in only 14/27 cases. Location accuracies were 54%, for triple phase, and 50% for single or double phase CT. Also, there was no speci ic postcontrast phase in which insulinomas could be visualized best, however, triplephase CT was considered ideal. The sensitivity of lymph node metastases was 67% and liver metastasis was 75% (Buishand et al. 2018). MRI detected abnormal islet tissue in four of four dogs with insulinoma (Walczak et al. 2019). Contrast-enhanced ultrasound was used to assist the visualization of pancreatic insulinomas in three dogs (Nakamura et al. 2015). Somatostatin receptor scintigraphy (using the radiolabeled somatostatin analog pentetreotide) showed abnormal foci of pentetreotide activity (attributed in each case to the presence of an insulinoma) in four of ive dogs, but only de ined the anatomical location of the primary tumor in one of four dogs (Garden et al. 2005). Lester et al. (1999) also reported successful use of somatostatin receptor scintigraphy to assist the presurgical diagnosis of an insulinoma in one dog, where abdominal ultrasound failed to image the pancreas. Nuclear scintigraphy using radioactive labeled octreotide is sensitive for masses as small as 3 mm (Robben et al. 1997). Pancreatic ultrasound has been used to identify small insulinomas intraoperatively (Robben et al. 2005). Endoscopic ultrasound, using a high-frequency (10 MHz) transducer to visualize the pancreas from the adjacent stomach or duodenum, is used in humans and has been investigated in dogs. Good sensitivity and visualization of pancreatic parenchyma (i.e. lobular structure, pancreatic duct, and vessels, except for the tips of the pancreatic limbs) was reported (Morita et al. 1998) and is likely to be useful for detecting small pancreatic lesions. Glucagonoma Most dogs with glucagonoma have metastatic disease at the time of diagnosis, which may be detected by abdominal ultrasound (Allenspach et al. 2000; Oberkirchner et al. 2009). Abdominal ultrasonography was

conducted in eight cases of canine glucagonoma, but a pancreatic mass was visible in only one case (Gross et al. 1990; Miller et al. 1991; Bond et al. 1995; Torres et al. 1997a, 1997b; Allenspach et al. 2000). Contrast-enhanced CT diagnosed a primary pancreatic mass in one dog, where gas- illed loops of intestine had precluded its visualization on abdominal ultrasound (Langer et al. 2003). Gastrinoma Abdominal ultrasound and endoscopy may demonstrate the gastrointestinal ulceration commonly seen with gastrinoma (Zerbe and Washabau 2000). Abdominal ultrasound does not reliably show a pancreatic mass, as they are often small or microscopic (Roche et al. 1982). Somatostatin receptor scintigraphy (using the radiolabeled somatostatin analogs) may assist in diagnosis (Schirmer et al. 1995; Gibril et al. 1996; Altschul et al. 1997).

Imaging of Exocrine Neoplasia Carcinoma Many nonmalignant diseases such as pancreatic nodular hyperplasia, which is a common incidental inding in old dogs and cats, can mimic pancreatic carcinoma ultrasonographically (Jubb 1993). Therefore, imaging indings need to be related to clinical signs, laboratory data, and ultimately cytology or histopathology to obtain a de initive diagnosis (Hecht and Henry 2007). Ultrasound may reveal metastatic spread to the mesentery (carcinomatosis), which manifests as numerous hypoechoic nodules associated with the connecting peritoneum, often with concurrent abdominal effusion (Hecht and Henry 2007). Radiographically, a lack of serosal detail (four of six cats) and abdominal mass effect (six of six cats) is commonly seen in cats with malignant pancreatic neoplasia (86% of malignancies were carcinomas) (Hecht et al. 2007). The Airedale terrier is reported to be predisposed to pancreatic adenocarcinoma (Priester, 1974).

Metastatic sites reported include the liver, small intestine, lungs, heart, diaphragm, and regional lymph nodes in cats (Seaman 2004) and liver, regional lymph nodes, mesentery, intestine, spleen, adrenal gland, diaphragm, lung, and lumbar vertebrae in dogs (Bennett et al. 2001).

Thoracic Imaging for Staging Purposes Insulinoma The presence of radiographically detectable thoracic metastatic disease has not been reported (Kruth et al. 1982; Caywood et al. 1988; Steiner and Bruyette 1996; Tobin et al. 1999; Polton and Brearley 2007). However, thoracic radiographs can be performed to rule out other causes of hypoglycemia. Glucagonoma Thoracic radiographs may demonstrate the presence of metastasis in cases of glucagonoma (Lurye and Behrend 2001; Brentjens and Saltz 2001; Bailey and Page 2007). Gastrinoma Metastasis is common, with 70–75% documented in dogs and cats at presentation (Zerbe and Washabau 2000; Feldman and Nelson 2004). The sites for metastasis reported include the liver, regional lymph nodes, spleen, peritoneum, and mesentery (Zerbe and Washabau 2000; Feldman and Nelson 2004). Thoracic radiographs usually do not identify pulmonary metastatic disease; however, they may be used to reveal megaesophagus (secondary to severe esophagitis). Contrast luoroscopy may show esophageal hypomotility (Kyles 2003). Carcinoma Metastatic sites reported include the liver, small intestine, lungs, heart, diaphragm, and regional lymph nodes in cats (Seaman 2004) and liver, regional lymph nodes, mesentery, intestine, spleen, adrenal gland, diaphragm, lung, and lumbar vertebrae in dogs (Bennett et al. 2001).

Surgical Procedures and Principles

Pancreatic Biopsy Biopsies may be used to differentiate pancreatitis, ibrosis, pancreatic carcinoma or other tumors, pancreatic abscess, pancreatic pseudocyst, pancreatic nodular hyperplasia, or multiple cystic adenomas. Preoperative biopsies are usually not performed when endocrine pancreatic tumors are suspected. Incisional biopsy options for pancreatic biopsy include ultrasoundguided needle core biopsy (Tru-Cut) and open surgical approaches such as wedge, suture fracture technique, or blunt dissection and ligation. These procedures are performed without signi icant concerns for morbidity as long as special attention is paid to protect the pancreatic vasculature and duct system. A small portion of the caudal aspect of right pancreatic limb is generally biopsied at surgery for diffuse disease, using a small scalpel blade. Crushing of tissues should be avoided where possible, and the pancreas should be handled gently. Laparoscopic biopsy is an additional option that is less invasive than full abdominal exploration and allows the acquisition of excellent tissue samples while minimizing operative morbidity (Barnes et al. 2006). Fine Needle Aspiration FNA can also be performed for sample collection of pancreatic abnormalities and is generally performed with the assistance of ultrasound guidance. This can be very successful for the diagnosis of exocrine neoplasia (see below). In a series of 92 dogs undergoing FNA of the pancreas, the diagnostic yield was 73.5%. There were seven adverse events, all in dogs with signi icant comorbidities or undergoing other invasive procedures. Correlation of cytology and histology results was available for 14 cases ( ive were correctly identi ied as pancreatic necrosis/abscess/pancreatitis, ive were correctly diagnosed with various types of neoplasia. Incorrect or inconclusive diagnosis was made using FNA in four cases (including one case incorrectly diagnosed with a neuroendocrine tumor) (Cordner et al. 2015). In another study, ultrasound-guided FNA correctly diagnosed pancreatic carcinoma in 92% of cases in the dog and cat (Bennett et al. 2001). A diagnosis may

be obtained from cytology of ascitic luid in cases where there is a malignant effusion. Partial Pancreatectomy Partial pancreatectomy involves the removal of one section of the pancreas and can be performed using either a suture fracture technique or blunt dissection. With any surgical procedure involving the pancreas, it is essential to pay close attention to the pancreatic vasculature and the ductal system. Suture fracture technique is most appropriate for focal lesions near the extremity. Small tumors can be enucleated using blunt dissection (Figure 7.19). A wider margin of grossly normal tissue may be preferable for malignant disease, although this has not been conclusively proven to assist survival or recurrence with a small number of cases in one study (Mehlhaff et al. 1985). Many papers do not specify if surgical removal was via enucleation or partial pancreatectomy, and the use of adjunctive medical management is also inconsistent (see Table 7.5). However, partial pancreatectomy is recommended in preference to enucleation, where feasible. Blood vessels and ducts supplying the portion of pancreas to be removed are identi ied and ligated. From 75 to 90% of the pancreas can be removed without any impairment of endocrine or exocrine function if the duct system to remaining portion is left intact. The pancreas has signi icant regenerative capacity (Cornell and Fischer 2003). Mono ilament, synthetic absorbable suture material is used; nonabsorbable, braided, or cat-gut sutures are avoided. Hemoclips or TA-30 or -55 staples (Bellah 1994), or an electrothermal bipolar vessel-sealing device (Wouters 2011) can also be used to assist in removal. Handling of the pancreas should be minimized to avoid postoperative pancreatitis and because identifying abnormal areas of the pancreas such as small tumors can be more dif icult, once the pancreas has been in lamed.

Figure 7.19 Enucleation of a pancreatic mass (insulinoma) using blunt dissection. Source: Image courtesy of Dr. Simon Kudnig.

Table 7.5 Reported survival times for dogs with insulinoma treated with surgery ± medical therapy. Reference Number Survival of cases time (ST)

Surgical technique Adjunctive medical managementa

Kruth et 25 al. (1982)

12.3 Unspeci ied in 23 months dogs, partial (mean ST) pancreatectomy speci ied in 2 dogs

Yes

Mehlhaff et al. (1985)

10

11.5 Local enucleation months (mean ST)

Yes

Mehlhaff et al. (1985)

15

17.9 Partial months pancreatectomy (mean ST)

Yes

Leifer et 18 al. (1986)

435 days (14.5 months) (median ST)

No

Caywood et al. (1988)

18 months Partial (stage 1 pancreatectomy data) (median ST)

Yes

381 days (12.7 months) (median ST)

Yes

47

Tobin et 26 al. (1999)

Unspeci ied

Partial pancreatectomy

Reference Number Survival of cases time (ST)

Surgical technique Adjunctive medical managementa

Polton and 28 Brearley (2007)

547 days (18.2 months) (median ST)

Partial pancreatectomy

Yes

Trifonidou 31 et al. (1998)

258 days (8.6 months) (median ST)

Unspeci ied

No

a Medical management options reported included frequent feeding, oral glucose, oral glucocorticoids, diazoxide. ST, survival time.

Indications Partial pancreatectomy may be used to treat (and diagnose) pancreatic insulinoma, gastrinoma, glucagonoma, abscess, or pseudocyst. Insulinoma is the most common endocrine tumor of the pancreas, and adenocarcinoma is the most common exocrine tumor of the pancreas (Jubb 1993). Insulinoma is rare in cats. Total Pancreatectomy Total pancreatectomy is generally avoided in dogs with clinical pancreatic disease due to the dif iculty in maintaining duodenal blood supply. Pancreaticoduodenectomy is also avoided due to a high morbidity and mortality. It has, however, been performed experimentally for research involving diabetes mellitus or exocrine pancreatic insuf iciency. The primary dif iculty associated with total pancreatectomy is maintaining the duodenal blood supply with removal of the right limb of the pancreas. Care must be taken to maintain the primary branch of the splenic artery with removal of the left pancreatic limb or splenectomy will be required (Cornell and Fischer 2003). Regardless of the technique used in clinical cases,

generally, the amount of edema, adhesion, or ibrosis prevents removal of the right limb of the pancreas while maintaining a viable duodenum (Cornell and Fischer 2003). Pancreaticoduodenectomy is similarly generally not performed clinically because of the high associated morbidity and mortality (Cornell and Fischer 2003). This procedure requires rerouting of the biliary tract and life-long pancreatic supplementation of both endocrine and exocrine functions.

Aftercare Prevention of pancreatitis is assisted by intravenous luid therapy. Small amounts of oral water are offered irst, from 24 to 48 h after surgery, and if no vomiting is seen, a few teaspoons of low-fat bland food are provided. A jejunostomy tube or jejunostomy-throughgastrostomy tube may be needed to bypass the pancreas, and this is often placed preemptively at the initial surgery. Alternatively, a nasogastric tube can be used to feed animals postoperatively with a low-fat liquid diet. Partial or total parenteral nutrition may also be required postoperatively in individual animals. Antiemetic and antinausea medications are generally given preemptively as part of postoperative management.

Surgery for Endocrine Pancreatic Neoplasia Insulinoma Medical management to stabilize blood glucose is required prior to and following surgery (see Chapter 13). Surgical exploration is recommended if there is persistently low blood glucose, appropriate clinical signs, and a high insulin level, even if a pancreatic mass is not identi ied with abdominal ultrasound (Tobin et al. 1999). The optimal treatment for insulinoma is partial pancreatectomy to remove the primary tumor, and if possible, metastatic lesions such as enlarged lymph nodes (Figure 7.20). Greater than 85% of primary insulinomas are single nodules (Steiner and Bruyette 1996). Multiple intrapancreatic masses have been reported in approximately 15% of cases (Mehlhaff et al. 1985; Caywood et al. 1988). The pancreas is

gently palpated for small nodules (less than 1.0–1.3 cm diameter); however, up to 20% are not palpable (Steiner and Bruyette 1996). If a nodule is identi ied, it is removed, paying close attention to the pancreatic vasculature and ductal pattern (Figure 7.20). Diffusely in iltrative lesions diagnosed only by partial pancreatectomy and histopathology have also been described (Kruth et al. 1982; Feldman and Nelson 2004). Random removal of one limb of the pancreas is not recommended because unidenti ied tumors are most often located in the body and no single limb is more commonly affected than another (Siliart and Stambouli 1996). Removal of insulinomas located in the body of the pancreas might be at greater risk of developing severe, lifethreatening pancreatitis and leading to death (Nelson 2015). Caywood et al. (1988), Tobin et al. (1999), and Trifonidou et al. (1998) did not ind any correlation between tumor location and prognosis. Tumor thrombus formation with extension of the tumor into the pancreaticoduodenal vein has been reported and treated successfully with primary tumor removal, venotomy, and thrombectomy (Hambrook and Kudnig 2012). The presence of tumor thrombus did not seem to adversely affect prognosis in this report. Metastases are present in up to 51% of dogs at the time of initial surgery (Steiner and Bruyette 1996). Metastasis is most common to the liver and regional lymph nodes (see Table 7.6 and Figure 7.20), but also to the mesentery, omentum, and duodenum, and has not been reported in the lung (Mehlhaff et al. 1985; Caywood et al. 1988). Multiple suspicious masses seen on abdominal ultrasound correlate poorly with metastatic disease at the time of exploratory surgery (Tobin et al. 1999). Enlarged lymph nodes seen at surgery are also not always due to metastatic disease, and it is therefore not recommended to euthanize animals based on gross lymph node enlargement alone.

Figure 7.20 (a) Insulinoma within the body of the pancreas (black arrow) and enlarged adjacent regional lymph node (white arrow). (b) Excised insulinoma via partial pancreatectomy (black arrow) and excised enlarged regional lymph node (white arrow). (c) Large insulinoma within the body of the pancreas (black arrows) and metastatic liver nodule (white arrow). Table 7.6 Staging for insulinoma. Stage I

Con ined to pancreas

II

Pancreas and regional lymph nodes

III

Distant metastasis (i.e. liver)

During surgery, regional lymph nodes should be removed for staging purposes if they are visible or enlarged, and a liver biopsy should also be taken for staging purposes. Pancreatic blood supply should be preserved, and the pancreas handled gently to minimize postoperative pancreatitis. In selected patients, debulking of gross disease by enucleation of larger liver nodules may be a feasible option, but in many dogs, liver metastasis is diffuse and small, making surgical debulking very dif icult. Studies have shown that survival can be prolonged in dogs that receive tumor debulking and medical management compared to dogs receiving medical treatment only (Tobin et al. 1999; Polton and Brearley 2007). Close monitoring of blood glucose is essential with this treatment regime (Siliart and Stambouli 1996). Euthanasia of dogs with stage III disease at surgery is potentially unwarranted because even dogs with widespread metastasis have been managed for up to one year with a combination of medical and surgical management (Polton and Brearley 2007). However, if postoperative clinical signs associated with hypoglycemia are not controlled, or other serious postoperative complications are not controlled with medical management, euthanasia is then appropriate. Potential Complications of Surgery for Insulinoma

Intraoperative complications. The inability to ind a pancreatic nodule is reported in up to 20% of insulinoma cases (Siliart and Stambouli 1996). The detection of a nodule can be facilitated by the use of intraoperative ultrasound, partial pancreatectomy, or methylene blue injection. Elie and Zebra (1995) reported that 3% of dogs will have diffuse pancreatic insulinoma without a speci ic mass, and no predisposition for tumor location within the pancreas (left limb, body, or right limb) has been identi ied (Caywood et al. 1988). Other intraoperative complications include the identi ication of previously unseen metastatic disease, the identi ication of multiple pancreatic tumors (found in up to 15% of cases) (Tobin et al. 1999), and hemorrhage due to disruption of pancreatic or duodenal blood supply, with the potential to cause duodenal or pancreatic devitalization (see above). Postoperative Complications: Postoperative complications following partial pancreatectomy for insulinoma are common. A 12% (3 of 26) perioperative mortality rate has been reported after partial pancreatectomy, due to pancreatitis or sepsis and diabetic ketoacidosis (Tobin et al. 1999). Mehlhaff et al. (1985) and Trifonidou et al. (1998) reported low (8.7 and 10%, respectively) postoperative mortality rates after partial pancreatectomy or enucleation. Leifer et al. 1986 reported a mortality rate of 3 of 40 dogs (7.5%) due to pancreatitis, cardiac arrest, and sepsis. Postoperative pancreatitis occurs in up to 10–43% dogs, particularly following resection of tumors located in the body of the pancreas (Mehlhaff et al. 1985; Trifonidou et al. 1998; Tobin et al. 1999; Feldman and Nelson 2004; Nelson 2015). Approximately 15– 26% of dogs remain hypoglycemic following surgery (Mehlhaff et al. 1985; Caywood et al. 1988; Trifonidou et al. 1998; Tobin et al. 1999) due to inoperable disease or metastatic disease. Recurrent hypoglycemia and the associated recurrence of clinical signs occur in 52–100% dogs (Tobin et al. 1999; Kyles 2003) with the meantime to recurrence and initiation of prednisone treatment being 60 days (Tobin et al. 1999). When hypoglycemia returns, medical management, repeat exploratory surgery, or euthanasia are possible options (Mehlhaff et al. 1985). Diabetes mellitus occurs in 8–35% of dogs due to the prolonged hyperinsulinemia and hypoglycemia resulting in atrophy of normal islet tissue, exacerbated by partial pancreatectomy, further decreasing

insulin reserves (Kyles 2003). Hyperglycemia is usually transient, but can be permanent, and these animals may require long-term insulin therapy. Pancreatic abscesses or pseudocyst formation can occur subsequent to postoperative pancreatitis. Fatal gastric dilation-volvulus has also been reported as a postoperative complication in three dogs (Mehlhaff et al. 1985; Leifer et al. 1986). As such, prophylactic gastropexy may be worth considering at the time of initial surgery in predisposed breeds. Recurrent severe hypoglycemia can result in irreversible brain damage and persistent seizures (Mehlhaff et al. 1985; Feldman and Nelson 2004) as well as a paraneoplastic peripheral neuropathy (see Chapter 13). Prognosis for Insulinoma Treated with Surgery Caywood et al. (1988) reported a MST of 18 months for stage I disease, and an MST of six months for stage II and III disease treated with surgery. Steiner and Bruyette (1996), reported a mean survival time with surgical treatment of 11.5 months for 114 dogs. The overall prognosis is usually guarded as a surgical cure is unlikely to be achieved. However, when insulinoma dogs previously treated with partial pancreatectomy showed relapse of hypoglycemia, treatment with oral prednisolone as adjunctive medical management resulted in an MST of 1316 days (Polton and Brearley 2007). Poor prognostic factors that are reported with insulinoma include the following. Conservative treatment. MST is 74 days with conservative treatment vs. 381 days for partial pancreatectomy (Tobin et al. 1999). Age. Survival time is signi icantly decreased in younger dogs (Caywood et al. 1988). Serum insulin levels. High preoperative serum insulin levels indicate poorer prognosis (Caywood et al. 1988). Higher stage of disease. Stage III insulinomas have MST less than 6 months vs. 18 months for stage I and II disease. About 80% of dogs are alive at 14 months when the disease is con ined to the

pancreas, whereas less than 20% of dogs with metastasis are alive at 12 months (Caywood et al. 1988). Persistent postoperative hypoglycemia. MST is 90 days vs. 680 days for normoglycemic dogs (Trifonidou et al. 1998). Another study followed 49 dogs postoperatively for resolution of hypoglycemia. Persistently, hypoglycemia occurred in 20%, and all of these dogs died within a year of surgery. The MST for all dogs was 561 days. The MST for dogs that had resolution of hypoglycemia was 746 days, with 44% experiencing a relapse by two years, and median overall euglycaemic time of 424 days. Pathological stage was a predictor of persistent postoperative hypoglycemia which, in turn, was a predictor of survival time (Cleland 2020). Clinical stage. Clinical stage in luences the duration of normoglycemia following surgical resection. Dogs with stage I insulinomas maintain normoglycemia for a median of 14 months vs. one month for dogs with stage 2 and 3 disease (Caywood et al. 1988). In another study, dogs with stage I disease and resolution of hypoglycemia had an MST of 766 days vs. 13 days for dogs with stage I disease and persistent hypoglycemia. Dogs with stage 2 disease with resolution of hypoglycemia had an MST of 574 days. Dogs with stage 3 disease with resolution of hypoglycemia had an MST of 379 days vs. 122 days for those with persistent postoperative hypoglycemia (Cleland NT 2020). Tumors with a high mitotic count. These tumors are thought to carry a worse prognosis, although only 11 cases were reported (Dunn et al. 1993). Enucleation. Mehlhaff et al. (1985) reported that enucleation (10 dogs) was associated with a shorter mean survival time than partial pancreatectomy (15 dogs; 11.5 months vs. 17.9 months); however, the number of cases reported was small (see Table 7.5). Paraneoplastic peripheral neuropathy. Dogs with concurrent paraneoplastic peripheral neuropathy or brain damage from chronic hypoglycemia have a guarded prognosis for neurological recovery (Mehlhaff et al. 1985; Kyles 2003), although improvement

in peripheral neuropathy is possible with medical or surgical treatment (Kyles 2003). Gastrinoma Gastrointestinal ulceration (with or without perforation) is common and occurs in 80% of cats and dogs with gastrinomas (Altschul et al. 1997; Simpson and Dykes 1997; Green and Gartrell 1997; Brooks and Watson 1997; Zerbe and Washabau 2000; Feldman and Nelson 2004). Part of the surgical management should involve resection of gastrointestinal ulceration/perforation with treatment of the resultant intra-abdominal sepsis. Gastrinomas are usually solitary, with 60% in the right lobe, 40% in the pancreatic body, and rare involvement of the left lobe (Zerbe and Washabau 2000). Partial pancreatectomy of the right limb can be performed if the tumor is not found due to a high percentage of right limb involvement (Feldman and Nelson 2004). Debulking of disease can be palliative (Zerbe and Washabau 2000; Kyles 2003). Glucagonoma Skin biopsies are required to con irm super icial necrolytic dermatitis (SND), although the diagnosis of SND does not con irm the presence of glucagonoma (Langer et al. 2003). Complete surgical resection of the glucagon-secreting tumor is the treatment of choice. Biopsies of lymph nodes and the liver are taken for staging purposes (as for insulinoma). Palliation of clinical signs can be achieved by surgical debulking of tumor burden (Langer et al. 2003).

Surgery for Exocrine Tumors Carcinoma is the most common tumor of the exocrine pancreas in dogs and cats (Jubb 1993) and is more common than insulinomas. Overall, however, they are very uncommon (less than 0.5% of all tumors) (Withrow 2007a). These tumors originate from either acinar cells or ductal cells (Withrow 2007a). The clinical features can be dif icult to differentiate from pancreatitis in many cases. A palpable abdominal mass is common in cats but uncommon in dogs (Withrow 2007a). These tumors have often metastasized before the appearance of clinical

signs and are therefore usually at an advanced stage when diagnosed (very extensive disease locally and with metastasis). Abdominal effusion is common, and carcinomatosis is seen occasionally (Hecht et al. 2007; Hecht and Henry 2007). The prognosis is extremely poor because of their aggressive nature and resistance to chemotherapy. In one study, the overall MST was only one day but was confounded by the large number of dogs that were euthanized shortly after diagnosis without any treatment. Metastatic disease was detected in 78% of cases at the time of diagnosis (Pinard et al. 2021). The prognosis with treatment remains largely unknown. There are also limited reports of feline exocrine pancreatic carcinomas- with common presenting clinical signs were weight loss, decreased appetite, vomiting, palpable abdominal mass, and diarrhea. The overall MST was 97 days. The median survival times for patients who received chemotherapy or had their masses surgically removed was 165 days, MST for cats with abdominal effusion was 30 days (Linderman et al. 2013). Complete pancreatectomy has been reported to be successful in 78 of 80 normal experimental dogs (Cobb and Merrell 1984). However, the preservation of duodenal blood low in the presence of pancreatic disease is much more dif icult (Cornell and Fischer 2003). In humans, complete pancreatectomy and pancreaticoduodenectomy (Whipple procedure) have a 5–30% operative mortality rate (Withrow 2007a). GJ can be performed as a palliative procedure bypassing an obstructed duodenum (Withrow 2007a). Cholecystoduodenosotomy/cholecystojejunostomy may also be a palliative option if extramural biliary obstruction exists. However, heroic surgical procedures are generally not recommended due to the universally poor prognosis (due to a metastatic rate and the anatomical location of the tumor) and associated high morbidity and mortality (Cornell and Fischer 2003). Other exocrine tumor types include adenoma, lymphoma, squamous cell carcinoma, lymphangiosarcoma, and spindle cell sarcoma (Andrews 1987; Münster and Reusch 1988; Hecht et al. 2007). Panniculitis, polyarthritis, and osteomyelitis have been reported in association with exocrine pancreatic tumors in two dogs (Gear et al. 2006). In both cases, there was no response to medical management,

resulting in euthanasia. Postmortem examination revealed a pancreatic exocrine adenoma in one dog and a pancreatic adenocarcinoma with widespread metastases in the other.

Small Intestine Diagnostic Workup and Biopsy Techniques Radiography, contrast studies, and ultrasonography are commonly employed imaging modalities used in the diagnosis and staging of animals with suspected intestinal neoplasms (Paoloni et al. 2003; Penninck et al. 2003). Based on the high incidence of systemic metastasis, radiographic screening of the thorax via a three-view metastatic series is indicated in any animal suspected of an intestinal neoplasm. Standard two-view abdominal radiographs may identify intestinal gas dilation orad to a soft-tissue density, supporting a diagnosis of an intestinal mass that is causing obstruction of the bowel. Additional radiographic indings can include the presence of free gas or luid within the peritoneum, indicating a potential perforation of the intestinal tract. In one study, 32% (8 of 25) of animals with spontaneous (nontraumatic) pneumoperitoneum had gastrointestinal tract rupture attributable to neoplasia (Saunders and Tobias 2003). Contrast radiographic studies may provide additional information in the detection of annular or intraluminal lesions within the intestinal tract because they more precisely outline narrowing of the lumen at the site of tumor development (Paoloni et al. 2003). Contrast studies may be contraindicated if there is a concern for a ruptured intestinal mass. Ultrasonography has been described as the most effective and least invasive diagnostic modality available in small animals to detect gastrointestinal tumors (Paoloni et al. 2003). Abdominal ultrasound can be particularly useful in differentiating neoplasia from other commonly encountered intestinal diseases such as enteritis (Penninck et al. 2003). In the study by Penninck et al., loss of ultrasonographically detectable intestinal wall layering was predictive for dogs with intestinal tumors. When loss of wall layering was documented, dogs were 50.9 times more likely to have an intestinal tumor compared to

in lammatory conditions within the bowel (Penninck et al. 2003). Another distinct bene it of ultrasound is that it allows for sampling of an intestinal mass with FNA as well as visualization of the abdomen as a whole in the evaluation for regional metastasis. Advanced imaging with CT and MRI can be used in the staging of dogs with intestinal neoplasia; however, studies evaluating the clinical ef icacy of these modalities in veterinary medicine are lacking. Three tissue sampling options exist for small intestinal neoplasms prior to full surgical abdominal exploration. These include FNA, which generally requires ultrasound guidance, endoscopic mucosal biopsies (limited to the duodenum), and laparoscopic-assisted biopsies. FNA cytology has an approximate 95% speci icity and 70% sensitivity when compared with histological diagnoses for intestinal lesions (Bonfanti et al. 2006). Intraoperative cytological impression smears are more likely to agree with histology than FNA. Surgical impression smears are able to facilitate intraoperative decision-making but may not be able to provide a de initive diagnosis prior to an invasive surgical procedure. FNA has a 71% sensitivity for GI lymphoma and 44% sensitivity for smooth muscle tumors as compared to histopathology (Bonfanti et al. 2006). Endoscopy is an important diagnostic tool used for staging the dog or cat with suspected intestinal neoplasia (Willard et al. 2001). However, limitations of this modality must be recognized as de iciencies in technique, instrumentation, and variability between pathological interpretations that can yield inaccurate or uninterpretable results. In two studies, the range of nondiagnostic samples submitted for histopathological assessment was 19–46% in dogs and 21–50% in cats, respectively (Van der Gaag and Happe 1990; Willard et al. 2001). As a result, it is generally recommended that a minimum of eight individual tissue pieces be submitted when performing endoscopic biopsies of the duodenum in dogs and cats (Willard et al. 2001). Differentiation between in lammatory bowel disease (IBD) and intestinal lymphoma (LSA) is essential prior to the initiation of therapy for cats and dogs. Endoscopic biopsy samples have a limited ability to differentiate between these two disease processes in cats. In the study by Evans et al. (2006), endoscopic duodenal biopsies con irmed a

diagnosis of LSA in only 33% (three of nine) of cats that had biopsycon irmed LSA in that region of the bowel. Since the majority of gastrointestinal LSA cases are associated with the small intestine (jejunum and ileum) in cats, full-thickness biopsies are recommended when clinical signs consistent with GI lymphoma are present within this species and FNA has been nondiagnostic (Evans et al. 2006). Laparoscopic-assisted biopsy is another useful technique for the diagnosis of small intestinal neoplasia prior to a full abdominal exploration (Evans et al. 2006; Barnes et al. 2006; Freeman 2009). A standard three-portal laparoscopic technique is used, with one portal placed caudal to the umbilicus and two additional portals placed in paramedian locations, lateral to the third mammary glands. Successful completion of laparoscopic-assisted intestinal surgery in both dogs and cats has also been reported using just a single, specialized port such as the Single Incision Laparoscopic Surgery (SILSTM, Covidien, Mans ield, MA) or EndoConeTM (Karl Storz, Veterinary Endoscopy, Goleta, GA) ports (Case and Ellison 2013). Laparoscopy allows good visualization for full abdominal exploration. Laparoscopic samples can be collected from parenchymal organs such as the liver, spleen, adrenal glands, and pancreas. Laparoscopic-assisted samples can be obtained from the stomach, small intestine, and urinary bladder. Small intestinal and gastric samples are obtained by exteriorizing the tissues to be biopsied through a 4-cm ventral midline incision just cranial to the umbilicus. Samples can then be collected using standard antimesenteric sampling techniques or with the aid of a harmonic scalpel. There is no signi icant difference in the sample quality between tissues collected with the standard open and laparoscopic-assisted techniques (Barnes et al. 2006; Freeman 2009).

Technical Aspects of Surgical Procedure Anatomy A signi icant amount of redundancy exists within the small intestine. The overall intestinal length is relative to animal size and is approximately ive times the trunk length in dogs and cats. The small intestine is about four times the length of the large intestine (Grandage

2003). The jejunum is freely moveable and easily manipulated for resection procedures. The duodenum, on the other hand, has several anatomical constraints that potentially complicate surgical procedures associated with this section of the small intestine. Surgical resections associated with the proximal duodenum are especially challenging because of the association of the pancreatic and biliary systems and particularly the entry of their respective duct systems into the proximal duodenum. The presence of the body and right limb of the pancreas in the mesoduodenum also signi icantly complicates any proposed surgical resections involving the duodenum. The descending duodenum is also relatively immobile because of regional anatomical constraints such as the duodenocolic ligament (Grandage 2003). The arterial blood supply to the small intestine is primarily derived from branches of the cranial mesenteric artery. Branches of this main aortic branch anastomose with the celiac and caudal mesenteric arterial branches in the most orad and aborad portions of the small intestine, respectively. The jejunum is entirely supplied by cranial mesenteric arterial branches (Grandage 2003). The venous return from the small intestine is through the portal vein. The portal vein is composed of four visceral branches in the dog. These include the cranial mesenteric, splenic, caudal mesenteric, and the gastroduodenal branches (Grandage 2003). The majority of the small intestine is drained by the cranial mesenteric branch. The pylorus, duodenum, and right limb of the pancreas are drained by the gastroduodenal and the large intestine is drained by the caudal mesenteric branch of the portal vein (Grandage 2003). Lymphatics from the duodenum and jejunum drain into paired hepatic lymph nodes (adjacent to the portal vein) and the pancreaticoduodenal nodes at the origin of jejunal arteries (Grandage 2003). Lymphatics from the ileum drain into multiple colic lymph nodes and jejunal nodes (Bezuidenhout 1993). For staging purposes, mesenteric lymph nodes should be biopsied with any lesion of the small intestine, regardless of size (Crawshaw et al. 1998). For any surgical procedure involving the gastrointestinal tract, it is highly advised to follow the Halstedian principles of uncomplicated

tissue healing (Webster 1955). These include minimization of tension, maintenance of blood supply to the surgical site, minimization of contamination, and gentle tissue handling (Webster 1955). Repeated moistening of visceral tissues is necessary to minimize desiccation and resultant in lammation and adhesion formation. Tension is generally not a concern with surgical procedures involving the jejunum because it is freely moveable. Tension, however, can be an issue with procedures associated with the duodenum because of its relatively ixed location in the right paralumbar region. The area of the proximal duodenum must be respected at all times. This is an extremely dif icult area for resection procedures for several reasons. First, special attention must be paid to the location of the major duodenal papilla because of the entry of the bile duct and pancreatic ducts in both dogs and cats. In cats, the pancreatic duct entering the major duodenal papilla is the only source of pancreatic drainage in 80% of animals (Grandage 2003). It is therefore essential to prevent obstruction with surgical procedures in this species. If the major duodenal papilla is compromised in cats, then life-long exocrine pancreatic enzyme supplementation is required. In dogs, the minor duodenal papilla is most often the primary entry point for pancreatic secretions; therefore, the major duodenal papilla can be excised and normal exocrine pancreatic function will be maintained in most dogs (Grandage 2003). Because of the close association of the proximal duodenum with the body and right limb of the pancreas and their shared blood supply, excision of the duodenum without signi icant compromise of the pancreas is tedious and risky. Technical Options Segmental resection of the small intestine is performed in a standard manner, whereas there are several surgical options for intestinal anastomosis. If the affected area of small intestine involves a loop of jejunum, then there are no anatomical constraints associated with the procedure. The affected area of small intestine is isolated and packed off from the remainder of the abdomen with laparotomy sponges. The vasculature to the area of intestine to be removed is identi ied and ligated using hemostatic clips, electrothermal coagulation, or encircling

ligatures. The mesentery is then incised approximately perpendicular to the long axis of the bowel, leaving as much mesentery intact as possible to facilitate closure of the mesenteric defect at the conclusion of the procedure. Intestinal contents are then milked away from the area of transection. Noncrushing (i.e. Doyen) tissue clamps are placed approximately 1–2 cm away from the incision line on the tissue that will remain following anastomosis. The gross margins of the neoplasm are identi ied. The transection of the intestine is performed a certain distance from the palpable edge of the tumor on either side (orad, aborad, and mesenteric). In a study looking at the length of intestines required to achieve complete excision, all nonlymphoma tumors (carcinomas and sarcomas) had complete margins at 3 cm from the palpable edge of the tumor, 95% at 2 cm, and 76% at 1 cm in formalinixed canine intestines (Morris 2019a). Considering that the canine small intestine contracts by about 26% on average, but up to 36%, after resection and formalin ixation (Clarke 2014), it is appropriate to recommend a transection that is performed with 5 cm margins of normal intestine on either end of the mass in vivo in the dog. A similar study done in cats concluded that seven of the nine intestinal carcinomas had complete margins with histological margins of 4 cm in orad and aborad directions. Two of two sarcomas and had complete margins with 4 cm histological margins in orad and aborad directions and two of two mast cell tumors had complete margins with 5 cm histological margins (Morrice 2019b). No data exists regarding the amount of contraction of the feline small intestine after resection and ixation. If similar to the dog, the recommendation is to transect the small intestines 6–8 cm orad and aborad to the palpable edge of the tumor in vivo in cats. The cut edges of the remaining intestine are then placed in close proximity to one another and the anastomosis is performed. Several options exist for anastomosis of the intestine following the resection procedure. Hand-sewn anastomoses are most commonly performed. They are generally straightforward and require no specialized instrumentation. One-layer appositional suture patterns are recommended for small intestinal anastomoses. This can be performed using either a simple interrupted or continuous pattern.

Simple Interrupted Intestinal Anastomosis For the simple interrupted hand-sewn technique, the mesenteric suture is placed irst, followed by a single suture placed at 180° from the irst suture (placed along the antimesenteric border). Two additional sutures are then placed at the midpoint between the mesenteric and antimesenteric sutures. Additional sutures are then equally spaced out along the circumference of the intestine at 2–3 mm intervals and 2–3 mm from the cut edge of the intestine. Sutures must engage the submucosa layer. Once all sutures have been placed, the intestinal lumen can be occluded with the opposed ingers of an assistant 4–5 cm away from the anastomosis, and the surgical site is leak tested using sterile saline. Saline is injected into the antimesenteric surface of the intestinal lumen using a 25-ga needle and an appropriately sized syringe. The injection is continued until modest pressure is created at the anastomosis. If additional pressure is needed, the area between the inger occlusion can be carefully pressed between the index inger and thumb of the surgeon. Special attention is paid to the mesenteric border as this is the most common area of leakage because of poor visualization associated with mesenteric fat deposits. Careful dissection of the mesenteric fat along the mesentery can be performed in order to improve the precision of suture placement in this region. It should be noted, however, that excessive intraluminal distension, beyond the bursting strength of the anastomosis, can result in leakage. The volume of saline required to achieve physiologic intraluminal peristaltic pressure (34 cm water) is 16–19 ml in a 10-cm segment of jejunum when the occlusion is created digitally and 12–15 ml with Doyens in dogs weighing 7–25 kg (Saile 2010). Once the anastomosis is completed, the mesenteric defect is then closed using a mono ilament absorbable suture material. During mesenteric closure, iatrogenic trauma to the segmental intestinal vasculature must be avoided. For the simple continuous sutured anastomosis, sutures are placed at the mesenteric and antimesenteric margins as described for the simple interrupted pattern. The free suture tag is, however, left long so that it can be tied to the advancing continuous pattern from the suture placed at 180° from its location. Full-thickness suture bites are then taken at 2–3 mm intervals until one-half of the intestinal lumen has been closed.

Once the continuous pattern has advanced to the level of the previously placed suture at 180° from its origin, the suture is tied to the long suture tag. This process is continued for both sides of the intestinal lumen. Following completion of the anastomosis, leak testing can be performed as described for the simple interrupted pattern (Weisman et al. 1999). As an alternative to the hand-sewn technique, the intestinal anastomosis can be performed using 4.8 × 3.4 mm surgical skin staples. The primary advantage of this stapling technique is the rapidity with which the procedure can be performed. Stapled small intestinal anastomoses are performed in approximately one-seventh time as simple interrupted hand-sewn anastomoses (Coolman et al. 2000b). The technique begins with the placement of three stay sutures placed at equal distances, beginning at the antimesenteric margin. An assistant creates tension between adjacent stay sutures, and staples are placed at 3 mm intervals for a total of 12–15 staples. No differences are reported in complication rates between hand-sewn and skin staple anastomoses (Coolman et al. 2000b). An additional alternative to the end-to-end appositional anastomosis is a functional side-to-side anastomosis, which is performed using GIA and TA stapling devices (interestingly sometimes referred to as functional end-to-end stapled intestinal anastomoses [DePompeo 2018; Sumner 2019]). The resection procedure is performed for any small intestinal anastomosis. Once resection is complete, stay sutures are placed in the mesenteric border of the transected intestinal segments and the antimesenteric borders of the two cut ends of the remaining intestines are placed adjacent to one another in a parallel position (Figure 7.21a). The GIA stapler is advanced into the lumen of each small intestinal ori ice (Figure 7.21b). The stapler is then ired, which creates a large stapled side-to-side anastomosis between the two lumens. At this point, a common lumen has been created between the two intestinal loops with the free end remaining open. The GIA stapler is then removed and an appropriately sized TA stapler (TA-55 with blue cartridge usually suf ices) is used to close the free end of the common lumen (Figure 7.21c). An anchoring suture is always placed at the end of the anastomotic staple line (often referred to as the crotch of the GIA

staple line [Sumner 2019]) because this region is under the greatest amount of tension (Figure 7.21d). The mesenteric defect is then closed. Oversewing the transverse staple line (where the TA was used) is associated with a reduced occurrence of postoperative dehiscence (Sumner 2019). Leak testing can then be performed using sterile saline as previously described (Ullman et al. 1991). Occasionally, signi icant luminal size disparity is created between the oral and aboral portions of the small intestine, especially if the intestinal mass has created a chronic partial obstruction or an anastomosis is being performed between the small intestine and the colon. If this is the case, then several surgical maneuvers are available to address luminal disparity. If small disparities exist, then differential spacing of sutures can be performed between the larger and smaller lumens. Smaller bites are taken between sutures of the smaller lumen than between bites of the larger lumen. Transecting the smaller lumen bowel at an angle away from the mesenteric margin can also be used to rectify luminal disparities. More tissue is removed from the antimesenteric border than the mesenteric border. If larger disparities exist, then differential suturing can be combined with spatulation of the smaller lumen. Spatulation is accomplished by making a longitudinal incision along the antimesenteric border of intestinal lumen. Finally, luminal disparities can be eliminated by partial closure of the antimesenteric border of the larger intestinal segment, followed by routine completion of the handsewn anastomosis.

Figure 7.21 (a) Intraoperative image of a dog undergoing a functional end-to-end anastomosis of the jejunum secondary to an intestinal adenocarcinoma. The mass has been resected with 5 cm margins, and the luminal ends have been occluded with atraumatic tissue clamps. The antimesenteric intestinal borders are apposed in preparation for insertion of the GIA stapling device. (b) The GIA stapling device has been inserted into the apposed intestinal segments. Preplaced stay sutures facilitate proper alignment of the bowel in preparation for discharging the stapling device. (c) A TA stapling device is then positioned across the open stoma and ired to complete the functional end-to-end anastomosis. Take care to ensure that all tissue layers of both of the terminal ends of the stoma re-included in the staple line. (d) Intraoperative image of the completed stapled anastomosis. Anchoring suture(s) must be placed across the base of the anastomosis (black arrowheads) in order to reinforce the staple line. This region is prone to tension, which can result in disruption of the staple line. Source: Images courtesy of Dr. Pam Schwartz.

Anastomosis Augmentation Techniques Surgical site reenforcement is regularly performed to promote rapid and uncomplicated healing. The two most commonly performed procedures are omental and serosal patching. The omentum promotes healing by providing a source of additional blood low and lymphatic drainage (Hosgood 1990). Increase in blood low to the surgical site helps to control infection if compromised blood low results from the disease process or surgical procedure. Following completion of the intestinal anastomosis, the omentum is wrapped around the surgical site. Several partial-thickness sutures may be used to facilitate adherence of the omentum to affected region of bowel. Lengthening of the omentum can be performed based on the right or left gastroepiploic artery/vein (Hosgood 1990). Alternatively, an omental pedicle extension technique can be used; however, this is rarely indicated during routine intestinal procedures for neoplasia (Ross and Pardo 1993). Serosal patching is another useful technique for reinforcement of surgical incisions involving the gastrointestinal tract. Serosal patching

involves the mobilization of a portion of the freely moveable jejunum. The procedure generally involves the placement of two separate loops of jejunum directly over the surgical site. Either a simple interrupted or continuous suture pattern using 3-0 or 4-0 absorbable mono ilament suture material is placed between the seromuscular layers of the two pieces of intestine directly over the surgical site. This is repeated until two sections of normal jejunum have been sutured over the surgical site (Crowe 1984).

Aftercare The intensity of postoperative management will vary greatly based on the preoperative status and intraoperative (i.e. septic peritonitis secondary to ruptured intestinal mass) indings within the clinical patient. Aftercare involves attention to several different facets of the patient’s status. Consideration of the patient’s preoperative nutritional status should be used to determine whether or not supplemental enteral nutrition would be required in the postoperative setting. Indications for immediate assisted (enteral) feeding because of malnutrition include prolonged anorexia (i.e. longer than 48 h), weight loss of greater than 10% of body weight, inadequate muscle mass, and low albumin concentration (i.e. less than 2.5 g/dL in cats or less than 2.1 g/dL in dogs) (Rasmussen 2003). Animals suffering from septic peritonitis as a result of a ruptured intestinal mass should also be considered ideal candidates for intraoperative feeding tube placement. This author generally prefers GJ feeding tubes in cases of extensive bowel resection or in patients with peritonitis. The bene it of GJ tube feeding includes dual lumen access to both the stomach and small intestine, yet operative morbidity is minimized since only a gastric incision is required for tube placement (Cavanaugh et al. 2008). Gastroparesis is common after intestinal surgery, and gastric decompression in the early postoperative period improves patient comfort and facilitates a reduction in nausea and vomiting, which if not alleviated can result in aspiration pneumonia in severely debilitated animals. If signi icant impairment in gastric motility is present, GJ tubes allow feeding to commence through the jejunostomy component (J tube) of the tube

system while the gastric dysfunction is monitored (gastric residual luid volume is quanti ied every 4–6 h by aspirating the gastric component of the tube system) and managed (motility medication is titrated based on trends in calculated residual volumes). With the GJ-tube system, J-tube feedings are generally initiated within 12 h of surgery using a continuous rate infusion of a commercially available lique ied diet. The required energy requirements (resting energy requirement [RER] = 30 × B.W. [kg] + 70) are calculated and then initiated at 25% of the patient’s need. Supplementation rates are generally doubled every 24 h if the patient is tolerating feeding. We caution exceeding 75% of the RER through the J tube as this will commonly precipitate vomiting due to an inability to handle this volume of luid through the small intestine. Solitary placement of gastric or enterostomy feeding tubes can also be extremely useful in the management of animals recovering from treatment of an intestinal neoplasm. Clinical variables such as the procedure to be performed, anticipated outcome, and preoperative status should be assessed to decide which type of feeding tube would ultimately meet the needs of the individual patient. A comprehensive description of the surgical technique for placement of these feeding tubes can be found in the gastric neoplasia section of this text. Postoperative monitoring of serum biochemical and objective clinical parameters is important to ensure that recovery is progressing uneventfully. Animals undergoing elective treatment of an intestinal mass will generally need nothing more than supportive care (i.e. maintenance luid therapy and appropriate analgesia) for 24–48 h after surgery. On the contrary, animals presenting with septic peritonitis or with signs consistent with intestinal obstruction may need intensive monitoring and treatment in the postoperative period. Daily evaluation of serum electrolytes and renal values allow objective interpretation of the animal’s hydration status. Monitoring of blood albumin and TP levels will be useful in assessing the need for colloidal supplementation in the form of intravenous hydroxyethyl starch therapy (Hespan; B. Braun Medical Inc., Melsungen, Germany) or fresh frozen plasma transfusion. Severe protein de iciencies may require transfusions of human or canine albumin in order to control clinical signs and facilitate wound

healing while protein de iciencies are replaced through enteral nutritional supplementation. Although controversial, clinical studies have found that systolic blood pressure, serum albumin, and total solid levels are signi icantly increased with albumin administration and that human albumin is safe to be administered to dogs (Mathews and Barry 2005; Trow et al. 2008). Owners should always be counseled of the risks of albumin transfusion, however, as serious hypersensitivity (acute and delayed) reactions have been reported in both healthy and hypoalbuminemic dogs (Yamaya et al. 2004; Francis et al. 2007; Cohn et al. 2007). As an alternative to albumin, some clinicians will use plasma transfusions to combat hypoperfusion and hypoalbuminemia. It should be known, however, that the effects of plasma administration on serum albumin and colloid osmotic pressure in critically ill dogs has not been reported, and the cost to effectively increase serum albumin in the clinical patient may be cost prohibitive, as a plasma dosage of 22.5 ml/kg may be required to increase serum albumin by 0.5 g/dL (Mazzaferro et al. 2002; Trow et al. 2008). For most intestinal procedures, a irst- or second-generation cephalosporin is prescribed perioperatively; however, antibiotics are not indicated in the postoperative period unless active infection is identi ied at the time of the surgical procedure. Daily monitoring of blood glucose is useful to establish trends toward hypoglycemia. If hypoglycemia is present, concern for intestinal dehiscence should be raised as septicemia commonly results in this inding. Trends in the patient’s body temperature, abdominal comfort, and intraabdominal luid volume are also useful to assess healing because pyrexia, pain, and an increase in luid volume could be indicative of intestinal-mediated surgical complications. Shifts in the immature white blood cell lines (development of a degenerative left shift) within the irst two to ive days after surgery can also be an early indicator of intestinal dehiscence precipitating septic peritonitis.

Functional Outcome – Potential Complications Dehiscence

Dehiscence, resulting in septic peritonitis, is the most signi icant postoperative complication associated with small intestinal resection procedures. Dehiscence generally occurs within three to ive days of the surgical procedure. This is based on the lag phase of wound healing when the strength of the anastomosis is at its lowest point. Strength of intestinal healing approaches 100% of normal by 10–17 days (Coolman et al. 2000a). Reported rates of intestinal dehiscence range between 7 and 16% (Brown 2003; Duell 2016; DePompeo 2018; Davis 2018). The rate of dehiscence associated with small intestinal surgical procedures for neoplasia has been reported to be approximately 12% (Allen et al. 1992). Reported clinical factors contributing to an increased rate of dehiscence include poor preoperative nutritional status, generalized peritonitis at the time of the surgical procedure, and advanced age of the patient (Coolman et al. 2000a). Surgical factors affecting healing include poor intestinal blood supply or iatrogenic trauma to the anastomosed segment of bowel, excessive tension on the anastomosis, and inappropriate choice of suture material (Allen et al. 1992; Coolman et al. 2000a). In the study by Ralphs et al. (2003), dogs with two or more of the following factors were predicted to be at high risk for developing anastomotic leakage: Preoperative peritonitis, intestinal foreign body, and serum albumin concentration of 2.5 g/dl or less. Other clinical studies have not substantiated hypoalbuminemia as a risk factor for wound healing after intestinal surgery (Harvey 1990; Shales et al. 2005; Depompeo 2018). One study found no difference in the rate of dehiscence between stapled (11%) or hand-sutured (16%) anastomoses (Duell 2016) whereas another study found that dehiscence was signi icantly less with anastomoses performed with stapling devices than sutured (5% vs. 13%) (DePompeo 2018). In the presence of septic peritonitis or if surgery is performed because of a previous intestinal anastomosis dehiscence, stapling anastomosis is less likely to dehisce (29% dehiscence with handsewn anastomosis in presence of peritonitis) (Davis 2018; DePompeo 2018). Mortality rates up to 74% are reported following generalized peritonitis from intestinal dehiscence (Allen et al. 1992; Brown 2003). In the more recent veterinary literature, survival rates of 70 and 71% have been reported in dogs with septic peritonitis when either active peritoneal or

open peritoneal drainage is incorporated into the management of these animals, respectively (Mueller et al. 2001; Staatz et al. 2002). Stricture Dysfunctional stricture following small intestinal resectionanastomosis is rarely a problem with appositional suture patterns. The primary argument for appositional suture pattern techniques is avoidance of stricture. Apposition of the submucosal vascular plexus promotes wound healing without stricture formation. Inverting suture patterns are associated with the greatest decrease in lumen size at the anastomosis site (Ellison 1989). Everting suture patterns increase adhesion formation, lead to mucosal ischemia, and prolongation of the in lammatory (lag) phase and therefore should be avoided during the generation of an intestinal anastomosis (Ellison 1989). Impaction at the anastomosis site was identi ied months or years after surgery in 3 of 87 dogs that had functional end-to-end stapled anastomosis, either from stricture or entanglement with the exposed regions of staples in the intestinal lumen (DePompeo 2018). Recurrence Large-scale studies evaluating the local recurrence rate of gastrointestinal tumors have not been performed. In general, the rate of recurrence is dependent on the tumor type and its location within the intestinal tract. Local recurrence is generally not a problem with jejunal masses because wide surgical margins are generally easily attained. Local recurrence is more likely with ductal sparing (i.e. bile and pancreatic ducts) procedures associated with the proximal duodenum; however, this can be circumvented with the use of more aggressive excisions (see GJ procedure [Billroth II] earlier in this chapter). The potential morbidity and mortality associated with more aggressive excisions, such as a Billroth II, must be considered in the decisionmaking. Mechanical and Physiological Complications Short bowel syndrome (SBS) can occur with aggressive small intestinal resections. Clinical signs include diarrhea, steatorrhea, malnutrition,

and weight loss. Gut adaptation occurs over time through increases in enterocyte number and size, increased villus height and crypt depth, and intestinal diameter (Brown 2003). Intestinal villi increase the surface area of the intestinal lumen by approximately eight times in dogs and 15 times in cats (Brown 2003). Experimentally, several surgical procedures to treat SBS have been described. These include construction of intestinal valves, interposition of reversed intestinal segments, colonic interposition, and reversed electrical intestinal pacing (Brown 2003). None of these have been successfully used in a clinical setting. Maintenance of the ileocolic component of the ileocecal valve is thought to be important to minimize clinical signs associated with SBS in dogs or cats with extensive intestinal resections. In the study by Gorman et al. (2006), risk factors (age of patient, percentage of intestine removed, underlying disease) for the development of complications after extensive small bowel resection were evaluated. No risk factors were identi ied and 12 of 15 (80%) of the dogs and cats that underwent extensive small bowel resection were reported to have good long-term outcomes (Gorman et al. 2006). Postoperative ileus is common after intestinal surgery and generally occurs within the irst 24 hours of the postoperative period. Factors that promote the development of ileus include extensive intestinal manipulation, long operative time, and extensive tissue resection (Brown 2003). When present, ileus should be aggressively managed using injectable motility modifying agents and antiemetics such as metoclopramide, maropitant, and ondansetron. Length Limits to Intestinal Resection The minimum length of small intestine required for survival with oral nutrition alone is unknown in dogs, however, up to 75% of the small intestine can often be removed without resultant clinical signs. Jejunal resection is better tolerated than removal of the ileum, and preservation of the ileocolic valve is important in prevention of bacterial overgrowth. Experimentally, 20% of dogs have survived for over one year with 70–90% of their intestines removed (Yanoff et al. 1992). Unfortunately, risk factors for the development of SBS in dogs and cats undergoing extensive intestinal resection have not been

identi ied. As a result, owners should be warned of the potential for development of this syndrome when greater than 50% of the small intestine is planned to be removed (Gorman et al. 2006).

Common Tumors and Prognosis Four general categories of tumors occur within the small intestine. These include epithelial, smooth muscle (mesenchymal), neuroendocrine, and round cell neoplasms (Selting 2007). Lymphoma is generally reported as the most common intestinal neoplasm, comprising approximately 30% of all feline tumors and 6% of all canine tumors (Selting 2007). Nonobstructive lymphomatous intestinal disease is generally managed medically, and prognosis and treatment recommendations vary depending on the tumor subtype. Although controversial, solitary obstructive lymphomatous lesions can be effectively managed with surgical excision. If obstruction is suspected but not con irmed clinically (i.e. patient is not showing severe intestinal signs), trial treatment with chemotherapy can be attempted and an objective clinical response can be measured with serial abdominal ultrasound exams. If the tumor does not respond to chemotherapy or if progressive disease or perforation is documented, then surgical excision is warranted. Surgery may have a role in cats with discrete intermediate/high-grade gastrointestinal lymphoma; in one study, cats that had a resection followed by CHOP-based adjuvant chemotherapy had a median disease-free interval of 357 days and a median overall survival time of 417 days (Gouldin 2017). Achieving incomplete margins when excising LSA is common, particularly in cats (Morrice 2019b). Importantly, cats with alimentary lymphoma do not appear to be at high risk of postoperative dehiscence after full-thickness GI surgery (Smith 2011). When a large tumor burden is present, owners should be counseled about the possibility of intestinal perforation if a rapid response to chemotherapy is elicited. Adenocarcinoma (ACA) is the most commonly treated intestinal tumor in dogs and cats but is reported to be the second most common tumor type to occur within the bowel (Selting 2007). Approximately 40% of adenocarcinomas have metastasized at the time of surgical exploration. These tumors primarily metastasize to regional lymph nodes; however,

other commonly reported sites of metastasis include the liver, peritoneum, mesentery, and omentum. In dogs, the overall prognosis for surgically treated small intestinal ACA is 7–15 months with localized disease and three months with metastatic disease (Birchard et al. 1986; Crawshaw et al. 1998; Paoloni et al. 2003). Untreated dogs have been reported to have a mean survival time of 12 days (Selting 2007). In the study by Crawshaw et al. (1998), when lymph nodes were negative for metastasis, the one-year survival rate was reported to be 66.7% compared to 20% if documented lymph node metastasis had occurred. In contrast, the study by Smith et al. (2019) did not identify lymph node metastasis as a negative prognostic indicator and reported an MST of 544 days (95% con idence interval, 369–719 days) with oneand two-year survival rates of 60 and 36% of the tumor was surgically excised. Age was the only independent predictor of survival in that study with dogs younger than eight years old having signi icantly longer median survival times (1193 vs. 488 for dogs ≥8 years) (Smith et al. 2019). Nonetheless, it is still recommended to sample regional lymph nodes (if they are accessible) prior to surgery with ultrasoundguided needle aspirates so that as many variables as possible can be integrated into the establishment of a prognosis prior to more invasive treatment. Regional lymph nodes should also be biopsied at the time of de initive surgery for disease prognostication, and sampling should be performed even if the lymph nodes appear grossly normal. Currently, the therapeutic value of regional lymphadenectomy at the time of primary tumor excision is unknown, and this procedure is generally not recommended due to its potential for associated morbidity (Crawshaw et al. 1998). In surgically treated cats with intestinal ACA, reported survival times range from 20 weeks (median) to 15 months (mean) (Turk et al. 1981; Kosovsky et al. 1998). The reported survival time of untreated cats with intestinal ACA is approximately two weeks (Birchard et al. 1986; Kosovsky et al. 1998). Mesenchymal neoplasms of the gastrointestinal tract have recently been divided into GISTs and leiomyosarcomas (GILMs). GISTs are most commonly identi ied in the cecum and large intestine, and GILMs occur more commonly in the stomach and small intestine. GISTs have a higher rate of intestinal perforation but increased long-term survival times when compared to GILMs (Maas et al. 2007). No perforations have been

reported with GILMs. The higher perforation rate for GISTs is thought to be a result of their typical cecal location, which leads to delayed development of clinical signs as compared to more orad positioned neoplasms. GISTs are composed of a high percentage of interstitial cells of Cajal, which regulate intestinal motility. These tumor types are differentiated based on immunohistochemistry. In one study, a MST of 37.4 months was reported for dogs with GISTs (cecum and large intestine) and 7.8 months for dogs with GILMs that survived perioperative period (Russel et al. 2007). Another study did not show a signi icant difference in survival rates between GILMs or GISTs and with both tumor types; approximately 80% of dogs were tumor free at one year and 65% at two years (Maas et al. 2007). Feline gastrointestinal mast cell tumors are uncommon, accounting for just 4% of all intestinal neoplasms in cats, compared with the more common lymphoma and adenocarcinoma. Metastasis to mesenteric lymph nodes is common, and metastasis to the liver or spleen may also occur. In one study of 31 cats, therapeutic approaches included chemotherapy alone (n = 15), surgery and chemotherapy (n = 7), glucocorticoid only (n = 6) and surgery and glucocorticoid (n = 3) (Barrett 2018). Overall MST was 531 days. Surgical and medical treatments (including prednisolone alone) were both associated with prolonged survival times (Barrett 2018).

Adjuvant Therapies There is no evidence of bene it associated with the administration of chemotherapy in animals suffering from epithelial- or mesenchymalbased neoplasms. Chemotherapy is generally also not thought to be helpful in humans with small intestinal neoplasia (Stanclift and Gilson 2004; Smith 2019). Nonsteroidal anti-in lammatories also did not improve survival in dogs with small intestinal adenocarcinoma (Smith 2019). Medical treatment with tyrosine kinase inhibitors and imatinib mesylate (Gleevec) is being explored in people with GIST. A partial response is observed in approximately 50% of human cases treated with Gleevec (Maas et al. 2007). Tyrosine kinase receptor inhibitor

therapy has recently received a great deal of attention in veterinary medicine. Toceranib (Palladia) has been shown to have biological activity against GISTs in dogs. In one study, ive of seven dogs with gross disease experienced a clinical bene it (three complete responses, one partial response, one stable disease). Median PFI in dogs with gross disease was 110 weeks (Berger 2018). The role of Toceranib for the management of dogs with GISTs still remains to be fully worked out.

Colorectal Tumors Clinical Workup and Biopsy Principles During a complete physical examination of dogs with colorectal tumors, abdominal palpation may identify a palpable abdominal mass in some cases. During a digital rectal examination, the tumor is often palpable as most colorectal tumors in dogs are located 2–8 cm from the anus; stenosis may be felt if the tumor growth is circumferential. In rare cases, what appears to be a palpable anorectal stricture on rectal examination may actually be the result of anorectal spastic contraction. This condition may occasionally be seen in German shepherd dogs and disappears under general or epidural anesthesia (Niebauer 1993). It is important during palpation to identify in iltrative tumors. As the normal rectum is freely movable, full-thickness wall in iltration may render the rectal tube to be variably ixed to the surrounding tissues. In iltration may be caused by the primary rectal tumor (most commonly an adenocarcinoma) that subsequent to full-thickness growth into the intestinal wall, invades surrounding tissues; as an alternative, the rectum may be secondarily invaded by tumors arising from pelvic organs (most commonly the prostate gland; see Chapter 10). During digital rectal examination, the sublumbar lymph nodes are also palpated to detect any enlargement. Colorectal tumors can primarily spread to sublumbar and colic lymph nodes, the latter located in the mesocolon. The term sublumbar refers to all lymph centers present in the sublumbar region: The iliosacral lymph center (which includes the medial iliac, internal iliac, and sacral lymph nodes) and the

iliofemoral lymph nodes (Bezuidenhout 1993; Llabrés-Diaz 2004; Majeski et al. 2017; Pollard et al. 2017). The sublumbar lymph nodes draining the anus, rectum, and colon are the internal iliac (ventral to the sixth or seventh lumbar vertebrae and adherent to the external and internal iliac arteries, medial to the external iliac arteries) and the medial iliac lymph nodes (paired and sometimes double, ventral to the ifth and sixth lumbar vertebrae, between the deep circum lex and external iliac arteries, lateral to the latter). These lymph nodes, if enlarged, may be variably felt, depending on both their size and the dog’s size. Cytology samples from these lymph nodes may be collected transrectally using a long 22-gauge spinal needle coaxial to the index inger and interposed between a surgical rubber glove and the inger part of another glove on the same index inger. The animal may need to be sedated for the procedure. After manual evacuation of any feces from the caudal rectum, the lubricated index inger is introduced into the rectum and advanced until it reaches the caudal pole of one of the enlarged lymph nodes. The needle is introduced after passing it through the needle-protecting inger-glove irst and the entire thickness of the intestinal wall second. The stylet is removed, a 3–5 ml syringe is connected, and aspiration is performed (Figure 7.22). Slides are prepared in a routine manner. Complications of this procedure are very rare and are generally related to small-sized lymph nodes and inadvertent puncture of blood vessels. In larger dogs, these lymph nodes may not be palpated when they are enlarged only slightly. Alternatively, a transabdominal ultrasound-guided FNA can be performed. During a complete laboratory workup (blood, urine), possible changes seen are anemia (usually microcytic hypochromic due to chronic blood loss or normocytic normochromic in chronic disease), thrombocytopenia, hypoproteinemia (chronic bleeding) or hyperproteinemia (paraneoplastic) (Trevor et al. 1993), hypoglycemia (Bagley et al. 1996), and erythrocytosis (Sato et al. 2002). Paraneoplastic leukocytosis (left shift neutrophilia, monocytosis, and eosinophilia) has been reported in dogs in association with a rectal adenomatous polyp (Thompson et al. 1992; Knottenbelt et al. 2000a)

Biopsy samples may be collected using one or more of these procedures. 1. For super icial tumors that are very friable and palpable with a rectal exam, a sample can sometimes be obtained, without anesthesia, by fracturing the tumor with the inger, by gently strumming the tumor. Bleeding may be a concern with this technique; another disadvantage is the sample may not be representative of the entire tumor because the biopsy may be too super icial (Valerius et al. 1997; Morello et al. 2008; Nucci et al. 2014; Adamovich-Rippe et al. 2017). Less often, after the mass has been prolapsed through the anus, a sample may be obtained with a blade. 2. A needle core biopsy (Tru-Cut needle) may be obtained through the anus after rectal eversion by traction on four stay sutures applied 1–2 cm cranially to the anorectal line (Figure 7.23). This procedure requires anesthesia (performing an epidural can be helpful). 3. As an alternative, an incisional biopsy may be performed. This procedure requires anesthesia (including an epidural). Biopsies of rectal tumors by themselves do not yield any information regarding the large intestine cranial to the lesion. 4. Endoscopic examination (proctocolonoscopy) is highly advised. Proctocolonoscopy allows to evaluate the entire large intestines and to characterize the tumor (single or multiple lesions, position, size, length, and circumferential extension) (Figure 7.24a–c) and to obtain a biopsy. One limitation of biopsies obtained by endoscopy is it procures only super icial samples. Therefore, endoscopic biopsies can sometimes be inadequate and for this reason, histology should always be repeated after de initive tumor excision (Valerius et al. 1997; Morello et al. 2008; Nucci et al. 2014; Adamovich-Rippe et al. 2017). This is especially important for colorectal adenocarcinoma, in terms of both depth of wall in iltration (from mucosa, submucosa to muscularis), and histological differentiation (Morello et al. 2008; Adamovich-Rippe et al. 2017) (see later). The large intestine cranial to the lesion is

also inspected for multiple tumors; however, in one study evaluating rectocolonoscopy in 82 dogs, no further tumors orad to the caudal neoplasm were found, even in cases of multiple epithelial masses (7.3% of cases). An epithelial tumor was diagnosed in 58 of 64 dogs (benign adenoma or polyp in 71% of cases; carcinoma in situ or adenocarcinoma, 29% of cases; other tumor types were plasmacytoma, lymphoma, and leiomyoma). Based on this study, more cranial lesions should be considered uncommon (Adamovich-Rippe et al. 2017). Annular or diffuse lesions were more likely high-grade adenocarcinoma when compared with pedunculated, cauli lower-like, and sessile tumors (Adamovich-Rippe et al. 2017). Preparation for endoscopy is done by fasting the animal 1.5–2 days before the procedure; drinking is allowed until eight hours before the procedure. The day before the procedure, warm water enemas (10–20 ml/kg twice daily) are performed; inally, the evening before, an osmotic laxative is administered orally to the patient. The complication rate of lexible colonoscopy is very low (mortality rate of 0.28%), and major complications such as fatal aspiration of colon electrolyte solution (used for bowel cleansing prior to colonoscopy), colonic perforation, and excessive hemorrhage after biopsy have been rarely reported (Leib et al. 2004). 5. Another procedure is through a colotomy, only occasionally performed for tumor biopsy. After caudal celiotomy, the colonic lesion is palpated, and the surgical area is packed with laparotomic sponges. For intramural tumors, the lumen may not need to be entered and the biopsy sample is obtained by cutting a wedge of tissue with a blade or a sample is obtained with a punch; suturing of the defect may be attempted but not required for intramural lesions where the lumen was not penetrated. For intraluminal tumors, the colonic wall is incised full-thickness for a few centimeters at the level of its antimesenteric border at a point close to the lesion. The lesion is a visualized and a biopsy sample is obtained. Finally, the colonic incision is closed with some fullthickness appositional simple interrupted sutures using 3-0 or 4-0 absorbable mono ilament material (polydioxanone or

polyglyconate). Any enlarged regional lymph node should be excised or biopsied.

Figure 7.22 Phases of FNA of enlarged sublumbar lymph nodes. (a) After the lymph node has been penetrated by the needle, the stylet is removed, and aspiration is performed. (b) The inger is extracted from the anus, and the material is sprayed on a slide for cytological examination.

Figure 7.23 The rectal mass is exposed by traction on four stay sutures applied full-thickness 1–2 cm cranially to the anorectal line (pull-out). Another stay suture has been applied on the rectal wall close to the caudal margin of the mass in order to facilitate exteriorization. In this particular case, an excisional biopsy was performed (see Figure 7.29f, g) after incision of the mucosal layer, since the tumor was intramural (histology of the biopsy revealed a leiomyosarcoma). After the histological result was known, a colorectal resection was performed (Figure 7.42). Source: Buracco (2007). Used by permission.

Figure 7.24 Endoscopic view of (a) a rectal leiomyosarcoma (the same as in Figure 7.23); (b) a rectal adenocarcinoma; and (c) and (d) a 35 cm long 360° colorectal adenocarcinoma ((c): CT view; (d): endoscopic view). Source: Photos in (a) and (b) from Buracco (2007). Used by permission. Endoscopic pictures courtesy of Dr. Caccamo Roberta.

Imaging Techniques Radiography and Contrast Studies At present, radiography and contrast studies have been largely superseded by ultrasonography as it is more effective for evaluating intestinal intramural lesions. However, survey radiographs may identify an abdominal mass (Slawienski et al. 1997) and suggest an obstructive

condition (Figure 7.25a) whereas contrast studies may outline the site of obstruction (Figure 7.25b)

Figure 7.25 (a) Megacolon caused a colorectal adenocarcinoma in a dog; (b) barium enema in a case of colonic lymphoma in a dog showing a illing defect. Ultrasound Ultrasound examination of the abdomen (Myers and Penninck 1994; Rivers et al. 1997; Slawienski et al. 1997; Paoloni et al. 2003; LlbrésDiaz 2004; Arteaga et al. 2014) is considered to be the most appropriate for intestinal malignancies, even though the precise site (small or large intestine) may not be clearly distinguished. Abdominal ultrasonography should always be performed with colorectal tumors,

despite the fact that the bone of the pubis prevents imaging of the rectum in the pelvic canal, therefore potentially resulting in an unremarkable study. Ultrasound may identify areas of localized, irregular thickening of the intestinal wall (more than 4 mm) with loss of delineation of the normal intestinal wall layers, luid and/or fecal material accumulation (obstructive lesion), and/or abdominal lymphadenomegaly (colic, sublumbar) as well as other abdominal abnormalities (mainly involving the omentum, mesentery, and mesenteric lymph nodes). It has been reported that the different tumor histologic types should have distinct ultrasonographic appearance. Diffuse echogenicity is described in the case of adenocarcinoma in most dogs. Ultrasound-guided FNA (with a 22- or 20-gauge spinal needle) or biopsy (with an 18-gauge Tru-Cut biopsy needle) of the lymph nodes as well as of any intestinal lesion, may be attempted transcutaneously. Ultrasound has also been applied rectally with endoscopy to ascertain the wall invasion depth of rectal polypoid lesion in 25 dogs. The lesions were classi ied as invading the mucosa only, the mucosa/submucosa, and the muscularis. The lesions con ined to mucosa were all in lammatory polyps while those extending through the mucosa were all adenocarcinomas (Hayashi et al. 2012). Thoracic Radiography Radiographic evaluation of the thorax (three views: Two lateral, one dorsoventral) is needed to evaluate the presence of lung metastases, although they are rare in these diseases. Contrast‐Enhanced CT and MRI Contrast-enhanced CT and MRI are indicated to detect intrapelvic in iltration of the rectal tumor, determine the extent of the disease, and con irm intrabdominal/sublumbar lymphadenomegaly (Figure 7.24 and 7.26). CT pneumocolonography may also represent a further diagnostic tool (Steffey et al. 2015).

Figure 7.26 (a) Intraoperative view of an in iltrative colorectal adenocarcinoma. This should be recognized before surgery as it represents a negative prognostic factor both for surgery and metastatic spread to regional lymph nodes (in this picture colic lymph nodes – arrow – appear enlarged; at histology they were metastatic). (b, c): CT scan of the same lesion showing both the in iltration and obstruction caused by the tumor (b) and an enlarged sublumbar lymph node (white arrow) (c). (d) The tumor is resected through a combined approach, abdominal irst and then transanal (see also Figures 7.42 and 7.35). The two enlarged colic lymph nodes are visible and resected with the tract of the intestine that is removed. Source: (a) and (b) reprinted with permission from Buracco (2007).

Laparoscopy If laparoscopy is available and in the hands of an experienced operator, it may be useful to inspect the entire abdomen and the sublumbar region as well as to take biopsies.

Surgical Techniques Preparation for Colorectal Surgery A canine experimental study has demonstrated the bene icial role of preoperative mechanical bowel preparation (started 24 hours before surgery with fasting and ingestion of 20 ml of magnesium hydroxide plus 15 ml/kg 10% mannitol orally) in decreasing the early mortality rate due to dehiscence and peritonitis after segmental colectomy and end-to-end anastomosis (Feres et al. 2001). Present recommendations to decrease the risk of intraoperative contamination vary slightly among clinicians, but in general, they include, when possible, a lowresidue diet started from two to three days (Radlinsky 2013b) to one week before surgery and no warm water enema or laxative within the preoperative hours, from 3 to 72 hours (Holt and Brockman 2003; Radlinsky 2013b), if a standard surgical excision is to be performed. The author of this section of the chapter avoids performing an enema within 72 hours before surgery. In the case of obstruction and suspected perforation (the latter mainly in cats with lymphoma), enemas are avoided. In preoperatively debilitated patients, enteral or parenteral nutrition, plasma, or blood transfusion may be considered. Animals are prepared by withdrawing food and water for 12–24 hours and 8 hours before surgery, respectively. Some surgeons, however, allow preoperative access to water until anesthesia begins (Radlinsky 2013b). Preoperative antibiotic therapy started 24 hours before surgery is controversial, but given that the risk of infection is high, antibiotics against anaerobes and gram-negative aerobes may be used. Drugs that decrease colorectal anaerobic bacteria include third-generation cephalosporins, neomycin or kanamycin, metronidazole, and combination neomycin and erythromycin (Holt and Brockman 2003;

Radlinsky 2013b). Cephalosporins are used at induction of anesthesia with subsequent doses every two hours of operative time. Positioning of the patient varies depending on the surgical procedure: Dorsal recumbency is utilized for ventral midline celiotomy (typhlectomy, colectomy, ventral approach to rectum-colon) or sternal recumbency for anal, transanal, and para-anal approaches. For sternal recumbency, the perineal area and the proximal one-third to one-half of the tail are clipped, and manual evacuation of rectum and anal sac contents is performed. Animals are positioned with their perineal area elevated, with the tail bandaged and secured dorsally and cranially, with the hind legs hanging over the padded end of the surgical table (to avoid pressure lesions to both skin and femoral nerves). After tumor resection has been completed, the resection margins are identi ied with China ink staining or other tissue inking systems (Davidson Marking Systems, Bradley Products Inc., Bloomington, MN) and/or with one or more sutures usually placed orad or aborad to the lesion, depending on the resection performed. The specimen is then immersed in neutralbuffered 10% formalin. Surgical instruments and gloves are changed at this stage.

Surgical Procedures Typhlectomy This procedure is indicated for tumors con ined to the cecum. The cecum can be removed from the colon only or in conjunction with the aborad portion of the ileum and orad end of the colon, depending on the extent of resection required to achieve complete margins. In the former case, after dissection of the ileocecal fold, the cecum is isolated and two Doyen clamps, one of which is placed at its base, are applied. After double ligation of the appropriate vessels (cecal branches of the ileocecal artery running in the ileocecal fold), the cecum is resected by incising between the two clamps with a scalpel. A Parker-Kerr suture is usually used to close the defect (3-0/4-0 polydioxanone, polyglyconate, poliglecaprone 25) (Figure 7.27a and b). As an alternative, the intestine may be closed with simple interrupted sutures or by using a TA or GIA stapler, resulting in the eversion of the

cut edge of all layers. Further manual oversewing of the staple line is optional (Holt and Brockman 2003; Tobias 2007). In the case of larger tumors, after double ligation of the corresponding ileocolic arterial branches, the cecum is removed together with both the aborad end of the ileum and orad end of the colon (Figure 7.27c and d). Care is taken to ensure that the diameters of the two intestinal stumps are the same using one of the following techniques: Spatulating the small intestine on the antimesenteric border in order to increase its diameter; incising the smaller intestine at an oblique angle (45–60°, with the antimesenteric border shorter than the mesenteric one; or partially oversewing the colon to reduce its diameter. An ileocolic end-to-end anastomosis is then performed. Manual anastomosis is accomplished using full-thickness appositional simple interrupted sutures with 3-0 or 4-0 absorbable mono ilament material (polydioxanone, polyglyconate, or poliglecaprone 25) with the knots in an extraluminal position. As an alternative, end-to-end anastomosis may be performed with a circular EEA stapling device (see below) (Kudisch and Pavletic 1993; Holt and Brockman 2003; Tobias 2007; Banz et al. 2008; Radlinsky 2013b). After checking that there is no gross leakage from sutures (by carefully inspecting the anastomosis or by gently distending the affected intestinal segment with sterile saline while either side of the anastomosis is digitally occluded), an abdominal lavage with warm sterile saline and suction precede both wrapping of the anastomotic site with omentum and standard closure of the abdomen. For postoperative care see the section on the colectomy, below. Functional outcome is usually good. Potential Complications Complications may include dehiscence, infection, stricture (caused by inappropriate surgical technique and/or suture material; it may require surgical exploration if it has resulted in obstruction), tumor recurrence, and metastasis. The removal of the ileocolic junction in cats (Sweet et al. 1994) and dogs may result in clinical signs, such as increased frequency of defecation and looser stool for a variable period of time (from weeks to months). This should be communicated to owners prior to surgery.

Figure 7.27 (a) Intraoperative view of a small cecal gastrointestinal stromal tumor (GIST) in a dog. (b) A typhletomy has been performed, including a Parker–Kerr suture for closure. (c and d) A more extensive typhectomy has been performed in two other dogs for a large leiomyosarcoma (c) and hemangiosarcoma (d), and the cecum has been removed together with a portion of both small and large intestine. Source: Photograph (c) courtesy of Dr. Romanelli Giorgio.

Colectomy Indications for colectomy are tumors con ined to the colon only. Although this situation is rare, particularly in dogs where large intestinal tumors are more frequently colorectal (Selting 2013), subtotal colectomy is a common consideration in cats as feline colonic adenocarcinomas are often amenable to surgical removal by colectomy alone (Slawienski et al. 1997; Arteaga et al. 2012). One unusual report

of a pure canine colonic adenocarcinoma involved the entire colon, although this tumor was not resected (Prater et al. 2000). Colectomy may be total or subtotal, depending on the extent of resection required to achieve complete margins. In the latter case, the ileocecocolic valve is preserved, taking care to transect the ascending colon 3–5 cm from the cecum to obtain a inal tension-free end-to-end anastomosis. The colon is exteriorized, and the area to be removed is identi ied. If possible, feces are digitally milked away from the portion of colon to be resected. The colon is isolated with moistened sponges, and two Carmalt clamps are applied at the extremities of the section to be removed; two noncrushing clamps (Doyen) are each applied orad and aborad to the two Carmalt clamps on the section of intestine to be preserved; as an alternative, the assistant may use his or her ingers (index and middle ingers) as a noncrushing digital clamp. In applying the two Carmalt clamps, close attention is paid to the margins of resection (see later). Vasa recta (coming from both the ileocolic artery, a branch of the cranial mesenteric artery, and the caudal mesenteric artery for the caudal half of the descending colon) are double ligated. For segmental colectomy, care is taken to ligate only vasa recta and to spare vessels that run parallel to the bowel (Holt and Brockman 2003; Radlinsky 2013b). If most or all the colon and the cranial part of the rectum requires removal, the caudal mesenteric artery (which emerges from the abdominal aorta at the level of the caudal aspect of the 5th lumbar vertebra and from which the cranial rectal artery is derived) may require ligation, even though this may potentially decrease the blood supply at the anastomotic site and increase the risk of postoperative dehiscence and stricture. Every effort, therefore, is made to preserve major colic vessels when the extent of the disease allows it. Despite this recommendation, no postoperative complications were seen in a report in which ligation of the caudal mesenteric artery was required in two dogs to enable adequate tumor resection (Sarathchandra et al. 2009). Finally, the colon is transected between the clamps with a scalpel or Metzenbaum scissors and is opened to con irm that suf icient macroscopic margins have been achieved. Further resection, using a new set of surgical instruments and gloves, can be considered in the event that complete margins are questionable. End-to-end anastomosis (ileocolonic or colocolonic) may be achieved by manual suturing (see

typhlectomy and Figure 7.28a) or by stapling, depending on the surgeon’s experience, preference, and costs. The circular stapling device may be introduced through the anus or through a small cecal incision (Kudisch and Pavletic 1993; Banz et al. 2008) (Figure 7.28b and c). Stapling may be problematic in cats and small dogs because of size limitations (Holt and Brockman 2003; Radlinsky 2013b), however, the equipment that is now available (21-, 25-, 28-, and 31-mm diameter sizes) may be used in most cats and small dogs (Banz et al. 2008). A successful end-to-end colocolic anastomosis technique with biofragmentable rings after subtotal colectomy in cats has been reported (Ryan et al. 2006) (Figure 7.28c). After checking that there is no gross leakage from sutures (by carefully inspecting the anastomosis or by gently distending the affected intestinal segment with sterile saline while either side of the anastomosis is digitally occluded), an abdominal lavage with warm sterile saline precedes both wrapping the anastomotic site with omentum and standard closure of the abdomen. Postoperative Care Postoperative care includes analgesia for 24–48 hours, luid and electrolyte therapy, antibiotics in the case of gross contamination during the surgery or established postoperative infection and peritonitis, and Elizabethan collar. A small amount of water should be provided 8–12 hours after surgery and a light feeding (e.g. Hill’s i/d) 12–24 hours after surgery. Return to normal feeding is usually within three days (Holt and Brockman 2003). Functional outcome is usually good. Potential Complications Complications may include short-term rectal bleeding, loose feces, tenesmus, stricture (which may necessitate a second surgery if it results in obstruction), dehiscence and peritonitis (requiring urgent patient stabilization and surgical exploration), and potential loss of reservoir continence if most of the colon is removed (see also section on additional technical details for colorectal anastomosis – potential complications). Loss of reservoir continence results in more frequent

conscious defecation (Guilford 1990; Dean and Bojrab 1993). Cats tolerate a larger colonic resection (90–95% of the colon) than dogs (Bertoy et al. 1989); however, no long-term adverse effects are seen in dogs following removal of up to 70% of the entire colon (Bertoy et al. 1989; Jimba et al. 2002; Radlinsky 2013b). It has been reported that subtotal colectomy with preservation of the ileocolic junction in dogs results in elimination of liquid stools 10–12 times a day; normalization of fecal output (normal fecal consistency and two to three daily defecations without tenesmus) is achieved within 5–10 weeks (median 7 weeks) (Nemeth et al. 2008).

Figure 7.28 (a) Colocolonic end-to-end anastomosis obtained in a dog using a manual suture technique. (b) Colocolonic end-to-end anastomosis obtained in a dog with a circular EEA stapling device. (c) Sutureless colocolonic end-to-end anastomosis with Valtract biofragmentable anastomosis ring (BAR) device in one cat (Ryan et al. 2006). Source: Photographs (b) and (c) courtesy of Dr. Eric Monnet.

Simple Excision of the Mass This procedure should be reserved for small, single, and super icial benign tumors (e.g. polyps) located in the caudal-midrectum (Figure 7.29b–d). In general, simple excision should be considered as a biopsy procedure and further surgeries should be considered based on the histology results (Morello et al. 2008). Standard surgical excision relies on prolapse of the rectum (pull-out procedure) through a transanal

approach (Figure 7.29a, b, and f). Excision may be performed using sharp instruments (Figure 7.29c) or with an electrosurgical snare or cautery tip used in conjunction with proctocolonoscopy (Palminteri 1966; Holt and Durdey 1999) (Figure 7.30). In case of a sessile lesion, a preemptive submucosal injection of sterile saline solution with a 25gauge endoscopic injection needle has been shown to be useful to elevate the mucosa from the muscularis layer beneath the lesion prior to submucosal snare polypectomy, thus facilitating resection and decreasing the risk of inadvertent rectal wall perforation (Coleman et al. 2014). As an alternative, cryosurgical, laser, or TA stapler devices may be used [see later] (Valerius et al. 1997; Shelley 2002; Tobias 2007; Swiderski and Withrow 2009). For a standard surgical excision, following routine surgical preparation of the area, the rectal wall is everted through the anus via traction on four stay sutures applied 1–2 cm cranially to the anocutaneous line. The lesion is exposed externally, which may require the sequential placement of additional more cranial stay sutures as necessary (see Figure 7.23); traction should be not excessive, however, as the author has experienced a full-thickness rupture of the rectal wall requiring pelvic osteotomy to repair the colorectal defect, rather than performing a simple submucosal excision. If the lesion is attached to the wall through a stalk, the latter is simply ligated and transected. If the lesion has a sessile attachment, excision is performed by incising the normal mucosa along the periphery of the lesion and deep to the lesion (Figure 7.29c). Closure is performed in one to two layers, depending on the depth of the incision, with a simple interrupted or simple continuous suture pattern with absorbable mono ilament material (3-0 or 4-0 polydioxanone, polyglyconate, or poliglecaprone 25) (Figure 7.29e–g). In many cases, a sequential resection and suturing technique (without touching the tumor) may be used (Figure 7.31). As an alternative, a linear stapling device may be used. In one report, the use of a 30 mm, vascular TA stapling device applied in a transverse or longitudinal orientation at the base of the mass allowed tumor resection, leaving three rows of staggered staples with a minimum of 0.5 cm surgical margins (Figure 7.32) (Swiderski and Withrow 2009). The procedure is indicated for super icial tumors located in the caudal third of the rectum, with a base of attachment to the rectal wall of less than 3 cm;

the reported complication rate was low, operative time was short (around 15 minutes. It appears that a full-thickness wall excision is achievable with this technique. Because the staples are placed before any incision is made in the rectal wall, there is no gross contamination of an open wound, which makes infection unlikely. Regardless of the procedure performed, the stay sutures are then removed. Functional outcome is usually good. Potential Complications Possible complications are rectal bleeding and tenesmus for one to four or more days. Cryosurgery has been associated with complications such as stricture, rectal prolapse, and the development of perineal hernia secondary to tenesmus (Church et al. 1987). Extent of Resection This is a conservative procedure (marginal excision). Colorectal Resection (Variable Portions of Both Descending Colon and Rectum) This procedure is mainly applicable to dogs, but it can also be used in cats. The colorectal junction is about at the level of the pelvic inlet near the caudal peritoneal re lection; the latter is at the level of the second caudal vertebra. The rectococcygeus muscles (that attach the rectum to the ventral ifth caudal vertebra) are caudal to this re lection. Each side of the rectum is supported laterally by the levator ani and coccygeus muscles (also known as pelvic diaphragm). On each side, at the level of the peritoneal re lection, the pelvic plexus provides innervation to the rectum via the parasympathetic pelvic and sympathetic hypogastric nerves. The rectal blood supply is derived from essentially three arteries: The cranial rectal artery (from the caudal mesenteric artery) and the middle and caudal rectal arteries (from the internal pudendal artery). If the cranial rectal artery is ligated, most of the intrapelvic rectum should be resected to ensure adequate blood supply to the anastomosis; in fact, it has been shown that the cranial rectal artery is the most important vessel for both the terminal colon and rectum (Goldsmid et al. 1993). Resection may be performed using a number of

different approaches. Any colorectal resection may be problematic or even contraindicated when in iltration of the extrarectal tissues is evident (see Figures 7.24 and 7.26a and b).

Figure 7.29 Pull-out procedure. (a) Application of a stay suture 1–2 cm cranially to the anorectal line. (b) Eversion of the rectum by traction on four of these stay sutures and exposure of two rectal polyps that are resected with a marginal excision (c and d). In this case, the rectal incision was closed with a one-layer continuous suture (4-0 poliglecaprone 25) (e). (f and g) are from the case in Figures 7.23 and 7.24a. Excisional biopsy was performed by incising the rectal mucosa at the periphery of the lesion and using blunt dissection and traction (f). The rectal wall is sutured with a simple interrupted suture pattern using absorbable mono ilament material (g). Source: Photographs (f) and (g) are from Buracco (2007). Used by permission.

Figure 7.30 Endoscopic polypectomy. The polypectomy snare is opened and the polyp is surrounded at the base. The snare is then gently closed around the base of the polyp until a mild color change in the polyp head is observed. The snare is now tightly closed, the current is activated and the polyp excised. Source: Photograph courtesy of Prof. Gualtieri Massimo.

Dorsal Inverted (Dorsal Perineal) Approach The technique described here re lects the procedure originally reported in two studies (Mckeown et al. 1984; Anderson et al. 1987). Indications for this procedure include marginal resection of benign intramural leiomyoma located dorsally in the rectum (Figures 7.33 and 7.34) or rectal resections for small malignant tumors located in the caudalmidrectum. The anal sac content is evacuated prior to the placement of the purse-string suture in the anus. Urethral catheterization is advised if extensive dissection is expected (Holt et al. 1991). An inverted Ushaped incision is made over the dorsal aspect of the anus, terminating

on both sides just medial to the tuber ischium. Meticulous hemostasis and dissection are performed to the level of the dorsal rectum and several muscles such as the levator ani (just lateral to rectum), coccygeus (lateral to the levator ani), external sphincter (around the caudal end of rectum), and the rectococcygeus (dorsally, located on the midline from the coccygeal vertebrae and dividing into two bundles that surround the rectum laterally) are identi ied. The rectococcygeus muscle is severed between the coccygeal vertebrae and rectum or more dorsally to free the rectum (Figure 7.33b). Blunt dissection is performed bilaterally between the rectum and the external sphincter and levator ani muscles, taking care not to damage the pudendal nerve and its termination as the caudal rectal nerve, which innervates the external sphincter muscle. If necessary, both levator ani muscles are transected to increase surgical exposure. The rectum is then further freed by circumferential blunt dissection in a cranial direction until the caudal peritoneal re lection is identi ied. The rectum is then pulled caudally, and stay sutures using 2-0 suture material are applied, as needed, both on the section to be removed and on the cranial rectal extremity that will be spared. This helps manipulation, avoids leakage of fecal material into the pelvic canal after incision, and prevents cranial retraction of the orad intestinal segment; transection is completed both cranially and caudally (1–2 cm cranial to the external sphincter muscle) with a scalpel or Metzenbaum scissors. The part of the rectum bearing the tumor is removed and opened to con irm that the macroscopic normal margins are wide enough; if not, further resection is performed using a new set of surgical instruments and new gloves. Moistened gauze is inserted into the cranial intestine as needed in order to avoid spillage of fecal material into the surgical ield. End-to-end approximating anastomosis is performed using a simple interrupted suture pattern with absorbable mono ilament material (3-0 or 4-0 polydioxanone, polyglyconate, or poliglecaprone 25). In order to triangulate the lumen and to facilitate the application of sutures 3 mm apart, three full-thickness appositional interrupted stay sutures are applied at the 12, 4, and 8 o’clock positions around the rectal circumference. Care is taken during suturing not to incorporate the opposite wall and inadvertently close the rectal lumen. Ventral sutures are applied after having rotated the bowel by 120°. Knots are placed on

the serosal surface in order to decrease postoperative rectal irritation (Holt et al. 1991). As an alternative, end-to-end anastomosis may be performed with a circular EEA stapling device inserted in the rectum through the anus (after removal of the purse-string suture) (Tobias 2007; Banz et al. 2008; Radlinsky 2013b). Both levator ani muscles are reattached with mattress sutures if previously severed; the rectococcygeous, if still present, may also be sutured to the intestine. The use of postoperative drainage tubes depends on the degree of fecal contamination that occurred during surgery; however, it has been suggested that healing at the anastomotic site could be disturbed if the drain is adjacent to the anastomosis (Radlinsky 2013b). Interposition of fat between the anastomotic site and the soft latex drain has been proposed to avoid this (Holt et al. 1991). After routine closure of both subcutaneous tissues and skin, the anal purse-string suture is removed, and the gauze sponges in the rectum are extracted.

Figure 7.31 Following pull-out (on the left) and exteriorization of a relatively pedunculated rectal GIST, progressive tumor resection and mucosal suturing (on the right) with a ine mono ilament absorbable suture material (without touching the tumor) are performed. Histology of the surgical margins revealed no tumor in iltration.

Figure 7.32 Pull-out (prolapse) and stapling procedure. (a) The rectum has been prolapsed to exteriorize the tumor and stay sutures have been placed to maintain the prolapse. (b) Stay sutures were placed to retract the tumor. (c) The TA stapling device is placed 0.5–1 cm from the base of the tumor. (d) The tumor has been excised and three rows of staggered staples have been placed (arrow).

Figure 7.33 Transanal pull-through procedure. (a) Eversion of the rectum by traction on stay sutures. (b) The rectococcygeus muscles have been isolated before transection. (c) The rectum is bluntly dissected and isolated. (d) The rectal section to be removed is opened longitudinally, and (e) progressive resection and suturing are accomplished sequentially without touching the tumor. (f) Interrupted suturing (one layer) with absorbable material is closed to completion, and the stay sutures have been released. Postoperative care, functional outcome, potential complications, and extent of resection are described below.

Lateral (Perineal) Approach This approach is usually not advisable for rectal tumor resection since only one side of the rectal tube is exposed and it provides very limited exposure to the rectum even on the ipsilateral side. Rectal Pull‐Through Procedure This procedure is indicated for con irmed malignant tumors and for recurrences of previously excised benign tumors located in the midcaudal rectum. Incision is started circumferentially over the anal skin (Figure 7.36a) or at the mucocutaneous junction (Figure 7.37); bilateral anal sac removal is often concomitantly performed if the approach encroaches upon their openings (Aronson 2012). Care is taken, if feasible, to save the external sphincter muscle, undermining inside the circumference of this muscle. Therefore, the dissection plane is between the external sphincter muscle and the rectal wall (Figure 7.37a). The rectum is progressively dissected cranially and concurrently pulled caudally out of the body with the help of stay sutures or grasping forceps; the rectococcygeus muscle is also transected (Figures 7.33b, 7.36b, and 7.37a). Cranial rectal transection is performed according to the extent of resection required to achieve complete margins, and stay sutures are applied to prevent the cranial rectal segment from retracting into the abdominal cavity after resection. As an alternative, the rectum is partially transected, and the closure is initiated (Figure 7.36c). The removed segment is then opened longitudinally to check that there is adequate macroscopically healthy tissue excised at the resection margins. As an alternative, the rectal section to be removed is opened longitudinally, and progressive resection and suturing are accomplished sequentially without touching the tumor (Figure 7.33d). Moistened gauzes are packed into the cranial rectum in order to avoid the spillage of fecal material in the pelvic canal. Closure is performed in one to two layers with simple interrupted sutures (3-0 or 4-0 polydioxanone, polyglyconate, poliglecaprone 25) (Figures 7.33e and 7.36e,). Spiraling the proximal colorectal stump of 225° during the 360° rectocutaneous plasty has been reported in a cat in attempt to create a natural barrier to feces (Pavletic et al 2012).

Figure 7.34 a) and (b) CT scan appearance of a leiomyoma dorsal to the rectum, thus causing obstruction to defecation. (c) and (d) Postexcisional appearance of the tumor that was marginally resected through a dorsal approach to the rectum.

Figure 7.35 a) Blunt undermining of a leiomyoma in a dog through a dorsal approach to rectum. The tumor was dorsal to the rectum and caused marked rectal obstruction. (b) Postexcision aspect of the tumor.

Figure 7.36 Rectal pull-through procedure. (a) Circumferential skin incision. (b) The rectum is exteriorized by blunt dissection and traction (the arrow indicates where the rectococcygeus muscle has been severed). (c) Partial transection and suturing (one layer) are accomplished sequentially. (d) The part of the rectum that has been removed and (e) the inal image appearance of the area is shown. Source: Photographs from Buracco (2007). Used by permission.

Figure 7.37 Rectal pull-through procedure for a rectal adenocarcinoma 2 cm from the anus. (a) The circumferential incision has been performed in this case at the anocutaneous junction; the rectal dissection has been performed sparing the external sphincter muscle as much as possible and both anal sacs have been removed; the rectococcygeal muscles have not been resected yet. (b) Postoperative appearance of the area after completion of suturing. The single-layer suture pattern would be preferable because the double-layer suture pattern has been associated with a higher risk of dehiscence when performed outside of the abdomen (Everett 1975). In the double-layer suture pattern, the deeper layer approximates the intestinal serosa (or adventitia)/muscularis to the perianal subcutaneous tissues, and the super icial layer approximates the submucosa/mucosa to the skin (Aronson 2012). The author usually performs a single-layer closure.

Postoperative care is discussed below. Functional outcome is usually good. Potential Complications Fecal incontinence is an undesirable complication of this procedure (discussed below). Extent of Resection The only limit to resection is the maintenance of a tension-free end-toend anastomosis. Resection with this approach usually involves only the rectum; however, it can be extended beyond the caudal peritoneal re lection for a small portion of the caudal descending colon. Transanal Pull‐Through Procedure This procedure is indicated for con irmed but con ined primary malignant tumors and for con ined recurrences of previously excised benign tumors located in the midcranial rectum (Morello et al. 2008; Aronson 2012; Radlinsky 2013b). The major distinction between this procedure and the rectal pull-through previously described is that a short segment of the most caudal aspect of the rectum is preserved with the transanal pull-through procedure. This preserved caudal segment includes the anal canal, which is the terminal portion of the alimentary canal. The rectal wall is prolapsed through the anus with four stay sutures (see Figures 7.23, 7.29a, and 7.33a). A full-thickness circumferential incision is made through the rectal wall. When feasible, a minimum of 1–1.5 cm of caudal (aborad end) rectum is spared in order to preserve fecal continence (Morello et al. 2008; Nucci et al 2014). The plane of dissection then becomes outside of the rectal wall going cranially, through the circumferential incision into the rectum. The rectum is mobilized following transection of the rectococcygeal muscles (Figures 7.33b, 7.36b, and 7.37a), and blunt dissection is performed along the external surface of the bowel (Figures 7.33c and 7.36b). The mobilized rectum is pulled caudally out of the body, and stay sutures are applied to prevent the cranial segment of the rectum from retracting into the abdominal cavity after resection. Cranial rectal transection is then performed. To establish the point of cranial

resection, the rectum is either externally palpated or opened longitudinally, the latter avoided when there is a 360° circumferential tumor. If a longitudinal opening is used, progressive resection and suturing are accomplished sequentially without touching the tumor (Figure 7.33d). If not opened previously, this is done after resection to con irm that resection margins are adequate. Moistened gauze sponges are packed in the cranial rectum to avoid the spillage of fecal material in the pelvic canal. Finally, the normal cranial rectum or descending colon is manually anastomosed with the preserved caudal rectal stump with one (preferably full-thickness sutures) or two layers (sero-muscular and mucosal-submucosal layers). When tension is present at the anastomotic site, simple appositional interrupted sutures are preferred (3-0 or 4-0 polydioxanone, polyglyconate, poliglecaprone 25) (Figure 7.33e). The release of the stay sutures allows the rectal anastomotic site to return into the pelvic canal (Figure 7.33f). As an alternative, an endto-end anastomosis is performed with a circular EEA stapling device introduced through the anus (Tobias 2007; Banz et al. 2008). This is discussed later. Postoperative care, potential complications, and extent of resection are all described later. Functional outcome is usually good but serious complications may occur (see later). Caudal abdominal approach with either sagittal pubic symphyseal separation or osteotomy

Figure 7.38 Green line shows site of osteotomy for symphyseal separation. Red lines indicate the sites for osteotomies for pubic and ischial retraction. Red lines indicate the sites for osteotomies of the pubis and ischium. Red crosses indicate the site for predrilling holes to facilitate subsequent closure. Source: Courtesy Bernard Séguin.

This approach is indicated for tumors located in the cranial rectum and for those tumors with further extension into the caudal colon (Davies and Read 1990; Allen and Crowell 1991; Aronson 2012; Radlinsky 2013b). The urethra is catheterized, and the skin incision is ventral (from the xiphoid process of the sternum to the cranial vulva in females or from the xiphoid, parapreputially to the scrotum in males). The subcutis is then bluntly undermined and the external obturator muscles are separated to expose the pubic symphysis. Both the pubis and ischium are separated exactly on the midline with an osteotome and mallet or an oscillating saw and spread apart with a Finochietto retractor (Figures 7.38 and 7.39).

Figure 7.39 Both the pubis and ischium are spread apart with a Finocchietto retractor. Source: Photo courtesy of Dr. Julius Liptak.

If a symphysiotomy has been performed, the symphysis is repaired by passing a 0.8 mm stainless steel wire through a wire passer and then through both the obturator foraminae; Davies and Read (1990) suggested that the wire should pass along the borders of the obturator foramina, rather than through predrilled holes given that the bone at the symphysis can collapse when the wire is tightened. Care is taken not to incorporate any vessel or nerve in the wire suture loop. The wire is then tightened, and its ends trimmed and bent; the two obturator muscles are then apposed with interrupted sutures. To increase exposure, osteotomy of both the pubis and ischium has also been described (Yoon and Mann 2008). The various steps are described in detail as follows (Figures 7.38, 7.40, and 7.41).

1. Subperiosteal elevation of adductor muscles up to two-thirds of the obturator foramina (Figure 7.40a) 2. Incision of the prepubic tendon along the pubis rim as needed. 3. Predrilling of a hole using a pin and Jacob’s chuck or drill on each side of the four planned longitudinal osteotomies (two pubic and two ischial) to facilitate subsequent closure (Figure 7.38). 4. Pubic and ischial osteotomy (with an oscillating saw), taking care to protect the two obturator nerves and vessels using a malleable retractor (osteotomies are medial to the lateral border of the obturator foramina, bilaterally) (Figures 7.38 and 7.40a). 5. The bone segment is gently pulled up and subperiosteal elevation of only one of the two internal obturator muscles from the pubis/ischium is performed to enable re lection of the osteotomized bone plate on the other side. Alternatively, both internal obturator muscles are elevated, and the bone plate is re lected caudally (Figure 7.40b). 6. Excision of the affected segment of bowel. The bladder and urethra are irst re lected caudally and protected with moistened laparotomy sponge. The colorectum is then isolated by careful undermining, accurate hemostasis, and placement of moistened laparotomy sponges with or without stay sutures. Clamps are then placed to allow transection and removal of the diseased segment at the appropriate level (see colectomy section). Once the colorectal segment is removed from the body, it is opened to con irm that enough macroscopically healthy tissue has been maintained at resection margins; manual or stapling end-to-end anastomosis is then performed as previously described (Figure 7.40c). 7. Preplacement of sutures (orthopedic wire or 0 polydioxanone, the latter in small dogs and cats) in the predrilled holes and reduction of the segment of bone plate by tightening the sutures (Figure 7.41a and b). 8. Reapposition of the two adductor muscles with 3-0 polydioxanone in a simple interrupted cruciate pattern.

9. Drilling of four holes along the pubic brim to allow reapposition of the prepubic tendon with 3-0/2-0 polydioxanone interrupted sutures through the bone tunnels (Figure 7.41c). 10. Thorough lavage of the area prior to routine skin closure.

Figure 7.40 The phases of the osteotomy of both the pubis and ischium to remove a colorectal tumor with an end-to-end anastomosis. (a) adductor muscles have been elevated to expose part of the obturator foramina and the prepubic tendon has been already incised along the pubis rim. Both pubic and ischial osteotomies have been performed. (b) caudal elevation of bone plate. (c) postexcisional appearance of the completed end-to-end anastomosis.

Figure 7.41 Reconstruction following pelvic osteotomy and colorectal resection. (a) sutures are placed in the predrilled holes. (b) sutures are tightened. (c) sutures are also placed and tightened to reappose the prepubic tendon in another dog. The exposure provided by sagittal pubic symphyseal separation to perform both colorectal resection and anastomosis can be limited (Williams and Niles 2005; Schlicksup et al. 2013). The osteotomy procedure to create a pubic and ischial bone lap reported by Yoon and Mann (2008) appears to offer several advantages, including good operative exposure as well as the option to bluntly dissect both the cranial peritoneal re lection and pelvic nerves (on both sides of the rectum) and to ligate only speci ic vessels as needed (cranial rectal artery or individual vasa recta, depending on the bowel segment to resect). Postoperative Care Effective analgesia (constant-rate infusion of lidocaine, opioids) for at least two to three days has been recommended by many surgeons (Davies and Read 1990; Williams and Niles 2005). In the case of symphyseal distraction with a Finochietto retractor, sharp pain may be caused by sacroiliac subluxation/luxation (Schlicksup et al. 2013). After osteotomy of both the pubis and ischium, the use of hobbles applied at the level of the hock region helps to avoid an excessive abduction of the two legs (potentially resulting in skin dehiscence) during the irst four to six days postoperatively. Functional Outcome

Limping may be evident for some days after surgery (mainly after symphyseal distraction), but prolonged analgesia with nonsteroidal anti-in lammatories may improve the clinical signs. For speci ic complications related to colorectal resection, see below. Specific Complications Reported possible complications include a sinus tract related to the wire cerclage suture (Davies and Read 1990). A risk of sacroiliac subluxation/luxation after pubic symphyseal distraction has also been reported in a cadaveric study (after distraction equal to 25 and 100% of the sacral width respectively, respectively) (Schlicksup et al. 2013). This can potentially result in pain, a reluctance to walk, and delayed recovery. After the repair of a pubic/ischial osteotomy, nonunion may occur, with the need to restrict activity for a minimum of four months to allow a clinical healing (Allen and Crowell 1991). No major complications (e.g. hemorrhage, postoperative lameness, avascular bone necrosis, infection, urinary or fecal incontinence, etc.) were reported after pubic/ischial osteotomy (Yoon and Mann 2008). In the latter report, all the animals had exercise restricted for four weeks postoperatively, and the authors argue that absorbable suture material is adequate in small dogs and cats as an alternative to orthopedic wire, given that neither the pubis nor the ischium are weight-bearing segments of the pelvis. The author of this section of the chapter has used heavy braided absorbable suture materials (size 1 or 2) also in dogs between 20 and 25 kg of body weight without complications. The extent of resection is described below. The So‐called Swenson’s Pull‐Through and Modifications This procedure is indicated for tumors of the midcranial rectum extending to the caudal colon, and it is an alternative to sagittal pubic symphyseal separation or osteotomy. The animal is positioned in dorsal recumbency, and both the ventral abdomen and the perineal area are prepared for surgery. For easier access to the perineal area, the dog is placed with the perineal area at the end of the surgical table and the tail hanging down. The hind limbs are pulled cranially, placed alongside the abdomen. A caudal celiotomy is performed irst. The descending colon

is isolated by double ligation of the corresponding vasa recta, two Doyen clamps are applied cranially and caudally to the proposed point of transection, which is cranial (orad) to the tumor (Figure 7.42a), and the colon is divided. The length of the rectocolonic tract to be removed should be determined preoperatively, based on a combination of colonoscopic, ultrasonographic, and CT indings. Due to the risk of intraperitoneal contamination, it is not recommended to open the resected intestinal segment intraoperatively to assess excisional margins. After division, each colonic stump is oversewn with a continuous Parker-Kerr inverting suture (3-0/4-0 PDS); as an alternative, the two colonic stumps may be closed by stapling. At this point, different techniques may be used.

Figure 7.42 (Same case as Figure 7.23; see also Figures 7.26d and 7.49.) (a) Two Doyen clamps are applied on the colon cranially and caudally to the proposed point of division, which is cranial to the tumor. (b) After division, the two colonic stumps are closed with a continuous Parker-Kerr inverting suture and then connected with four 2-0 sutures, two diagonal and two straight, leaving a space of about 1–2 cm between the two intestinal stumps. (c) A transanal pull-through procedure is performed until the cranial (orad) stump emerges. At this point, the procedure is terminated as in the transanal pull-through procedure. Source: Photograph (c) is from Buracco (2007). Used by permission.

1. The irst technique is the so-called Swenson’s pull-through (Swenson and Bill 1948; White and Gorman 1987; Holt and Brockman 2003) (Figure 7.43a–f). With the dog still positioned in

dorsal recumbency, a second surgeon at the perineal end introduces an Allis tissue forceps into the anus and rectum and grasps and everts the rectum through the anus, essentially intussusepting and prolapsing the rectum with the tumor (Figure 7.43b and c). The surgeon in the abdomen can help by pushing the closed-end caudally. Once prolapsed, this everted portion is resected circumferentially over 360° aborad to the tumor with suf icient margins. Contaminated instruments are discarded, and gloves are changed. The surgeon in the abdomen places stay sutures on the stump of the colon. The surgeon at the perineal end introduces Allis tissue forceps or Carmalt through the open caudal end of the prolapsed rectum and advances the forceps in the abdomen (Figure 7.43d). The surgeon in the abdomen places the stay sutures in the forceps. While the surgeon at the perineal end pulls the forceps back out, the surgeon in the abdomen helps to push and feed the colon into the pelvic canal. The colon is pulled through the pelvic canal until the stump exits through the open end of the caudal segment (Figure 7.43e). The Parker–Kerr suture is removed, or if staples were used the tip is excised. The open end of the colon is sutured circumferentially to the open end of the rectum and the anastomosis is pushed back into the pelvic canal (with the surgeon in the abdomen helping by gently pulling on the colon) thereby reducing the prolapse (Figure 7.43f). 2. In a modi ied technique reported by Morello et al. (2008), steps are taken in order to achieve a further tension-free end-to-end rectocolonic anastomosis. After ligation of the appropriate vessels, the colon is divided according to the required excisional margins, the two stumps are oversewn. The two stumps are then connected, leaving about 1 cm between them, with two to four 2-0 sutures (if four, two are diagonal and two are straight; Figure 7.42b). The abdomen is closed routinely. The dog is then positioned in sternal recumbency. A transanal rectal pull-through amputation is performed as previously described (see Figures 7.26d and 7.42c), with sparing of a longer tract of caudal rectum in comparison with the standard transanal procedure. After exteriorization of both the entire colorectal segment bearing the tumor and the emerging colonic cranial stump (Figure 7.42c), the sutures connecting the

two stumps are cut. The cranial stump is pulled through the remaining caudal rectum using the stay sutures, the Parker–Kerr suture oversewing the cranial stump is removed, and the end-toend anastomosis is performed as previously described. The release of the stay sutures placed in the rectal cuff attached to the anus allows the anastomotic site to return to the pelvic canal. As an alternative, a stapling device may be used to perform an end-toend anastomosis (as discussed below). The procedure may also be performed with the animal remaining in dorsal recumbency, with the advantage of a surgeon in the abdomen who can help “feed” the sutured stumps into the pelvic canal. 3. A study reporting the surgical management of idiopathic megacolon in two cats (Barnes 2012) has described a technique that could be potentially modi ied for use in the resection of more orad colorectal tumors. The described technique does not involve the division of the colon intra-abdominally but is performed extraabdominally via the anus as per rectal amputation for a rectal prolapse. Following midline celiotomy, isolation of the tract of colorectum to be resected and ligation and transection of the associated vessels, an Allis tissue forcep is introduced into the rectum through the anus with a “contaminated hand” that is no longer placed intra-abdominally until the affected segment is exteriorized through the anus. The Allis tissue forcep then clamps the colonic wall beyond the cranial extent of the tumor (therefore orad to the tumor). A progressive intussusception of the colorectal tract is then achieved by pulling the Allis forcep (with the assistance of a contralateral “sterile” hand working intraabdominally) until the affected segment is exteriorized through the anus. Application of several stay sutures is performed to avoid the retraction of the intestine in the pelvic canal, during the subsequent transection. After transient closure of the abdomen (with towel clamps and a sterile drape), resection of the predetermined colonic segment outside the abdomen and beyond the anus is performed: The wall of the intestines is progressively cut (from the mucosa to the serosal surface on the external loop of bowel and from the serosal surface to the mucosa on the internal loop of bowel) with the cut edges of the walls being sutured

progressively circumferentially with a simple interrupted pattern. This creates an end-to-end anastomosis. Finally, the stay sutures are removed, the remaining prolapsed segment is reduced, surgical instruments and gloves are changed, the mesentery closed, the anastomotic area omentalized, the abdomen is lavaged, and then de initively closed. Potential limitations of this technique include the spread of the tumor during the exteriorization phase and the ability to correctly determine the surgical margins. The technique may only be indicated, therefore, for very localized colorectal malignancy that is not circumferential.

Figure 7.43 Illustration of Swenson's pull-through (a) an intraabdominal approach is used to divide the colon proximal to the lesion and the proximal colon is oversewn. Shaded area represents the section of rectum to be removed. (b) A pair of Carmalt tissue forceps is introduced through the anus and the distal rectal segment is grasped and everted through the anus. (c) Once everted the everted portion is resected circumferentially over 360º aborad to the tumor with adequate margins. Dashed line represents where the incision will be made in the rectum. (d) Stay sutures have been placed and the affected rectal segment has been removed. The surgeon in the abdomen places stay sutures in the stump of the colon. The surgeon at the perineal end passes a Carmalt forcep through the prolapsed rectum and the stay suture is grasped. (e) The sutured caudal end of the colon is pulled through the pelvic canal until the stump exits through the open end of the caudal segment. The sutured end of the colon is transected in a cutand-sew fashion (inset). (f) The completed anastomosis is pushed back into the pelvic canal. Source: Illustrated by Molly Borman.

Postoperative care, potential complications, and extent of resection are described later. Functional outcome is usually good, but complications may develop. Complications are described later in this chapter. Metastasis Resection Intra-abdominal metastatic lesions amenable to surgical resection are excised through a midline celiotomy (see also the section on perianal tumors). Care is taken to evaluate all potential sites where metastasis can be found, including the sublumbar (medial iliac, see Figures 7.26c, 7.58, 7.70 and 7.71; internal iliac, see Figures 7.44, 7.56 and 7.71b); colic (see Figure 7.26a and d), and mesenteric lymph nodes, liver, spleen, and omentum. If feasible, metastatic lesions are excised and submitted for histological examination; alternatively, biopsy samples are taken when the lesions are in iltrative and/or multiple. Intraoperative radiation, if available, can be performed in selected cases at the site of metastatic sublumbar lymphadenopathy.

Surgical Palliation The use of an incontinent end-on-colostomy as a fecal diversion technique for inoperable and obstructive colorectal malignancies, or when there is failure of a pull-through colorectal amputation, has been reported (Hardie and Gilson 1997; Kumagai et al. 2003; Radlinsky 2013b). In this author’s experience, such procedures are rarely accepted by owners due to the dif icultly in managing the animal. The permanent end-on-colostomy (Radlinsky 2013b) is performed after resection of the abnormal colon by creating a stoma at the level of the left abdominal wall and suturing the seromuscular layer of the colon orad to the lesion to the abdominal musculature with a 3-0 mono ilament absorbable suture and a full-thickness suture between the colon and skin. A colopexy is then performed adjacent to the stoma to avoid herniation/prolapse and to stabilize the stoma. The abdomen is closed routinely. A fecal storage device is then attached to the stoma. A temporary fecal diversion may be performed as a “loop colostomy” at the level of the left lank (Radlinsky 2013b). In this case, the descending colon is not resected but used for the colostomy. For this technique, after applying the loop ostomy rod to stabilize the intestine at the level of the abdominal wall incision, the stoma is created by suturing the colonic seromuscular layers to the subcutis of the abdominal incision; the colon is then incised longitudinally and the stoma is completed by suturing the colonic mucosa and submucosa layer to the skin. A fecal storage device is then attached to the stoma and the stoma is closed when it is no longer required. An example of such a salvage procedure that was used following the dehiscence of a colorectal end-to-end anastomosis subsequent to transanal colorectal amputation is provided in Figure 7.45 (Cinti and Pisani, 2019). It should be noted that a fecal storage device (coming from the human medicine) may be dif icult to adapt, ix and manage in our patients.

Figure 7.44 (See also Figure 7.26) (a) Enlarged metastatic sublumbar lymph nodes (internal iliac lymph nodes), one of which is pointed out with the tip of a cotton swab. (b) Excision of one of these lymph nodes. To achieve palliation for extensive benign colorectal tumors and as an alternative to radical and full-thickness excision, a transanal endoscopic treatment has been proposed in a retrospective study involving 13 dogs (Holt 2007). Tumor resection, even during recut procedures, was achieved by varied combinations of an electrode-cutting loop, an electrocautery with a ball-end electrode, and traditional surgery (the latter was only needed in a single dog after two endoscopic treatments). Results included a cure in ive dogs, palliation in three, and were poor in ive dogs. Complications of the technique (arising usually four to ive days after the treatment) included rectal perforation with peritonitis and death. A study (see also the section above describing Simple Excision) has described the removal of a sessile lesion via the preemptive submucosal injection of sterile saline solution, with a 25gauge endoscopic injection needle, to elevate the mucosa from the

muscularis layer beneath the lesion prior to submucosal snare polypectomy (Coleman et al. 2014). Nonsurgical Treatments Local radiotherapy has been used for small nonmetastatic rectal adenocarcinomas less than 3 cm in size and localized to the caudal half of rectum and anal canal (Turrel and Theon 1986). The radiation was applied as a single high dose from an orthovoltage machine in one report (Turrel and Theon 1986). According to this report, tumor control and survival rates at one year were 46 and 67%, respectively, with a median and mean tumor-free period of 6 and 9.7 months, respectively, and a median and mean survival times of 7 and 11.3, respectively. Complications reported included occasional tenesmus within one to two days of the procedure that usually resolved within two weeks (Turrel and Theon 1986). Perforation with subsequent peritonitis was reported in a second study (Church et al. 1987), and no further use of this procedure has been reported. The role of radiation for colorectal tumors still remains to be well de ined in veterinary medicine. In an experimental model using normal dogs undergoing proctectomy and stapling anastomosis, the possibility of treating colorectal recurrence with photodynamic therapy with motexa in lutetium was evaluated. The results of this study show that the technique could have a role as an adjuvant treatment together with chemotherapy and radiotherapy (Ross et al. 2006). Finally, the use of stents for the palliative treatment of obstruction caused by colonic/colorectal tumors has also been proposed, both in the dog (Culp et al. 2011) and cat (Hume et al. 2006).

Figure 7.45 (a) The clinical appearance of the perianal/perineal region in a dog that experienced dehiscence at day ive after transanal colorectal pull through. (b) Following two failed attempts to repair the colorectal dehiscence, the abdomen was opened and lavaged and the descending colon was sutured the left lank (while the caudal colonic stump, still in the abdomen, was temporarily closed with a Parker–Kerr suture). (c) A fecal storage device was tentatively attached to the stoma and from day 13 to 40 several surgical procedures were performed to help the colorectal stump to heal and recanalize. (d) At day 97, the stoma was closed and the more orad colon was successfully anastomosed to the reopened colorectal stump. Source: Pictures courtesy of Dr. Pisani Guido (Cinti and Pisani 2019).

Additional Technical Details for Colorectal Anastomosis

The discussion below addresses all colorectal resections. For more information, see also speci ic sections. For manual end-to-end anastomosis, trimming the exuberant mucosa with Metzenbaum scissors helps achieve an appositional anastomosis. Care is taken to include all the layers of the intestinal wall with the sutures. Importantly, ensure that the suture engages the submucosa, which is the holding layer of the suture when closing the intestines, are included. Engage slightly more serosa than mucosa. Surgical Stapling The stapling equipment used in the large intestinal surgery includes TA, gastrointestinal (GIA), and circular staplers (EEA, CEEA) (Holt and Brockman 2003; Tobias 2007; Banz et al. 2008; Schmiedt 2012; Radlinsky 2013b). TA staplers (or even skin staplers, which are less expensive) may be used for an end-to-end intestinal anastomosis using a triangulating technique. The result is an everting anastomosis. A TA linear stapler may also be used for typhlectomy and, transanally, for removal of polyps of the caudal rectum with a base of attachment of less than 3 cm (Figure 7.32) (Swiderski and Withrow 2009). GIA staplers are linear devices that are usually employed in small intestinal surgery. However, they may also be used for typhlectomy. The inal result is an everting closure. Circular staplers (EEA, CEEA) may be used for both colonic and rectal end-to-end anastomosis and may be inserted in the anus (Banz et al. 2008) or through a separate small incision as appropriate (e.g. the cecum) (Kudisch and Pavletic 1993). Two pursestring sutures secure the two intestinal ends to be anastomosed to the anvil of the EEA device. After iring, a double row of circumferential full-thickness B-shaped titanium staples are applied. This results in a two-layer inverting anastomosis that may reduce the intestinal lumen; this technique has not resulted in any reported complications (Kudisch and Pavletic 1993). The incision site used to insert the instrument is sutured manually or with a TA stapler. All reported descriptions of large intestinal anastomosis in veterinary medicine using a circular EEA stapling device (Kudisch and Pavletic 1993; Holt and Brockman 2003; Tobias 2007; Banz et al. 2008; Radlinsky 2013b) use a double approach (abdominal–

transcecal, transcolonic, etc., and abdominal or transanal) (see Figure 7.28b and c). A study using a porcine model has proposed a technique whereby transanal pull-through is achieved via sigmoidectomy using pneumoperitoneum, gastrotomy access to work intraperitoneally, a circular stapler inserted through the anus, a linear stapler introduced in the colon through a colotomy, excision of the sigmoid, and a stapled colocolonic anastomosis (Leroy et al. 2009). Advantages of intestinal stapling procedures include decreased surgical time, good approximation of the two intestinal ends, good hemostasis without compromising vascularization, higher bursting pressure during the early stage of healing, and higher tensile strength at seven days postsurgery compared to hand sutured anastomosis, and minimal in lammation and necrosis. Potential complications include stricture, adhesion, dehiscence, and peritonitis (caused by excessive tension, poor blood supply, or inappropriate staple size), mucosal ulcerations (more frequent compared to manual anastomosis), hemorrhage, transient anal dysfunction (mainly in cats), and rectovaginal istula (Klein et al. 2006; Tobias 2007; Banz et al. 2008).

Postoperative Care Appropriate postoperative care requires analgesia (opioids and nonsteroidal anti-in lammatory drugs if appropriate), luid, and electrolyte therapy, as dictated by the acid-base status of the animal, until the animal eats spontaneously. Antibiotics are administered only when indicated as in the case of an established infection. The animal should also be monitored for disseminated intravascular coagulation (DIC) (Morello et al. 2008) and treated as appropriate. Elizabethan collars are used as needed. A small amount of water is offered 8–12 hours after surgery, and a small amount of food (e.g. Hill’s i/d) 12–24 hours after surgery if there is no vomiting and then three to four times a day, with a return to normal feeding after two to three days. Stool softeners (e.g. lactulose) can be started when the animal starts to eat and should be mixed with food. Functional outcome is usually good if complications do not occur.

Potential Complications Complications of rectal pull-through procedure in 74 dogs have been retrospectively evaluated in a VSSO multi-institutional study (Nucci et al. 2014). In total, 58 dogs (78.4%) developed complications. Fecal incontinence was observed in 42 dogs (56.8%) with permanent incontinence in 23 (54.8% of those with incontinence to begin with, 31% of all dogs in study). Other complications included diarrhea (32 dogs), tenesmus (23 dogs), stricture formation (16 dogs), rectal bleeding (8 dogs), constipation (7 dogs), dehiscence (6 dogs), and infection (4 dogs). Tumor recurrence was observed in 10 dogs. The MST was 1150 days for all dogs and 726 days for those with malignancy; the two most common rectal tumors were carcinoma and carcinoma in situ (median survival times of 696 and 1.006 days, respectively). The authors conclude that, considering the high incidence of complications of rectal pull-through, it is important, before proceeding, to discuss with the owners about both the oncological outcome and the risk and impact of the potential postsurgical complications on the quality of life of their pets. The duration of postoperative hematochezia and dyschezia (from one to two days up to one to two weeks after surgery), and tenesmus (up to one to two months; see below) may depend on the amount of the colorectal resection performed. These complications, however, are usually self-limiting. Both the length of the resected rectum and the ratio of body weight to length of rectum resected may be signi icantly associated with the development of postsurgical diarrhea; this may also be potentially associated with transient hypermotile syndrome (Nucci et al. 2014). Postoperative stricture may usually be felt by digital rectal exploration. It may be caused by excessive colorectal resection (which leads to tension), excessive in lammation and/or inadequate blood supply (Goldsmid et al. 1993), improper anastomosis and/or suture material, and localized infection. Tenesmus can persist longer, and fecal softeners may be used for several weeks unless colitis and diarrhea are present (in the latter case, reservoir incontinence may be observed even though sphincter continence has been preserved; see below). Sometimes the

use of excessively stiff mono ilament material for suturing may be the cause of a persistent colorectal in lammation and pain. If the problem persists, a colonoscopy is warranted in order to evaluate the severity of the lesion, to procure a biopsy, and to decide if balloon dilation (Figure 7.46) or bougienage with or without a second surgery is required. Infection may develop due to manipulation of the rectum with intraoperative spillage of fecal material or dehiscence. Appropriate surgical technique, intraoperative use of antibiotics, abundant lavage, and a change in surgical gloves and instruments should they become contaminated, are key factors in reducing bacterial contamination. Surgical drainage devices have been advocated when fecal contamination has occurred during surgery, despite the adverse effect they can have on anastomotic healing (Radlinsky 2013b); the interposition of fat between the anastomotic site and the soft latex drain has been proposed to minimize this effect (Holt and Durdey 1999). This author avoids the use of drains in surgical procedures involving the colorectum and prefers to pay particular attention to minimizing intraoperative contamination, combined with adequate preoperative patient preparation (no preoperative enema for at least three days before surgery and the use of preoperative antibiotics). The use of sponges packed in the intestinal stump helps to limit contamination that can occur after removal of the more controllable hard feces adjacent to a site of obstruction (see Figure 7.63 in the perianal section). In selected cases, such as when there is a substantial amount of fecal material evident radiographically, colorectal resection may be preceded by colotomy and fecal emptying, particularly when abdominal exploration is performed for the inspection and removal of other masses (such as sublumbar lymph nodes) and/or simple colectomy. As outlined above, postoperative dehiscence is a potential cause of infection. The most common time for postoperative dehiscence is three to ive days after surgery (Holt and Lucke 1985; Anderson et al. 1987). This is a very serious complication that can be fatal, particularly if it occurs within the pelvic canal. Potential causes include excessive tension at the anastomotic site, inadequate blood supply (a potential cause being the rupture of important vessels as a result of excessive

caudal traction of the rectum during the transanal procedure), improper technique, and inappropriate selection of suture material. It has been reported that the risk of dehiscence is greater with resections greater than 6 cm (Anderson et al. 1987; Phillips 2001). As a salvage procedure, de initive or temporary colostomy may be considered (Figure 7.45).

Figure 7.46 Balloon dilation in a small dog that developed a stricture following transanal colorectal amputation and end-to-end anastomosis for a colorectal carcinoma. The pathogenesis of fecal incontinence following a rectal pull-through surgery is still debated. The two major factors contributing to fecal continence are external anal sphincter function (provided by the integrity of both the muscular component and the caudal rectal branch of the pudendal nerve) and reservoir continence (the ability of the rectum and descending colon to distend and store feces before voluntary expulsion; reservoir continence is provided by the integrity of both colonic length and motility) (Dean and Bojrab 1993). Other factors that seemingly contribute to continence include the length of the caudal rectum preserved after rectal resection and sparing of the rectal cranial peritoneal re lection (Swenson and Bill 1948; Gaston 1948a, 1948b; Karlan et al. 1959; Gaston 1961; Anderson et al. 1987; Anson et al. 1988). A minimum of 1–1.5 cm of caudal rectum has been

recommended to preserve fecal continence. This explains why the transanal approach may be a preferred option, provided that the extent of resection required to achieve complete margins is adequate. In one study using a transanal approach in dogs, the caudal rectum was spared. The dogs were all clinically continent, except one dog that had a resection at the anorectal junction and subsequently became clinically continent at ive months postoperatively for no identi iable reason (Morello et al. 2008). With the rectal pull-through procedure or when the caudal rectal resection is at the level of the anocutaneous junction, fecal incontinence remains a risk due to a combination of the caudal rectum being removed, iatrogenic neurological trauma to the caudal rectal branch of the pudendal nerve, and damage to the external anal sphincter muscle during dissection (Figures 7.36d, 7.37, and 7.47). It has also been identi ied that the circumference of resection of the caudal rectum may also be important. A 360° full-thickness resection has been found to be 18.6 times more likely to result in a transient or permanent incontinence than a resection less than 360°; this inding was only signi icant for fecal incontinence in general and not for permanent incontinence. Therefore, tumors located in the terminal 1.5 cm of the rectum or at the anocutaneous junction should be excised, if this does not compromise a complete margin excision, by means of a partial rectal pull-through procedure to reduce the risk of fecal incontinence (Nucci et al. 2014). Fecal incontinence has also been associated with amputations involving more than 6 cm of rectum in combination with transection of the caudal peritoneal re lection (Anderson et al. 1987). In two studies, however, colorectal amputation of greater than 6 cm in length and including the peritoneal re lection, did not result in permanent fecal incontinence (Morello et al. 2008; Nucci et al. 2014). Similar results have also been reported after anastomosis of the colon to the caudal 1.5 cm of rectum (Swenson and Bill 1948). Furthermore, colorectal resections including limited parts of the descending colon and rectum, with preservation of its caudal segment, should have little in luence on the fecal reservoir continence that may be lost after more extensive colonic resections that render it impossible to store feces (Gaston 1948a, 1948b, 1951, 1961; Karlan et al. 1959; Peck and Hallenbeck 1964; Dean and Bojrab 1993). Clinical signs of fecal reservoir

incontinence include more frequent conscious defecation (Guilford 1990). Provided the caudal rectum has been spared, it appears that transient loss of fecal continence is generally associated with complications of wound healing, including in lammation/colitis with diarrhea and stricture with tenesmus, particularly in small dogs that seem, in this author’s experience, to be more prone to develop such problems. However, a short- to long-term follow-up is needed to thoroughly assess changes in continence (Sapin et al. 2006; Morello et al. 2008). In conclusion, the key factors that increase the probability of maintaining fecal continence include sparing the caudal rectum, appropriate surgical technique and choice of suture material, absence of infection, avoidance of tension at the anastomotic site (therefore, justifying why extensive rectal amputation through a transanal approach should be avoided), and careful preservation of blood supply (which can become compromised by excessive caudal traction during a transanal approach). Finally, it should also be noted that the veterinary literature has not fully addressed the effect on fecal continence of anastomosis between the aborad portion of the ileum and the caudal rectum; in humans, fecal continence is often preserved in these cases, even though reservoir continence may be impaired or lost (Günther et al. 2003; van Laarhoven et al. 2004). With ileoanal anastomosis, however, fecal continence in dogs is lost (Karlan et al. 1959; Peck and Hallenbeck 1964).

Figure 7.47 In this case, the pull-through procedure was performed for an in lammatory disease. The last 1 cm of rectum was not spared (a). (b) The inal result. This dog was permanently incontinent. Another dog with a similar surgery regained clinical fecal continence after ive months for unknown reasons (Morello et al. 2008). One study has suggested that in dogs, as in humans, there is an increased tendency to develop pigment gallstones after proctocolectomy, which is associated with an increase in the concentration of unconjugated bilirubin in gallbladder bile (Noshiro et al. 1996). It is not known if this is clinically relevant in domestic animals.

Extent of Resection During resection of the large intestine beyond the caudal peritoneal re lection, care should be taken to ligate only those vessels that are to be de initively transected, in order to maximize the preservation of blood supply to the remaining segment of bowel. This necessity limits the amount of rectum that should be resected via the transanal approach. Following resection, the end-to-end approximating intestinal

anastomosis should always be tension-free to avoid complications. The combined procedures (the so-called Swenson’s pull-through and modi ications described previously in this chapter), carry a high complication rate and should be reserved for very extensive malignant tumors located at the mid and/or cranial third of the rectum requiring extension into the descending colon to achieve complete margins (Morello et al. 2008). In these cases, pubic/ischial osteotomy may be a better alternative (Yoon and Mann 2008). The pubic/ischial osteotomy approach may offer more advantages for resection of malignant tumors over the combined procedures due to a more accurate vessel ligation and anastomotic technique.

Posttreatment Prognosis Dogs Intestinal tumors account for less than 10% of all tumors (Selting 2013). The large intestine is more frequently affected and represents 36–60% of all canine intestinal neoplasia. Colorectal tumors are more prevalent in male dogs (Patnaik et al. 1977; Holt and Lucke 1985; Birchard et al. 1986; Church et al. 1987). The reported mean age is around seven to eight years, with a mean weight of 30 kg (range 3.7– 57) (Seiler 1979; Holt and Lucke 1985; Church et al. 1987; Phillips 2001). More than half of colorectal cancers are malignant, with adenocarcinoma being the most prevalent malignant tumor (Cotchin 1959; Patnaik et al. 1977; Church et al. 1987). Other less common colorectal neoplasia include leiomyoma (McPherron et al. 1992); leiomyosarcoma (Brueker and Withrow 1988; Kapatkin et al. 1992; Bagley et al. 1996; Cohen et al. 2003); plasmacytomas (Kupanoff et al. 2006; Rannou et al. 2009); carcinoids (Patnaik et al. 1980; Sykes and Cooper 1982; Selting 2013); lymphoma (Van den Steen et al. 2012; Richardson et al. 2019); and rectal malignant melanoma (presumably at the anorectal junction) (Clarke and Rissi 2018). Adenomatous polyps account for the majority (up to 50%) of benign rectal tumors (Holt and Lucke 1985; Birchard et al. 1986). In situ carcinoma (Tis), a transition between adenomatous polyp and invasive carcinoma has been reported to have histological evidence of atypia

that may progress to malignancy in 17–50% of cases (Seiler 1979; Patnaik et al. 1980; Holt and Lucke 1985; Birchard et al. 1986; Valerius et al. 1997; Danova et al. 2006). After marginal resection, the recurrence rate has been reported to be as high as 55% for carcinoma in situ and 17% for adenomatous polyps (Valerius et al. 1997; Phillips 2001). Local resection yields a survival of 5–24 months (Seiler 1979). A minimum 2 cm margin of resection is recommended for excision of both these lesions because polyps excised marginally may recur (Morello et al. 2008) and progress to malignancy. In most clinical situations, however, these lesions are often marginally resected initially (via excisional biopsy; see the discussion on simple excision above), and should the histopathology identify an adenomatous polyp, periodical monitoring is warranted. A more radical surgery is indicated if there is recurrence of the mass and a biopsy con irms malignant progression (Morello et al. 2008). It should also be understood, however, that endoscopic biopsies may be too super icial to demonstrate malignant progression such as the development of carcinoma in situ. For this reason, a resection margin of a minimum of 2 cm (see also discussion on adenocarcinoma) should be recommended for the excision of recurrent polyps and carcinoma in situ previously excised marginally (Morello et al. 2008). A predisposition of Japanese miniature dachshunds to in lammatory colorectal polyps (ICRP), commonly involving the descending colon and rectum, has been suggested. ICRP is a nonneoplastic disease and is thought to represent a novel form of IBD; it should be differentiated from adenomatous polyps by histology as, potentially, the two diseases may be concurrent or asynchronous. As the long-term prognosis of ICRP is unknown, periodical monitoring via endoscopy is warranted as the progression to adenocarcinoma is thought to occur (Saito et al. 2018). Suggested treatments include immunosuppressive therapy, marginal (submucosal) excision, and endoscopic polypectomy (Igarashi et al. 2012; Ohmi et al. 2012; Ohta et al. 2013; Horikirizono et al. 2019). Canine adenocarcinoma is described as nodular (single or multiple), pedunculated, or annular-constrictive (Patnaik et al. 1980; Church et al. 1987; Phillips 2001). It has been reported that pedunculated or polypoid lesions have a good prognosis after surgical resection,

whereas the annular colorectal adenocarcinoma is characterized by the worst prognosis. The latter is often a high-grade adenocarcinoma; based on the extent of histological differentiation, adenocarcinoma has been described as well, intermediately or poorly differentiated or anaplastic (Adamovich-Rippe et al. 2017). A high expression of both Ki67 and MCM-3 has been associated with malignancy (Spużak et al. 2017). The reported metastatic rate for rectal adenocarcinoma ranges from 0 to 80% (Patnaik et al. 1980; Church et al. 1987); however, a high expression of both β-catenin and E-cadherin (markers of intercellular connection) would justify a low metastatic rate despite a high-grade histological pattern (Spużak et al. 2017). In an older report dealing with 78 colorectal adenocarcinomas (of which about 50% con ined to the mid-rectum), dogs with annular tumors had the shortest mean survival (1.6 months), while those with single and pedunculated tumors had the longest mean survival (32 months). Dogs that did not have any surgical treatment had a mean survival time of 15 months; for dogs that received a surgical treatment, the survival was seven to nine months longer in comparison with the untreated animals. In particular, the mean survival was 24 months after cryosurgery, and 22 months after local excision (Church et al. 1987). In other reports, the mean survival time ranged from 6 to 14 months (White and Gorman 1987; Williams and Niles 2005). In a later study, with more aggressive excision in 11 dogs (of which eight had a rectal adenocarcinoma and two had carcinoma in situ, median disease-free interval and survival times not reached), the mean disease-free and overall survival times were 44.3 and 44.6 months (range, 0–75 months), respectively; the postoperative recurrence and metastatic rates were 18.2 and 0%, respectively (Morello et al. 2008). Finally, in a VSSO multicenter study, the median survival times for rectal carcinoma in situ and adenocarcinoma were 33 and 23 months, respectively (Nucci 2014). Recommended margins of resection vary among authors: From 1 to 2 cm, either for rectal polyps or malignancy, to a minimum of 2 cm to 4 to 8 cm for malignancies of both the small and large intestine (Palminteri 1966; Crawshaw et al. 1998; Phillips 2001; Williams and Niles 2005; Danova et al. 2006; Aronson 2012). A modi ied TNM system for canine

colorectal adenocarcinoma has been reported (Turrel and Theon 1986), and a further modi ication of this TNM system, with respect to the T grading, has been proposed (Morello et al. 2008; AdamovichRippe et al. 2017). The modi ied scheme is as follows: T0 (no evidence of tumor); Tis (in situ carcinoma – mucosal; intraepithelial or invasion of the lamina propria); T1 (tumor in mucosa and submucosa only); T2 (tumor extending to muscularis and serosa); and T3 (tumor extending to a contiguous structure). This modi ication has been tentatively correlated to margins of resection: Eight adenocarcinomas and two Tis were removed with 3–6 cm of grossly normal tissue on both sides of the resection, and one Tis was removed with 2 cm of grossly normal tissue on both sites of the resection. Postoperative recurrence and metastatic rates for adenocarcinoma were 18.2 and 0%, respectively. Applying the modi ied staging system, long survival times are therefore expected after complete surgical excision of TisN0M0 and T1N0M0 adenocarcinoma. Resection margins of a minimum of 5 cm are recommended given that in one case incomplete margins were detected at 5 cm (Morello et al. 2008). This principle should be applied for any intestinal malignancy; however, for colorectal tumors this extent of excision is not always feasible. At present, it is this author’s opinion that aggressive colorectal resection should be reserved for high-grade tumors only. From a cancer biology perspective, a recent study compared canine and human colorectal cancers and demonstrated a strong degree of genetic homology in terms of copy number alternatives (CNAs), suggesting a high probability of these genetic alterations being cancer causative rather than passenger changes (Tang et al. 2010). A preliminary study on the characterization of the expression pattern of claudin tight junction proteins (implicated in epithelial cellular adhesion and therefore in colorectal carcinogenesis) in canine colorectal cancer has been published (Jakab et al. 2010b). Reported potential markers for canine colorectal cancer are both CDX-2 and HER-3 (Doster et al. 2011). The expression of E-cadherin, beta-catenin, and APC (adenomatous polyposis coli) protein has been evaluated and correlated with the degree of malignancy (Restucci et al. 2009; Aresu et al. 2010; Youmans et al. 2012; Spużak et al. 2017).

Leiomyoma and leiomyosarcoma are more frequent in medium to large canine breeds; the age of affected dogs normally ranges from 9 to 11 years (the latter mainly in the case of cecal leiomyosarcoma) (Maas et al. 2007); however, dogs younger than two years have been reported with these tumors (Holt and Lucke 1985). Even if benign, leiomyoma may cause obstruction depending on its size and location (Katamoto et al. 2003) (Figure 7.35). Rarely, leiomyosarcoma may be associated with paraneoplastic hypoglycemia (Bagley et al. 1996). Leiomyosarcomas (see Figures 7.23 and 7.24a) are invasive but slow to metastasize. They may occur both in the small and large intestine (in the latter most commonly in the cecum). GISTs have been reported in dogs and are differentiated from leiomyosarcoma using immunohistochemistry (positivity for c-kit immunoreactivity and, more recently, also for DOG1) (LaRock and Ginn 1997; Frost et al. 2003; Maas et al. 2007; Gillespie et al. 2011; Hayes et al. 2013; Selting 2013; Dailey et al. 2015). Canine GISTs are more frequent at the level of the cecum and small intestine and may metastasize (Frost et al. 2003; Maas et al. 2007; Hayes et al. 2013; Hobbs et al. 2015). Histological malignancy in dogs is more often observed in cecal GISTs; in these cases, perforation and peritonitis may occur (Maas et al. 2007). In humans, GISTs are the most common mesenchymal tumor of the gastrointestinal tract and originate from the interstitial cell of Cajal and distinctiveness from smooth muscle tumors has been documented (Corless 2014). Ki-67 expression may be prognostic for recurrence in humans (Belev et al. 2013). Similar evaluations have also been conducted in canine GISTs, but no de initive result has been reached (Gillespie et al. 2011). At present, treatment in humans is based on surgery (when feasible) and speci ic inhibitors of KIT tyrosine kinase function (e.g. imatinib mesylate [Li and Meng 2015]) when molecular studies demonstrate KIT protooncogene mutations (Corless 2014). These inhibitors may be used either as adjuvant treatment or palliation for unresectable and metastatic tumors (Gold and DeMatteo 2006), but resistance to the drug may occur (Antonescu and DeMatteo 2015). The same positivity for KIT proto-oncogene mutations in dogs (Frost et al. 2003; Maas et al. 2007; Gregory-Bryson et al. 2010) may also justify, in selected cases, the use of such KIT tyrosine kinase inhibitors in this species (Kobayashi et al.

2013; Irie et al. 2015). Nevertheless, a complete and durable (at least nine months) response to toceranib phosphate was obtained in a dog affected with a widely metastatic caecal GIST, negative for both exons 8 and 11 c-kit mutation (Elliot et al. 2017). Finally, in a recent retrospective study including 27 dogs affected with GIST and treated with toceranib, a clinical bene it was reported in ive of seven dogs with advanced disease (three complete responses, one partial response, and one stable disease), with a median PFI of 110 weeks (range 36–155); when used adiuvantly, the median PFI was 67 weeks (range 9–257) (Berger et al. 2018). Surgical margins for leiomyosarcoma and GIST should carry the same rules as those applied to adenocarcinoma while leiomyoma may be resected marginally (Figures 7.33 and 7.34). Marginal resection for colorectal leiomyosarcoma or GIST (Figures 7.23, 7.29, and 7.31) may be then followed by a more radical excision following de initive diagnosis (Figure 7.42). Long disease-free intervals are expected after surgery for smooth muscle neoplasms. Reported median survival (with or without metastasis) is about 21 months; the reported one- and twoyear survival rate is 75 and 66%, respectively (Brueker and Withrow 1988; Kapatkin et al. 1992; Cohen et al. 2003). No statistical difference was found when GISTs were compared with non-GIST smooth muscle tumors. In one study, the one- and two-year recurrence-free period for cecal tumors was 83.3 and 61.9%, respectively. Interestingly, both castrated and spayed dogs showed a longer survival (Maas et al. 2007). Plasmacytomas may be secretory, resulting in hyperproteinemia and monoclonal gammopathy (Trevor et al. 1993). They are characterized by slow growth and lack of recurrence after complete excision (Kupanoff et al. 2006). While the de initive margin of resection is not known, a 1–2 cm margin of macroscopically healthy tissue is generally recommended around the tumor. Isolated rectal lymphoma in 11 dogs has been retrospectively evaluated (Van den Steen et al. 2012). Median age at diagnosis was 6.5 years (range 2.6–13.7 years). Excisional surgery was performed in six dogs (clean margins in two and narrow in one), while the others had an incisional biopsy only. Immunohistochemistry revealed a B-cell origin in all the samples examined. Treatment consisted of surgery only (one

dog), chemotherapy only (one dog), surgery/chemotherapy (six dogs), prednisone/lactulose (one dog), and no treatment (one dog). The mean survival time was 1697 days (95% con idence interval 935.5 to 2460.4); the MST was not reached. Dogs that received chemotherapy lived signi icantly longer than those which did not (2352 vs. 70 days). A further characterization of three canine primary colorectal follicular lymphomas has been recently reported (Richardson et al. 2019). Carcinoids are rarely reported and may metastasize (Patnaik et al. 1980; Sykes and Cooper 1982; Selting 2013); if complete excision is attempted, the same recommendations applied to any colorectal malignancy are followed. One case of rectal ganglioneuroma has been reported in a dog that was still alive 2.5 years after excision (Reimer et al. 1999). A case of colorectal hamartomatous polyposis and ganglioneuromatosis has been reported in a ive-month-old Great Dane puppy (Bemelmans et al. 2011). Finally, the author of this chapter has observed a case of rectal mast cell tumor that was metastatic to sublumbar and colic lymph nodes (Figure 7.48). Cats Most reported information for colonic neoplasms in cats comes from the publication by Slawienski et al. (1997). Colonic neoplasms account for less than 1% of all feline tumors and 10–15% of all alimentary tumors. In this species, the small intestine is more frequently affected than the large intestine (Selting 2013). The reported mean age is 12.5 years, and a predisposition has been reported in Siamese cats. The most prevalent neoplasms include adenocarcinoma, which may cause colonic obstruction (Bedford 1998), lymphoma (many of which are localized at the ileocecal valve and can result in ileocolonic intussusception and rectal prolapse) (Demetriou and Welsh 1999); mast cell tumors; and carcinoids (neuroendocrine carcinoma). Hemangiosarcoma has also been described in cats (Sharpe et al. 2000); surgery is recommended whenever possible to increase survival times, and resection margins should comprise 2.5–5 cm of macroscopic healthy tissue and include excision and biopsy of any metastatic lesion.

Prognosis is poor, as all the four cats with hemangiosarcoma in one study died or were euthanazed within one week (Sharpe et al. 2000).

Figure 7.48 (a) The clinical appearance of a prolapsed rectal mast cell tumor in a nine-year-old spayed female Rottweiler. (b) The tumor was attached to the rectum with a sessile base at about 3 cm from the anus. (c) Colic lymph nodes were excised and histologically examined to con irm their metastatic involvement; multiple sublumbar lymph nodes were also enlarged and were biopsied. The primary tumor was marginally excised during a pull-out procedure. After con irmation of the diagnosis, further treatment was declined by the owner and the dog was lost to follow-up.

For feline colonic adenocarcinoma, the reported median survival after complete excision is about 138 days (range 119–314). Metastasis has been associated with poorer prognosis. Chemotherapy with doxorubicin has been shown to increase survival times (Slawienski et al. 1997). More recently, the results of subtotal colectomy and adjuvant carboplatin (median dose of 200 mg/m2 [range 200–254] every four weeks, two to seven times [median of 5]) in 18 cats (median age at presentation of 11 years [4.6–19]) have been published (Arteaga et al. 2012). Surgical margins were complete in all cases while local and systemic metastasis in the perioperative period (as a result of both preand postoperative staging) was detected in eight and three cats, respectively. The reported median disease-free interval was 251 days (range 37–528, with weight loss at presentation interestingly being a positive prognostic indicator), while the MST was 269 days (range of 40–533 days, with metastasis [nodal and distant] representing a negative prognostic indicator [178 vs. 328 days and 200 vs. 340 days, respectively]). During the follow-up, distant metastasis developed in all 18 cats. In another study, palliation in two cats was provided by colonic stenting (placed under luoroscopy guidance, with colonic patency achieved until death) and nonsteroidal anti-in lammatory medication, with a survival of 274 and 54 days (Hume et al. 2006). Cats may also be affected with colorectal adenocarcinoma; resection may be performed in selected cases (Figure 7.49). Large intestinal mast cell tumors are rare in cats and some may be at the level of the ileocecocolic junction (Laurenson et al. 2011). Metastasis at presentation to the colic and mesenteric lymph nodes and the liver is frequent. Complete surgical excision should be attempted for isolated lesions. The reported median survival is 199 days (range 69– 412 days) (Slawienski et al. 1997).

Figure 7.49 Phases of colorectal resection for a colorectal adenocarcinoma in a cat placed in dorsal recumbency. The technique looks like the so-called Swenson’s pull-through modi ied by Morello et al. (2008). (a) Via a caudal celiotomy, the descending colon and cranial rectum have been isolated; the caudal colonic stump has been closed with a single suture at a point thought to be adequate in terms of excisional margins. (b) and (c) Via a standard transanal approach, the intestinal segment bearing the tumor has been exteriorized from the anus and then detached from the orad colonic stump. (d) End-to-end anastomosis of the colonic stump to the caudal rectal stump. (e) Final appearance of the anus. The abdomen has been closed routinely. Source: Pictures courtesy of Dr. Massari Federico.

Feline large LSA may be multicentric at presentation to colic and mesenteric lymph nodes, the liver, and the kidney. The role of both

surgery and chemotherapy is unknown (Slawienski et al. 1997), but surgery may occasionally be indicated when the lesion is isolated and/or in the case of colonic obstruction. Carcinoid tumors (neuroendocrine carcinoma) are very rarely reported. In the two feline cases reported by Slawienski et al. (1997), both were metastatic at presentation to the colic and mesenteric lymph nodes, liver, and the peritoneum. If complete excision is to be performed, the same recommendations applied to other colorectal malignancies are followed.

Adjuvant Therapies The administration of cyclooxygenase-2 (COX-2) inhibitors (e.g. piroxicam) has been suggested in dogs with polyps and malignant epithelial colorectal cancers (Knottenbelt et al. 2000a, 2000b, 2006). In humans, their prolonged administration has shown promising results in preventing the progression of epithelial colorectal cancer, but serious cardiovascular side effects may arise from these treatments (Bertagnolli 2007). More recently, new formulations of piroxicam have been studied for palliation/adjuvant treatment of colorectal malignancy in humans (Vats and Pathak 2012). Anecdotally, piroxicam suppositories have also been used to palliate the clinical signs of colorectal malignancies in dogs, but prospective studies are warranted to con irm the clinical utility. Adjuvant doxorubicin for feline colonic adenocarcinoma may lead to an MST that is longer (280 days; range, 210–354) compared to cats that did not receive doxorubicin (56 days; range, 2–259) (Slawienski et al. 1997). Chemotherapy (doxorubicin or mitoxantrone) and radiotherapy have also been suggested for both canine leiomyosarcoma and adenocarcinoma, but their ef icacy in large clinical trials has not been demonstrated (Ogilvie et al. 1991; Cohen et al. 2003). Intraoperative radiotherapy, if available, may be recommended for the excision sites of metastatic sublumbar lymph nodes.

Finally, the use of speci ic inhibitors of KIT tyrosine kinase function should be considered in cases of either inoperable and/or metastatic GISTs or as an adjuvant treatment; the evaluation of the KIT protooncogene mutation status may help to interpret the therapeutic results. Toceranib (Palladia), a KIT inhibitor, has been shown to have biological activity against GISTs in dogs. In one study, ive of seven dogs with gross disease experienced a clinical bene it (three complete responses, one partial response, one stable disease). Median PFI in dogs with gross disease was 110 weeks (Berger 2018).

Perianal Tumors Surgical Procedures Surgical procedures for perianal tumors include castration only, cytoreduction or marginal excision of perianal hepatoid adenoma/epithelioma in conjunction with castration, en bloc excision of any perianal malignancy with or without anoplasty (rectocutaneous suture), mono- or bi-lateral anal sac removal, and metastasis resection.

Clinical Workup and Biopsy Procedures The clinical work-up and the biopsy principles for perianal tumors include a complete physical examination as well as the following. Digital Rectal Examination Perianal hepatoid tumors originate from the circumanal modi ied sebaceous glands that are called hepatoid due to their resemblance to liver cells on cytology and histology. They are usually visible and palpable (Figures 7.50 and 7.51), and in the case of malignancy, circumferential growth can result in palpable stenosis (Figure 7.52). Stricture in this area, however, is not pathognomonic for neoplasia as it may occur secondary to trauma and in lammatory diseases such as perianal istulas (the latter particularly in German shepherd dogs) and infection (chronic sacculitis). Anal stricture can also be idiopathic as a result of anorectal spastic contraction. This condition, observed also by this author, is very rare and seen more frequently in German shepherd

dogs; it usually disappears under general or epidural anesthesia (Niebauer 1993). Tumors of anal sacs are only sometimes detectable by palpation and can be palpated during rectal examination at the 4 o’clock and 8 o’clock positions (Figure 7.53), sometimes as an incidental inding (Williams et al. 2003). This maneuver may facilitate performing an FNA for a cytological examination. Rectal palpation may also de ine the size of the anal sac mass (Schlag et al. 2020) or of any kind of perianal tumor, the degree of its ixation to the surrounding tissues, and the degree of circumferential involvement of the anal ring. Dogs with tumors involving less than 180° of the circumference of the sphincter are expected to maintain a “clinical” continence or regain fecal continence following surgery, while those with an involvement greater than 180° are likely to become permanently fecally incontinent.

Figure 7.50 Three different clinical presentations of canine hepatoid adenoma: (a) Single perianal adenoma; (b) “invasive” perianal adenoma; and (c) multiple perianal adenoma. These lesions may only be correctly diagnosed by biopsy and histological examination. Rectal palpation is also useful to detect any so-called sublumbar lymphadenomegaly (see also the discussion on “colorectal tumors”). In dogs, this iliosacral lymphocenter includes the sacral (variably present, and ventral to the sacrum), internal iliac (previously called hypogastric

lymph nodes, ventral to the sixth or seventh lumbar vertebrae at the bifurcation of the internal iliac arteries, and medial to the external iliac artery), and medial iliac lymph nodes (ventral to the ifth to sixth lumbar vertebrae, between the deep circum lex and external iliac arteries, lateral to the latter, paired and sometimes double) (Bezuidenhout 1993; Llabrés-Diaz 2004; Majeski et al. 2017; Pollard et al 2017). An indirect computed tomographic lymphangiography (ICTL), to be performed just before the surgical excision of anal sac adenocarcinomas in dogs placed in sternal recumbency, has been proposed (Majeski et al. 2017). ICTL, that consists of a peritumoral subcutaneous injection of 1 ml of nonionic iodinated contrast material, may help the identi ication of the lymphatic pathways and sentinel lymph nodes of this iliosacral lymphocenter to be biopsied (Majeski et al. 2017). This applies to cases characterized by a subclinical sublumbar lymphadenopathy.

Figure 7.51 (a and b) Two different presentations of canine perianal adenocarcinoma.

Figure 7.52 Hepatoid perianal adenocarcinoma in an 11-year-old male German shepherd causing anal stenosis. Complete laboratory workup (blood, urine). Possible changes observed include hypercalcemia, in 25–50% and even reported in as high as 90% of cases with anal sac adenocarcinoma; it is occasionally seen in cases of perianal adenocarcinoma (White and Gorman 1987; Berrocal et al. 1989; Rosol et al. 1990; Ross et al. 1991; Bennett et al. 2002; Williams et al. 2003). Serum calcium should be evaluated; ionized calcium is preferred over total calcium (Messinger et al. 2009). Secondary hypophosphatemia (Potanas et al. 2015) and increases in renal parameters can be seen after prolonged hypercalcemia. In anal sac adenocarcinoma, hypercalcemia is caused by a parathyroid hormonerelated protein (PTHrp) produced by the tumor (Rosol et al. 1990; Gröne et al. 1994; Mellanby et al. 2006); in perianal adenocarcinoma, the cause of hypercalcemia is uncertain, and the author has not observed this inding in any clinical cases. Cardiologic Examination This examination is particularly important in hypercalcemic dogs to reveal potential arrhythmias. Tumor Biopsy FNA and cytological examination can con irm the hepatoid nature of the tumor without, in many cases, giving an exact diagnosis (adenoma vs. epithelioma vs. adenocarcinoma). The proportion of basal cells at cytology fails to indicate a potential hepatoid malignancy (Evans et al. 2018). A tentative algorithm to cytologically distinguish between benign and malignant hepatoid tumors has been recently reported (Sabattini et al. 2019); besides, another author has also suggested the evaluation of speci ic nuclear morphometric variables as an adjunct for distinction between benign and malignant hepatoid tumors (Simeonov 2019). Anyhow, as the differentiation between hepatoid adenoma and adenocarcinoma or squamous cell carcinoma (as well as perianal istulas) may be often dif icult, an incisional biopsy and histology can be necessary. Nonetheless, diagnostic information is often provided by cytology for other tumor types found in this region, including apocrine gland adenocarcinoma of the anal sac.

Figure 7.53 (a) Right anal sac adenocarcinoma in a dog, and (b) in a cat. Source: Picture (b) courtesy of Dr. Farese James.

Biopsy samples from perianal tumors can be obtained by using a Trucut needle (needle core biopsy), which may require sedation, punch biopsy (also done without anesthesia if the lesion is already ulcerated), incisional biopsy, or excisional biopsy. FNA from enlarged sublumbar lymph nodes can be performed during a digital rectal exploration (see also section on colorectal tumors, Figure 7.22) or via transabdominal ultrasonographic-guided aspiration (Llabrés-Diaz 2004).

Imaging Techniques The features of normal anal sacs using ultrasound, MRI, and contrast radiography, both in dogs and cats, are available in the veterinary literature (Jung et al. 2016). There are several imaging techniques used to stage perianal tumors.

Lateral radiographic evaluation of the abdomen may be useful to assess for sublumbar lymphadenomegaly (Figure 7.54). In selected cases, urethrocystography may be useful to outline urethral compression by an exceedingly large metastatic sublumbar lymph node (Hoelzler et al. 2001).

Figure 7.54 Lateral abdominal radiograph which shows an enlargement of the sublumbar lymph nodes secondary to an anal sac adenocarcinoma in a dog. The ventral aspect of both the sacrum and seventh lumbar vertebra show some productive changes. Source: Courtesy Dr. Sheldon Padgett.

Ultrasound examination of the abdomen is more useful than radiology to evaluate the sublumbar region (Llabrés-Diaz 2004), liver, spleen, and

all the other abdominal organs. However, sacral lymph nodes, not always present, may require the use of a combination of imaging techniques to be visualized because of their intrapelvic localization (Anderson et al. 2015; Potanas et al. 2015; Palladino et al. 2016; Majeski et al 2017; Pollard et al. 2017). While MRI has been shown to be superior to ultrasound in detecting abnormal lymph nodes in dogs with anal sac adenocarcinoma (Anderson et al. 2015), another study has shown that contrast-enhanced CT is superior to ultrasound in identifying the number of apparently normal iliosacral lymph nodes, in particular medial iliac and sacral lymph nodes, but, surprisingly, ultrasound was slightly more speci ic in detecting abnormal lymph nodes (Pollard et al 2017). Indirect Computed Tomographic Lymphagiography (ICTL) has been proposed to identify the lymphatic pathways and sentinel lymph nodes of the iliosacral lymphocenter to be biopsied in the case of anal sac adenocarcinoma (Majeski et al. 2017). A pilot study for lymphoscintigraphic sentinel lymph node mapping of the anal sacs in dogs has also been recently published (Linden et al 2019). The rationale for using CT is also the identi ication of the full extent of the sublumbar lymphadenopathy, as indicated by enlarged lymph nodes, and detection of further metastatic sites that may in luence both treatment and prognosis (Palladino et al. 2016). During ultrasound, transabdominal guided FNA (using a 22- or 20gauge spinal needle) or biopsy (using an 18-gauge Tru-Cut biopsy needle) may be performed. Interestingly, even though not demonstrated histologically, all sublumbar lymph nodes greater than 1 cm have shown neoplastic progression in one report (Polton and Brearley 2007). The inding of large vessel in iltration in the sublumbar area from metastatic lymph nodes may be a contraindication for surgery; in this case, palliative procedures such as radiotherapy with or without chemotherapy should be considered (Polton and Brearley 2007). Ultrasound examination of both testicles can be used to evaluate the presence of lesions that are not palpable clinically (frequently, this would be an interstitial cell tumor concomitant with a hepatoid adenoma).

Radiographic evaluation of the thorax is performed with the standard three views (two lateral, one dorsoventral) to assess for lung metastasis, which is more commonly seen with anal sac adenocarcinoma and malignancies other than those of hepatoid origin (Figure 7.55). A case of lung metastases caused by an anal sac adenocarcinoma associated with paraneoplastic hypertrophic osteopathy in a dog has been reported (Hammond et al. 2009). Another dog has been reported to develop hypertrophic osteopathy late in the progression of a hypercalcemic anal sac adenocarcinoma that developed a sublumbar metastatic lymphadenopathy without clear and progressive lung metastasis (Giuliano et al. 2015).

Figure 7.55 Multiple lung metastases from an anal sac adenocarcinoma in a dog. Metastasis is also present in a humerus. Laparoscopy, if available and in the hands of an experienced operator, can be useful to inspect the entire abdomen and the sublumbar space,

allowing for biopsy collection or sublumbar lymph node excision. A technique of laparoscopic bilateral excision of bilateral medial iliac lymph node has been reported (Lim et al. 2017). CT can be used to assess the lungs, presence of lymphadenomegaly (as discussed previously), and abdominal organs. In the case of sublumbar lymph node involvement, different imaging procedures (Anderson et al. 2015; Potanas et al. 2015; Palladino et al. 2016; Pollard et al. 2017) may provide valuable (but not de initive) information regarding tumoral involvement of great vessels and surgical resectability of nodes (Figures 7.56–7.58).

Figure 7.56 The CT appearance of an extensive iliac internal lymphoadenopathy, metastatic from an anal sac adenocarcinoma in a dog. During the dissection, a rupture of one internal iliac artery occurred; this vessel was closed, without any clinical consequence. Bone scintigraphy, if available, may be used in selected cases of anal sac adenocarcinoma to assess for bone metastases.

Surgical Techniques and Procedures Surgery of the perianal region may be performed traditionally, with a CO2 laser, or only for small lesions using cryosurgery (Liska and Withrow 1978; Dow et al. 1988; Shelley 2002). Histology should be performed on all surgical specimens. The evaluation of the excisional margin is not possible if laser or cryosurgery are used, and this is considered acceptable only for benign lesions (Turek and Withrow 2013); testicles and lymph nodes that are excised are also submitted for histology. Gloves and surgical instruments are changed after the tumor has been excised, and at any time contamination from the anus, anal sacs, and/or rectum has occurred.

Figure 7.57 (a) CT scan of a large sublumbar lymph node that caused a signi icant obstruction of the colorectum at the pelvic inlet in a dog. Metastatic lymphadenomegaly originated from a perianal adenocarcinoma. (b) At necropsy, the tumor surrounded the blood vessels; a thrombus is also evident in the caudal vena cava (arrow).

Figure 7.58 (a) CT scan of a large medial iliac lymph node secondary to a perianal adenocarcinoma. The great vessels are peripheral. (b) Intraoperative view after node resection (top of the picture is cranial). (c) Postoperative macroscopic view of the node. Castration Castration may be the sole procedure required in intact males for small, nonulcerated, and histologically con irmed hepatoid adenomas (perianal and/or tail gland) as it induces progressive tumor shrinking. As an alternative, an incisional or excisional biopsy is performed, with histology as a guide to plan further steps (clinical observation over a period of two months, marginal or en bloc excision with or without castration, depending on the histological result). Cytoreduction or Marginal Excision This technique is used for histologically con irmed hepatoid adenoma (perianal and/or tail gland) together with castration in intact males (Figures 7.59 and 7.60). In females, marginal excision of perianal adenoma, usually of small size, may be suf icient. In this author’s opinion, the use of either a braided or mono ilament absorbable suture material is suitable in the perianal region; however, the latter is somewhat stiffer and can cause discomfort to the animal.

Correction of Perineal Hernia Correction of perineal hernia may be required as it is observed in 10% of dogs with perianal adenoma (Wilson and Hayes 1979). It should also be noted that a testicular interstitial cell tumor may be present in combination with a perineal hernia. En bloc Excision With or Without Anoplasty A minimum of 1–3 cm of macroscopically normal tissue should be included around a malignant tumor; reconstruction often requires suturing the rectum to the skin (Figure 7.61). En bloc excision in this region includes removal of variable portions of perianal/perineal skin, part or all of the external sphincter muscle, one or both anal sacs (Figures 7.61 and 7.62), part or all of the anal canals up to the caudal rectum (pull-through [Figure 7.63]), and in some instances amputation of the tail (Figure 7.64). The reconstruction may warrant the use of local skin advancement or transposition laps (Figure 7.65). Moistened gauze sponges are packed into the rectum to avoid the spillage of fecal material into the pelvic canal. In a standard anoplasty, closure may be performed in one or two layers with simple interrupted sutures. The single-layer suture pattern, involving the full thickness of the rectal wall, approximates the submucosa/mucosa of the rectal stump to the subcutis/skin (using 3-0 or 4-0 absorbable braided, e.g. polyglactin 910, or mono ilament material); in the two-layer suture anoplasty (recommended), absorbable mono ilament material (3-0 or 4-0 polydioxanone, polyglyconate, poliglecaprone 25) is used for the irst layer (adventitia/muscularis of the rectum/subcutaneous perianal tissue), and in the second layer the epithelial lining (skin/rectal submucosa-mucosa or skin/skin depending on the excision performed) is approximated with either 3-0 or 4-0 absorbable braided (e.g. polyglactin 910) or mono ilament material. The sutures must be applied with as minimal tension as possible (Aronson 2012). This author often uses a single-layer closure and reserves the two-layer closure for cases with excessive tension.

Figure 7.59 (a–d) Marginal excision of a large perianal adenoma. Source: Photos from Buracco (2007). Used with permission.

Figure 7.60 (a) Multiple perianal adenomas. (b) Postoperative view after marginal excision.

Figure 7.61 Phases of anoplasty. (a) The anal region, together with both anal sacs and the external sphincter muscle have been excised, and (b) the rectum has been sutured to the skin. As the external sphincter muscle has been removed, this dog will be permanently incontinent. This issue should be discussed with the owner before surgery. Anal Sac Removal If hypercalcemia is present, this should be treated before surgery using parenteral luid therapy, and if necessary, furosemide, prednisone, bisphosphonate, and calcitonin. Anal sacculectomy for neoplasia is usually performed unilaterally, but it should be noted that anal sac adenocarcinoma may also be bilateral in up to 10% of cases at initial presentation (Ross et al. 1991; Emms 2005; Turek and Withrow 2013; Liptak 2015) or become bilateral later in the course of the disease (Emms 2005; Bowlt et al. 2013; Turek and Withrow 2013; Barnes and Demetriou 2017). Prolonged survival can be achieved even when concurrent excision of metastatic regional lymph nodes is performed

(Hobson et al. 2006; Polton et al. 2007; Barnes and Demetriou 2017). Surgical excision is also indicated for any local recurrent lesion and/or further sublumbar lymphadenopathy, if feasible (Barnes and Demetriou 2017). Anal sac adenocarcinoma occurs rarely in cats and excision is performed in a similar manner to canine anal sac tumors (Chun et al. 1997; Mellanby et al. 2002; Parry 2006; Wright et al. 2010; Elliot and Blackwood 2011; Amsellen et al. 2019).

Figure 7.62 Phases of the excision of a perianal soft tissue sarcoma in a dog. (a) Clinical appearance of the tumor. (b) The surgical excision has been completed, and variable amounts of skin, fascia, and muscles (including part of the external sphincter) have been removed. (c) Final appearance of the wound (the use of skin laps was not required in this case). The dog experienced transitory fecal incontinence.

Figure 7.63 (a) The clinical appearance of an anal carcinoma causing fecal obstruction in a eight-year old male Dobermann dog. (b) The circumferential incision has been started on the skin and both the anus (including the remnant of the external sphincter muscle and both anal sacs) and rectum have been brought externally (after resection of both rectococcyeal muscles, dorsally on the midline). Dorsal incision on the dorsal wall of the mid-rectum has been started and the proximal impacted feces are removed. (c) After that, rectal resection is completed, with also application of 2 stay sutures; the rectal stump is then sutured in place. (d) Post-excisional appearance of the en bloc resected tumor. (e) The clinical appearance of the dog after 20 days from surgery; on the right side the second intention healing (after partial suture dehiscence) resulted in a ibrosis that did not cause obstruction. Fecal incontinence at this time was much less problematic for the owners and more controllable than before surgery.

Figure 7.64 (a) The clinical presentation of a recurrent perianal adenocarcinoma. (b) To achieve suf icient margins of macroscopically normal tissue, the tail was amputated. For reconstruction, the dorsal skin of the tail was spared and used as a skin lap. Anal sac tumor excision is often performed marginally, but wide excision is attempted in all cases where this is feasible and indicated (small-sized primary tumor and absence of distant metastasis, including those to sublumbar lymph nodes). Examples of anal sac adenocarcinoma excision in dogs are provided in Figures 7.66 and 7.67; a wide anal sac excision in one cat is provided in Figure 7.68. In case of bilateral anal sac adenocarcinoma, marginal excision may be the preferred choice (Emms 2005) to minimize the risk of postoperative fecal incontinence. Surgical techniques described for anal sacculectomy can be divided into open and closed techniques. Only closed techniques are used to remove an anal sac tumor as the open techniques increase the risk of tumor cell seeding. Resection of the entire anal sac duct en bloc with the anal sac is also recommended when the surgery is done for tumor excision. This may help achieve complete margins.

Resection of Metastases (Metastasectomy) Resection of metastases from a perianal tumor refers mainly to the sublumbar lymphadenectomy through a midline celiotomy. It is performed most commonly in cases of anal sac adenocarcinoma (Hobson et al. 2006; Polton and Brearley 2007; Liptak 2015; Barnes and Demetriou 2017) and less commonly in cases of perianal adenocarcinoma or other malignancies such as squamous cell carcinoma, malignant melanoma, and various sarcomas. More than one sublumbar lymphadenectomy is often performed (Hause et al. 1981; Hobson et al. 2006; Liptak 2015; Barnes and Demetriou 2017) (Figure 7.69).

Figure 7.65 Advancement lap in a rectocutaneous plasty. These laps have the tendency to dehisce when one of its borders is adjacent to the base of the tail due to movement. In this case, there was dehiscence and the wound was allowed to heal by second-intention healing.

Figure 7.66 (a) Marginal excision of an anal sac adenocarcinoma in a dog. (b) Macroscopic appearance of the tumor.

Figure 7.67 Clinical (a) and CT view (b) of a large anal sac adenocarcinoma in an 11-year-old spayed female dog that was hypercalcemic at presentation. (c and d) Intraoperative pictures of the marginal resection of the primary tumor. (e) The surgical site after closure of the wound. (f) The macroscopic view of the tumor. A preoperative ICTL may help identify the sentinel lymph nodes that are not enlarged (Majeski et al. 2017). Intra-operative identi ication of enlarged sublumbar lymph nodes to be removed (see also the section on colorectal tumors) is facilitated by retracting the descending colon on one side and palpating the pulse of the descending aorta. The medial iliac lymph nodes are identi ied between the deep circum lex and external iliac arteries (on the lateral aspect of the external iliac artery) at the level of the ifth and sixth lumbar vertebrae (Figure 7.70 and 7.71); the internal iliac lymph nodes are identi ied between and in close association with the external and internal iliac arteries (medial to the

external iliac artery), ventral to the sixth and seventh lumbar vertebrae (Bezuidenhout 1993) (see also Figure 7.44, colorectal section). Lymph node removal is performed with careful undermining and dissection, more often using ingers, and only occasionally pelvic opening is performed. However, in some cases, irm adhesion of the nodes to either the sublumbar musculature or a vessel wall makes excision high risk due to hemorrhage (Ross et al. 1991) or even impossible (see Figure 7.57). One single report has described an unresectable metastatic cystic iliac lymph node that was omentalized with palliation for 18 months (Hoelzler et al. 2001). Removal of metastatic nodules in the liver via partial or total liver lobectomy), spleen (via splenectomy), lung (via partial or total lung lobectomy), or lymphadenectomy of lymph nodes other than the sublumbar lymph nodes, is occasionally performed for these tumors.

Postoperative Care Depending on the surgical procedure performed, systemic analgesics are administered for 12–72 hours and food and water are offered within 8–12 hours. An Elizabethan collar is recommended to prevent self-trauma, and ionized calcium levels should be monitored once a day during the irst 48 hours, when preoperative hypercalcemia has been documented. Normalization of ionized calcium levels usually occurs within 24 hours, when adequate resection has been performed. After an anoplasty, the perianal region should be frequently lubricated with petrolatum until the sutures are removed.

Figure 7.68 Wide excision of an anal sac adenocarcinoma in a cat. (a) The area of excision is depicted. (b) During dissection for the excision. (c) The area after excision and (d) after the inal closure. Source: Courtesy of Dr. Julius Liptak.

Figure 7.69 Macroscopic view of several sublumbar lymph nodes after excision. One of these was removed piecemeal. Removal of all affected nodes (together with the primary tumor) is essential if the dog is hypercalcemic in order to normalize calcemia.

Cosmetic and Functional Outcome Poor cosmesis may be a concern in some cases of anoplasty with or without tail amputation. Functionally, the main concern is fecal incontinence (see below).

Potential Complications Postoperative hypocalcemia caused by prolonged hypercalcemia suppressing parathyroid function rarely occurs (Williams et al. 2003; Saba et al. 2011; Olsen and Sumner 2019). It requires adequate symptomatic treatment (10% calcium gluconate intravenously in the acute phase, with monitoring of the cardiac rhythm during administration [Radlinsky 2013a]); rarely, further calcium supplementation and calcitriol administration are also indicated.

Figure 7.70 (a) Intraoperative appearance of an enlarged medial iliac node in a dog with anal sac adenocarcinoma. (b) Intraoperative appearance of the lymph node almost completely resected. Source: Photos from Buracco (2007). Used by permission.

Hematochezia can be seen for 8–48 hours or longer, depending on the surgical procedure performed. This complication is usually selflimiting. Transient tenesmus is usually self-limiting within one to ive days, depending on the surgical procedure performed. It may be associated with poor pain control. Dehiscence of an anoplasty may occur as a result of excessive tension or infection, which can be present secondary to the manipulation of the rectum and anus. If possible, the wound should be resutured to avoid stricture, otherwise the wound can be left to heal by second-intention, which necessitates frequent wound management, including warm hydrotherapy two to four times per day (Figures 7.72 and 7.73). Skin lap dehiscence is more likely if one border of the lap is adjacent to the base of the tail, as tail movement may impede lap healing (see Figure 7.65). Dehiscence may also occur after anal sac tumor removal, especially after excision of more advanced tumors; surgical revision may be sometimes necessary (Barnes et al. 2017). Another reported

complication of anal sac tumor removal is the development of rectocutaneous istula (Barnes et al. 2017).

Figure 7.71 The region of both the medial iliac (on the lateral aspect of the external iliac artery) and internal iliac (medial to the external iliac artery) metastatic lymph nodes before (a) and after (b) excision. The deep circum lex iliac artery has been ligated (arrow) during the dissection.

Figure 7.72 (a) This male German shepherd dog experienced a wound dehiscence. (b) The wound was not sutured and was managed conservatively for two weeks. In dogs undergoing sublumbar lymphadenectomy, septic shock has been reported (Ross et al. 1991; Williams et al. 2003). Temporary urinary incontinence may be a complication of sublumbar lymphadenectomy because of damage to the innervation of the bladder during resection (Ross et al. 1991). Hemorrhage, which can require a blood transfusion, is another risk. Stenosis and strictures occur mainly after anorectal surgery, including anal sac removal. Anal stricture may be the result of a poor epithelial apposition during surgery or excessive tension and infection, with further dehiscence followed by a second-intention healing resulting in cicatricial stenosis. It results in protracted tenesmus. Treatment options include bougienage, a simple incision, or a wedge resection with careful mucocutaneous apposition during suturing. If the problem persists, en bloc excision should be performed.

Figure 7.73 (a) Anoplasty; (b) following a partial dehiscence, healing has occurred via second-intention healing. Fecal incontinence is unlikely after perianal hepatoid adenoma resection as the excision is usually marginal and does not involve the external sphincter muscle, which typically is deep to the lesion. Fecal incontinence can occur following anoplasty (Ross et al. 1991). If half or less of the circumference of the sphincter is removed, incontinence is often transient, if present at all (see Figure 7.62) (Turek and Withrow 2013). If resection involves more than 180° of the circumference (Figures 7.61, 7.63, and 7.72–7.74), fecal incontinence is likely and needs to be discussed with the owner before surgery. This also applies to anal sac tumors and the degree of the circumference of the anus involved. However, in a series of 52 dogs treated surgically for an anal sac adenocarcinoma, fecal incontinence developed only in 6.9% of dogs and it was transient. Resolution of the incontinence occurred within

three weeks in three dogs and three months in another dog (Barnes et al 2017). Provided that tissue undermining is performed as close as possible to the anorectal wall (skin, super icial perianal area region containing the hepatoid glands +/– anal sacs), continence may be partially preserved (Figure 7.75), especially if a solid stool consistency is maintained with a low-residue diet. This may be acceptable for many owners, but this clinical result is dif icult to predict preoperatively. A possible explanation of preserved and progressively acquired partial fecal continence relies on the fact that the healing process provides adhesions between the rectum and adjacent tissues and muscles of the pelvic diaphragm, including the levator ani, coccygeus, retractor penis or constrictor vulvae muscles, and coccygeal fascia (Lewis 1968). It should also be noted that in a normal dog, all of these structures are anatomically connected to some extent with the external sphincter muscle. Fecal incontinence may heavily in luence the quality of life of both the animal and owner, sometimes resulting in euthanasia. Surgical procedures have been reported to help. After excision of the entire anal ring with inclusion of the last tract of the rectum, a procedure of a 225° spiralization of the remaining colorectum during the 360° rectocutaneous plasty has been reported in a cat in attempt to create a natural resistance for the passage of feces (Pavletic et al 2012). Transposition of the semitendinous muscle has been described to recreate the action of a sphincter (Doust 2003; Morello et al. 2015) (Figure 7.76). Other experimental procedures have been described (Barnes and Aronson 2018).

Figure 7.74 Incontinent dog two years after surgery.

Figure 7.75 Anoplasty in a German shepherd dog 10 days after surgery. In this case, the external sphincter muscle was spared, and after a transient period of fecal incontinence, the dog was able to consciously retain feces. Recurrence of the perianal tumor rarely occurs when an adenoma is treated with castration with or without excision of the primary tumor. Recurrence in a castrated male dog suggests possible malignancy, and further diagnostic investigation is warranted (Turek and Withrow 2013). Recurrences are likely in cases of incompletely excised perianal adenocarcinoma. Local recurrence has been reported in 4.76–44% after anal sacculectomy for anal sac adenocarcinoma (Potanas et al. 2015; Wouda et al. 2016; Barnes et al. 2017; Pradel et al. 2018; Skorupski et al. 2018). The status of the surgical margins (complete vs. incomplete) is not de initively related to local recurrence (Wouda et a. 2016; Pradel et al. 2018; Skorupski et al 2018). As previously noted, a second anal sac adenocarcinoma may rarely develop within the contralateral sac subsequent to the removal of a unilateral anal sac adenocarcinoma (Ross et al. 1991; Emms 2005; Bowlt et al. 2013; Turek and Withrow 2013; Liptak 2015; Barnes and Demetriou 2017).

Figure 7.76 This dog has been operated several times for bilateral perineal hernia and was faecally incontinent (the owner has been applying a diaper at least twice a day). There was cicatricial ibrosis at the level of the anal ring and pain, with complete absence of the external sphincter muscle. (a) All the cicatricial tissue causing stenosis has been excised. (b) Divided semitendinosus laps (medial parts) are bilaterally prepared. (c) Positioning one of the two muscular laps around the terminal portion of the rectum. At completion the two laps completely surround the distal rectum. (d) Bilateral laps are in positon. (e) Reconstruction has been completed. (f) 24th postoperative day. (g) 128th postoperative day. The dog is occasionally incontinent, especially when feces are soft but is pain-free and a diaper is not required. The owner periodically clips the hair and a small ulcer is visible ventrally.

Figure 7.77 (a) Ulcerated hepatoid adenoma of the “tail gland” in a dog. The tumor was marginally resected and castration was performed. (b) Hepatoid adenocarcinoma of the tail in an 11-year-old male German shepherd. No metastasis was found, and the tail was amputated. Additional metastases are more likely in anal sac adenocarcinoma and occur less frequently with perianal adenocarcinoma. With malignant tumors, clinical, laboratory, and diagnostic imaging evaluations are recommended every three months during the irst year following surgery and every 6–12 months thereafter. Disease progression may result from local recurrence and/or further metastasis and hypercalcemia.

Common Perianal Tumors and Prognosis Cats have only anal sacs and not perianal hepatoid glands. Canine Hepatoid Tumors

In dogs, most tumors originate from the modi ied sebaceous hepatoid glands located in the perianal or circumanal region (see Figures 7.50– 7.52), tail (Figure 7.77), prepuce (Figure 7.78), trunk, and hind leg. These glands are also present in bovines (Blazquez et al. 1988). Their function, both in carnivores and bovines, is unknown; however, it has been suggested the perianal or hepatoid glands may be odorproducing glands via proteins that may act as an olfactory marker (Shabadash and Zelikina 1995; Martins et al. 2008). Canine benign tumors are referred to as hormonally dependent perianal adenomas as they can be stimulated by androgens or inhibited by estrogens (Turek and Withrow 2013). Hence, they regress in male dogs after castration. Perianal adenomas occur more frequently in elderly intact males and less frequently in spayed than intact bitches (Figure 7.79). Marginal excision and castration are the treatment of choice for perianal adenomas (Turek and Withrow 2013), and recurrence is very rare, particularly in male dogs (Wilson and Hayes 1979). Hyperadrenocorticism can be a concurrent inding in female dogs, and the adrenal gland is the source of androgenic stimulation (Dow et al. 1988; Hill et al. 2005).

Figure 7.78 The clinical appearance of a preputial hepatoid adenoma at the level of the preputium in a dog.

Perianal adenocarcinoma is relatively slow growing, locally invasive, and often is characterized by a protracted clinical history that may include multiple previous excisions. In a recently published case report, a dog, at presentation, displayed an intrapelvic mass only, but historically the dog had orchiectomy and a hepatoid adenoma excised six years before (Jardin et al. 2018). This tumor may clinically and cytologically be misdiagnosed as a more benign tumor when well differentiated (McCourt et al. 2018); a tentative algorithm to cytologically differentiate benign and malignant perianal lesions has been recently published (Sabattini et al. 2019), together with the evaluation of nuclear morphometric variables (Simeonov 2019). Perianal adenocarcinoma metastasizes to the sublumbar lymph nodes in up to 15% of cases, and distant metastasis (lungs, liver, spleen, and sublumbar lymph nodes) is also reported (Wilson and Hayes 1979; Vail et al. 1990). Concurrent hypercalcemia is exceptional, the etiology of which is, at this time, unknown. These tumors are most prevalent in elderly male or female dogs (Berrocal et al. 1989; Vail et al. 1990) and do not demonstrate hormonal dependence despite the fact that hepatoid gland carcinomas still express androgen receptors (Wilson and Hayes 1979; Vail et al. 1990; Pisani et al. 2006). In one study, 8 of 16 canine perianal adenocarcinomas overexpressed mutated p53 tumor suppressor protein (Gamblin et al. 1997). Predisposition is seen in large male dogs such as Arctic breeds and German shepherds (Vail et al. 1990). Surgery, when feasible, is the irst option for this tumor. The only prognostic factor identi ied is clinical stage (Owen 1980), and dogs with tumors over 5 cm have an 11 times higher risk of death compared to dogs with smaller tumors. Dogs with tumor staging T1N0M0 (T1 = tumor of less than 2 cm, super icial or proliferative) and T2N0M0 (T2 = tumor of 2–5 cm or, with minimal invasion independent of size) had a two-year disease-free interval of about 75 and 60%, respectively, and dogs with tumor stages beyond T2 (T3 = tumor of more than 5 cm or invasive tumors independent of size; T4 = invasive tumor) had a median survival of 6–12.5 months (Vail et al. 1990). The reported MST in dogs with con irmed metastasis (15% of cases at presentation) was seven months (Vail et al. 1990).

Figure 7.79 Perianal adenoma in a spayed bitch. This followed a similar excision nine months previously for the same lesion. Canine Hepatoid Tumors: Histopathologic Features and Prognosis The vast majority of perianal adenomas are well-differentiated tumors, with only about one-quarter being moderately or poorly differentiated neoplasms (Berrocal et al. 1989; Vail et al. 1990; Turek and Withrow 2013). In a review of 240 perianal tumors (Martins et al. 2008), the Goldschmidt et al. (1998), histological classi ication was applied and compared to the older classi ication produced by Berrocal et al (1989): Hyperplasia was diagnosed in 4% of cases, well and moderately differentiated adenoma in 54% of cases (20 and 34%, respectively), poorly differentiated adenoma (or hepatoid gland epithelioma) in 19% of cases, carcinoma in 20% of cases, and other tumors (of mesenchymal/vascular origin) in 13% of cases (Martins et al. 2008). Independently of the histological classi ication adopted, gland differentiation (that also implies the presence of androgenic receptors on the surface of cells) has been associated with both hormonedependence and favorable prognosis after surgery (adenoma and epithelioma). Nucleolar organizer regions associated with argyrophilic proteins (AgNORs) have been evaluated in perianal tumors and a high correspondence with the tumor’s proliferative activity/tumor grade has been found (Preziosi et al 1995). Martins et al. (2008) suggested that immunohistochemistry for proliferating cell nuclear antigen (PCNA) may be used, together with histomorphology, to distinguish benign and malignant tumors of the perianal gland (the cut-off value of the PCNA index suggested is about 0.60%); the apoptosis index should follow a similar trend given that whereas carcinoma cells divide more frequently than adenoma cells, they also have a higher death rate. In this study, the net growth was expressed as a net growth index, correlating with both the PCNA and apoptosis indices. It has also been proposed that differentiation between hepatoid adenoma vs. carcinoma can be based on the use of mouse monoclonal antibodies (Ganguly and Wolfe 2006). Immunohistochemistry for growth hormone was found to be positive in 23 of 24 canine perianal adenomas and in ive of ive perianal adenocarcinomas (Petterino et al. 2004). It has also been

shown that the expression of Ki-67 (a nuclear protein associated with cellular proliferation) is signi icatively higher in perianal carcinoma (18.50% ± 2.68) than in normal tissue (7.63% ± 2.12), hepatoid adenoma (7.33% ± 1.06), or epithelioma (11.95% ± 1.96) (Brodzki et al 2014). In a second paper dealing with the Ki-67 index evaluation by computer-assisted image analysis, it has been found an index of up to 0.07% for normal tissue (positive cells in the stratum basale only), 0.36% (0.00–1.43%) for adenoma, 2.66% (0.54–7.10%) for epithelioma (positivity mainly among the basaloid cells), and 9.87% (3.09–24.82%) for carcinoma (diffuse positivity) (Pereira et al. 2013). The difference in Ki-67 expression between carcinoma and adenoma/epithelioma was signi icant. When the computer-assisted image analysis was compared to manual counting, data obtained with the former were considered more reliable and less time-consuming; it was also suggested a cut-off value of 9.305% to discriminate carcinomas able to recur after a previous surgery from those that did not (Pereira et al. 2013). The evaluation of computer-assisted nuclear cytological morphometric parameters has demonstrated that mean nuclear area, mean nuclear perimeter, maximum nuclear diameter, and minimum nuclear diameter may be used as prognostic indicators for canine perianal adenocarcinoma; signi icant differences in survival were seen in all of these parameters between metastatic tumors with positive regional lymph nodes and nonmetastatic tumors (Simeonov and Simeonova 2008b). Finally, it has also been reported a decrease in the expression of claudin-4 in undifferentiated hepatoid carcinoma, when compared to both less aggressive and benign hepatoid tumors (Jakab et al. 2009); on the other hand, expression of claudin-5 was determined to be decreased in low/moderate-grade malignancy (epithelioma and well-differentiated carcinoma) and increased in highgrade malignancy (poorly differentiated carcinoma) (Jakab et al. 2010a). Anal Sac Adenocarcinoma These neoplasms are less common (2% of all skin tumors in dogs) (Liptak 2015) than perianal hepatoid tumors and generally affect elderly dogs; dogs as young as ive years, however, have also been reported (White and Gorman 1987; Ross et al. 1991; Williams et al.

2003; Turek and Withrow 2013). At present, no gender predisposition has been documented with certainty (Ross et al. 1991; Straw et al. 1994; Bennett et al. 2002; Williams et al. 2003; Polton et al. 2006; Polton and Brearley 2007; Potanas et al. 2015). However, in one study, the mean relative risk estimate associated with being neutered was 1.4, and the effect of neutering appeared to be more signi icant in male dogs compared to female dogs (Polton et al. 2006; Polton and Brearley 2007). Breed predisposition is reported in spaniels (English cocker spaniels, mean relative risk estimate of 7.3, and Springer and Cavalier King Charles spaniels) (Polton and Brearley 2007), and heritability in these dogs is suspected (Polton 2009; Aguirre-Hernández et al. 2010). Recurrent anal sac impaction and infection have been suggested as predisposing factors in one report (Bowlt et al. 2013). Speci ic computer-assisted cytological nuclear morphometric parameters have been suggested to facilitate the differentiation between anal sac adenoma (indeed very rare) and anal sac adenocarcinoma (Simeonov and Simeonova 2008a). Metastasis is evident at presentation in 26– 96% of dogs, with the main sites including regional lymph nodes (sublumbar and only rarely inguinal), but also lungs, liver, spleen, other abdominal organs, and the skeleton, including lumbar vertebrae (7– 9%) (Goldschmidt and Zoltowski 1981; Ross et al. 1991; Bennett et al. 2002; Turek et al. 2003; Williams et al. 2003; Brisson et al. 2004; Hammond et al. 2009; Turek and Withrow 2013; Potanas et al 2015; Wouda et al. 2016; Barnes and Demetriou 2017) (Figures 7.80 and 7.81; see also Figures 7.54–7.56 and 7.58 and 7.71). In a recent study, dogs with primary tumors of over 2.5 cm (therefore stage T2) were signi icantly more likely to display metastatic disease (Schlag et al. 2020). In rare cases, lung or bone metastasis may develop without evidence of regional lymphadenopathy (Turek and Withrow 2013) (Figure 7.81). In one study, micrometastasis was detected at the level of the bone marrow via cell block cytology (Taylor et al. 2013), but the impact of this inding on prognosis is currently unknown. The expression of Ecadherin has also been evaluated and correlated with survival; if expressing cells were less than 75%, this has been associated with a shorter survival (Polton et al. 2007).

Hypercalcemia at initial presentation is present in 16–90% of cases, and it is less common in male dogs than in spayed bitches (White and Gorman 1987; Rosol et al. 1990; Ross et al. 1991; Bennett et al. 2002; Williams et al. 2003; Potanas et al. 2015; Wouda et al. 2016; Barnes and Demetriou 2017; Pradel et al. 2018); the percentage of hypercalcemic dogs on presentation, however, may be as low as 3% (Skorupski et al 2018). When present, hypercalcemia caused by the PTH-like compound (PTHrp) produced by the tumor (Rosol et al. 1990; Gröne et al. 1994; Mellanby et al. 2006) can be used as a marker for both metastasis and recurrent lesions. The primary tumor rarely involves both anal sacs (up to 10% of cases) and may be very small (or occult) even in the presence of large metastatic lymphadenopathy (Ross et al. 1991; Bertazzolo et al. 2003; Turek et al. 2003; Emms 2005; Liptak 2015; Potanas et al. 2015; Rossi et al. 2015). In some cases, bilateral tumors may be clinically asynchronous, with the second tumor occurring later (50 to 390 days after the removal of the irst tumor in one report) (Bowlt et al. 2013).

Figure 7.80 Ventral vertebral changes caused by an adjacent metastatic sublumbar lymphadenomegaly originating from an anal sac adenocarcinoma in a dog. Source: Image courtesy of Dr. Sarah Boston.

Figure 7.81 Humeral metastasis secondary to an anal sac adenocarcinoma in a nine-year-old spayed female Schnauzer. The dog presented with lameness; abdominal ultrasound did not reveal any lesion. Bone biopsy was consistent with a metastatic adenocarcinoma. The primary anal sac adenocarcinoma was unilateral and 2 mm small. Surgery plays a fundamental role in the treatment of this tumor (Williams et al. 2003; Barnes and Demetriou 2017; Skorupski et al. 2018). When feasible, an aggressive resection of the anal sac adenocarcinoma should be performed (Figure 7.68); however, only marginal excision is achievable in most cases (Wouda et al. 2016) (see Figures 7.66 and 7.67). Marginal resection should nevertheless be effective given the indings of recent studies, which found that completeness of excision did not correlate with survival (Potanas et al. 2015; Skorupski et al. 2018). After surgical excision, survival has been reported to be about 1–1.5 years, with a wide range (few days up to 96 months) (White and Gorman 1987; Ross et al. 1991; Bennett et al. 2002; Williams et al. 2003; Hobson et al. 2006; Potanas et al. 2015; Barnes and Demetriou 2017; Skorupski et al. 2018). Hypercalcemia, which together with regional metastatic lymph node involvement, has been described as a negative prognostic factor, may normalize only after gross cytoreduction. The role of hypercalcemia as a negative prognostic factor (decreased survival) has been controversial (Ross et al. 1991; Bennett et al. 2002; Turek et al. 2003; Williams et al. 2003; Emms 2005), unless secondary renal failure has already occurred. One report failed to demonstrate that hypercalcemia acts as a negative prognostic factor (Potanas et al. 2015). Additionally, the prognostic signi icance of regional metastatic lymphadenopathy is unclear since it will likely develop later, even if it is not present at the initial presentation, or it may be actually present despite not being clinically detectable (Ross et al. 1991; Turek et al. 2003; Williams et al. 2003). If not evident at initial presentation, however, a long survival (MST up to 1237 days) should be expected (Pradel et al. 2018; Skorupski et al. 2018). In a retrospective study on 39 cases, lymph nodal metastasis correlated with speci ic postoperative histological features such as incomplete excision margins, marked peripheral tumor in iltration, a predominant solid pattern, moderate nuclear pleomorphism, and lymphovascular invasion (the latter in 33% of cases only). A poorer

outcome was associated with a solid growth pattern, a moderate or marked tumoral peripheral in iltration, necrosis, and lymphovascular invasion; no association with the mitotic index was revealed. Interestingly, the two cases with a histological papillary pattern had a favorable outcome (Pradel et al. 2018). In another study, only the extent of cellular pleomorphism was associated with the development of metastasis while no other factor (tumor size, histologic pattern, vascular invasion, mitotic index, E-cadherin localization, and Ki-67 percentage [median 25%, range 13–48%) was statistically associated with survival, recurrence or metastasis (Skorupski et al. 2018). It has been advocated that the concurrent excision of regional metastatic lymph nodes usually results in increased survival times (Hobson et al. 2006; Polton and Brearley 2007). A study that compared dogs with and without sublumbar lymphadenopathy at initial presentation, showed a signi icant difference in both survival and disease-free interval (422 vs. 529 days and 197 vs. 529 days, respectively), with also an increased risk for death in dogs with sublumbar lymphadenopathy at initial presentation (Potanas et al. 2015). Death is usually the consequence of recurrence or metastasis. However, dogs with local recurrence and/or further regional sublumbar metastasis may have an increased survival if further tumor removal or chemotherapy and/or irradiation is performed (Barnes and Demetriou 2017; Pradel et al. 2018; Skorupski et al. 2018). Lung metastasis and primary tumors greater than 10 cm in size have been associated with a decreased survival (Williams et al. 2003). TNM clinical staging is the same as that used for skin tumors. With respect to tumor size and prognosis, a modi ied and more simpli ied clinical staging system that tentatively correlates with survival time has been proposed (Polton and Brearley 2007). According to this study, stage 1 and 2 is when the primary tumor is less than or greater than 2.5 cm without evidence of metastasis, respectively. In stages 3a, 3b, and 4, the size of the primary tumor is irrelevant, with regional lymph nodes less than 4.5 cm of diameter in stage 3a, more than 4.5 cm in stage 3b, and with distant metastases in stage 4. Dogs in this report were divided into two groups: One was evaluated retrospectively (80 dogs) and one prospectively (50 dogs). As expected, median survival was longer in stage 1 and 2 dogs (40 and 24 months, respectively), with a signi icant

gap between stage 3a and 3b dogs in both the retrospective group (16 and 11 months, respectively) and in the prospective group (15 and 10 months, respectively). The shortest survival (less than three months) was documented in dogs with stage 4 disease. Despite the fact that chemotherapy did not in luence outcome, the authors of this report still recommended its use in stage 3b lesions. More recently, one report evaluating 42 cases of canine anal sac adenocarcinoma failed to demonstrate any signi icant difference in survival when the cut-off for the primary tumor size was set at 4.2 cm; furthermore, there was no difference in survival when carboplatin or cisplatin was used or not (Potanas et al. 2015). Finally, in a study reporting 34 dogs treated with surgery alone for a nonmetastatic anal sac adenocarcinoma of less than 3.2 cm at its largest diameter, the reported MST was 1237 days; recurrences occurred in 7 dogs (median 354 days, range 117–947) and metastasis in nine dogs (median 589 days, range 99–1147) (Skorupski et al. 2018). Also, the asynchronous development of a bilateral disease reported in four dogs did not seem to in luence survival (median survival of 1035 days, range 901–2299 days, after the initial diagnosis, and 807 days after the diagnosis of the second anal sac gland tumor) (Bowlt et al. 2013). Based on this, at the present time, it does not seem reasonable to recommend performing a bilateral sacculectomy in the presence of a clinically unilateral anal sac adenocarcinoma. Nonetheless, owners should be strongly encouraged to follow a plan of periodical check-up of their dogs in order to restage the disease and discover early signs of disease progression (Chambers et al. 2020). Further data regarding canine anal sac adenocarcinoma comes from a Veterinary Society of Surgical Oncology (VSSO) multi-institutional study involving 585 dogs (Liptak 2015); the study is still in progress at the time of writing and more cases have been added. Preliminary data show that the tumor was bilateral in 8.4% of cases (53.5% simultaneously). Metastatic sublumbar lymphadenopathy was detected in 50.4% of cases at initial presentation while 31.3% of dogs developed new or further lymph node metastasis after treatment. Distant metastasis at initial presentation was diagnosed in 5.2% of dogs while 13.7% developed new or further distant metastasis after treatment.

Treatment involved surgery (with 54 and 46% incomplete and complete margins, respectively) +/– chemotherapy +/– radiotherapy. Sublumbar lymphadenopathy was resected in 237 cases. Cause of death was local recurrence (18.6%), sublumbar lymph node metastasis (55.2%), and distant metastasis (22.8%). Overall MST was 960 days (1009 days in case of unilateral tumor, 776 days if bilateral [419 days if bilateral at initial presentation, 1038 if staged bilateral not at the same time]); for cases without metastasis, overall median survival was 1745 days vs. 551 days for cases with metastasis. This tumor, as previously discussed, is not commonly reported in cats (Chun et al. 1997; Mellanby et al. 2002; Parry 2006; Wright et al. 2010; Elliot and Blackwood 2011; Raleigh et al. 2018) and represents 0.5% of all skin tumors in this species. One larger study involved 64 cats in the United Kingdom (Shoieb and Hanshaw 2009). In that study, the female:male ratio was 1.56, without any breed predisposition, and age ranged from 6 to 17 years (mean and median, 12 years); reported median survival for 39 of 64 cats was three months, with a one- and two-year survival rate of 19 and 0%, respectively; reported local recurrence rate was 50%. Adjuvant treatment (radiotherapy for local control and chemotherapy with carboplatin) has been advocated (Wright et al. 2010; Elliot and Blackwood 2011). A VSSO multiinstitutional study evaluated 30 cases of feline anal sac adenocarcinoma. There was a prevalence of the disease in both domestic short-haired and Siamese cats (17 and 7 cats, respectively). Common clinical signs on presentation were swelling, perineal ulceration, or discharge (Figure 7.53b). Metastatic sublumbar lymphadenopathy was con irmed in only three cats; paraneoplastic hypercalcemia was suspected in three cats, but further investigation is warranted. After surgical excision, local recurrence occurred in 11 cats (median time of 96 days, range 23–347); risk factors were incomplete surgical margins and nuclear pleomorphism. A higher nuclear pleomorphic score (from 1 to 3) was also associated with a shorter disease-free interval. The reported median disease-free period was 234 days (range 0–1039) and the MST was 260 days (range 42–1390); the one-, two-, and three-year survival rates were, 42%, 27%, and 18%, respectively. Both local recurrence and increased nuclear pleomorphic score were risk factors for mortality (euthanasia in 16 cats). While the

role of both radiotherapy and chemotherapy remains unknown for this tumor in cats, a wide excision (Figure 7.68) is recommended to control local recurrence, that ultimately represents the main reason for euthanasia as distant metastasis appears to be rare (Amsellem et al. 2019). A case of an anal sac adenocarcinoma in a cat, presented for rapid development of a caudal myelopathy, has been reported. At necropsy, medial iliac lymphadenopathy and metastasis to peripheral nerves and cauda equina was found (Raleigh et al. 2018). Other Perianal Tumors Squamous cell carcinoma is a rare tumor that may develop from the anal sac, both in dogs (Esplin et al. 2003; Mellet et al 2015; Giuliano et al. 2017) and cats (Kopke et al. 2020), anal canal, and perianal skin (Figure 7.82). Anal sac squamous cell carcinoma has also been reported in a spotted hyena (Goodnight et al. 2015). These tumors demonstrate malignant behavior, both in terms of local in iltration and regional and distant metastasis. Surgery for local tumor control may be problematic in terms of complete vs. in iltrated margins and/or potential fecal incontinence. In one report, two dogs with incomplete surgical resection of an anal sac squamous cell carcinoma resulted in recurrence and euthanasia within two and months, respectively (Esplin et al. 2003); when palliatively treated with meloxicam only (0.1 mg/kg/day), survival in three dogs ranged between 79 days and 7 months (Mellet et al. 2015). In another report, a dog with a recurrent anal sac squamous cell carcinoma was successfully treated (complete remission for at least one year) with a combination of chemotherapy (four carboplatin administrations at the standard dose) and radiotherapy (four fractions, once a week, 8.5 Gy for fraction, 12 MeV electrons) (Giuliano et al. 2017). One cat with an anal sac squamous cell carcinoma treated with surgery, radiation, and chemotherapy (toceranib phosphate irst and carboplatin at recurrence occurrence) survived 552 days; a second cat treated with meloxicam only was euthanazed after 28 days (Kopke et al. 2020). Malignant melanoma is another rare lesion that may develop from the perianal region, although it has also been thought to derive from the anal sac (Kim et al. 2005) (Figure 7.83). Its behavior is unknown, but it

is likely to be highly malignant, similar to the more typical oral counterpart (Kim et al. 2005). One report has documented a transient local palliation by electrochemotherapy with cisplatin in a dog (Spugnini et al. 2007). A recent study reported 11 dogs (mean age of 10.3 years, range 10–14) with anal sac melanoma; eight underwent surgical excision, one had adjuvant chemotherapy, and three had adjuvant vaccination (OnceptR melanoma vaccine, Merial). The median mitotic index of these tumors was 50/10 high power ields (range 10– 83). The median progression-free survival time was 92.5 days while the median overall survival time was 107 days; 10 of 11 dogs were euthanazed for local or distant progression (regional metastatic lymphadenopathy and/or lung or other sites metastasis) and only one dog was alive at one year (Vinayak et al. 2017).

Figure 7.82 Squamous cell carcinoma of the anal region in two different German shepherd male dogs ((a) 11-year-old and (b) 10-yearold).

Figure 7.83 The clinical (a) and post-excisional (b) appearance of a melanoma of the right anal sac in a dog. Multiple sublumbar lymphadenectomies were also performed. No further treatment was administered. The dog survived one year and the cause of death was lung metastasis. Lymphoma (Figure 7.84), mast cell tumors, benign tumors (lipoma, leiomyoma, hemangioma – Figure 7.85), plasma cell tumor (Figure 7.86 and soft tissue sarcomas (see Figures 7.62 and 7.87), and hemangiosarcoma are also seen in the perianal region (Ueno et al. 2002; Brønden et al. 2010; Choi 2019). To consider as a differential, perianal infundibular follicular cysts (in the form of papules of 0.2–0.5 cm), potentially as a result of self-trauma caused by chronic sacculitis, have been described in a dog (Park et al 2010).

Adjuvant Therapies For perianal adenoma, no adjuvant treatment is needed. Alternative treatments are the administration of diethylstilbestrol (which should be avoided due to the potential for bone marrow suppression), cryosurgery, radiation, and hyperthermia (Gillette 1970; Liska and Withrow 1978; Grier et al. 1980). The excellent results achieved with surgical treatment render these procedures unattractive (Turek and Withrow 2013). A potential treatment is the use of drugs for chemical

castration (Turek and Withrow 2013). The local injection of pardaxin (an antimicrobial peptide isolated from marine ish) has been advocated for the local control of perianal adenoma (Chieh-Yu et al. 2014). Also, a decrease in size of a perianal adenoma has been documented in a dog treated with cyclosporine used for concurrent perianal istulas due to its antiproliferative effect (Chul et al. 2010). Another study has reported that tamoxifen, apart from its antiestrogen effect, may act as an antiangiogenic drug. After one month of administration (2 mg/kg), complete remission of a hepatoid adenoma/epithelioma was noted and with the case of adenoma only, a progressive and durable decrease in VEGF levels was also reported; the authors of this study also concluded that VEGF overexpression observed after six months of tamoxifen treatment may constitute a negative prognostic factor for disease progression (Sobczyńska-Rak and Brodzki 2014).

Figure 7.84 Lymphoma of the anal region in a seven-year-old female mongrel dog.

Figure 7.85 Large hemangioma located between the anus and the tail base in a ive-year-old male Leonberger. For perianal adenocarcinoma, radiation may be an option, even though this tumor type is often considered radioresistant (Vail et al. 1990). Radiation can be applied both locally and to the site of the excised metastatic sublumbar lymph nodes (Straw et al. 1994; Bley et al. 2003). There is, however, only scant information regarding outcomes available

in the literature. At present, there is no evidence that adjuvant chemotherapy (doxorubicin with or without cyclophosphamide, cisplatin, or actinomycin D) is useful, and remission, if any, is usually partial and transient (Vail et al. 1990; Hammer et al. 1994). Perianal adenoma and adenocarcinoma have also been treated with chemotherapy using bleomycin or cisplatin combined with electroporation (electrochemotherapy [Tozon et al. 2005; Spugnini, Dotsinsky et al. 2007]). For anal sac adenocarcinoma, reported chemotherapeutic agents (usually for maximum dose tolerated [MTD] protocols and only occasionally in a metronomic regimen – Barnes and Demetriou 2017) include cisplatin, carboplatin, doxorubicin with or without cyclophosphamide, mitoxantrone, epirubicin, melphalan, actinomycin D, mithramycin, chlorambucil, vincristine, L-asparaginase, gemcitabine, and piroxicam or meloxicam (Ross et al. 1991; Hammer et al. 1994; Bennett et al. 2002; Turek et al. 2003; Williams et al. 2003; Emms 2005; Polton and Brearley 2007; Bowlt et al. 2013; Potanas et al. 2015; Wouda et al. 2016; Barnes and Demetriou 2017; Skorupski et al. 2018). The role of chemotherapy is unclear. It has been reported that the adjuvant use of platinum compounds may allow a longer survival (Bennett et al. 2002), whereas in other reports no difference was found independently of the protocol used (Williams et al. 2003; Polton and Brearley 2007). In one study, 74 dogs with an anal sac adenocarcinoma were surgically treated and 44 received adjuvant carboplatin; the median overall survival was 703 days while the median time to progression was 384 days. There was no statistical difference between the two groups of dogs (surgery vs. surgery + carboplatin) and only the primary tumor size and lymph node metastasis in luenced the prognosis (Wouda et al. 2016). The positive expression (more than 50% of the neoplastic glandular cells) of cyclooxygenase isoform 2 (COX-2) in 76% of these tumors in a study suggests the potential role of COX-2 inhibitors in the multimodal treatment of this tumor type (Knudsen et al 2013) but further studies are warranted, also because positive COX-2 expression was also detected at the level of the ductal epithelial cells of the normal anal sac (Knudsen et al. 2013). Finally, an increasing interest has been recently

focused on the use of receptor tyrosine kinase (RTK) inhibitors (TKI), especially toceranib phosphate (Palladia, P izer Animal Health, Madison, NJ, USA), due to the fact that this drug has shown to have some activity against this tumor (in 28 out of 32 treated dogs, eight partial response and 20 stable disease) (London et al. 2012). Some studies have also tried to characterize the receptor status of this tumor type (Brown et al. 2012; Urie et al 2012; Yamazaki et al. 2019). This drug is often included in the list of drugs used for canine anal sac adenocarcinoma (Pradel et al. 2018; Skorupski et al. 2018) and three more recent studies have concentrated on its clinical use. When toceranib phosphate was used as a palliation in 15 dogs affected with advanced (stage 4) anal sac adenocarcinoma, 13 dogs experienced a bene it in terms of clinical signs, but no partial or complete response were recorded; MST was 356 days (Elliot 2019). When used adjuvantly (Yamazaki et al 2019), it did not result in a signi icantly longer time to progression (main endpoint in this study) in comparison with surgery alone (surgery plus toceranib = 360 days vs. surgery alone = 298 days). In the third study (Heaton et al. 2019), 36 dogs received toceranib either as unique medication or adiuvantly after surgery plus/minus other chemotherapeutic drugs; a clinical bene it was observed in 69% of dogs (20.7% partial response and 48.3% stable disease), with increased progression-free survival and overall survival time in dogs treated with toceranib. Finally, it should be noted that a phase 1 study on the combined administration of toceranib and carboplatin, that warrants further evaluation for the treatment of anal sac adenocarcinoma, is available in the veterinary literature (Wouda et al. 2018). Finally, a recent study has explored the expression of human epidermal growth factor receptor 2 (HER2) in canine anal sac adenocarcinoma; the strong positivity that was revealed may offer the chance for a HER2-targeted therapy (Yoshimoto et al. 2019).

Figure 7.86 (a) The clinical appearance of an ventrally located plasma cell tumor in a dog. (b) The en bloc excision included the skin and the perianal (hepatoid) region, sparing both the external anal sphincter muscle and the dorsal skin. Both anal sacs were removed. (c) The appearance of the wound post-excision. (d) Completed anoplasty. The dog, after a transient fecal incontinence, became clinically continent within three weeks.

Figure 7.87 (a) The clinical appearance of a large soft tissue sarcoma involving the perianal region and the tail in a 10-year old castrated male DSH cat. (b) An en bloc excision has been performed including all of the anus and most of the rectum; the wound has already been partially closed. (c) The reconstruction has been completed and the colorectum has been sutured to the skin. (d) The appearance of the resected tumor post-excision. (e) The clinical appearance of the cat 40 days post surgery; the cat was clinically continent.

Mitoxantrone administration associated with radiotherapy resulted in an overall MST of 31 months, with improved local and regional tumor control. Complications of radiation therapy were observed in more than 50% of cases; however, control of these complications was possible in the majority of instances (Turek et al. 2003). In cats, doxorubicin or carboplatin may be used after surgery but the role of chemotherapy remains unknown. Adjuvant or intraoperative radiation, both for local (48–50 Gy delivered in small fractions) and metastatic disease (Straw et al. 1994; Turek et al. 2003; Williams et al. 2003; Polton and Brearley 2007; Turek and Withrow 2013; Pradel et al. 2018) has been reported. Radiation has also been reported in a neoadjuvant setting in one dog (Barnes and Demetriou 2017) or for recurrent/progressive disease (Wouda et al. 2016; Skorupski et al 2018). For the sublumbar metastatic sites, radiation is usually applied once intraoperatively with 15–19 Gy. Acute adverse effects of adjuvant radiation may be skin desquamation, colitis (that may be refractory to medical treatment), and tenesmus, and these signs are usually self-limiting in approximately one month. Possible chronic adverse radiation-induced effects may include tenesmus secondary to rectal stricture, intestinal perforation, diarrhea, and fecal incontinence (Turek et al. 2003). In order to avoid adverse effects to the colon, smaller fractions (2.7–2.9 Gy) and avoidance of radiation potentiators are recommended for pelvic irradiation (Anderson et al. 2002; Arthur et al. 2008). Hypofractionated radiotherapy (900 cGy a week), both as a neoadjuvant and adjuvant treatment, or as a salvage procedure in inoperable cases, has been also used (Polton and Brearley 2007). In a recent study dealing with 77 dogs with an advanced anal sac adenocarcinoma (of these, 26 dogs experienced anal sacculectomy before radiation and 52 some sort of chemotherapy), hypofractionated radiation (3–9 Gy per fraction, 3–10 fractions on a daily basis [Monday to Friday]), total dose 18–32 Gy) resulted in a partial response in 38% of cases (improvement or resolution of clinical signs in 63% of dogs), resolution of hypercalcemia in 31% of cases and in 46% of dogs when prednisone +/– bisphosphonates were combined with radiation; toxicity was reported to be mild and infrequent. Median overall survival was 329 days (range, 252–448) while median progression-free survival

was 289 days (range, 224–469); none of the different medical treatments in luenced statistically the survival (McQuown et al. 2017). Efforts to decrease radiotoxicity to surrounding tissues have been made using 3D conformal radiation treatment planning (Keyerleber et al. 2012; Meier et al. 2017), and a protocol for IMRT (intensity-modulated radiotherapy) has been reported in detail (Meier et al. 2018). In another study looking at stage 3b anal sac adenocarcinoma, surgery was performed in 15 dogs while 13 received conformal radiotherapy only (8 × 3.8 Gy over a period of 2.5 weeks). The median progressionfree and survival times for dogs treated by surgery were 159 and 182 days, respectively, while for those treated with radiation, these results were 347 and 447 days, respectively; this difference was statistically signi icant (Meier et al. 2017). Electrochemotherapy with cisplatin has also been reported in a dog as an adjuvant treatment for an incompletely excised anal sac adenocarcinoma (Spugnini et al. 2008).

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8 Respiratory Tract and Thorax Marina Martano, Sarah Boston, and Emanuela Morello

Rhinotomy The diagnosis of nasal and paranasal tumors may occur late in the course of the disease because of their anatomical location and the non-speci ic clinical signs at presentation. Moreover, the surgical treatment of endonasal malignant tumors does not allow a wide margin excision, therefore is not considered a irst-line treatment, but mostly an adjuvant therapy to radiation and chemotherapy, or as a method to obtain a biopsy when other biopsy techniques have failed. The nasal cavities can be surgically approached by a dorsal, ventral, or lateral rhinotomy. The latter procedure gives access only to the nasal vestibule, and it is therefore rarely indicated in oncologic surgery.

Clinical Workup and Biopsy Principles Diagnosis of nasal tumors can be made by combining clinical indings with imaging and biopsy results. The most frequent clinical sign is unilateral epistaxis (Bissett et al. 2007); however, it can become bilateral once the tumor has invaded into the contralateral nasal cavity. Other signs include nasal and/or ocular discharge, occasional sneezing, signs of occlusion of the nasal cavities, facial deformities (Figure 8.1), and exophthalmos; in cats, vomiting could also be observed (Henderson et al. 2004; Demko and Cohn 2007; Lobetti 2009; Plickert et al. 2014). Clinical signs may be present for approximately 1–6 months prior to diagnosis. Clinical suspicion is con irmed by biopsy, which can also rule out other nasal diseases, such as fungal or bacterial infections, nasal foreign bodies, non-speci ic rhinitis, parasites, or systemic diseases (ehrlichiosis, leishmaniasis, coagulopathies, etc.) (Ogilvie and LaRue 1992; Plickert et al. 2014). In cats, nasopharyngeal polyps should also be considered, mainly in younger animals, as reported by Ferguson et al., which also found rhinitis as the most prevalent disease in this species, followed by neoplasia (2020). Nasal polyps that caused clinical signs compatible with nasal disease, turbinate destruction, and lysis of the surrounding bones have been reported in ive dogs (Holt and Goldschmidt 2011). Blood testing, while usually unremarkable, is necessary to evaluate the

overall condition of the patient, and to help rule out infectious diseases; a coagulation pro ile is always recommended to evaluate the risk of hemorrhage from biopsy procedures or rhinotomy. Biopsy specimens are needed to obtain a diagnosis, and they can be obtained either blindly or with endoscopic or advanced imaging guidance. With endoscopy, a rigid endoscope is introduced through the nares and, after the procedure has been completed, a small biopsy sample is withdrawn with forceps (see video clips 8.1–8.3). With this technique, a false negative result (i.e., in lammatory rhinitis) may be obtained because of inadequate and/or super icial sampling. Better results can be achieved using a large-bore cannula or tube biopsy technique, applicable mainly in medium- to large-sized dogs. The animal is placed in sternal recumbency, under general inhalation anesthesia, with the nose parallel to the operating table (as for endoscopy). A cuffed endotracheal tube is always placed and the pharynx is occluded with gauze sponges to avoid aspiration of debris or secretions. A rigid plastic cannula, such as the outer sleeve of a metal catheter or a rigid plastic urinary catheter, attached to a 12 mL syringe is used for collection of the biopsy sample (Turek and Lana 2007). To avoid entering the cribriform plate and the brain, the distance from the tip of the nose to the medial canthus of the eye is measured on the instrument and identi ied using a piece of tape or a pen mark (Figure 8.2a). The plastic tube attached to the syringe is then introduced past the wing of the nostril, no further than the mark on the tube (Figure 8.2b), and moved in and out repeatedly while suctioning to collect neoplastic material (Figure 8.2c). The moment the tumor is entered can be perceived as an increased resistance to the passage of the cannula. After this procedure, bleeding often occurs; however, it is usually moderate and self-limiting. In cases of copious bleeding, the nasal cavity can be illed with a gauze sponge soaked in diluted epinephrine (1:100 000); alternatively, oxymetazoline 0.05% can be used.

Figure 8.1 (a) Gross appearance of a cat with a nasal tumor. (b) Gross appearance of a dog with a nasal tumor. The nasal pro ile is dis igured to this degree only late in the course of the disease. The withdrawn material is evacuated from the tube by using the syringe illed with air and rolled onto a dry gauze to eliminate the blood. It is then placed in 10% buffered formalin and sent for histologic examination. The same procedure can be performed with a small curette or cup forceps introduced via the nostril, especially in small dogs and cats; the material is scooped out or grasped and the nasal cavity lushed with cold saline in order to stop the bleeding. This core biopsy usually allows a good specimen to be obtained and can be superior to those collected via rigid endoscopy (Ogilvie and LaRue 1992). A similar technique has been successfully applied to 11 dogs using a spirotome device (a large bore cannula with a cutting helical tip design) under computed tomography (CT) guidance (Tamburro et al. 2020). Another non-invasive technique has been described by Ashbaugh et al. (2011), which can be performed during the endoscopy procedure. It is based on retrieval of sample material by forced hydropulsion with 20–60 mL of sterile saline infused forcefully into the nasal cavity. Good occlusion of the nasopharynx with gauze sponges and having the cuff of the endotracheal tube well in lated is mandatory before lushing. A success rate of 90.2% for de initive diagnosis is

reported, and it may temporarily improve clinical signs while waiting for de initive treatment. The same procedure has been proposed as a last-resort palliative treatment when other treatments are not considered for any reason. The procedure was repeated as needed, and good quality of life with the survival of 12 and 20 months was reached in a cat and a dog, respectively. Cribriform plate integrity should be ascertained before treatment (Bienes et al. 2019).

Figure 8.2 Nasal biopsy with cannula. (a) The dog is positioned in sternal recumbency, with the nose parallel to the table; the distance between the medial canthus of the eye and the tip of the nose of the dog is measured on a large-bore urinary catheter. (b) The catheter is cut and a mark or a piece of tape is applied at the measured distance. (c) The catheter is connected to a 12 mL syringe and introduced into the nostril, applying a moderate amount of pressure to the plunger until the mass is penetrated. Suction is applied to the syringe, the cannula is withdrawn, and the material collected. A study conducted by Harris et al. (2014) retrospectively compared nasal biopsies obtained by rhinoscopy, advanced imaging (CT or magnetic resonance imaging, MRI), and blind grasp. They concluded that, in dogs with a con irmed nasal mass, the biopsy technique employed did not signi icantly affect the likelihood to achieve the diagnosis. In this study, the irst biopsy was diagnostic for neoplasia in only 56.4% of cases, meaning that, if tumor is strongly suspected, multiple biopsies could be necessary to reach the inal diagnosis. In cases where other sampling techniques have failed to retrieve diagnostic samples and for masses located in the caudal portion of the canine nasal cavity or nasal sinuses, a frameless CT-guided stereotactic biopsy system allowed collecting diagnostic samples from four out of ive dogs (Kuhlman et al. 2016). The drawback of this technique is the more sophisticated and expensive equipment required. If the tumor is con ined to the frontal sinus, a biopsy may be obtained by its direct trephination. Although previous studies reported that brush cytology is diagnostic only in about 50% of cases (Clercx et al. 1996), Caniatti et al. (2012) reported that the

primary pathologic process was correctly diagnosed by this technique in 86.2% of 138 cases analyzed, and the accuracy for diagnosis of canine malignant neoplasia was 70.1%. Similarly, De Lorenzi et al. (2008) found that squashpreparation cytology obtained by endoscopic retrieval was an accurate diagnostic tool for distinguishing benign from malignant nasopharyngeal masses in cats. A cytological evaluation of the biopsy sample collected is therefore worthwhile and should be considered while waiting for histopathology. In cases where less invasive techniques are unsuccessful, rhinotomy is indicated.

Imaging Techniques Each imaging technique should be performed before the biopsy is taken, as the blood and lavage solution can create artifacts that are dif icult to interpret; moreover, the evaluation of cribriform plate integrity and the knowledge of the presence and location of the mass can help in choosing the more appropriate biopsy technique. Survey radiographs of the skull can aid in the diagnosis, but they should be performed with the animal under general anesthesia. They can reveal increases in soft tissue density inside the nasal cavities and frontal sinuses, bone erosion or new bone formation, or the presence of radiodense foreign bodies. The best views are the open mouth ventrodorsal and dorsoventral intra-oral projections (Figure 8.3b); oblique and rostrocaudal projections should be used for evaluation of frontal sinuses (Figure 8.3a). The open-mouth ventrodorsal view provides the best information on the entire nasal cavity, since it avoids superimposition with the mandible, and should always be performed. While observed radiographic changes may be suggestive of neoplasia, they are not pathognomonic, since severe fungal or in lammatory diseases can have a similar radiographic appearance (O’Brien et al. 1996). Increased soft tissue density of the frontal sinuses without bone involvement should be considered with caution, since it can be due only to obstruction to the out low of mucous secretion (“frontal mucocele”) and not to the tumor itself. A high positive predictive value for nasal neoplasia has been reported for lytic bone lesions compatible with invasion, lesions affecting the entire nasal cavity, soft tissue/ luid opacity in the ipsilateral frontal sinus, generalized loss of turbinates detail, and generalized increased opacity of the nasal cavity. When all signs occurred together, the positive predictive value for neoplasia was 94% (Russo et al. 2000). Similar results have been reported in cats, but the positive predictive value for neoplasia was lower (56–73%); moreover, the visualization of the frontal sinus could be more dif icult, and a ventral 20° rostral-dorsocaudal

oblique projection is a better choice in this species (Lamb et al. 2003). Skull radiographs are not considered an accurate tool to de ine tumor extension and far superior modalities exist such as CT.

Figure 8.3 (a) Rostrocaudal view of the frontal sinuses in a dog. A radiodense material is present in the left (L) sinus; a differential between mucus and neoplastic material is not possible with radiography. (b) Open mouth ventrodorsal view of the nasal cavities in a cat. The tissue density is increased in the right nasal cavity. Care must be taken in interpreting the overlapping effect of oral tissues (i.e. the tongue). Three-view thoracic radiographs complete tumor staging, and they may also help detect comorbidities (Bigio Marcello et al. 2013). Survey or contrast-enhanced CT or magnetic resonance imaging (MRI) techniques are superior to radiography, as they allow more accurate assessment of the extent of the tumor and are more sensitive to early changes due to existing pathology (Figure 8.4a–c). These imaging techniques are now considered the gold standard for nasal tumor diagnosis and staging, and they are also necessary for precise 3D planning of radiation therapy. Conversely, the usefulness and accuracy of diagnostic imaging in the detection of lymph node metastasis are still debated, as reported by Skinner et al. in a study on CT assessment of head and neck lymph nodes (2018). MRI could be more effective in differentiating tumor tissue from retained secretions or necrotic tissue, thus helping in the collection of useful biopsy samples, while CT is more sensitive in

detecting bone erosion (Thrall et al. 1989; Codner et al. 1993; Schoenborn et al. 2003; Saunders et al. 2004; Lefebvre et al. 2005; Petite and Dennis 2006; Tromblee et al. 2006; Avner et al. 2008; Miles et al. 2008; Drees et al. 2009). Moreover, MRI may be more accurate than CT in detecting soft tissue and meningeal involvement (Lux et al. 2017). Rhinoscopy is performed after all other diagnostic imaging has been performed. This technique allows direct visualization of the nasal cavities and is usually performed both with a rostral and caudal approach (McCarthy and McDermaid 1990). The caudal approach is generally conducted irst, with a lexible endoscope introduced from the oral cavity, over the free edge of the soft palate, to visualize the caudal nasal passage, nasopharynx, and choanae. If a mass is present at this level, a biopsy forceps is introduced in the endoscope and a sample is taken (see video clip 8.2). The presence of a well-circumscribed mass is highly suggestive of neoplasia, while a diffuse rough proliferative or erosive appearance of the nasal mucosa without evidence of a mass or a fungal plaque are consistent with tumor but need further investigation (Finck et al. 2015) (see video clips 8.1 and 8.3). Rostral rhinoscopy is performed using a rigid scope introduced from the nostril, and it provides a view of the nasal meatus, ventral concha, alar cartilage, and the ventral and common nasal passages (Figures 8.5a and b). A rigid cystoscope is the best tool for this procedure, but it may be too large for use in cats and small dogs. The endoscope-guided biopsy is taken once the endoscopy is completed. A study compared rhinoscopy and CT results conducted on 30 animals and concluded that the two diagnostic techniques are complementary for the diagnosis of nasal tumors and both should be performed whenever possible. When a choice has to be made, CT is the better irst-line procedure (Finck et al. 2015).

Figure 8.4 Contrast-enhanced CT imaging of the nasal cavity. (a) Some hyperdense material referable to neoplastic in iltrate (lymphoma) is evident in the left nasal cavity. (b) Neoplastic invasion of the left nasal cavity with massive erosion of the turbinates and lysis of the nasal septum in a dog. (c) Neoplastic invasion of the nasal cavity with lysis of the right orbital bone and invasion of the retroorbital region in a cat.

Figure 8.5 Endoscopic view of nasal masses in dog. This imaging technique permits collection of a sample for histology. (a) Melanoma in the rhinopharynx. (b) Polyp in the rhinopharynx. A ventral rhinotomy was performed in this dog. Source: Image courtesy of Dr. Roberta Caccamo.

However, any imaging diagnosis should be con irmed by histopathology, since some indings, such as nasal septum deviation, may be a normal condition in some dogs, even though a higher deviation distance is often observed in nasal tumors (Miles and Schwarz, 2020).

Surgical Techniques

Rhinotomy, both via a dorsal or ventral approach, is indicated to collect biopsy samples from the nasal cavity when other procedures have failed to obtain a diagnosis and/or for debulking purposes. Surgery alone is not curative for nasal tumors and must always be associated with other treatment protocols, both in an adjuvant or neoadjuvant setting. In fact, its role in combination with radiation is still not well understood, although an increased disease-free interval has been reported when surgery was used as adjuvant to radiotherapy (Adams et al. 1995). In both dorsal and ventral procedures, after the animal is anesthetized and intubated, the pharynx is packed with sponge gauzes to avoid aspiration of blood or secretions during surgery. At the time of extubation, the tracheal tube is extracted with the cuff slightly in lated to facilitate the removal of accumulated blood or secretions from the trachea. Dorsal Rhinotomy The dorsal rhinotomy is the standard approach in dogs, but it is rarely performed in cats. It gives access to the entire nasal cavity and frontal sinus. The animal is positioned in ventral recumbency, with the nose parallel to the operating table (Hedlund 1998; Nelson 2003c). A midline skin incision is made from caudal to the nasal planum to the medial canthus of the eyes. If the frontal sinuses are to be explored, the incision is extended caudally to a line connecting the zygomatic process of the frontal bones. The incision is deepened to the subcutaneous tissue and periosteum (Figures 8.6a and b). Stay sutures or Gelpi retractors may help in keeping it wide open. The periosteum is then elevated with a periosteal elevator and re lected laterally on both sides of the incision to expose the underlying bone. A unilateral or bilateral lap is then created in the nasal, maxillary, and frontal bones using an osteotome and mallet or an oscillating saw (Figures 8.6c and d), and re lected rostrally, preserving its attachment to the nasal ligaments. Alternatively, it can be completely detached and kept moist with sponges, if it is to be repositioned, or it can be discarded. If the bone lap is to be repositioned, small holes can be preplaced on either side of the proposed osteotomy along the length of the osteotomy using a k-wire and drill or hand chuck. These holes will be used to place a suture at the time of closure to secure the lap. Additionally, the osteotomy can be made at an angle, going from lateral to medial, creating a beveled edge to help support the lap when repositioned and not fall in the nasal cavity. Once the nasal cavity is exposed, it is lushed with ice-cold sterile saline solution and suctioned to remove debris and blood clots before it is inspected. If the indication for rhinotomy is collection of a biopsy, gentle handling of nasal turbinates is necessary to avoid excessive bleeding, and the biopsy sampling is performed with scissors or a curette. If the surgery is performed for therapeutic purposes

(and not diagnostic purposes only), the turbinates of one or both sides, depending on tumor extension and as previously evaluated by the imaging studies, are removed with rongeurs or a curette (Figure 8.6e). The frontal sinuses are inspected, mucous secretions are removed by suction, and tumor debulking is also completed in this area if necessary. Bleeding can be copious but can be controlled by lushing with ice-cold saline, applying digital pressure with gauzes soaked in diluted epinephrine (1:100 000) or 0.05% oxymetazoline, or careful use of electrocautery. Temporary carotid artery occlusion can facilitate the control of intraoperative bleeding in dogs (Hedlund et al. 1983). This procedure, however, is avoided in cats.

Figure 8.6 Dorsal rhinotomy. (a) Dorsal view of the canine skull. Osteotomies are performed in the nasal and maxillary bones (dotted lines). The rhinotomy may be uni- or bilateral according to tumor extension and it can be extended caudally in the frontal bones if frontal sinus(es) need to be inspected. (b) After a midline incision, the skin and subcutaneous tissues are re lected laterally and the nasal bone exposed. (c) A bone lap is created using a high-speed burr or an oscillating saw. (d) The bone lap is elevated with an osteotome and discarded (or kept moist in sterile gauze sponges). (e) The nasal cavity is inspected and the turbinates removed. The cavity is then washed with cold sterile saline solution. (f) The subcutaneous tissues and skin are closed using the standard technique. Source: Courtesy of Mr. F. Lavezzi, from Prof. P. Belgioioso’s class, Academy of Fine Arts, Turin.

The nasal cavity is lushed and suctioned before closure to eliminate the majority of blood clots and reduce obstruction during the postoperative period. The bone lap can be repositioned, if not invaded by the tumor, or discarded (particularly if adjuvant radiation will follow). If preserved, the lap is sutured in place with non-absorbable mono ilament sutures using the prepositioned holes drilled in the bone. Metal wires should not be used if follow-up radiotherapy is planned. If the bone is discarded, the soft tissues are closed with absorbable mono ilament sutures in a simple continuous pattern (Figure 8.6f). The skin is sutured routinely. To avoid subcutaneous emphysema, which occurs if the bone lap is not replaced, a small (1 cm) gap can be left in the caudal (frontal) end of the suture line (Birchard 1986), or a tube drain is positioned in the frontal sinuses and nasal cavity for some days. The gap will naturally close within a few days. Another way to control emphysema is by placing a gauze stent over the incision for two to three days and suturing it with mattress sutures (Schmiedt and Creevy 2012). Packing the nasal cavities with sponges can help to control severe hemorrhage, but it obstructs nasal air low, thus creating discomfort to the animal, and subsequent removal 48 hours after surgery can be painful. Ventral Rhinotomy The ventral approach provides access to the nasal cavities, nasopharynx, and the rostral half of the frontal sinuses. It allows a better cosmetic result as compared to the dorsal approach, the risk of subcutaneous emphysema is limited, and the dog is already in the correct position for temporary carotid artery occlusion, if this is required. One disadvantage is the risk for oronasal istula formation and the fact that the frontal sinus is not completely visible. Holmberg et al. (1989) found that animals treated with this approach seemed to

experience less discomfort and returned to their preoperative eating and grooming habits faster than those treated with the dorsal procedure. If this approach to the nasal cavity is chosen, adjuvant radiotherapy can be delivered only by megavoltage machines. The animal is positioned in dorsal recumbency, with the front legs secured caudally, parallel to the chest (Hedlund 1998; Nelson 2003c). The mouth is kept wide open by securing the mandible dorsally with a tape and/or applying a mouth gag. To allow better access to the oral cavity, especially in cats, a guarded pharyngostomy tube placement may be preferred to orotracheal intubation. A midline longitudinal mucoperiosteal incision is made from the canine tooth to the level of the fourth premolar. The palate periosteum is undermined and elevated laterally with a periosteal elevator (Figures 8.7a,b, and 8.8a); stay sutures can help with retraction and provide better exposure of the underlying bone. Alternatively, the incision can be U-shaped, parallel to the dental arcade, with the U open caudally; the mucoperiosteal lap is then re lected caudoventrally. Care is taken to avoid damage to the major palatine arteries that emerge from the major palatine foramen at the level of the fourth maxillary premolar tooth and run rostrally, midway between the midline and the dental arcade. A rectangular bone lap is created with a bone saw, air drill, or osteotome and mallet (Figure 8.8b) and discarded. Unlike the dorsal rhinotomy where it is a possibility, the bone lap is not repositioned with a ventral rhinotomy. In cats, a K-wire can be used instead to make two holes in the bone, then completing the cut with rongeurs. The lap can be wide enough to explore one or both nasal cavities, according to the extension of the disease. Hemorrhage is controlled as previously described, but electrocautery is avoided whenever possible in the oral cavity because of the increased risk of dehiscence after closure. Once the nasal cavities are entered, the gross tumor is removed with a curette (Figures 8.7c and 8.8c), or a biopsy is taken as described for the dorsal approach. The nasal cavity is then lushed with cool sterile saline solution.

Figure 8.7 Ventral rhinotomy in a dog. (a) Ventral view of the canine skull. The palatine and maxillary bones are osteotomized as per the dotted lines. The incision may be uni- or bilateral according to tumor extension. (b) A midline incision is made through the mucoperiosteal tissues of the hard palate with two shorter perpendicular incisions made at the extremities of the irst incision. (c) The tissues are elevated and kept retracted with four stay sutures. A lap of the underlying bone is created with an oscillating saw and discarded. The nasal cavity is inspected, and the neoplastic mass and turbinates are removed. (d) After lavage of the nasal cavity with cold sterile saline, the soft tissues are closed in one or two layers with simple interrupted long-lasting absorbable sutures. This is the same dog as in Figure 8.5b. Source: Courtesy of Mr. F. Lavezzi, from Prof. P. Belgioioso’s class, Academy of Fine Arts, Turin.

Figure 8.8 Ventral rhinotomy in a cat. The procedure is similar to that described in the dog. The bone lap can be created either with an osteotome or an oscillating saw. The mucoperiosteal tissue is closed in a one- or two-layer pattern with simple interrupted sutures using 3-0 to 5-0 mono ilament long-lasting absorbable material (Figures 8.7d and 8.8d). If the nasopharynx is to be inspected, the midline incision is extended caudally to the level 5–10 mm rostral to the edge of the soft palate. The caudal aspect of the soft palate is not completely divided, unless absolutely needed, to facilitate wound closure. The incisional margins are kept open with stay sutures, and the

exploration is performed. The soft palate defect is closed in two or three layers with simple interrupted or continuous absorbable mono ilament sutures. The hard palate defect is closed as previously described. The end of the soft palate is then re lected rostrally and the nasopharynx is lushed with saline and aspirated to remove clots. Lateral Rhinotomy Lateral rhinotomy is rarely performed in oncologic surgery, due to the limited access to the nasal cavity achievable. A combined rostrolateral approach has been described by Ter Haar et al. (2015) to remove a squamous cell carcinoma of the rostral nasal septum in ten dogs. The masses removed varied in size from 1 to 4 cm; perforation of the nasal septum was not evident at presentation and the nasal planum was not involved. Careful patient selection based on CT or MRI imaging is needed to avoid incomplete excision of the tumor. Temporary Carotid Artery Occlusion The advent of more sophisticated surgical equipment has improved the ability to achieve hemostasis, thereby reducing the need for this procedure. Temporary carotid artery occlusion can be performed without problems in dogs due to collateral brain perfusion coming from the vertebral arteries. In cats, despite ongoing debate regarding the risks associated with carotid artery occlusion, the serious risks of brain hypoperfusion make this procedure, even with only temporary occlusion, contraindicated (Holmberg 1996). Temporary carotid artery occlusion in dogs is performed with the dog positioned for ventral rhinotomy and the neck positioned over a pad; the skin is incised on the midline from the larynx to the midtrachea. The paired sternohyoideus muscles are separated and retracted to expose the trachea. The external carotid artery is then palpated dorsolaterally to the trachea and exteriorized after blunt dissection of its sheath. After separation from the other neurovascular structures, it is occluded with a bulldog clamp (Figure 8.9), umbilical tape, or a vascular tie. The procedure is then repeated on the other side (Hedlund 1998). The skin incision is temporarily sutured in a continuous pattern or with staples, and the rhinotomy is performed. At the end of the procedure, using new surgical gloves and instruments, the skin suture and vascular clamps are removed. The carotid arteries are repositioned, the surgical ield lavaged with sterile saline solution prior to closure of the sternohyoideus muscles. The wound is closed in a routine manner. An alternative technique to achieve temporary carotid artery ligation is to place a

Rumel tourniquet around each common carotid artery and to leave the ends of the tourniquets exiting the incision when it is closed (Figure 8.10). Once the rhinotomy procedure is completed, the tourniquets can be removed without reopening the neck incision. This shortens surgery time and avoids the necessity to reprepare the cervical site for reexploration and removal of the vascular clamps after completion of the rhinotomy procedure. In most cases, release of the vessel occlusion at the completion of the procedure does not initiate profuse nasal bleeding.

Aftercare The oro- and nasopharynx are cleaned of luids and blood clots before extubation. The animal’s head is kept slightly down to avoid aspiration, and signs of aspiration pneumonia are monitored in the irst days following surgery. Sneezing and bleeding are expected after surgery and can last for several days. Serous discharge can persist for days to weeks after surgery. Rhinotomy is a painful procedure, and analgesia must be provided for three to ive days using opioids and anti-in lammatory drugs. An antibiotic (e.g., cefazolin) is administered intravenously at induction of anesthesia, but it is necessary in the postoperative period only if an avascular bone lap is repositioned or if the tumor was associated with infection.

Figure 8.9 Temporary carotid artery occlusion in a dog. After a blunt dissection of the cervical muscles, the carotid arteries are exteriorized and clamped with bulldog vascular forceps. The skin is temporarily sutured over the clamps and a rhinotomy performed. At the end of the nasal surgery, the skin over the vessels is reopened and the clamps removed.

Figure 8.10 Intraoperative view demonstrating the Rumel tourniquet placed around the carotid artery after it is isolated from adjacent structures. The muscular planes, the subcutis, and the skin are sutured in place, leaving the mobile part of the tourniquet protruding out of the suture. At the end of the rhinotomy, the tourniquet is released and the carotid artery freed again without opening the wound. The nares should be kept clear from blood clots and secretions, especially in cats. Appetite is usually restored in a few days in dogs after these procedures, and a feeding tube is rarely required. In cats, appetite stimulants such as diazepam, oxazepam, and mirtazapine and warming the food to make it more odorous, may be indicated in some cases as well as an esophagostomy feeding tube placement. If the ventral approach is performed, the animal is offered only soft food for the irst 10 days, and gradually switched to canned food that will be offered for the next four to six weeks. Chewing hard objects is not recommended for the same period of time.

Cosmetic and Functional Outcome

Functional outcome is good with both procedures. The elimination of the dorsal bone lap does not preclude good respiratory function once the soft tissues have healed. Serous nasal discharge and occasional sneezing can be present for an extended period of time after rhinotomy, and it should not be a concern for either owners or the veterinarian. The cosmetic appearance is superior with the ventral approach. An acceptable cosmetic result has been described also after rostrolateral approach to the nasal cavity in dogs (Ter Haar et al. 2015).

Potential Complications Hemorrhage can be copious with both approaches and a blood transfusion may be needed in some cases. Temporary carotid artery occlusion can limit this complication in dogs. Interestingly, in a study evaluating surgical procedures at risk of severe hemorrhage requiring blood transfusion, none of the 16 animals undergoing rhinotomy received transfusions, compared to 40% of the animals having a liver lobectomy (Haley et al. 2015). Packing the nasal cavity with sponges for several days is another option to avoid hemorrhage, however, it is not well tolerated. Weisse et al. (2004) proposed percutaneous embolization of the terminal branches of the maxillary artery as an alternative non-invasive procedure to control hemorrhage. Subcutaneous emphysema with movement of the skin over the suture line, in association with respiration, usually occurs with the dorsal rhinotomy approach when the bone lap is removed, unless a small rhinostomy is left or a rhinostomy tube is placed. This is, however, usually self-limiting and resolves in one to two weeks. Airway obstruction by blood clots is another potential complication that can be limited by abundant lushing of the nasal cavity before wound closure and by keeping the nares clean afterward. When rhinotomy is combined with radiotherapy, even in an adjuvant setting, rhinitis and osteomyelitis-osteonecrosis may be observed (Adams et al. 2005). If the cribriform plate is eroded by the tumor or if the biopsy or the curettage procedure breaches the cribriform plate, a brain lesion may occur. Ventricular pneumocephalus and septic meningoencephalitis were described after dorsal rhinotomy and polypectomy in a dog, due to a cribriform plate defect (Fletcher et al. 2006). This underlines the need for careful evaluation of bone integrity during tumor staging.

With the ventral approach, an oronasal istula can develop, particularly if hard food is offered prematurely, or can be secondary to self-trauma. Ventral rhinotomy should be avoided in growing animals since damage to the vomer bone may alter muzzle growth in dogs (Latham et al. 1975), while in cats transverse palatal length may be retarded (Freng 1981). While anorexia is not frequent, it is more commonly seen in cats. Tumor recurrence is always expected since wide excisional margins cannot be achieved.

Common Nasal Tumors Nasal tumors are rare in both dogs and cats, representing about 1–3% of all tumors (Rassnick et al. 2006; Turek and Lana 2007; Manuali et al. 2020). About 80% are malignant, and 60–75% are of epithelial origin in dogs (Rassnick et al. 2006), with carcinoma and adenocarcinoma being the most common histotypes (Turek and Lana 2007). Squamous cell carcinoma and undifferentiated carcinoma are the other types frequently encountered, together with chondrosarcoma, osteosarcoma, and other mesenchymal tumors (Turek and Lana 2007). Nasal lymphoma is one of the more frequent nasal tumors in cats (Turek and Lana 2007; Ferguson et al. 2020; Manuali et al. 2020). Animals affected with tumors in this location are generally older (>10 years), and there appears to be a predilection for male cats (Ogilvie and LaRue 1992). Dolichocephalic and mesocephalic dogs seem to be more often affected (Bukowski et al. 1998; Cohn, 2020). Regardless of histotype, distant metastases are not frequent at diagnosis and occur late in the disease, developing in about 40–50% of animals at the time of death (Turek and Lana 2007). Therapy is therefore directed principally against the primary lesion. Untreated dogs with nasal carcinomas have a life expectancy of about three months (Rassnick et al. 2006). Rassnick reported that the only factor that seemed to have a negative prognostic value was the presence of epistaxis at presentation (median survival 88 days vs. 224 days for dogs without epistaxis). The high COX-2 expression found in a great number of epithelial nasal tumors (Kleiter et al. 2004; Impellizeri and Esplin 2008; Belshaw et al. 2011) does not seem to have prognostic signi icance, and medical treatment with steroids or COX-2 inhibitors did not improve prognosis, even when, at least in epithelial tumors, COX-2 expression had been detected. However, their administration seemed to improve the quality of life in another prospective study (Cancedda et al. 2015). More prospective studies are needed to elucidate the role of COX-2 inhibitors in the treatment of nasal tumors.

The expression and localization of the receptors for the vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF)-α, and PDGF-β have also been evaluated in 187 canine nasal tumor samples, and a high positivity rate was demonstrated. This information may justify the use of tyrosine kinase inhibitors to treat canine nasal tumors (Gramer et al. 2016). The standard of care for nasal malignancies is megavoltage radiation therapy. Surgical debulking by dorsal rhinotomy is indicated before radiation therapy if an orthovoltage machine is used since its tissue penetration is inferior to that of megavoltage radiation. Median survival of dogs with nasal adenocarcinoma treated with megavoltage radiation is about 14–21 months (Henry et al. 1998; Adams et al. 2005), which is signi icantly longer than that of animals treated with surgery alone (median 126 days). In cats, a median overall survival of 452 days after curative-intent radiotherapy of nasal carcinomas was reported by Stiborova et al. (2020). Older studies reported that the response to radiotherapy of mesenchymal tumors, such as chondrosarcoma, is not as good as for epithelial tumors (Popovitch et al. 1994); however, more recent studies reported that tumor type does not signi icantly affect overall survival when appropriate staging and treatment is applied (Adams et al. 2009; Sones et al. 2012; Morgan et al. 2018; Stevens et al. 2020), or, conversely, better results are achieved in cases of sarcomas (Nell et al. 2020). Reirradiation of nasal cavities after tumor recurrence has proved to prolong survival without signi icantly increasing the side effects to normal structures (Bonmarito et al. 2011; Tan Coleman et al. 2012; Gieger et al. 2013; Rancilio et al. 2016) (Table 8.1). Palliation of clinical signs can be obtained with either surgery (median 270 days) or hypofractionated radiotherapy (Gieger et al. 2008; Tan Coleman et al. 2012; Giuliano and Dobson, 2020). The latter allowed a progression-free interval of 10 months with the complete resolution of clinical signs in 100% of cases (Buchholz et al. 2009; Maruo et al. 2011) and can be indicated in both dogs and cats, where an overall survival of 432 days has been reported (Fujiwara-Igarashi et al. 2014). With the advent of stereotactic radiosurgery (SRS), 3D-conformal radiotherapy and intensity-modulated radiation treatment (IMRT), an improvement in controlling acute and late side effects to normal tissues, such as eyes, while maximizing the radiation dose to the tumor are being achieved (Buchholz et al. 2009; Hunley et al. 2010; Lawrence et al. 2010; Glasser et al. 2014; Rancilio et al. 2016). However, overall median survival has still not improved signi icantly, compared with other radiation treatment protocols (Kubicek et al. 2016; Gieger and Nolan, 2018; Mayer et al. 2019; Fox-Alvarez et al. 2020; Stevens et al. 2020). Surgery is not indicated for nasal lymphoma.

In cats with nasal lymphoma, radiation therapy alone (Straw et al. 1986; Meier et al. 2019) or combined with chemotherapy (Haney et al. 2009; S iligoi et al. 2009) can achieve long-term survival and is better tolerated than surgery. Antivascular photodynamic therapy (PDT) was evaluated with good results as an alternative treatment in seven dogs with nasal tumors. The one-year survival rate was 71% (Osaki et al. 2009). Electrochemotherapy with bleomycin has been administered to 11 dogs as a single treatment, with an overall response of 91% and a mean overall survival of 16.8 months (Maglietti et al. 2017). In selected cases, functional endoscopic sinus surgery can be considered (Marchesi et al. 2019).

Adjuvant Treatments Surgery itself can be used in an adjuvant setting after radiotherapy for nasal tumors, especially in dogs. An improvement in survival time compared to treatment by radiation alone has not been observed by Bowles et al. (2014), but they supported the idea that dorsal rhinotomy may be indicated following radiotherapy in cases where complete tumor response (evaluated by postradiation CT scans) has not been achieved; the procedure did not seem to increase acute and late side effects and was well tolerated. Adams et al. (2005) demonstrated an improvement in survival time when radiotherapy was followed by surgical exenteration of the tumor (Figure 8.11).

Table 8.1 Median Overall Survival (OS) and/or Progression-Free Interval (PFI) in days for dogs and cats with malignant nasal tumors treated with radiation with or without other treatments. Author, No. of Curative Palliative SRS/IMRT RT and Total dose year of animals RT RT surgery delivered publication treated (Gy) Henry et al. 64 dogs (1998) Mellanby et 8 cats al. (2002)

OS 424

Nadeau et 31 dogs al. (2004) Adam et al. 40 and 2005 13 dogs

OS 433

S iligoi et al. 19 cats (2007) Gieger et al. 48 dogs (2008) Buchholz et 38 dogs al. (2009)

OS 955 PFI 945

Lawrence et 31 dogs al. (2010) Hunley et al. 12 dogs (2010)

OS 420

42 IMRT

OS 446

54 IMRT

OS 382

OS 1410 42

OS 146

22–48 plus chemotherapy 24

PFI 300

30

OS 197

32

OS 201

34–36

OS 927 (median TTP 513 days between courses)

Sones et al. 86 dogs OS 523 (2012) with sarcomas

16–48 no lymphoma 48–50

OS 570

Maruo et al. 63 dogs (2011) Belshaw et 42 dogs al. (2011) Bonmarito 9 dogs et al. (2011)

OS 302

50 and 36 (reradiated)

OS 305

Author, year of publication Tan Coleman et al. (2012)

No. of Curative Palliative SRS/IMRT RT and Total dose animals RT RT surgery delivered treated (Gy) 18 dogs OS 309 20

Gieger et al. 37 dogs (2013)

OS 453 OS 180 (2nd course RT)

Fujiiwara et 36 dogs al. (2013)

OS 512 PFI 245

Bowles et 16 dogs al. (2014) Fujiiwara et 65 cats al. (2014)

24 and 20 (reradiated)

OS 457 54 +/− chemotherapy 16-36

OS 432 PFI 229

Glasser et al. (2014)

19 dogs

OS 399

27

Kubicek et al. (2016)

57 dogs

OS 255

33 +/− chemotherapy

Rancilio et al. (2016)

1 dog

OS 694

Gieger and Nolan (2018)

29 dogs

PFS 354 OS 586

117 (over 3 treatment courses) 30, 6 dogs reirradiated

Morgan et al. (2018)

15 dogs

OS 435

54

Mayer et al. 28 dogs 2019

OS 388

Fox-Alvarez 17 dogs et al. (2020)

PFS 359 OS 563

20–30 2 dogs had chemotherapy 30

Giuliano 28 cats and Dobson (2020)

OS 342

34

Author, No. of Curative Palliative SRS/IMRT RT and Total dose year of animals RT RT surgery delivered publication treated (Gy) Nell et al. (2020)

22 dogs

PFI 144

Stevens et al. (2020)

29 dogs

OS 177

42

Figure 8.11 (a) Positioning of a dog undergoing adjuvant unilateral dorsal rhinotomy to debulk the residual tumor mass after a course of megavoltage radiation therapy for a nasal chondrosarcoma. (b) Intraoperative view of the ibrosis following radiation treatment after skin incision. (c) After the bone has been removed, the nasal cavity looks almost empty, apart from the remnants of the tumor, which is extracted with a curette and thumb forceps. (d) Nasal cavity following tumor removal. Chemotherapy is considered after rhinotomy, if radiation is not available, to treat both epithelial and mesenchymal nasal tumors in dogs. A combination of intravenous doxorubicin and carboplatin, together with oral piroxicam, was associated with a survival time varying from 150 to 540 days (Langova et al. 2004). A larger study conducted on 29 dogs, using a comparable protocol, reported a median overall survival of 234 days (Woodruff et al. 2019). Mitoxantrone in combination with carboplatin or radiotherapy has also been used in dogs (Henry et al. 1998; Bowles et al. 2014). Chemotherapy as a radiosensitizer (cisplatin) has been proposed (Nadeau et al. 2004), but no statistically signi icant differences in survival time were noted with this treatment. Chemotherapy can be used to treat nasal lymphoma in both dogs and cats, but the overall results are not as good as with radiation alone or with the combined treatment (George et al. 2016). Endoscopic photodynamic therapy has been performed with good results in three dogs for the treatment of nasal tumors recurring after radiotherapy (Ishigaki et al. 2018). PDT with acridine orange as an adjuvant to surgery, with or without radiotherapy, has also been applied with good disease-free and overall survival in six dogs (Maruo et al. 2015). The complete work plan for nasal tumors diagnosis and treatment is shown in Figure 8.12.

Figure 8.12 Flow chart of the decision-making process for the diagnosis and treatment of canine and feline nasal tumors.

Laryngeal Tumors Biopsy Principles If there is a suspicion of a laryngeal mass, general anesthesia for examination by direct laryngeal examination and laryngoscopy is usually the next diagnostic step (Figures 8.13 and 8.14). Patients often present for dyspnea, and it may not be possible to pass an endotracheal tube past a laryngeal mass. The patient should be prepared for a potential tracheostomy, and instruments to perform a tracheostomy should be on hand. Tracheostomy may need to be performed to maintain general anesthesia for examination and biopsy or may be required after biopsy due to swelling of the laryngeal mucosa. Depending on the amount of time required for examination, it also may be possible to perform a direct laryngeal examination under short-acting injectable anesthetic drugs. Ideally, an incisional biopsy of the mass should be performed for impression smears and/or histopathology. In patients with severe respiratory compromise, this may not be possible without tracheostomy. In some cases, rapid progression to excision may be necessary due to the status of the patient. Biopsy is performed orally if the mass is accessible. A small wedge of tissue is excised. Closure of the biopsy site should be attempted but may not be possible. Hemostasis can be achieved with pressure on the biopsy site. Cytology alone has been shown to be inaccurate in the diagnosis of rhabdomyosarcoma in dogs and aspirates can cause further swelling (O’Hara et al. 2001; Henderson et al. 1991; Jakubiak et al. 2005). It may be useful in cats to distinguish between lymphoma and squamous cell carcinoma. Ideally, a histological diagnosis is achieved prior to initiating therapy. Incisional biopsy was found to be a reliable method for the de initive diagnosis of laryngeal masses in cats. In some cases, however, a diagnosis of lymphoid hyperplasia was found to be inaccurate on subsequent biopsies. The diagnosis of lymphoid hyperplasia is relatively rare, and a second biopsy may need to be considered if the diagnosis does not correlate with the rest of the clinical picture (Jakubiak et al. 2005).

Figure 8.13 Endoscopic image of an arytenoid chondrosarcoma in a nine-yearold Doberman that was treated with arytenoidectomy. Source: Image courtesy of Dr. Richard White.

Figure 8.14 Oral examination of a dog with a laryngeal rhabdomyosarcoma. Source: Image courtesy of Dr. Richard White.

If a tracheostomy is performed, it should be done with separate instruments and gloves from those used for an incisional biopsy to prevent seeding of tumor cells at the tracheostomy site. Cytology or biopsy of the mandibular lymph nodes should be performed to evaluate for metastatic disease. However, the medial retropharyngeal lymph nodes are the primary lymph nodes that drain the larynx (Belz and Heath 1995) and consideration should be given to either ultrasound-guided aspiration of these lymph nodes or removal during de initive surgery. One non-invasive method of evaluating the deeper lymph nodes of the head and neck is advanced imaging. However, it is important to note that in a study evaluating the diagnostic accuracy of CT for assessment of mandibular and retropharyngeal lymph node metastasis, the accuracy was 67.5 and 76.3% for the mandibular and retropharyngeal lymph nodes, respectively (Skinner 2018). Identi ication of the sentinel lymph node(s) for a laryngeal tumor using indirect lymphography has not been evaluated in dogs and cats and could prove challenging given the anatomic location and the potential risk of injecting into the larynx.

Imaging Tests

Radiographs of the larynx can be helpful to localize disease. Common indings with laryngeal tumors include soft tissue opacity in the lumen and decreased margination of laryngeal structures (Figure 8.15) (Jakubiak et al. 2005). In one study, only 10% of cases with laryngeal neoplasia had no radiographic lesions. Ultrasound has also been reported as a method of diagnosing laryngeal masses (Rudorf et al. 1997, 2002). The advantage of this technique is that it allows examination in awake patients in sternal recumbency, which may be more feasible in patients with respiratory compromise. Ultrasound-guided ine needle aspiration (FNA) has also been reported with this technique in cats.

Figure 8.15 Lateral radiograph of a dog with a laryngeal rhabdomyosarcoma. Source: Image courtesy of Dr. Paolo Buracco.

Figure 8.16 CT examination of a dog with a laryngeal rhabdomyosarcoma. Source: Image courtesy of Dr. Paolo Buracco.

Three-view thoracic radiographs should be performed to evaluate for pulmonary metastasis and aspiration pneumonia. For cases where a surgical resection is being considered, a CT scan is necessary for surgical planning. The CT scan will help to determine the extent of disease and the feasibility of a curative-intent surgery (Figures 8.16 and 8.17). A mass that is amenable to a partial or complete laryngectomy is one relatively con ined within the larynx

and that has not invaded the pharynx or esophagus. The CT scan will also help to determine the origin of the mass (within the larynx or a mass invading from outside the larynx). The lymph nodes and thorax can also be assessed for evidence of metastasis by CT scan. Ideally, a CT scan would be performed prior to biopsy if they are done under the same general anesthetic. This is because the edema, in lammation, and hemorrhage caused by the biopsy may distort the CT image. A tracheostomy tube may be required to maintain general anesthesia if an endotracheal tube cannot be placed orally.

Surgical Techniques Vocal Cordectomy Laryngectomy Vocal cordectomy laryngectomy is limited to small benign tumors of the vocal folds. It is similar to vocal cordectomy performed for devocalization in dogs. Similar to devocalization in dogs, a transoral approach is not recommended due to the increased risk of the formation of granulation tissue and webbing of mucosa in this region that may lead to upper airway obstruction. The patient is positioned in dorsal recumbency with the head extended. A ventral midline approach is made from the basihyoid to the third tracheal ring. The ventral midline incision continues through the cricothyroid ligament and thyroid cartilage. Self-retaining retractors are used to retract the thyroid cartilage. The affected vocal cord is resected. The mucosa is sutured in a simple continuous pattern with a small-gauge, mono ilament, absorbable suture material. Care must be taken to ensure accurate closure of the mucosa to prevent the development of granulation tissue and scarring of the larynx. The cricothyroid ligament and thyroid cartilage are closed using simple interrupted sutures. The site is lavaged with sterile saline. The subcutaneous tissue and skin are closed routinely. Hemilaryngectomy The approach to the larynx is the same as for cordectomy (Figure 8.18). The tumor is excised full thickness through the mucosa and thyroid or cricoid cartilages. The soft tissue attachments to the segment of larynx are excised along the larynx with blunt or sharp dissection. The resultant defect is closed primarily, if possible. If feasible, the mucosa is closed separately with simple continuous or simple interrupted sutures. The remaining laryngeal cartilage is closed using simple interrupted sutures.

Figure 8.17 CT reconstruction of a dog with laryngeal chondrosarcoma. From the same dog as in Figure 8.21. Source: Image courtesy of Dr. Charles Kuntz.

Figure 8.18 Ten-year-old malamute with a grade II mast cell tumor of the arytenoid. (a) Tracheostomy and ventral midline approach to the larynx. (b) Ventral midline approach to the larynx. (c) Hemilaryngectomy. Source: Images courtesy of Dr. Bart Van Goethem.

If it is not possible to close the site primarily, there are several techniques to close the defect. A myocutaneous lap can be elevated based on the sternohyoid muscle (Nelson 2003a). Preplanning is necessary if this lap is going to be used because the muscle and skin are not separated from one another during the approach. An island lap of the appropriate size is planned. The medial edge of the lap is the ventral midline incision. The rest of the island lap is harvested. The vessels supplying the lap are branches of the cranial thyroid artery. The lap is depilated by shaving the epidermis down to dermis to prevent hair growth. The lap is rotated so the dermis is facing into the airway. The dermis is sutured to the mucosa in a simple interrupted suture pattern. The site is

lavaged. The rest of the closure is routine. Free tissue transfer has also been reported to replace laryngeal defects but is not routinely used (Nelson 2003a). Temporary tracheostomy should be placed in these patients to prevent obstruction due to postoperative laryngeal edema and in lammation. A gastric feeding tube should be considered in these patients as they may not eat normally after surgery. Epiglottectomy Epiglottectomy has also been reported anecdotally and in one case report in a dog (De Lorenzi 2015). In this case report, an epiglottic chondrosarcoma was removed via diode laser epiglottectomy. This patient did well with normal eating and respiratory functions. Epiglottectomy can be performed via a transoral approach (Figure 8.19). The patient is placed in sternal recumbency and the head is suspended with the mouth open. The epiglottis is grasped and resected with a sharp dissection or a laser. If possible, the mucosa at the base of the epiglottis is closed using a simple interrupted pattern of mono ilament, absorbable suture material.

Figure 8.19 Images from a dog with ibrosarcoma of the epiglottis. (a) Oral approach for epiglottectomy/partial laryngectomy. (b) Closure of the epiglottectomy site. (c) Specimen photo. Source: Images courtesy of Dr. Laurent Findji.

Total Laryngectomy The patient is positioned in dorsal recumbency with the head extended. A roll under the neck may facilitate the dissection. An esophageal tube placed orally during the procedure may help facilitate orientation during the procedure. A

ventral midline approach is made that extends several centimeters cranial and caudal to the larynx. The paired sternohyoid muscles are bluntly dissected at midline, they are elevated from the basihyoid bone, and this attachment is incised bilaterally. Similarly, the paired sternothyroid muscles are transected at their cranial attachment. The muscles are retracted laterally. A patent airway is maintained by either a preplaced tracheostomy that is attached to the anesthetic machine during surgery or by placing a sterile endotracheal tube through the transected end of the trachea at the time of surgery. If a tube is placed intraoperatively, the fascial attachments are bluntly dissected from the cranial trachea at the level of the cricoid or irst tracheal ring. The orally placed endotracheal tube is retracted. The trachea is transected as cranially as possible. A sterile endotracheal tube is placed in the trachea and the orally placed tube is removed. If a tracheostomy tube has been placed, the trachea is resected at the same level. The larynx is removed en bloc by transection of all of its attachments to the skull by the hyoid apparatus and to the pharynx, tongue, hyoid bone, and sternum by the extrinsic muscles of the larynx (Figure 8.20). The hyoid apparatus is disarticulated bilaterally at the level of the thyrohyoid bone. The thyropharyngeus, cricopharyngeus, and thyrohyoideus muscles are transected at their attachments to the larynx bilaterally. Care must be taken to avoid damage to the nerves in this area, which provide sensory and motor function to the pharynx and esophagus and are necessary for normal swallowing. The larynx is retracted from caudal to cranial. The remaining soft tissue attachments are sharply and bluntly dissected from the larynx, including the hyoglossus muscle, which is severed from the ventral epiglottis. The pharyngeal mucosa is then transected cranial to the larynx starting at the base of the epiglottis and the larynx is removed en bloc (Figures 8.21 and 8.22). Some descriptions of this technique advocate closing the mucosa as it is incised to improve orientation. Stay sutures may also be used to facilitate this dissection. The area is lavaged with sterile saline. The pharyngeal mucosa is closed with a one- or two-layer simple continuous inverting suture pattern. The paired thyropharyngeal and cricopharyngeal muscles are closed ventral to the pharyngeal mucosa and dorsal to the trachea.

Figure 8.20 Total laryngectomy specimen from a Sheltie with a laryngeal squamous cell carcinoma. Source: Image courtesy of Dr. Ralph Henderson.

Figure 8.21 Laryngeal chondrosarcoma in a 10-year-old dog. The trachea distal to the mass is being palpated with ingers. Source: Image courtesy of Dr. Charles Kuntz.

A permanent tracheostomy must be created. This will involve either converting the previously placed temporary tracheostomy into a permanent one or creating a tracheostoma with the severed end of the trachea (Figure 8.23). To convert a temporary tracheostomy to a permanent one, the severed cranial end of the trachea is lattened and closed using simple interrupted sutures. Alternately, the irst two remaining tracheal rings are excised without removing the dorsal tracheal membrane. The dorsal tracheal membrane is rotated ventrally and closed to the proximal end of the trachea. With either technique, an airtight seal should be created in the proximal trachea. The existing stoma site is enlarged and is oval or rectangular in shape. The sternohyoideus muscles are sutured dorsal to the trachea to hold it ventrally. Excessive skin folds are excised to prevent interference with the tracheostomy. The subcutaneous tissue is sutured to the tracheal wall around the stoma. The skin is sutured to the tracheal mucosa using a simple interrupted suture pattern. The remaining skin and subcutaneous tissue are closed routinely.

Figure 8.22 Same dog as in Figure 8.21. En bloc resection of the larynx including the hyoid apparatus. Source: Image courtesy of Dr. Charles Kuntz.

Figure 8.23 Photograph of a Sheltie seven days after surgery with a laryngeal squamous cell carcinoma treated with total laryngectomy and permanent tracheostomy (as depicted in Figure 8.20). Source: Image courtesy of Dr. Ralph Henderson.

To create a tracheostoma, the proximal trachea is directed ventrally between the sternohyoideus muscles. The sternohyoideus muscles are sutured to the trachea dorsally to hold the trachea in a ventral position. The tracheal ori ice is trimmed to it the contour of the exit site. The excess skin folds and a circular portion of skin are removed. The subcutaneous tissue is sutured to the tracheal wall. The tracheal mucosa is sutured to the skin in a simple interrupted suture pattern. The advantages of the creation of the tracheostoma are that the opening is wider and has less risk of stricture as it heals. Because of the larger stoma, this will facilitate endotracheal intubation if required in the future. A stomach tube should be placed postoperatively until the patient can eat and swallow normally. In some cases, the stomach tube feeding may need to be permanent.

For information about surgical techniques, consult Fossum et al. (2007a), Nelson (2003a), Block et al. (1995), Dyce et al. (1987a), Crowe et al. (1986). This technique was recently reported by Matz et al (VSSO Second Scienti ic Meeting, Asheville, NC, 2014). In that report, total laryngectomy and permanent tracheostomy were reported with excellent long-term local control and function. If possible, preservation of the cricoid cartilage and end-to-side anastomosis of the tracheostomy site may provide a more robust stoma. Palliative Surgical Management In some cases, an intralesional or marginal excision of a low-grade rhabdomyosarcoma may provide palliation of the laryngeal obstruction caused by the mass. This approach can be considered in well-circumscribed, low-grade lesions when the goal is short-term relief of respiratory compromise.

Aftercare After cordectomy, patients will need to be monitored in an intensive care unit for dyspnea. There is a risk of laryngeal edema due to cordectomy, and patients should be treated with dexamethasone perioperatively at an anti-in lammatory dose. After hemilaryngectomy patients will need to be monitored in an intensive care unit for care of their temporary tracheostomy tubes and for pain management. The tracheostomy tubes can be removed three to four days after surgery. This can be done by either covering the end of the tube if there is room for the air to low by, or by removing the tube, and assessing respiratory function. This should be done in a quiet, controlled environment, and the clinician should be prepared to sedate or anesthetize the patient to replace the tube quickly if needed. Potential complications of cordectomy, epiglottectomy, and hemilaryngectomy include scar formation and stenosis of the upper airway, incomplete margins of tumor excision, and aspiration of either blood in the immediate postoperative period or food due to laryngeal dysfunction. After total laryngectomy and permanent tracheostomy, patients will require intensive care and monitoring. The tracheostomy site will need to be kept clean. The patient is fed via the gastric feeding tube until the pharyngeal mucosa has healed. The irst oral feeding should be done under supervision to ensure normal swallowing function. Pain control should be provided for ive to seven days. For long-term management of these patients, the owners will need to keep the stoma site clean and trim the hair around it. No neck leads can be used, and the patients cannot swim. After this procedure, dogs will be unable to pant.

Unrestricted activity should be avoided. As well, dogs will not be able to thermoregulate by panting and they should not be outdoors in hot weather (Henderson et al. 1991). Reported complications include dehiscence of the pharyngeal mucosa and iatrogenic hypoparathyroidism (Henderson et al. 1991). It is also possible that these patients will not be able to swallow normally, and the owners should be prepared for a permanent gastrostomy tube.

Cosmetic and Functional Outcome Successful cordectomies and laryngectomies have been reported for the treatment of benign and malignant neoplasia of the larynx (Meuten et al. 1985; Block et al. 1995; Henderson et al. 1991). Descriptions of hemilaryngectomy are largely based on human reports. This is likely because the surgical cases are going to be either benign diseases such as rhabdomyoma, that is amenable to local resection, or malignant neoplasia that is not con ined to a small area of the larynx. An article that discusses two cases of laryngeal mast cell tumors in dogs reports that a partial laryngectomy was attempted that resulted in recurrence in both dogs (Crowe et al.1986). This is because it is dif icult to achieve adequate surgical margins for a malignant neoplasm of the larynx with a partial resection. In general, by the time that they are diagnosed, most malignant tumors of the larynx will require total laryngectomy for successful local treatment of the tumor. The entire larynx has been reported to be successfully removed with a good long-term outcome (Block et al. 1995). However, this procedure is uncommon in veterinary medicine, and most of the information on this procedure is anecdotal.

Most Common Tumors – Prognosis and Decision‐Making In cats, lymphoma and squamous cell carcinoma are the most commonly reported tumors (Jakubiak et al. 2005; Carlisle et al. 1991; Saik et al. 1986). In dogs, there are many different tumor types reported, with rhabdomyoma and rhabdomyosarcoma being reported relatively commonly (Block et al. 1995; Carlisle et al. 1991; Meuten et al. 1985; O’Hara et al. 2001; Henderson et al. 1991; Clercx et al. 1998). Other reported laryngeal tumors in dogs include squamous cell carcinoma, mast cell tumor, osteosarcoma, melanoma, lipoma, adenocarcinoma, chondrosarcoma, leiomyoma, ibropapilloma, ibrosarcoma, chondroma, myxochondroma, invasive thyroid carcinoma, granular cell tumor, and plasmacytoma (Carlisle et al. 1991; Saik et al. 1986; Rossi et al. 2007; Hayes et al. 2007; Carpenter 2012; Dunbar 2012; Muraro 2013; Ramirez 2015). Oncocytoma is another tumor type that has been reported. It is thought to be likely that the tumors that have been diagnosed previously as oncocytomas are

in fact rhabdomyomas (Meuten et al. 1985). Oncocytomas, rhabdomyomas, and granular cell tumors can all have similar appearances under standard light microscopy, and immunohistochemistry may be necessary for a de initive diagnosis.

Adjunctive Therapy Laryngeal lymphoma in cats is a non-surgical disease that should be managed with chemotherapy and/or radiation. Chemotherapy should be considered in cases of malignant tumors with a high chance of systemic spread. Radiation was reported in a case of a solitary plasma cell tumor of the larynx in a dog with no effect. This was a surprising inding. However, the dog went into a complete and long-standing remission when treated with melphalan and prednisone (Hayes 2007). In another case report of laryngeal plasma cell tumor, melphalan and prednisone provided excellent local control of the tumor for six months (Witham 2012). Radiation is not commonly used for tumors of the larynx but should be considered in cases of incomplete resection or when a surgical resection is not thought possible. With the advent of stereotactic radiosurgery, local control of malignant tumors in this area may become possible. One example for which radiation therapy would be useful is an invasive thyroid carcinoma. In cases of laryngeal tumors where a surgical resection is not thought to be possible, a permanent tracheostomy can be placed to relieve the upper airway obstruction and the tumor site can be treated with radiation. Tracheostomy alone can also be considered as a palliative measure to relieve the upper airway obstruction.

Thoracotomy Thoracotomy is performed to explore the thoracic cavity and to take surgical biopsies in situations where other diagnostic tools have failed, or to excise either primary or metastatic intrathoracic tumors. Since the preoperative diagnostic rate is low for intrathoracic neoplasia (Tattersall and Welsh 2006), thoracotomy is almost always performed with both diagnostic and curative intent. The most commonly employed techniques are lateral thoracotomy and median sternotomy; both procedures require assisted ventilation. For biopsy purposes, thoracoscopy is usually preferred because it is less invasive (Kovak et al. 2002; Schmiedt, 2009). For the lungs, pericardium, pleura, and for mediastinal masses, ectopic thyroid tumors, and other space-occupying masses, biopsies can be performed by thoracoscopy. This technique, however, does not allow the excision of large intrathoracic masses, whereas small lung

tumors located away from the hilus, especially in the left caudal lung lobe, can be excised (Lansdowne et al. 2005).

Imaging To choose the best approach to access the thorax (intercostal thoracotomy vs. median sternotomy) and to decide which side and intercostal space to use, left and right lateral and dorsoventral or ventrodorsal radiographs of the thorax must be performed (Figure 8.24). The use of contrast-enhanced CT has improved the ability to visualize small intrathoracic masses that may not be visible with radiography (Figure 8.25a) and has become the best diagnostic imaging tool for thoracic evaluation and surgery planning in veterinary medicine (Figure 8.25b) (Prather et al. 2005). MRI is not usually employed because it requires more complicated respiratory-gated techniques to image the chest.

Figure 8.24 Chest radiographs. (a) Ventrodorsal view of a dog with an intrathoracic mass, which appears to be pulmonary (arrow). (b) Laterolateral view of the same dog. This view alone does not allow the determination of whether the lesion is pulmonary or mediastinal. (c) Feline thymoma. In this case, the ventrodorsal or dorsoventral view is needed to correctly locate the lesion.

Figure 8.25 CT images of a canine thorax. (a) Contrast-enhanced CT is a more accurate method compared to radiography for the detection of small lung metastases (arrows). (b) The use of CT allows evaluation of the full extent of thoracic wall masses that tend to grow in a centripetal direction. In this picture, a rib metastasis of a previously resected contralateral humeral osteosarcoma is evident.

Surgical Techniques Intercostal Thoracotomy Generally, a limited area of one side of the thorax is explored if a solitary lesion has been previously identi ied. Usually, one-third of one thoracic cavity and the corresponding mediastinal area are fully visualized with this approach. The intercostal space (third to tenth) is chosen according to radiographs or CT scans taken before surgery (see Table 8.2). If a lung tumor is to be resected via lobectomy, the ifth intercostal space should preferentially be chosen, regardless of the lobe affected, because the lung lobe hilus is accessible most easily by this approach (Kuntz 1998). For caudal lung lobes, access to the pulmonary ligament situated dorsally can be facilitated by performing a sixth intercostal approach instead. It should be kept in mind that the ribs can be moved cranially to allow a slightly improved exposure of structures cranial to the intercostal space chosen but ribs cannot be moved caudally.

Table 8.2 Access to the main thoracic structures for tumor excision. Organ Intercostal space Side Cardiac structures 4–5 Both Lung lobes

5 [6]

Right or left

Cranial esophagus 3–4

Left

Caudal esophagus 7–9 3 [4] Thymusa

Both Left

[x] indicates alternative space. a Thymomas are usually excised by median sternotomy.

The animal is positioned in lateral recumbency, with a sandbag or a rolled drape beneath the thorax, to facilitate the spread of the contralateral ribs and the exposure of the intrathoracic structures. An incision in the skin, subcutaneous tissue, and cutaneous trunci muscle is made with a scalpel, parallel to the desired intercostal space. The incision is extended from the costovertebral junction, past the costochondral arch to the sternum. The latissimus dorsi and pectoralis muscles are incised, or alternatively, can be retracted. At this point, it is easy to count the ribs by passing a inger cranially underneath the latissimus dorsi muscle to identify the irst rib. The ifth rib is easily identi ied by the caudal insertion of the scalenus and the cranial insertion of the external abdominal oblique muscles. One of these two muscles is incised, depending on the intercostal space chosen, and the incision is continued by separating the bellies of the serratus ventralis muscle. Recently, a muscle-sparing technique has been described by Yoon et al. (2015) to reduce post-surgical pain. No signi icant differences in surgical time compared to the traditional technique, or in the ease of visualization of the thoracic cavity were noted, while postoperative pain was signi icantly reduced. The ventral border of the latissimus dorsi is bluntly dissected and retracted dorsally by a Senn-Miller retractor; the scalenus muscle is then detached from the rib insertion and the serrations of the serratus ventralis muscle are split at the desired intercostal space. The pectoral muscles are retracted by a Senn-Miller retractor. The muscle-sparing intercostal lateral thoracotomy leads to decreased postoperative pain and decreased lameness of the ipsilateral thoracic limb (Nutt et al. 2021). The intercostal muscles are then incised, in both techniques, midway between the two adjacent ribs, avoiding the nerves and vessels that run parallel to the caudal aspect of each rib, and the parietal pleura is exposed (Figure 8.26a). The thorax is entered by bluntly incising the pleura with hemostatic forceps or scissors, and continuing the cut dorsally and ventrally with scissors, paying attention to the internal thoracic arteries and veins that run lateral to the inner (dorsal) side of

the sternum (Figure 8.26b). The incision should be continued no more dorsally than the point where the ribs angle medially, to avoid damage to the epaxial musculature and the intercostal arteries. A Finochietto retractor is applied to spread the ribs, with moistened sponges placed between the retractor and the ribs (Figure 8.26c). The rib cranial to the incision is usually easier to retract than the caudal one. In the muscle-sparing technique, a Balfour retractor is used in place of the Finochietto, using the central blade to retract the latissimus dorsi muscle dorsally. At this point, the thorax may be inspected. Following lung lobectomy for a lung mass, the remaining lung in the exposed hemithorax is carefully palpated to detect the presence of other neoplastic nodules, and the hilar and sternal lymph nodes are evaluated and resected if needed. Prior to thoracotomy closure, blood clots are carefully removed, and a thoracostomy tube is inserted through a stab skin incision at the level of the tenth intercostal space, and by tunneling it in the subcutis for at least three ribs in a caudocranial direction, before its entrance in the thorax. The tube must not enter the thorax through the thoracotomy site (Figure 8.27). The thoracostomy tube is left open until airtight closure is accomplished, to avoid a tension pneumothorax. After having removed the sandbag from underneath the thorax, closure of the thoracotomy is achieved by preplacing four to eight sutures around the rib immediately cranial and caudal to the incision, using absorbable or non-absorbable heavy-gauge mono ilament (2-0 to 0 USP, polydioxanone or polypropylene in small to medium size dogs and cats; 0 to 2 USP in large dogs), and having an assistant approximating them while tying (Figure 8.26d); care should be taken to avoid overlapping of the ribs. To avoid damaging the underlying lungs and to decrease the risk of causing trauma to the intercostal vessels and nerves, the needle is inserted through the tissues with its blunt end irst. The suture can be passed through small holes drilled in the caudal rib itself (transcostal placement), instead of surrounding it (circumcostal placement), to reduce postoperative pain and to avoid damaging the nerve and vessels on the caudal aspect of the rib (Rooney et al. 2004). The trancostal closure has been shown to be less painful (Rooney et al. 2004).

Figure 8.26 Intercostal thoracotomy. (a) An incision in the skin, subcutaneous tissue, and cutaneous trunci muscle, extending from the costovertebral junction to the sternum, is made with a scalpel, parallel to the desired intercostal space. (b) After the thorax is entered, blunt incision is made with scissors in the pleura and continued dorsally and ventrally (c) A Finochietto retractor is applied to spread the ribs, protecting them with a moistened gauze sponge. (d) After the completion of the thoracic surgery, the chest wall is closed by preplacing four to eight large-gauge sutures around the rib immediately cranial and caudal to the incision and having an assistant approximating them while tying. Source: Image 8.24d courtesy Dr. R. Bussadori.

The serratus ventralis and scalenus or external abdominal oblique muscles are sutured in a simple continuous pattern; the latissimus dorsi, cutaneous trunci,

and subcutis are closed individually in simple continuous suture patterns, and the skin is closed routinely. At this point, the pleural space is evacuated and the thoracostomy tube is closed. Before completing the closure, a selective intercostal nerve block should be performed with 0.75% bupivacaine injected dorsally in the intercostal spaces one or two ribs cranial and caudal to the incision, and/or directly injecting the local anesthetic in the thoracostomy tube (up to a total dose of 2 mg/kg body weight [0.9 mg/lb]) while the animal is still anesthetized (given that bupivacaine is painful) and keeping the animal laterally recumbent with operated side down for 20 minutes, to allow the diffusion of the local anesthetic over the incision site. The area of the thorax that can be evaluated with intercostal thoracotomy can be extended using the rib pivot technique described by Schulman and Lippincott (1988). In this technique, a rib cranial to the incision is rotated (pivoted) out of the surgical ield. After the muscular incision, a transverse osteotomy is performed at the level of the costochondral junction of the cranial rib with an oscillating saw. The rib is grasped and rotated cranially, pivoting on the costovertebral junction. At the end of the surgical procedure, the rib is pivoted back into its standard position, and a small gauge orthopedic wire is used to stabilize the osteotomy site after having drilled two small holes just dorsal and ventral to the osteotomy. The remainder of the thoracic incision is closed as previously described. The rib pivot technique can be used on its own to perform the lateral thoracotomy (Appelgrein and Hosgood 2018). With the modi ied technique, the periosteum overlying the rib is elevated circumferentially, avoiding the intercostal neurovascular structures. Holes are pre-placed above and below the proposed osteotomy site. The rib is osteotomized close to the costochondral junction and pivoted cranially. The pleura is incised and the required intrathoracic procedure is then performed. Closure is done by pre-placement of a suture through the pre-placed holes within the osteotomized rib. The pleura and intercostal musculature are closed, avoiding the intercostal neurovascular structures. The rib is re-apposed and the lateral approach is closed (Appelgrein and Hosgood 2018).

Figure 8.27 (a) The thoracic drain is applied by making a stab incision two to three ribs caudal to the thoracotomy and tunneling the tube cranially in the subcutis. (b) The chest tube is secured to the skin with a inger-trap suture. (c) A Christmas tree adaptor is applied to close it, using a metal wire to achieve an air-thigh. (d) Chest radiographs after the application of the drain in order to determine the tube’s correct or incorrect (e) placement. Another variation used to extend the thoracotomy exposure, which is rarely performed in small animals, is rib resection thoracotomy. The advantage of this procedure is that, compared to the intercostal technique, it results in fewer adhesions between the lungs and the incision and provides better exposure of

the thorax. A secure closure is more dif icult to achieve, however, especially in large breed dogs, because the suture pullout strength is weaker compared to what can be achieved by anchoring the sutures to the ribs. After the muscular layers are incised, as for the intercostal thoracotomy, the periosteum of the rib to be resected is incised and bluntly elevated from its lateral and medial surface. The rib is then excised with a bone cutter and removed. The parietal pleura is bluntly opened and the incision extended as previously described. Closure is accomplished by preplacing interrupted mattress sutures in the medial and lateral periosteal edges and tying them. The wound closure is completed as described above. Median Sternotomy The median sternotomy is the only approach that allows complete access to both sides of the thoracic cavity. It is therefore indicated when a complete thoracic exploratory is necessary, as in the cases of multiple metastasis excision, thymoma removal, etc. The only structures that cannot be easily reached with this approach are the great vessels, the bronchial bifurcation, and the thoracic duct. As demonstrated in different studies (Ringwald and Birchard 1989; Williams and White 1993; Burton and White 1996), median sternotomy is not associated with a greater number of complications than the intercostal approach, nor is it a more painful technique. In one study, however, median sternotomy was associated with increased morbidity. Dogs that had a median sternotomy had increased luid production in their chest postoperatively, and more hypoxemia than dogs with a lateral thoracotomy (Bleakley et al. 2018). Nonetheless, it should not be considered an inferior approach and should be the chosen approach when indicated. The animal is placed in dorsal recumbency, with the front legs extended and secured cranially (Orton 1995b) or caudally, along the body wall, if the cranial part of the sternum needs to be accessed (Hunt 2018). A skin incision is performed over the midline of the sternum, from the level of the manubrium to the xiphoid process. The incision is deepened through the subcutis and pectoral musculature until the sternebrae are exposed. The sternum is then cut exactly on its midline with an oscillating saw, sternal splitter, or an osteotome (or scissors can be used in small-sized young animals) (Figure 8.28), paying careful attention to avoid damaging the underlying structures, such as the internal thoracic vessels. Scoring the midline of the sternebrae with a scalpel blade or electrocautery may help performing a more precise midline cut. Staying as close as possible to the midline also allows improved wound healing. Depending on the part of the thorax to be exposed, every effort should be made to leave either

the manubrium or the xiphoid process intact to achieve stable closure of the sternum and avoid dehiscence. Once the irst sternebra is split, a Gelpi retractor can be placed to facilitate opening the chest and extending the incision (Tillson 2015). A Finochietto retractor is applied to gently spread the incision once completed (Figure 8.28d), and the desired surgical procedure is performed. Before closure, a thoracostomy tube is inserted by tunneling it under the subcutis, lateral to the midline, from three intercostal spaces caudal to its proposed entrance point in the chest. The best way to obtain a stable closure of the sternum is to place igure-of-eight orthopedic wires (18–22 ga) around each sternebra, incorporating the costosternal junction (Figure 8.29) (Davis et al. 2006). The sutures are pre-placed and tightened once all have been placed, cutting the wire end after two to ive twists and bending them over to minimize soft tissue damage. In small dogs and cats, heavy-gauge mono ilament sutures can be used as an alternative to wire; however, they have been shown to result in delayed healing in large-breed dogs (Pelsue et al. 2002). Similar non-optimal results were obtained by Gines et al. (2011) using a 4 metric polydioxanone suture in medium-size dogs. The authors concluded that this type of suture could be indicated only in selected cases, such as dogs with severe muscle wasting, bone loss, pediatric animals, or when sternotomy was not performed on the midline. A recent cadaveric study found that mono ilament nylon leader is mechanically comparable to stainless steel wire, even if more implant failures were observed in the nylon group, and can be a suitable alternative to metal wire to close canine sternotomies (McReady et al. 2015). Alternating the orientation of sutures is recommended to achieve a better and more stable closure, thus reducing postoperative pain (Hunt, 2018) (Figures 8.29, 8.30). The pectoral muscles, subcutis, and the skin are closed in separate simple continuous layers. Median sternotomy may be extended cranially with a ventral midline cervical approach or caudally with a ventral midline celiotomy if access to these regions is required. When large masses cannot be removed by median sternotomy or intercostal thoracotomy alone, a transsternal thoracotomy can be performed. In this case, an intercostal thoracotomy on both sides is performed irst, and then the corresponding sternebra is sectioned in its center, after ligation of the internal thoracic artery and vein. However, this procedure is rarely performed since it is very painful (Hunt 2018).

Figure 8.28 Median sternotomy. (a) The skin and subcutaneous tissues are incised and separated until the sternum is reached. (b) The sternebrae are incised in their midline using an osteotome or an oscillating saw (c). (d) A Finochietto retractor is applied, and the thoracic surgery is performed. Source: Image 8.28B courtesy of Dr. R. Bussadori.

Transdiaphragmatic Thoracotomy This procedure has limited application in oncologic surgery but may be useful when both the caudal intrathoracic structures and the abdomen need to be accessed. With the animal in dorsal recumbency, the thoracic cavity is accessed via a median celiotomy, usually without the need for caudal sternotomy. Depending on the side to be explored, the diaphragm is incised on the right or left side by splitting the muscle in a radial direction and extending the incision along the circumference of the diaphragm as needed. A rim of muscle should be spared, to allow wound closure. Care is taken to avoid damage to hepatic veins and branches of the phrenic arteries (Tillson 2015).

At the end of the procedure, the diaphragmatic defect is closed in a simple continuous pattern with a 3-0 to 0 USP mono ilament absorbable suture, starting at the most dorsal part of the incision. The celiotomy is closed in a routine manner. The need for a thoracic drain placement should be evaluated. If a thoracic drain is not placed, the air in the chest can be evacuated with a catheter and extension set placed through the diaphragm after closure of the diaphragm but before closing the celiotomy.

Figure 8.29 (a) The closure of the sternum is achieved by preplacing some igure-eight wire sutures and tying them (b). Soft tissues are then sutured routinely. Source: Image 8.29a courtesy of Dr. R. Bussadori.

Aftercare Thoracic surgery is a painful procedure, and postoperative pain may result in respiratory impairment. Therefore, a good analgesic regimen, initiated before recovery of anesthesia, is essential. Parenteral or epidural opioids, selective intercostal nerve blocks (only for intercostal thoracotomy), or intrapleural analgesia may be used (Carregaro et al. 2014). Morphine, oxymorphone, fentanyl, butorphanol, or buprenorphine can be administered by a parenteral route. While the latter two have less detrimental effect on ventilation and are less likely to decrease the heart rate, they are not considered to be strong analgesics (in particular butorphanol) and may not provide adequate analgesia in some patients. Morphine can also be injected in the epidural space, with minimal cardiopulmonary effects and a 6- to 12-hour duration of action. Intrapleural administration of bupivacaine through the chest tube in conscious animals is painful and should be preceded by intrapleural administration of lidocaine. Transdermal fentanyl was found to provide adequate analgesia after

lateral thoracotomy in dogs, without serious side effects and better ease of administration, as compared to oral tramadol (Read et al. 2019). Monitoring of ventilation after surgery is essential, since it may be depressed by a number of factors including anesthetic agents, pain, postoperative complications such as pneumothorax, hemorrhage and pulmonary edema, or tight bandages. Blood gas analysis should always be performed to assess the ventilation and acid/base status of the patient. Supplemental oxygen is generally recommended, guided by the results of blood gas analysis, especially if lung lobectomy or pneumonectomy has been performed. Opening the chest usually results in a decrease in body temperature, therefore the patient should be actively warmed by circulating water or air blankets or warm water bottles. After chest-tube placement, it is recommended to assess its position by radiography (both lateral and dorsoventral views) and its patency by lushing with sterile warm saline solution. The thoracostomy tube is aspirated every hour for the irst four hours after surgery, then every two to four hours until removal. The presence of air, luid, or blood is evaluated and recorded, and the tube can be removed as early as two hours after surgery if it is non-productive or when the luid production is between 2.2 ml/kg/day (expected amount to be induced by the presence of the tube itself) and less than 8 ml/kg/day (1–3.6 ml/lb/day) (Kuntz 1998; Fossum et al. 2007c). Marques et al. (2009) reported that the amount of luid production at the time of chest drain removal does not seem to in luence either the time to discharge from the hospital or the outcome of the animal; therefore, the appropriate time of chest drain removal should be evaluated also based on general clinical conditions of the animal. If the tube is nonproductive after two hours, however, its position and patency should be checked by thoracic radiographs and lushing, respectively. Since the presence of the chest tube can cause discomfort to the animal, the insertion of a small-bore (14G) drain instead of a larger tube, as proposed by Valtolina and Adamantos (2009), could be considered, especially for cats and small dogs. Similarly, Sherman et al. (2020) demonstrated that the use of a Jackson-Pratt drain was associated with a lower incidence of complications compared to a traditional large trocar thoracostomy tube. Moreover, some authors (Tillson 2015) questioned the need for a thoracic drain placement after uncomplicated lung lobectomies or other thoracic surgeries where luid or air production is unlikely.

Figure 8.30 Figure-of-eight suture pattern for sternotomy closure. The wires are closed alternating the orientation: A. the wire is passed irst into the thorax at the far side of the cranial sternebra (1), and it exits the thorax at the level of the adjacent sternebra on the near side (2). It enters again the thorax at the level of the far side of the same sternebra (3) to exit on the near side of the cranial sternebra (4) and twisted (5). B. The wire enters the thorax on the far side of the cranial sternebra (1) and exits on the near side of the same bone (2), it enters again the thorax in the far side of the caudal sternebra (3) and exits on the near side of the same caudal bone (4). The wire is twisted between the two sternebrae (5). In cases where the need for long-term air or luid removal is foreseen, or where intrapleural administration of chemotherapy drugs is necessary to treat neoplastic effusions, the placement of a PleuralPort in place of the chest drain should be considered. The port can be left in place for months without complications and is usually well tolerated by the animal (Cahalane et al. 2007; Brooks and Hardie 2011; Tillson 2015). A thoracic bandage, which is applied loosely enough to avoid the restriction of breathing, helps reduce subcutaneous emphysema by sealing the thoracotomy incision. It may also make the animal more comfortable in the immediate postoperative period. Antibiotics (e.g. cefazolin) are administered in the perioperative period, but they are discontinued after 12–24 hours if infection was not present preoperatively (Fossum et al. 2007c).

Complications and Outcome Complications after both intercostal thoracotomy and median sternotomy are not frequent, and the incidence is similar for both procedures (Ringwald and Birchard 1989; Bleakley et al. 2018). Even if severe, they are infrequently fatal if the animal is closely monitored in the immediate postoperative period and during follow-up. In one study comparing median sternotomy and intercostal thoracotomy, the short-term (30 kg with tumors 3 to ≤5

Solitary

T3

>5 to ≤7

T4

>7

N N0

No lymph node metastasis

N1

Ipsilateral tracheobronchial lymph node

N2

Distant lymph node metastases

M M0

No distant metastasis

M1

Malignant effusion, contralateral lung lobe metastasis, extrathoracic metastasis Stage T1, N0, M0 1 Stage T2, N0, M0; T3, N0, M0; 2 T1-2, N1, M0 Stage T4, N0, M0; T3–4, N1, 3 M0; T1–4, N2, M0

Visceral pleura, main bronchi (not carina) Separate Chest wall, pericardium, phrenic nodule(s) in nerve same lobe Separate nodule(s) in ipsilateral lung lobe(s)

Mediastinum, diaphragm, heart, great vessels, recurrent laryngeal nerve, carina, trachea, oesophagus, spine

T Size (cm)

Solitary vs multiple nodules

Organ invasion

Stage T1-4, N1-2, M1 4 Survival times of dogs without clinical signs or lymph node involvement were 545 days and 452 days, respectively, compared with 240 days and 26 days in dogs with clinical signs or lymph node involvement (McNiel et al. 1997). Dogs with lymphadenopathy had a median survival time of 126 days vs. a median survival time that had not been reached in the dogs without lymphadenopathy (Paoloni et al. 2006). In a recent study on dogs with lung tumors that had lobectomy and an intrathoracic lymph node biopsy it has been found that the median survival time in lymph nodes positive dogs was longer than previously reported (167 days for the positive ones vs. 456 days for the negative ones) (Rose and Worley 2020). Primary tumor size has shown some in luence on prognosis, with larger tumors having a poorer prognosis (Ogilvie et al. 1989; McNiel et al. 1997; Rose and Worley 2020; Lee et al. 2020). Median survival time of 790 days, 196 days, 81 days have been reported for T1, T2, T3 tumors, respectively (McNiel et al. 1997). The median survival of dogs staged T1M0N0 was 555 days vs. 72 days for any other stage (Polton et al. 2008). Dogs with well-differentiated tumors have signi icantly longer survival times and disease-free intervals (median, 790 and 493 days, respectively) than do dogs with moderately (median, 251 and 191 days, respectively) or poorly (median, 5 and 0 days, respectively) differentiated tumors (McNiel et al. 1997). Dogs with adenocarcinoma (mean survival time [MST] 19 months) have a much better prognosis than dogs with squamous cell carcinoma (MST eight months) (Mehlhaff et al. 1984). Dogs with neoplasms located in the periphery of the lung lobe have a better prognosis than those with tumors located at the hilus, as the former tumors are more likely to be completely resected (Rebhun and Culp 2013). Dogs with small (diameter less than 5 cm), isolated, well-differentiated adenocarcinomas, without evidence of spread to regional lymph nodes and without pleural effusion, have the best prognosis; one-year survival can be expected in more than 50% of these animals (Mehlhaff et al. 1984; Ogilvie et al. 1989). Dogs with primary pulmonary histiocytic sarcoma treated with surgery and CCNU-based chemotherapy had signi icantly prolonged progression-free

survival (median 276 days) and overall survival (median 374 days) compared to dogs not receiving surgery (Marlowe et al. 2018). The prognosis in cats with primary lung tumors is considered less favorable than for dogs because of the advanced stage of the disease at the time of diagnosis and the aggressive metastatic behavior of the tumor. It has been suggested that over 75% of cats are not candidates for surgical excision at the time of presentation because of the presence of metastatic disease or due to the local extension of the tumor (Hahn and McEntee 1997; Hahn and McEntee 1998). The presence of respiratory signs, pleural effusion, any stage beyond T1N0M0, evidence of metastasis, and moderately or poorly differentiated tumors was found to be useful prognostic indicators for cats with primary lung tumors (Maritato et al. 2014). Similar to dogs, cats with tumors that have stage T1N0M0 lived signi icantly longer (median survival time 190 days) than cats with any other staging (median survival time three days) (Maritato et al. 2014). Cats with clinical signs of dyspnea are likely to have advanced disease (75% M1, 50% T3) and a poorer prognosis. Pleural effusion has also been associated with shorter survival times (Maritato et al. 2014). Cats with moderately differentiated tumors (median survival time 698 days) and those without enlarged nodes (median survival time 421 days) have signi icantly longer survival times than cats with poorly differentiated lung tumors (median survival time 75 days) or enlarged nodes (median survival time 73 days) (Hahn and McEntee 1998). Recently a modi ied human lung cancer stage classi ication has been proposed in dogs with surgically excised primary pulmonary carcinomas. The need to make changes to the clinical TNM system used so far for primary lung tumors in dogs and cats has been prompted by the development of new technologies and a more detailed ability to de ine tumor extent (Lee et al. 2020). Table 8.5 describes the proposed new classi ication system.

Metastasectomy for Sarcomas Sarcomas are very common cancers in dogs and cats. Even with permanent local control and adjuvant chemotherapy, the metastatic rate varies by tumor type, stage, site, species, and histologic grade. Common examples include canine appendicular osteosarcoma with a metastatic rate of over 90% vs. soft tissue sarcomas with a metastatic rate of less than 25%. Metastasis used to be considered a universal harbinger of imminent cancer-related death. Wide variation in metastatic rates, sites, symptoms, paraneoplastic syndromes, progression, and outcomes exist, however, and speaks to a biological

heterogeneity of metastatic disease progression that may occasionally allow a meaningful intervention with durable survivals. Canine osteosarcoma is a template for the following biological, temporal, imaging, and procedural principles that can be applied generally to all tumor types, assuming that permanent local control has been achieved with surgery or radiation and that the patient has often received adjuvant chemotherapy (O’Brien et al. 1993). The biology of metastasis is complex but can be thought of in the seed (tumor cell) and soil (site of metastasis) paradigm. Simplistically, most sarcomas spread hematogenously to the lungs, followed by the bones, lymph nodes (especially histiocytic sarcoma), and other soft tissue sites (Diemel et al. 2009). With this in mind, routine follow-up after primary treatment usually includes a physical exam and chest radiographs every two to three months for the irst year, with decreasing intervals for two years and beyond. Once metastasis is identi ied, full staging may be in order (involving CT of the chest, an abdominal ultrasound or CT, a nuclear bone scan, or positron emission tomography with CT [PET-CT]), or it can be delayed until a decision on possible treatment is made. Pulmonary metastasis of osteosarcoma is the most common setting where data exist to support metastasectomy in animals and will be used as an example (O’Brien et al. 1993; Turner et al. 2017). General considerations for metastasectomy include the following:

Time to Detection The longer the interval from primary tumor control to detection of metastasis, the better, with 275–300 days suggested as the break point from early vs. late onset. In theory, those metastases with late detection are less aggressive yet somehow have evaded complete and durable chemotherapy cytotoxicity. In rare cases, single new lung nodules may represent primary lung carcinoma.

Number of Lesions One or two metastases are biologically less tumor burden than three or more. The typical scenario is the asymptomatic detection of lung nodule(s) on plain radiographs. Three-view ilms in a conscious (fully aerated) patient are recommended (Prather et al. 2005). CT scans may help de ine lesions not clearly seen on plain ilms but can also reveal small non-neoplastic lung nodules of indeterminate origin (granulomas, osteoid osteomas, etc.) (Nemanic et al. 2006). Positron emission tomography/CT (PET/CT) should help distinguish metabolically active tumor tissue from non-tumor tissue (Ballegeer et al. 2006) but this has not been con irmed. CT may help determine the exact site of the tumor within the lung (surface tumors vs. tumors deep in the parenchyma),

which may aid in the decision to do an open thoracotomy rather than thoracoscopy. The number of pulmonary lesions is only a relative criteria for metastasectomy in humans where as many as 50 lesions are occasionally removed.

Doubling Times Once one or two nodules are noted in thoracic radiographs, it is usually recommended that repeat radiographs be taken in 30 days to determine a rate of growth and possible clinical detection of new lesions that would make surgical intervention more problematic. It is generally felt that patients most amenable to metastasectomy will still be good candidates in 30 days and that slow-growing tumors are better candidates than fast-growing tumors. The use of chemotherapy during this waiting time is not clear.

Technique Open intercostal thoracotomy is the usual surgical technique, although a median sternotomy can be considered for bilateral lesions or the rare larger lesions. Open approaches allow for more thorough palpation of lung lobes for unsuspected lesions (Quiros and Scott 2008). Selective lung de lation may aid in digital palpation of nodules. Thoracoscopy, or VATS, is becoming increasingly popular in the hands of experienced surgeons when lesions are de inable to accessible (visible) sites and not adjacent to the hilus (Lansdowne et al. 2005). Most lesions are peripheral, discrete, subpleural, and amenable to lobectomy, wedge resection with staples, or “cherry-picking” of small and subpleural lesions (this entails a suture ligature below the base of the lesion).

Outcomes after Metastasectomy In carefully selected patients (late onset, one or two lesions, slow growth, and resectable), long-term survival can occur after metastasectomy. Even with variable inclusion criteria, the one-year survival rate for canine osteosarcoma has been reported to be 30% for dogs with osteosarcoma and subsequent pulmonary metastasectomy (O’Brien et al. 1993).In a more recent study, for dogs that met the inclusion criteria (primary tumor under control, disease-free interval of greater than 275 days, and one or two nodules seen on radiographs), the survival of dogs following metastasectomy was signi icantly longer (median of 332 days beyond the metastasectomy) compared to dogs without metastasectomy (median of 99 days beyond diagnosis of pulmonary metastasis) (Turner et al. 2017).

The role of post-metastasectomy chemotherapy is unde ined, but considerations can be made for new adjuvant drugs that have not been previously used, clinical trials of new agents, or even metronomic low-dose chemotherapy regimes (Anderson et al. 2008). Post-metastasectomy surveillance begins again at 2–3-month intervals and repeats metastasectomy can be considered (Bielack et al. 2009). Metastasis of cancer is generally a poor prognostic sign, especially with carcinomas. Carefully selected patients may bene it from surgical resection of late onset, slow-growing, solitary metastasis. The paraneoplastic disease of hypertrophic osteopathy may also resolve after pulmonary metastasectomy (Liptak et al. 2004b). Non-pulmonary sites of metastasis are managed with the same general principles, for example, radiation or resection for boney metastasis, lymphadenectomy for lymph node metastasis, local resection for stump recurrences (especially with synovial cell sarcoma) (Pfannschmidt et al. 2009).

Thoracic Wall Resection Biopsy Procedures If the tumor is originating from the rib and de initive diagnosis will not change the owner’s intent to treat, a ine needle aspirate may be appropriate as the primary differential diagnoses for sarcoma at this site will receive the same local therapy. It is important to keep in mind that it can be challenging for a pathologist to distinguish between a chondroblastic osteosarcoma and chondrosarcoma with a small biopsy sample, so an incisional biopsy consistent with a chondrosarcoma may in fact be an osteosarcoma when the pathologist has the bene it of the entire specimen. An incisional biopsy may be indicated to determine the tumor type. This can be done as a wedge incisional biopsy or with a Trucut biopsy (needle core biopsy) technique. The advantage of the wedge biopsy is that a larger biopsy can be obtained. The size of the biopsy has been shown to be an important factor in achieving a correct diagnosis (Montgomery et al. 1993). The advantage of the Trucut biopsy technique is that it is a faster procedure that may not require general anesthesia and has less disruption of the tissue planes. Regardless of technique, the biopsy should be planned so that the entire biopsy tract can be easily removed at the time of de initive surgery. The biopsy should be taken centrally over the tumor with only one incision. There should be minimal disruption of tissue planes deep and lateral to the biopsy incision.

Imaging Tests Three-view thoracic radiographs are a good starting point to evaluate a mass over the thoracic wall. This will serve to determine the intrathoracic extent of the lesion and to evaluate for pulmonary metastasis. With chondrosarcomas, in particular, the palpable mass on the exterior of the thorax may be a small percentage of the total mass (Figure 8.55). The point of origin of the mass may be evident with radiography alone. However, this test is not as sensitive as 3D imaging, and it may not be possible to correctly determine the origin or extent of disease based on radiography alone. If the tumor is of rib origin, radiographs may indicate the degree of bone lysis or production. This has not been found to help distinguish between osteosarcoma and chondrosarcoma (Liptak et al. 2008).

Figure 8.55 (a) A ventrodorsal projection radiograph of a dog with a rib chondrosarcoma. (b) A lateral projection radiograph of a dog with a rib chondrosarcoma. Source: Image courtesy of Dr. Julius Liptak.

CT is the imaging modality of choice to evaluate chest wall tumors and is recommended prior to surgical excision (Figure 8.56). CT allows the accurate evaluation of the origin of the tumor and the other structures that are involved in the thorax. The length of rib involvement and extent of soft tissue involvement can also be accurately assessed for surgical planning. The lungs can also be evaluated for evidence of metastatic disease with CT.

Nuclear scintigraphy or positron emission tomography with CT (PET-CT) should be considered in cases of osteosarcoma to determine if there is evidence of metastatic disease or if the rib mass is a metastatic site. Liptak et al. (2008) found a 16% rate of metastasis to bone with primary rib osteosarcoma. Wholebody CT is an alternative to scintigraphy or PET-CT to evaluate for long bone metastasis. However, it has shown to be lack of sensitivity to diagnosis metastatic disease to bone in canine long bone osteosarcoma (Oblak 2015; Talbot 2017). Abdominal staging is recommended for known hemangiosarcoma or when a pleural effusion accompanies the thoracic wall mass or for general staging in older patients. CT of the thorax and abdomen can be performed concurrently. Abdominal staging with ultrasound has been shown to be a relatively low-yield test for long bone osteosarcoma in dogs, with a still low, but a higher chance of diagnosing a second malignancy than metastatic disease in one study (Wallace 2013).

Figure 8.56 Postcontrast transverse CT of anosteosarcoma involving the ifth rib. Source: Imagecourtesy of Dr. Simon Kudnig.

Description of Surgical Procedures Rib Tumors Preoperative surgical planning is very important for the surgical treatment of rib tumors. Rib tumors are usually sarcomas, with osteosarcoma and chondrosarcoma being the most common, and wide resection is critical to successful treatment. Completeness of surgical excision has been shown to have a signi icant effect on survival and disease-free interval in dogs with chest wall tumors (Pirkey-Ehrhart et al. 1995; Liptak et al. 2008). The planned margins of resection should include one rib cranial and one rib caudal to the lesion (Liptak et al. 2008; Baines et al. 2002). Dorsal and ventral margins should be 3 cm along the ribs (Liptak et al. 2008; Baines et al. 2002). One school of thought is that the entire rib should be removed by disarticulating the rib with the vertebra and sternum. However, this does not appear to be necessary. The reported maximum number of ribs that can be resected is six (Liptak et al. 2008; PirkeyEhrhart et al. 1995; Orton 2003) Anecdotally, seven ribs have been successfully removed (NJ Ehrhart NJ and SJ Withrow, personal communication). However, the removal of seven ribs increases the risk of causing severe respiratory compromise and dysfunction and the removal of eight ribs has been anecdotally reported to be fatal. The location of the tumor may determine the ability of the surgeon to remove more than six ribs. Large resections are better tolerated in the caudal thorax, where diaphragmatic advancement is possible. In the cranial thorax, the creation of a lail chest with the removal of more than six ribs may cause ventilatory failure (NJ Ehrhart, personal communication). In general, skin and overlying muscle is not resected en bloc with tumors arising from the rib. This is contrary to a study that used en bloc resection and a myocutaneous lap for reconstruction of primary rib chondrosarcoma in ive dogs (Halfacree et al. 2007). There may be exceptions to this if there is extensive invasion in the soft tissues lateral to the rib seen on CT (Figure 8.57). The common rib tumors such as osteosarcoma and chondrosarcoma tend to remain somewhat encapsulated within the periosteum. This concept is similar to the resection of distal radial osteosarcomas that spare surrounding soft tissues in a limb-sparing procedure. The 3D imaging should serve as a guide for whether or not skin resection is necessary. Another rule of thumb is to assess the mobility of the skin over the mass. If the skin is mobile over the mass, the need for resection is less likely. If a biopsy is performed, the biopsy tract will need to be resected with the tumor (Figure 8.58). The latissimus dorsi muscle can also be spared if appropriate based on imaging and its mobility. The latissimus dorsi muscle is an important source of autogenous tissue for reconstruction of the defect.

Figure 8.57 Resection of a subcutaneous hemangiosarcoma. In this case, skin was included in the chest wall resection. The patient is placed in lateral recumbency with the appropriate side up. The entire exposed hemithorax and a large portion of the abdominal skin should be clipped and prepared for surgery. The patient is positioned with the uppermost limb extended forward. The skin incision is made over the mass. The incision may be curvilinear, vertical, or T-shaped, depending on the size and location of the mass. An ellipse of skin is created around the biopsy tract. The biopsy tract should be sutured to the underlying tissues to prevent motion (Figure 8.58). The latissimus dorsi muscle is undermined and retracted dorsally if it is to be spared. An intercostal approach is made at either the cranial or caudal margin of the resection. This should be the margin that is most obvious based on preoperative imaging and palpation (Figure 8.59). The length of the intercostal approach is dictated by the size of the tumor. Once the initial lateral thoracotomy has been made, a hand should be placed within the thoracic cavity to explore the extent of the tumor and to investigate for any adhesions. Rib cutters are used to cut the ribs at the dorsal and ventral margins. If possible, the ventral margins should be cut irst as hemorrhage will be vigorous from the

dorsal margins. The intervening intercostal tissue is cut with Mayo scissors, electroscalpelor vessel sealing device (such as LigaSure). The intercostal vessels caudal to the ribs should be located and ligated or cauterized dorsally and ventrally. Care must be taken to locate and ligate the internal thoracic artery as unaddressed disruption of this vessel has been reported to cause fatal hemorrhage (Liptak et al. 2008).

Figure 8.58 The previous biopsy tract is removed with the resection; however, mobile skin is spared over the tumor. The skin involving the biopsy tract is sutured to the underlying fascia. This is the same case as Figure 8.56. Source: Image courtesy of Dr. Simon Kudnig.

Figure 8.59 Intraoperative photograph of a dog with a rib chondrosarcoma. The lateral thorax has been entered at the proposed intercostal space of excision. Source: Image courtesy of Dr. Julius Liptak.

The inal cranial or caudal intercostal incision is made to remove the chest wall en bloc (Figure 8.60). Generally, rib tumors originate at the costochondral junction (Montgomery et al. 1993). The thoracic mass may invade or be adherent to intrathoracic structures such as the lungs and pericardium. Adhesions should not be broken down as this may result in contamination of the ield with tumor cells. The involved tissues should be removed en bloc with the chest wall. This may involve a pericardiectomy or a partial lung lobectomy using a TA stapler (Figure 8.61) (Matthiesen et al. 1992; Liptak et al. 2008; Pirkey-Ehrhart et al. 1995).

Figure 8.60 Intraoperative photograph of a dog with a rib chondrosarcoma after thoracic wall resection. In this case, the overlying skin and muscle were not preserved. Source: Image courtesy of Dr. Julius Liptak.

For cranial rib resections, care must be taken to avoid the brachial plexus. Most importantly, the origin of the nerve roots that make up the radial nerve can be found coursing around the irst rib. Resection including the irst rib has been reported to be successful while preserving the limb and with no impairment of limb function (Liptak et al. 2008). Invasive Soft Tissue Masses of Tissues Lateral to the Ribs In general, invasive soft tissue masses lateral to the ribs are likely to be soft tissue sarcomas. They should be removed using the same principles as with sarcoma removal anywhere on the body. As with rib tumors, these tumors require 3D imaging for appropriate presurgical planning. On 3D imaging, these masses would involve the soft tissues from the subcutaneous tissue and skin medially to the chest wall. If there is not a fascial plane between the tumor and

the chest wall, these tumors require a true en bloc resection from skin through the chest wall (Figure 8.57). These tumors are more challenging as the soft tissue available for reconstruction is much less than a primary rib tumor, where most often the skin and latissimus muscle is preserved.

Figure 8.61 Adhesion between a lung lobe and the rib tumor. A TA stapler is placed across the lung parenchyma, away from the adhesion, to allow resection of the adhesed lung tissue en bloc with the rib tumor.

The patient will be prepared similarly for surgery. A more extensive clip may be needed to allow for skin reconstruction. Using a sterile marking pen, the mass should be drawn on the patient. The margins of excision should then be measured and drawn. The margins of excision should be 3 cm around the mass (Ehrhart 2005). The skin incision follows the planned margins. This incision is continued medially through the underlying muscle to the level of the chest wall. An electroscalpel may be helpful to aid in hemostasis. The skin over the tumor can be sutured to the underlying tissues to prevent the tissue planes from sliding on each other. It is important that the incision in the underlying tissues continues perpendicular to the original skin incision to ensure adequate margins. There is a tendency to make the subsequent incisions in deeper tissues toward the mass, causing a coning down of the excision. This can lead to inadequate surgical margins. Once the ribs and intercostal muscles are reached, intercostal incisions are made in the most appropriate locations based on the planned en bloc resections. Always err on the side of a larger resection when planning the cranial and caudal intercostal incisions. Bone cutters are used along the ribs and Mayo scissors or electroscalpel is used between the ribs to continue the en bloc resection. The entire mass and soft tissue margins are removed. Although it is rarely reported in veterinary medicine (Munday et al. 2006; Ferreira et al. 2005), lung or chest wall tumors may penetrate the chest wall at the level of the brachial plexus. Such tumors may require lung and chest wall resection combined with forequarter amputation. The same principles of en block resection are followed. Reconstruction After Thoracic Wall Resection There are several options for reconstruction of the thoracic wall defect after rib resection or true en bloc resection. These options include the use of prosthetic mesh implants such as Marlex, Gore-Tex, and Vicryl. Marlex is the most commonly reported implant used in veterinary and human thoracic wall reconstruction techniques. Local tissue laps have also been reported either alone or in combination with prosthetic mesh. The most commonly used local tissue is a latissimus dorsi lap, either alone or as a myocutaneous lap (Liptak et al. 2008; Halfacree et al. 2007; Raffoul et al. 2001; Mansour et al. 2002). Marlex mesh was irst described for reconstruction of thoracic wall defects in dogs by Bright in 1981. Its use has been largely adopted from widespread use in human thoracic reconstruction. The major advantages of Marlex mesh are that it is readily available, strong, easy to sterilize and it has been shown to develop rapid ingrowth of ibrous tissue (Bright 1981). In dogs, it is recommended to cut a piece of mesh that is slightly larger than the defect. The mesh is folded over by

1 cm around its periphery to allow a more solid area to hold sutures (Figure 8.62). The mesh is sutured in place by laying the mesh along the pleural surface of the defect and suturing it in place with circumcostal and mattress sutures through the chest wall (Figure 8.63) (Bright 1981). The mesh is stretched when it is sutured so that it is taut and affords some rigidity to the chest wall. When possible, soft tissues are closed over the mesh prior to skin closure. New biomaterials have been reported for chest wall reconstruction in research dogs (Zhang et al. 2011; Hamaji et al. 2015). Application of these techniques to our clinical patients should be considered. When a large number of ribs is removed, chest wall stability has also been restored by using spinal plates at the sites of rib resection. The plates are af ixed in place using hemicerclage wires through the remaining ribs (Ellison et al. 1981). There are currently no guidelines to determine when this method should be employed. Rigid reconstruction may not be necessary and is not currently commonly used for chest wall reconstruction.

Figure 8.62 Intraoperative photograph of mesh that is used to reconstruct a defect after chest wall resection.

Figure 8.63 Intraoperative photograph of a dog with a rib chondrosarcoma. The defect in the chest wall has been repaired using mesh. Source: Image courtesy of Dr. Julius Liptak.

The latissimus dorsi lap was irst reported as a method for chest wall reconstruction in humans in the late 1800s (Mansour et al. 2002). It is used commonly in people, often in combination with Marlex mesh (Mansour et al. 2002). It has been reported in dogs as a muscle lap and a musculocutaneous lap when skin is resected (Liptak et al. 2008; Halfacree et al. 2007). The latissimus dorsi muscle originates from the super icial leaf of the lumbodorsal fascia associated with the dorsal spinous processes of the thoracolumbar vertebrae and the last two to three ribs. Its insertion is also wide. It courses toward the shoulder and holds the dorsal scapular border against the chest. The latissimus dorsi muscle inserts on the teres tuberosity of the humerus (Pavletic 2003; Dyce et al. 1987b). It has been classi ied as a type V muscle, with the thoracodorsal artery being the main blood supply. The intercostal arteries also supply segmental branches to the muscle (Pavletic 2003; Purinton et al. 1992).

To harvest the latissimus dorsi lap, the skin incision made for tumor resection may need to be extended. The latissimus muscle is freed up ventrally with blunt dissection. The origin of the muscle is excised dorsally. The dissection is continued along the dorsal border of the muscle, parallel to the muscle ibers, allowing the muscle to be rotated into the defect. The dominant vascular pedicle containing the thoracodorsal artery is preserved (Pavletic 2003). The latissimus dorsi myocutaneous lap is planned using a sterile marking pen. The dorsal border is drawn from a point that is ventral to the acromion and caudal to the border of the triceps muscle. The line is drawn to the head of the 13th rib. The ventral border of the lap is drawn from a point at the forelimb skin fold, caudal to the triceps muscle. The line is drawn parallel to the dorsal border to the 13th rib. The caudal border is drawn by connecting the dorsal and ventral borders along the 13th rib (Figure 8.64). The ventral border is incised irst, and the ventral border of the latissimus dorsi muscle is located. The lap is developed by continuing the incisions from the skin to the ventral aspect of the latissimus dorsi. The myocutaneous lap can be rotated into the defect, and the donor site skin can be closed primarily (Figure 8.65) (Pavletic 2003; Halfacree et al. 2007). Recently, the use of a latissimus dorsi lap combined with an autogenous thoracolumbar fascial graft was reported to allow for the use of autogenous tissues for reconstruction after chest wall resection in a dog (de Battisti et al. 2015).

Figure 8.64 Outline of the borders of the latissimus dorsi myocutaneous lap. The dorsal border is drawn from a point that is ventral to the acromion and caudal to the border of the triceps muscle. The line is drawn to the head of the 13th rib. The ventral border of the lap is drawn from a point at the forelimb skin fold, caudal to the triceps muscle. The line is drawn parallel to the dorsal border to the 13th rib. The caudal border is drawn by connecting the dorsal and ventral borders along the 13th rib. Source: Illustrated by Kip Carter

The omentum can also be used to provide an autogenous, airtight seal if there is not enough local tissue to close the defect. This can be achieved by making a lank incision and tunneling the omentum in the subcutaneous tissue and into the defect. Skin is then closed over the omentum (Figure 8.66) (Orton 2003). This technique is particularly important to consider if a mesh is used for reconstruction, as it will improve the healing and sealing of the pleura and will prevent irritation of the pulmonary pleura as it comes into contact with the mesh. It also may provide a signi icant barrier if an infection causes wound breakdown over the mesh.

Figure 8.65 (a) Intraoperative photograph showing elevation of the latissimus dorsi muscle lap. (b) Intraoperative photograph showing rotation of the latissimus dorsi lap cranially. The lap will be brought ventrally to ill the defect in the chest wall. Source: Image courtesy of Dr. Julius Liptak.

Figure 8.66 The omentum has been placed over the thoracic defect to provide an additional autogenous tissue to close the defect. Source: Image courtesy of Dr. Simon Kudnig.

For tumors of the caudal chest wall, diaphragmatic advancement can be used to decrease the size of the thoracic defect to be closed or completely close the defect. This is performed by detaching the diaphragm from its attachments laterally and ventrally to allow mobilization of the diaphragm. The diaphragm is then advanced and sutured to the remaining chest wall to allow for an airtight, rigid ixation (Figure 8.67). A partial or complete caudal lung lobectomy may have to be performed concurrently to prevent atelectasis of the affected hemithorax and subsequent ventilation/perfusion mismatch (Orton 2003). This is best performed with a TA stapling device. The amount of the lung lobe resected depends on the degree of diaphragmatic advancement. Another technique for caudal thoracic wall reconstruction is the lateralization of the diaphragm (Gilman and Ogden 2021). With this technique, the ribs removed are cranial to the attachment of the diaphragm to the ribs. After removal of the necessary ribs for the rib tumor (the case report had the eighth, ninth, and tenth

ribs excised), the diaphragm is visible and accessible through the thoracic wall defect. The muscular portion of the diaphragm (which is the convex surface or thoracic side of the diaphragm) is grasped with forceps such as Debakey’s. Applying gentle traction, this surface is brought into contact with the cranial aspect of the thoracic wall defect with minimal tension. Interrupted sutures (non-absorbable or long-lasting absorbable suture material) are placed through the full thickness of the diaphragmatic surface while avoiding any branches of the phrenic nerve if visualized. The sutures are then passed circumcostally around the rib at the cranial aspect of the defect, avoiding the intercostal artery, to secure the diaphragm in position. The caudal aspect of the diaphragmatic surface is then secured in the same way to the rib at the caudal aspect of the defect, without incising or advancing the insertion of the diaphragm. When passing the needle through the diaphragm, care is taken not to go deep beyond the thickness of the muscle to avoid ensnaring or perforating any abdominal organs. The intercostal muscles are then sutured to the diaphragmatic sling with two simple continuous suture lines, one at the cranial rib and one at the caudal rib, to provide a seal to the thorax. The super icial tissues are closed routinely (Gilman and Ogden 2021). Liptak et al. (2008) compared autogenous, prosthetic, and composite methods of chest wall reconstruction retrospectively. They found that the complication rate was higher for prosthetic and composite techniques compared with autogenous reconstruction, with complications being 12.8 times more likely to occur with prosthetic techniques and 3.0 times more likely to occur with composite techniques compared with autogenous tissue reconstruction. The current recommendation for chest wall reconstruction is to use a latissimus dorsi lap when possible and to add Marlex mesh if necessary to augment the repair. In the human literature, there is a lot of importance placed on maintaining absolute rigidity of the chest wall after resection (Mansour et al. 2002; Weyant et al. 2006). This is usually achieved using a Marlex mesh methyl methacrylate sandwich (Weyant et al. 2006). However, the use of autogenous tissue alone has been successfully reported in human cases where the use of prostheses was precluded by infection (Raffoul et al. 2001). Maintaining rigidity of the thoracic wall after reconstruction is also stressed in the veterinary literature (Ellison et al. 1981; Bright 1981). Care should be taken to suture the muscle lap or mesh so that it is taut. However, absolute rigid reconstruction of the thoracic wall has not been shown to be necessary in dogs (Liptak et al. 2008). A chest tube is placed during the closure. Sternectomy Masses of the sternum can be approached in much the same way as masses in other areas of the thoracic wall. Incisional biopsy for tissue diagnosis and 3D

imaging will guide preoperative planning (Figure 8.68). The decision to include skin in the resection will be based on the same principles as for rib tumors. The overlying pectoral muscle may be resected with the tumor or, in cases of primary bone tumors, may be preserved to allow for autogenous tissue for reconstruction. The amount of sternum resected will depend on the amount of bone involved in CT imaging. Ideally, 3 cm margins should be taken cranial and caudal to the tumor. The ribs are cut 2–3 cm from the sternal mass. The sternum is cut using an oscillating bone saw, and the ribs are cut using bone cutters. The segment of the chest wall is removed en bloc (Figure 8.69).

Figure 8.67 (a) Intraoperative picture of a dog with a mass over the caudolateral thorax. Resection of the caudal thoracic and cranial abdominal portions of the lateral abdominal wall. The surgeon’s hand is in the thorax, pushing the diaphragm caudally. (b) Resection of the caudal thoracic and cranial abdominal portions of the lateral abdominal wall. The diaphragm is being excised from the lateral body wall. (c) Resection of the caudal thoracic and cranial abdominal portions of the lateral abdominal wall. The diaphragm is being excised from the lateral body wall. (d) Resection of the caudal thoracic and cranial abdominal portions of the lateral abdominal wall. The diaphragm is advanced cranially and sutured to the caudal edge of the remaining thoracic wall. (e) Resection of the caudal thoracic and cranial abdominal portions of the lateral abdominal wall. The diaphragm is advanced cranially and sutured to the caudal edge of the remaining thoracic wall. (f) Resection of the caudal thoracic and cranial abdominal portions of the lateral abdominal wall. The diaphragm is advanced cranially and sutured to the caudal edge of the remaining thoracic wall. Source: Images courtesy of Dr. Julius Liptak.

The defect is reconstructed using Marlex mesh (Figure 8.69), a Marlex mesh– poly(methyl methacrylate) sandwich, heterogenous bone and mesh, spinal plates (Figure 8.70), or an autogenous muscle lap. The pectoral muscle can be used in the reconstruction if it has not been removed with the en bloc resection. A deep pectoral muscle has been reported as a method to repair the chest wall after sternectomy in dogs (Liptak et al. 2008). This can be used alone or in combination with a latissimus dorsi lap and/or Marlex mesh. The use of omentum to augment the reconstruction should be considered. A chest tube is placed at the time of closure.

Figure 8.68 CT scan of a cat with a sternal chondrosarcoma. Source: Image courtesy of Dr. G. Romanelli.

Figure 8.69 (a) Preoperative picture of a cat with a sternal chondrosarcoma (b) Intraoperative picture of a cat with a sternal chondrosarcoma. (c) Intraoperative picture of a cat with a sternal chondrosarcoma after sternectomy. (d) Intraoperative picture of a cat with a sternal chondrosarcoma after sternectomy and reconstruction with mesh. Source: Images courtesy of Dr. G. Romanelli.

Figure 8.70 (a) Intraoperative photograph of a sternectomy for soft tissue sarcoma in a Jack Russell terrier. The mass has been resected with 2.5 cm margins en bloc. (b) Intraoperative photograph of a sternectomy for soft tissue sarcoma in a Jack Russell terrier. The mass has been resected with 2.5 cm margins en bloc. Lubra plates are used to reconstruct the sternal defect. The deep pectoral muscle is a type V muscle. The dominant vascular pedicle is the lateral thoracic artery that enters the deep face of the muscle cranially and supplies the craniodorsal portion of the muscle. The segmental branches of the internal thoracic artery enter along the sternal attachment and supply the cranioventral portion of the muscle (Purinton et al. 1992). The origin of the deep pectoral muscle is the ventral sternum and the ibrous raphe along midline. The insertion is to the greater tubercle of the humerus and the medial brachial fascia (Evans and DeLahunta 2000). The lap is harvested by incising its midline sternal attachments and undermining the muscle. The cranial attachment should be preserved to maintain the branches of the internal thoracic artery, if possible. The lap is rotated across ventral midline into the contralateral defect. Alternately, the lap can be rotated cranially and dorsally on the lateral thoracic pedicle (Liptak et al. 2008). The amount of rigidity required depends on the size and location of the defect. If many ribs are removed and/or if the manubrium is resected, an effort should be made to restore rigidity to the reconstruction. This can be done with a Marlex mesh (polymethyl methacrylate) sandwich and autogenous tissue. There was an increased incidence of early complications seen in sternal resections and reconstruction in dogs in a retrospective study (Liptak et al. 2008). This may indicate that sternal tumors are less forgiving in terms of reconstruction techniques.

Aftercare

Patients require intensive postoperative care for pain management and to monitor for respiratory dysfunction. Pain should be managed using opioid analgesics in combination with NSAIDs (if not contraindicated). Ketamine and lidocaine continuous rate infusions can also be considered. A chest tube should be placed intraoperatively to monitor for and manage pleural effusion, should it occur. An oxygen cage or nasal oxygen is recommended because chest wall resection will create some degree of hypoventilation after surgery due to pain and due to the change in the conformation of the chest wall. Blood gas analysis should be part of the postoperative monitoring plan to evaluate for potential respiratory complications such as hypoventilation, ventilation/perfusion mismatch, and aspiration pneumonia. An indwelling urinary catheter should be considered to allow strict rest of the patient for 12–24 hours and to allow the clinician to monitor urine output. All patients should be on intravenous luids until they are eating and drinking. In a large thoracic resection, luid loss from hemorrhage and evaporative losses intraoperatively can be substantial. Careful monitoring of the patient’s hydration and nutritional status in the postoperative period is important.

Cosmetic and Functional Outcome The reported maximum for removal of ribs is six. This is generally well tolerated. There is no effect on the functional outcome once the patient has recovered from surgery.

Potential Complications Reported complications of chest wall resection include seroma, pleural effusion, and peripheral and limb edema (Liptak et al. 2008; Pirkey-Ehrhart et al. 1995). Lameness, infection, and dehiscence are also possible complications. Necrosis of the latissimus dorsi muscle has also been anecdotally reported. It is possible that using a myocutaneous lap for reconstruction may result in improved performance of this lap due to preservation of the myocutaneous vessels (Halfacree et al. 2007) A rare but severe complication associated with chest wall resection is respiratory failure leading to death. This can be due to a combination of factors, including changes in the conformation of the chest wall due to a large resection, aspiration pneumonia, sepsis, and systemic in lammatory response or acute respiratory distress syndrome. Owners should be counseled before surgery that postoperative ventilation may become necessary and that an inability to wean the patient off of the ventilator may necessitate euthanasia.

Common Tumor Types

The most commonly reported primary tumors of the chest wall are osteosarcoma and chondrosarcoma. Other reported tumor types include ibrosarcoma, hemangiosarcoma, soft tissue sarcoma, and leiomyosarcoma (Baines et al. 2002; Montgomery et al. 1993; Liptak et al. 2008; Mattieson et al. 1992; Pirkey-Ehrhart et al. 1995).

Adjunctive Therapy Rib osteosarcoma has been shown to have a similarly aggressive biological behavior to appendicular osteosarcoma. Pirkey-Ehrhart et al. (1995) showed that dogs with rib osteosarcoma treated with surgery alone had a MST of 90 days, whereas dogs with rib osteosarcoma treated with surgery and chemotherapy had a MST of 240 days. Liptak et al. (2008) showed a MST of 290 days for rib osteosarcoma, with 19 or 23 of these dogs being treated with chemotherapy. Chondrosarcoma treated with surgery alone has a much more favorable prognosis, with reported median survival times of 1080 days (PirkeyEhrhart et al. 1995) and greater than 3820 days. Pulmonary metastasis has been reported in cases of chondrosarcoma (Liptak et al. 2008), but chemotherapy is not commonly used for rib chondrosarcoma. Radiation should be considered in cases of incomplete resection when a second surgery is not possible. An example of this would be a rib tumor with a dorsal extension into the vertebra.

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9 Cardiovascular System Simon T. Kudnig and Eric Monnet

Heart and Heart‐Base Tumors Common Surgical Procedures The most common surgical procedures undertaken for heart and heartbase tumors include subtotal pericardiectomy via open thoracotomy, pericardial window via thoracoscopy, right atrial auriculectomy, atrial mass removal, and heart-base tumor resection. Subtotal pericardiectomy alone does not improve survival times for dogs with hemangiosarcoma; however, it is generally performed as part of an exploratory procedure to obtain tissue for a de initive diagnosis (Dunning et al. 1998). Removal of the pericardium without cardiac tumor excision, however, does remove the potentially bene icial effect of increased pericardial pressure in controlling hemorrhage from a bleeding cardiac tumor. This may predispose the patient to fatal exsanguination due to uncontrolled hemorrhage from a cardiac tumor into the thoracic cavity. Subtotal pericardiectomy signi icantly decreases the risk of the recurrence of clinical signs in dogs with extracardiac masses as the cause of pericardial effusion (Dunning et al. 1998) and prolongs survival compared to medical treatment alone for dogs with heart-base tumors (Vicari et al. 2001). Subtotal pericardiectomy also improves survival in dogs with aortic body tumors independent of the presence or absence of pericardial effusion at the time of surgery (Ehrhart et al. 2002).

Biopsy Techniques Biopsy of heart and heart-base tumors is rarely performed prior to thoracotomy or thoracoscopy due to the location of the tumor and the risk of hemorrhage. A biopsy of a heart-base tumor is performed as an incisional biopsy at the time of open thoracotomy or via thoracoscopy.

With an open approach, a right or left fourth or ifth intercostal thoracotomy is used depending on echocardiographic indings, and the cranial lung lobe is packed caudally with a moistened laparotomy sponge. The mass is identi ied and the mediastinal pleura dissected over the mass via sharp dissection, being careful to avoid adjacent structures including the vagus and phrenic nerves, aorta, and the pulmonary artery. A biopsy of the mass is performed using a no. 11 blade or skin biopsy punch. Hemorrhage is controlled with gentle tamponade of the area and placement of simple interrupted 4-0 absorbable sutures in the capsule and mediastinal pleura. Thoracoscopy uses a minimally invasive technique with several advantages over an open technique, including improved visualization, decreased postoperative pain, fewer wound complications, and decreased morbidity (Walsh et al. 1999). For a thoracoscopic biopsy technique, the animal is positioned in left lateral recumbency and a right intercostal thoracoscopic approach is performed with a camera portal placed in the seventh or eighth intercostal space midway between the costochondral junction and the epaxial muscles. Operating portals are placed at the ifth and sixth or seventh intercostal spaces. Endoscopic dissecting scissors are used to dissect the pleura over the mass, exposing the tumor, if the mass is in the cranial mediastinum. Heart-base tumors and right atrial tumors require a pericardial window to gain access for exposure. Biopsy forceps are used to perform a biopsy of the mass. While one-lung ventilation techniques have been described in both dogs (Kudnig et al. 2003) and cats (Mayhew et al. 2015) to improve visualization, thoracoscopic biopsy and pericardiectomy techniques are generally achieved without pulmonary exclusion (Dupre et al. 2001). When a cardiac mass is suspected, the thoracoscope is introduced through a pericardial window and advanced to view the right auricular appendage and the right atrium (Skinner et al. 2014). A right intercostal thoracoscopic approach facilitates exposure of the right side of the heart; however, a subxiphoid approach can also be used with the dog in dorsal recumbency. Endoscopic cup biopsy forceps can be used to biopsy the mass or an excisional biopsy with an endoscopic stapler can be considered if the mass is small and on the tip of the right auricular appendage.

Diagnostic Tests and Imaging Modalities Heart-base tumors and tumors involving the right atrium and atrial appendage are best diagnosed with echocardiography. Echocardiography has 80% sensitivity and 100% speci icity for the detection of a cardiac mass, with 84% sensitivity and 100% speci icity for distinguishing right atrial masses from all other causes of pericardial effusion (MacDonald et al. 2009). Echocardiography is the most sensitive test for identifying pericardial effusion; however, it can be dif icult to differentiate cardiac tumors from idiopathic pericardial effusion (Boon 1998). Repeat echocardiographic examinations increase the sensitivity for the detection of cardiac masses (MacDonald et al. 2009). Echocardiography leads to a “presumptive diagnosis” based on the location of the mass and other indings such as echo texture and invasiveness. There is only a moderate correlation between echocardiographic indings and pathologic diagnosis, however, with one study identifying a 65% agreement between the presumptive diagnosis based on echocardiography and the de initive diagnosis. The presumptive diagnosis of hemangiosarcoma on the right atrial appendage was only correct in 50% of the cases (Rajagopalan et al. 2013). Fibrotic adipose tissue at the root of the aorta can be misinterpreted as a heart-base tumor when using echocardiography in dogs with chronic pericardial effusion. Affected animals often present with signs consistent with pericardial tamponade, and echocardiographic examination reveals pericardial effusion. This is visualized as a black space between the left ventricular wall and the pericardial sac (Figure 9.1). The pericardial luid does not extend much beyond the junction of the left atrium and left ventricle (Boon 1998). With pericardial tamponade, there is chaotic movement of the right atrium and right ventricle with collapse of the right atrial wall and the right ventricular wall, as the intrapericardial pressure increases further. Left parasternal cranial views provide the best approach for evaluation of cardiac masses, and scans can be performed with the patient in left and right lateral recumbency and in a standing position if pericardial effusion is identi ied (Boon 1998). During examination, the probe needs to be moved around to evaluate the region in a number of different imaging

planes (Boon 1998). Aortic body tumors are found around the aorta and aortic arch (Boon 1998). Smaller masses are seen on the transverse right-sided views of the aorta whereas larger masses appear to be within the atrial chambers (Boon 1998). Heart-base tumors are seen most often on transverse heart-base images between the aorta and the right or left atrium or to the left of the aorta between the right and left atrium (Boon 1998). The masses can be quite extensive before clinical signs occur, prior to the development of pericardial effusion, and when there is lack of involvement of the great vessels. Cardiac lymphoma in cats can be associated with pericardial effusion with a thickened septum and ventricular free walls with poor contraction during the cardiac cycle. The appearance of cardiac lymphoma in cats can mimic end-stage hypertrophic cardiomyopathy; however, there is in iltration of the left atrial free wall as well (J. Boon, personal communication). Cardiac tumors are most often seen within or around the right auricle; however, they can be found anywhere within the heart, including the right atrial and right ventricular free wall. They can penetrate into any cardiac chamber and interfere with valve function and blood low. The presence of pericardial effusion facilitates the identi ication of cardiac masses, and approximately 50% of masses can be missed during echocardiographic examination if there is no pericardial effusion present (Weisse et al. 2005). If the tumor comes off the tip of the right auricle, it may be visualized “ loating” in the pericardial sac (Boon 1998) (Figure 9.2).

Figure 9.1 Echocardiogram identifying pericardial effusion (PE). RV, right ventricle; LV, left ventricle; LA, left atrium; RA, right atrium. Therapeutic and diagnostic pericardiocentesis is recommended at the time of echocardiography to treat pericardial tamponade. The results of pericardiocentesis rarely provide a de initive diagnosis as there is signi icant overlap in pericardial pH between neoplastic and nonneoplastic effusions (Fine et al. 2003), and there is signi icant overlap between neoplastic and nonneoplastic effusions when biochemical variables are compared (de Laforcade et al. 2005). Evaluation of serum concentrations of cardiac troponin I (cTnI) in dogs presenting with pericardial effusion have identi ied a signi icantly higher concentration in con irmed cases of hemangiosarcoma compared to cases with idiopathic pericardial effusion (Shaw et al. 2004), however, no signi icant difference was identi ied in a separate

study (Linde et al. 2006). Abdominal ultrasonography is recommended when a cardiac tumor is identi ied to evaluate for primary or metastatic lesions in the abdomen. In one study, 29% of dogs presenting for cardiac hemangiosarcoma had a concurrent splenic hemangiosarcoma and 42% had nonsplenic metastases at presentation (Boston et al. 2011). Electrocardiographic changes are generally related to the effect of pericardial effusion which can result in dampening of the QRS, Pmitrale, electrical alternans, and cardiac arrhythmias. Thoracic radiographs are important for evaluation of pulmonary metastases, particularly in cases of hemangiosarcoma. Thoracic radiographs may also detect a globoid enlargement of the heart, with the result that the cardiac silhouette is rounded on all projections with loss of recognition of the speci ic cardiac chambers. There is often concomitant pleural effusion and enlargement of the pulmonary veins. A heart-base mass generally causes tracheal shift to the right on a ventrodorsal radiographic projection. Computed tomography (CT) can be used to further evaluate heart-base tumors and to assess for regional vessel invasion (Yoon et al. 2004). There can, however, be false-positive and false-negative results when CT is used to evaluate cranial vena caval invasion by mediastinal tumors (Yoon et al. 2004). Cardiac gated magnetic resonance imaging (MRI) and contrast-enhanced magnetic resonance angiography can provide detailed anatomic information regarding cardiac masses as well as the exact relationship with surrounding vessels and the hemodynamic consequences of the mass (Mei et al. 2010; Gallach and Mei 2013). Cardiac MRI is considered the gold standard for imaging of the pericardium and cardiac masses in humans (Ang and Gizzard 2007).

Figure 9.2 Right auricular mass (arrow) is seen in association with a pericardial effusion (PE). LV, left ventricle; RV, right ventricle; RA, right atrium.

Surgical Techniques Preoperative treatment of pericardial effusion is imperative prior to any surgical intervention. Cardiac tamponade is a potentially lifethreatening consequence of cardiac tumors and occurs when the intrapericardial pressure equals or exceeds right ventricular diastolic illing pressures, resulting in decreased cardiac output, right-sided heart failure, and cardiogenic shock. The physiological effects of a tumor within the pericardial sac depend on its size, location, and the presence of pericardial effusion or pericardial ibrosis. Pericardiocentesis is the recommended means to restore intrapericardial pressures and ventricular illing. The site of

pericardiocentesis is between the costochondral junction and the sternum of intercostal spaces four, ive, and six on the right side. Thoracic radiographs can be used to assist the site of centesis; however, ultrasonic guidance provides the best means of performing pericardiocentesis because the probe is positioned to maintain the pericardial space as close as possible to the probe. With the animal standing or in left lateral recumbency, a large-bore needle attached to an extension tube and a three-way stopcock is introduced through the thoracic wall through the middle to caudal portions of the intercostal space. The cranial aspect of the intercostal space is avoided to avoid the intercostal vessels. A right-sided approach uses the space created by the larger cardiac notch and also avoids laceration of the left anterior descending coronary artery and its branches. Electrocardiographic monitoring during pericardiocentesis is recommended to evaluate for premature ventricular contractions that can occur when the needle inadvertently touches the epicardium. As the needle is introduced, it can be felt to pop through the pericardium, and aspiration of the syringe yields a dark red luid that rarely clots. If the luid clots, it is likely to have been inadvertently collected from the ventricle or coronary artery. As the pericardial luid is removed, the resolution of the cardiac tamponade is manifested as a decreased heart rate, increased arterial pressure, and decreased central venous pressure (CVP). A minimum database and coagulation pro ile are recommended to evaluate for concurrent disease, to determine whether anemia needs to be corrected by blood transfusion prior to surgery, and to assess for an underlying coagulopathy such as disseminated intravascular coagulation. Surgical removal of a right auricular tumor can be considered if there is no evidence of pulmonary metastases and the echocardiographic appearance indicates resectability (Weisse et al. 2005). It should be noted that splenic hemangiosarcoma is seen in 29% of dogs with cardiac hemangiosarcoma (Boston et al. 2011), which impacts the decision to perform auriculectomy. Thoracoscopy can be used to assess the resectability of the mass prior to thoracoscopic-assisted resection or conversion to an open thoracotomy for tumor resection. Thoracoscopy can provide information superior to echocardiography regarding tumor resectability. Resectability is based on the size of the

tumor and its location (Ployart et al. 2013). Hemangiosarcomas are locally invasive tumors; clean margins are therefore dif icult to achieve. This is compounded by the importance of having adequate tissue between the base of the right atrial appendage and the tumor to enable both tumor resection and closure of the appendage. Whereas complete surgical removal of noncutaneous hemangiosarcoma has been shown to signi icantly improve survival time (Ogilvie et al. 1996), subtotal pericardiectomy alone has not been found to prolong survival times in dogs with cardiac hemangiosarcoma (Dunning et al. 1998). A right fourth or ifth intercostal thoracotomy is most commonly performed, and the cranial lung lobe is packed caudally with a moistened laparotomy sponge. A median sternotomy can also be performed, which has the advantage of providing the ability to evaluate both sides of the thoracic cavity for metastasis. The pericardial sac is identi ied and gently elevated with Debakey forceps, allowing a small incision with Metzenbaum scissors to be made. A stay suture placed into the sac can also be used to elevate the sac to allow incision without traumatizing the underlying epicardium. A large amount of pericardial luid is usually drained from the pericardial sac, and this is removed with gentle suction. The pericardial incision is enlarged, avoiding the phrenic nerve, and a pericardial basket is created by the placement of stay sutures from the pericardium to the skin. The right auricular appendage is visualized and can be removed by either of two techniques. Firstly, a TA 30-V3 stapling device is placed across the base of the auricle and ired, leaving three rows of staples in the base of the auricle. The auricle is then transected using the distal aspect of the staple gun as a cutting guide (Figure 9.3). The auricle is removed and submitted for histopathology, and the base of the auricle is observed for hemorrhage. A simple continuous suture using 5-0 Prolene or nylon can be used if there is bleeding from the staple line; however, a small amount of oozing can generally be controlled with gentle tamponade. If the tumor invades the base of the appendage or the atrium, stapling the appendage has a tendency to crush the tissue without adequately holding it. Severe hemorrhage, therefore, can subsequently occur when the staple gun is released. If the tumor is fairly large, it is therefore recommended to perform the resection with a hand suture. With the second technique, tangential

vascular clamps such as Satinsky forceps are placed across the base of the auricle (Figures 9.4 and 9.5), and the auricle is incised distal to the clamp leaving a “cuff” of tissue for suturing.

Figure 9.3 A TA 30 stapler is placed across the base of the right auricle and ired. The resection should ideally leave a 1 cm margin of normal auricular tissue distal to the resection. The cuff of tissue remaining beyond the Satinsky forceps is then oversewn with two layers of simple continuous using 5-0 Prolene or nylon. The suture lines are started from opposite ends of the auricle, and the short end of the initial knot can be used to tie the continuous suture from the opposite end. The Satinsky forceps are then removed, and additional simple interrupted 5-0 nylon suture can be placed if there is oozing from the resection site. In a case report, pericardial free patch grafting was performed as a rescue to stop hemorrhaging after staples and sutures failed and the atrial tissue kept

tearing (Morges et al. 2011). Thoracoscopic right auriculectomy can be performed using an Endo-GIA stapling device (Ployart et al. 2013). A right intercostal approach is required to perform an auriculectomy under thoracoscopy. After performing a large pericardial window, the right atrial appendage is gently grasped with grasping forceps. A 60 mm Endo GIA stapling cartridge is used to staple the right auricle. This is only possible if the auricular mass is small and localized at the tip of the right atrial appendage. The cardiopulmonary effects of thoracoscopy in anesthetized normal dogs have been described (Kudnig et al. 2004). Detrimental effects include a decrease in arterial oxygen partial pressure and arterial oxygen content and an increase in shunt fraction, physiological dead space, alveolar-arterial oxygen difference, and mean and diastolic pulmonary arterial pressures (Kudnig et al. 2004).

Figure 9.4 Placement of tangential forceps on the right auricle to remove a right auricular hemangiosarcoma.

Figure 9.5 Right auricle specimen after excision. Tumors involving the right atrium are more problematic to remove. Cardiopulmonary bypass or total venous in low occlusion with Rumel tourniquets placed around the caudal and cranial vena cava and the azygous vein (Verbeke et al. 2012) is required in these cases. The use of a pericardial patch graft to reconstruct the right atrium after resection of atrial tumors has been described (Brisson and Holmberg 2001; Verbeke et al. 2012). Alternatively, preplaced sutures are placed around the tumor, and these are tied after resection. Total venous in low occlusion times of up to eight minutes are well tolerated in dogs (Hunt et al. 1992a). Right atrial tumors extending from the right atrial appendage into the right ventricle and tumors from either the left or right ventricular wall can be excised via cardiopulmonary bypass to palliate clinical signs, which are related to interference with valve function. The limited long-term prognosis, however, generally precludes tumor excision in these cases.

Surgical removal of heart-base tumors is challenging; however, given the fact that only 20% of heart-base tumors metastasize, extended survival times can be achieved by performing a palliative subtotal pericardiectomy alone. Surgical excision can be considered depending on the size, location, and degree of local invasion, which are best determined intraoperatively (Brownlie and Jones 1985). Heart-base tumors invade the wall of great arteries, which makes their excision dif icult and risky. The heart-base tumor, therefore, is usually biopsied for histopathological diagnosis and a subtotal pericardiectomy performed to treat or prevent hemorrhage into the pericardial sac resulting in pericardial tamponade. Percutaneous balloon pericardiotomy, as a less invasive approach than a surgical pericardiectomy, has been proposed as a palliative measure for recurrent pericardial effusions secondary to heart-base tumors (Sidley et al. 2012). Premature closure of the stoma, however, is a potential cause of recurrence of the clinical signs of pericardial tamponade (Sidley et al. 2012). Radiation therapy of heart-base tumors is also an alternative to pericardiectomy with a three-dimensional conformal treatment reported in a dog (Rancilio et al. 2012) and stereotactic radiation also having been reported (Magestro et al. 2018; KruckmanGatesy et al. 2020). Median overall survival was 404 days in one study of stereotactic radiation (Kruckman-Gatesy et al. 2020) and 414 days in another (Hansen et al. 2021). Conventional fractionated radiation therapy is another therapeutic option with a median survival time of 817 days in ive dogs (Hansen et al. 2021). Toceranib is another treatment for canine heart-base tumors (Lew et al. 2019). About 90% of dogs with clinical signs improved with toceranib therapy and the overall median survival time was 823 days (Lew et al. 2019). Polytetra luoroethylene (PTFE) grafts can be used to bypass a heartbase tumor that is interfering with venous return resulting in chylothorax (Figure 9.6). The PTFE graft can be sutured from the cranial vena cava to the tip of the right atrial appendage (Figure 9.6). Alternatively, intravascular stenting using interventional cardiovascular procedures can be considered to ameliorate vascular obstruction from a heart-base mass (Grif iths et al. 2006).

Postoperative Care and Potential Complications

Postoperative management of surgical patients with cardiac or heartbase tumors is consistent with any other thoracotomy or thoracoscopic procedure. A chest tube is placed for approximately 24 hours after surgery and is aspirated every hour for 4 hours, then every 4–6 hours until it is removed. The quantity of air and luid is quantitated. Arterial blood gas analysis is the most accurate means of evaluating the respiratory status of the patient and is used to guide oxygen supplementation, which is often required after thoracotomy. Given the adverse effects of thoracotomy and thoracoscopy on gas exchange, cardiopulmonary monitoring after surgery is important to avoid postoperative hypoxemia (de Gray et al. 1997; Kudnig et al. 2004). Continuous electrocardiography should be used to monitor for postoperative arrhythmias. Analgesia after thoracotomy or thoracoscopy includes local intercostal nerve blocks, intrapleural administration of lidocaine/bupivacaine, epidural analgesia, and continuous rate infusion of a narcotic such as fentanyl. Infusion of therapeutic doses of bupivacaine and lidocaine intrapleurally or into the pericardial space has been shown to be safe in dogs following pericardiectomy, with a mild detrimental effect on cardiac output (Bernard et al. 2006). Analgesia is very important following thoracotomy and thoracoscopy as postoperative pain exacerbates the alterations to respiratory mechanics induced by anesthesia and an open chest by inducing restrictive ventilation and an abnormal breathing pattern (Sabanathan et al. 1990). Immediate postoperative complications following thoracotomy or thoracoscopy include pain and the associated hypoventilation, hypoxemia due to ventilation/perfusion mismatch and hypoventilation (de Gray et al. 1997; Kudnig et al. 2004), hypothermia, hypotension, hemorrhage, pneumothorax, and incisionalrelated problems (see also Chapter 8, Thoracotomy section). Hypoventilation can be exacerbated if a phrenic nerve was damaged. Damage to the recurrent laryngeal nerve as it comes off the vagal nerve is possible, leading to laryngeal paralysis, particularly in cases with heart-base tumors. Long-term complications include local disease recurrence, metastatic disease, and portal site metastasis (Brisson et al. 2006).

Figure 9.6 PTFE is being used to bypass a heart-base tumor that is inducing chylothorax secondary to impaired venous return. The white arrows are highlighting the heart-base tumor, the large black arrow is demonstrating the anastomosis to the cranial vena cava and the small black arrow is showing the right atrial appendage.

Common Tumor Types, Prognosis, and Adjuvant Therapy Cardiac tumor types include both benign and malignant tumors, with malignant tumor types being more common (Ware and Hopper 1999). Cardiac tumors can occur as primary or secondary metastatic lesions, with primary tumors being more common in a large case study (Ware and Hopper 1999) and less common than metastatic lesions in a smaller study (Aupperle et al. 2007). The most common primary cardiac tumor in dogs is hemangiosarcoma (Ware and Hopper 1999), which is most often located on the right auricular appendage. The majority (88%) of right atrial masses are due to hemangiosarcoma

(MacDonald et al. 2009). Other malignant cardiac tumor types include ibrosarcoma, rhabdomyosarcoma, and chondrosarcoma. The most common cardiac tumor types in cats are lymphoma and metastatic tumors (Tilley et al. 1981). Benign cardiac tumor types include ibroma, myxoma, and rhabdomyoma. The most common metastatic cardiac tumors in dogs include lymphoma, hemangiosarcoma, adenocarcinoma, osteosarcoma, and mast cell tumors (Ware and Hopper 1999; Aupperle et al. 2007). About 36% of dogs with malignant neoplasms in one study had histologically con irmed cardiac metastases, with malignant lymphoma and mammary adenocarcinoma being the most frequent (Aupperle et al. 2007). The left ventricular free wall was the most common site for metastasis (Aupperle et al. 2007). Heart-base tumors include ectopic thyroid or parathyroid carcinomas and aortic body tumors (chemodectoma). Given the high metastatic rate of hemangiosarcoma in dogs, adjuvant chemotherapy is recommended to improve survival times in dogs (Weisse et al. 2005). In one study, mean survival times for dogs undergoing subtotal pericardiectomy for cardiac hemangiosarcoma was 16 days, with all dogs dead within seven months of initial diagnosis (Dunning et al. 1998). Mean survival time in 38 dogs with cardiac hemangiosarcoma was four months in one study after surgery when adjuvant therapy was not used (Aronsohn 1985). Survival time in another study was signi icantly longer for dogs with right atrial hemangiosarcoma treated with adjuvant chemotherapy (median survival time 175 days) than for dogs that were not (Weisse et al. 2005). Resection of a hemangiosarcoma lesion involving the right auricular appendage, combined with adjuvant chemotherapy, will prolong survival, however, the median survival times are still less than six months (Weisse et al. 2005). Prolonged survival times can be achieved with heart-base tumors following subtotal pericardiectomy (Ehrhart et al. 2002), and adjuvant chemotherapy is generally not performed. In one study, dogs with aortic body tumors treated with subtotal pericardiectomy had a signi icantly longer survival time (730 days) compared to dogs that did not (42 days) (Ehrhart et al. 2002). A survival bene it from subtotal pericardiectomy was seen in dogs with or without pericardial effusion secondary to the heart-base tumor (Ehrhart et al. 2002).

Pericardial Tumors Common Surgical Procedures The most common surgical procedures performed for pericardial tumors are a subtotal pericardiectomy via thoracotomy or a pericardial window via thoracoscopy. Thoracoscopic pericardial window allows a minimally invasive approach, with drainage of the pericardial sac and acquisition of a pericardial biopsy to differentiate between idiopathic pericardial effusion and a pericardial tumor.

Diagnostic Tests and Imaging Modalities Echocardiography is the most sensitive diagnostic test to both diagnose pericardial effusion and evaluate for a cardiac tumor (Boon 1998). Thoracic radiographs demonstrate a globoid appearance to the heart and are evaluated for pulmonary metastasis. Electrocardiographic changes seen with pericardial effusion have been described above. Alterations to the intrapericardial pressure depend on the volume of the effusion, the rate of luid accumulation, and the physical characteristics of the pericardium. A reduction in pericardial compliance can be seen with either pericardial neoplasia or chronic pericardial in lammation. A Swan-Ganz catheter can be used to evaluate atrial and ventricular pressure tracings, which may demonstrate a “square root sign” with restrictive pericarditis, whereby a thickened noncompliant pericardium abruptly limits ventricular illing in mid to late diastole. This results in the atrial and ventricular tracings showing a rapid descent followed by an abrupt rise to an elevated diastolic plateau. Also, equilibration of diastolic pressures will occur between the right atrium, the right ventricle, and the pulmonary artery wedge pressure. Measuring CVP may demonstrate Kussmaul’s sign, whereby there is augmentation of venous pressure during inspiration. CVP does not decrease during inspiration as it does normally because the negative intrathoracic pressure is not transmitted to the cardiac chambers. Prior to surgery, pericardiocentesis is recommended to resolve pericardial tamponade and to decrease anesthetic risk. The technique has been described above. Pericardial luid analysis is rarely

diagnostic due to a dif iculty in distinguishing between reactive mesothelial cells and tumor cells. Cytology of the pericardium or pleural luid can be used to diagnose pericardial lymphoma in cats (Amati et al. 2014).

Surgical Techniques A pericardial window can be performed via thoracoscopy using a right lateral (Figure 9.7) or subxiphoid approach (Jackson et al. 1999; Dupre et al. 2001). The ventral mediastinum is opened to facilitate complete exploration of the thoracic cavity prior to performing the pericardiectomy. The pericardium is mobilized and tented with graspers to avoid trauma to underlying structures during the pericardiectomy (Figure 9.8). A 3 × 3 cm window is created with Metzenbaum scissors, and the pericardial biopsy is submitted for histopathology (Figure 9.9a).

Figure 9.7 The diaphragm insertion is underlined with a blue line. The scope enters the chest at the dorsal third of the ninth intercostal space. Instruments are placed craniad in order to grasp and cut the pericardium. Alternatively (as it is shown in the picture), a regular thoracic clamp can be placed ventral in order to apply traction to the pericardium. Source: Image courtesy of Dr. Gilles Dupré.

Figure 9.8 The pericardium is grasped under thoracoscopic visualization.

Figure 9.9 (a) Thoracoscopic pericardial biopsy. The white arrows are showing the pericardial biopsy harvested with a vessel sealant device. (b) Pericardioscopy following a pericardial window. White arrow is the aortic root and the black arrows are the right atrial appendage.

Creation of a larger opening does risk cardiac herniation through the pericardial defect. The thoracoscope is advanced into the pericardial sac to evaluate for heart or heart-base tumors (Figure 9.9b). A cadaveric study found that a more complete evaluation of the pericardial space and epicardial structures with a thoracoscope could be achieved with a subphrenic pericardiectomy, compared to a 4 × 4 cm apical pericardial window (Skinner et al. 2014). Subtotal pericardiectomy can also be performed via a routine open right lateral thoracotomy or median sternotomy. An open approach allows a more complete excision of the pericardium, particularly when a median sternotomy approach is used. Postoperative management and complications following thoracotomy and thoracoscopy have been discussed above. Portal site tumor seeding is a potential complication following thoracoscopic biopsy of pleura in dogs with mesothelioma (Brisson et al. 2006), but the true incidence is unknown.

Common Tumor Types, Prognosis, and Adjuvant Therapy The most common primary pericardial tumor type is pericardial mesothelioma. Subtotal pericardiectomy is considered to be palliative, and intracavitary cisplatin is recommended to improve survival times (Moore et al. 1991; Closa et al. 1999). An initial histologic diagnosis of idiopathic pericardial effusion is made in up to 25% of dogs with mesothelioma, and repeat pericardial biopsy is recommended in cases of idiopathic pericardial effusion that recur (Stepien et al. 2000). Subtotal pericardiectomy alone does not improve survival time in dogs with mesothelioma; however, it is required to obtain a de initive diagnosis (Dunning et al. 1998). Median survival time of 13.6 months has been reported for dogs with mesothelioma (Dunning et al. 1998). The pericardium can also be a primary site for lymphoma in cats (Amati et al. 2014) as well as a site for metastatic tumors in cats (George and Steinberg 1989) and benign tumor types in dogs (BenAmotz et al. 2007).

Carotid Body Tumors

Chemodectomas can arise from the carotid bodies at the bifurcation of the carotid artery in the neck. Old brachycephalics are most commonly affected, and dogs generally present for a neck mass either in the retropharyngeal area or caudal to the angle of the jaw (Obradovich et al. 1992). There may be concurrent Horner’s syndrome and laryngeal paralysis.

Diagnostic Tests and Imaging Modalities Ultrasonography can be used to evaluate the mass with color low Doppler sonography, which is useful to evaluate blood low. MRI is a useful imaging modality for carotid body tumors as it de ines the soft tissue extent of the mass (Figure 9.10). Thoracic radiographs or CT are recommended to evaluate for metastatic disease. CT can also be used to evaluate the primary mass or a carotid body tumor may be identi ied incidentally when performing a head and neck CT for another reason (Figure 9.11). Fine needle aspirate of these masses is often nondiagnostic (Obradovich et al. 1992). As with thyroid tumors, a preoperative incisional biopsy is not generally performed due to the risk of hemorrhage.

Surgical Techniques, Potential Complications, and Prognosis Surgical resection of carotid body tumors is the treatment of choice (Figures 9.12 and 9.13); however, local invasion can make removal dif icult, with high intraoperative mortality and postoperative morbidity (Obradovich et al. 1992). Postoperative Horner’s syndrome and laryngeal paralysis are potential complications (Obradovich et al. 1992), and a laryngeal tieback may be required if there is trauma to both recurrent laryngeal nerves resulting in bilateral laryngeal paralysis. Because of the close proximity of the vagal nerve in this area, damage to this nerve is possible and can lead to megaesophagus in some dogs, even with unilateral damage. Preoperative transcatheter embolization techniques have been used in humans to decrease the morbidity associated with the surgery (Ka ie and Freischlag 2001). The metastatic rate of carotid body tumors is quite high in dogs that survive the perioperative period, with reported sites of metastasis including

the liver, mediastinum, brain, heart, lungs (Obradovich et al. 1992), and multiple osseous metastases (Okajima et al. 2007). The median survival time after surgery alone in four dogs was 25.5 months in one study, with three out of six dogs that survived the perioperative period dying of distant metastases (Obradovich et al. 1992).

Figure 9.10 (a) Contrast-enhanced sagittal and (b) transverse T1 MRI of a carotid body tumor at the carotid bifurcation (see arrows). Source: Image courtesy of Dr. Ralph Henderson.

Figure 9.11 A soft tissue nodule (17 × 16 × 20 mm, DV × LM × CrCd, pink arrows) with moderate, mildly heterogeneous enhancement was identi ied during a CT examination for brachycephalic obstructive airway syndrome as well as a suspected otitis media. The mass is located at the level of the bifurcation of the carotid artery (red arrows) and histopathology was consistent with a carotid body tumor.

Figure 9.12 Surgical resection of a carotid body tumor at the carotid bifurcation. Source: Image courtesy of Dr. Ralph Henderson.

Figure 9.13 Carotid body tumor after resection. Source: Image courtesy of Dr. Ralph Henderson.

Vascular Oncologic Surgery – Tumor Thrombus Excision Tumor thrombus excision is most commonly performed for adrenal tumors invading the caudal vena cava and for thymomas invading the cranial vena cava. Involvement of the cranial vena cava can result in cranial vena cava syndrome. Involvement of the prehepatic caudal vena cava can result in rear limb edema, whereas involvement of the posthepatic caudal vena cava can also result in ascites. Only 8% of adrenal tumor thrombi, however, result in clinical signs associated with the thrombus (Kyles et al. 2003). Up to 32% of adrenal tumors have tumor thrombi, with the majority being caval thrombi (Kyles et al. 2003) (see also Chapter 13, Adrenal Gland section).

Diagnostic Tests and Imaging Modalities Diagnostic evaluation of animals with suspected tumor thrombi includes ultrasonography, vascular contrast studies, MRI, CT, and coagulation pro iles. Sensitivity and speci icity of abdominal ultrasound to detect caval thrombi secondary to adrenal tumors have been reported as 80 and 90%, respectively (Kyles et al. 2003). A minimum database and a coagulation pro ile, despite being a better indicator of hypocoagulability than hypercoagulability, are recommended. Thoracic radiographs or CTs are performed to evaluate for the primary tumor mass and metastatic disease. Thoracic ultrasonography with color low Doppler is useful to document intravascular thrombosis and vascular extension of tumors (Besso et al. 1997). Measurement of CVP is performed to assess the cranial vena caval pressure. Angiography is a useful technique to evaluate venous occlusion secondary to tumor thrombi. Nonselective angiography consists of a rapid injection of a water-soluble contrast agent into a peripheral vein. Nonselective angiography (positive-contrast venography) is useful to assess compression or obstruction of central veins, in particular, the cranial and caudal vena cava, and also to assess vessel patency following vascular reconstruction. An angiogram via the femoral vein is performed for the caudal vena cava and via the jugular vein for the cranial vena cava. Digital luoroscopy, which can provide four exposures per second, is useful for the rapid accumulation of images following a bolus injection of contrast. Advanced imaging techniques to evaluate for tumor emboli/vascular invasion include MRI and contrast-enhanced CT (Figure 9.14) (Holsworth et al. 2004; Louvet et al. 2005; Schultz et al. 2009).

Surgical Techniques Surgical options for tumor thrombi include venotomy and thrombectomy with primary repair of the vessel (Hunt et al. 1997) or en bloc resection and vascular reconstruction (Lascelles et al. 2003). Synthetic (Esato et al. 1981; Lascelles et al. 2003) and jugular venografts (Holsworth et al. 2004) have been described for vascular reconstruction. Ligation of the cranial vena cava cranial to the entrance of the azygous vein can result in chylothorax (Fossum and Birchard

1986), and acute ligation of the caudal vena cava cranial to the renal veins results in hind limb edema and renal dysfunction (Lespinasse 1947). To perform a thrombectomy, Rumel tourniquets are placed proximal and distal to the tumor thrombus. The proximal aspect of the thrombus can often be “milked” distally to facilitate the placement of a Rumel tourniquet proximal to it (Figure 9.15a). This is particularly useful for adrenal tumor thrombi that extend cranially in the caudal vena cava. A venotomy is then performed with a no. 11 blade, extended with Pott-Smith scissors, and the tumor thrombus is removed or “milked out.” (Figures 9.15b and c).

Figure 9.14 Sagittal and transverse CT angiograms demonstrating a caval thrombus secondary to a heart-base mass. (a) A sagittal projection showing the heart-base tumor (black arrow) and the occlusion of the vena cava with thrombus (white arrows). (b) Transverse CT angiogram with the white arrow showing cranial vena cava with a thrombus. The venotomy is best closed while the Rumel tourniquets are in place or after placement of Satinsky clamp and release of Rumel tourniquets. A simple continuous pattern using 4-0 to 5-0 nylon or Prolene is preferred. It is important to de-air the venotomy before completing the closure. Either the distal Rumel or the Satinsky clamp is released before completing the suture to allow the release of any air within the vein.

The proximal Rumel or the Satinsky clamp is then released and the vessel is observed for bleeding. Safe vascular occlusion times for the caudal vena cava have been described (Hunt et al. 1992a, 1992b). Complete occlusion of the intrathoracic portion of the caudal vena cava results in decreases in systemic arterial pressure, decreased CVP, and decreased cardiac output, with a rapid return to preocclusion values when the occlusion time is limited to less than 8 minutes (Hunt et al. 1992b). Total hepatic occlusion in clinical cases has been safely performed with occlusion times of 8–16 minutes (Hunt et al. 1996), and total venous in low occlusion time to the heart of 8 minutes is well tolerated in normothermic dogs (Hunt et al. 1992a). Clinically, however, much longer caval occlusion times have been reported with successful outcomes (Holsworth et al. 2004). A maximum occlusion time of 20 minutes has been reported for continuous occlusion of the hepatic artery and portal vein in dogs (Raffucci 1953). It has been demonstrated that portal triad clamping results in signi icant decreases in cardiac index, mean arterial pressure, portal pH, and oxygen delivery index after 8 minutes, and lactic acidosis develops in portal blood after 16 minutes of occlusion (Nemec et al. 2003). En bloc resection of the mass and vessel requires vascular reconstruction. Techniques using a jugular autograft (Holsworth et al. 2004) or using a synthetic substitute have been described (Esato et al. 1981; Lascelles et al. 2003). If there has been gradual occlusion of the vena cava, en bloc resection without vascular reconstruction can be considered, relying on collateral circulation via the vertebral sinus and azygous vein (Peacock et al. 2003; Louvet et al. 2005). Intravascular stents or angioplasty using balloon dilation have also been described to palliate vascular obstruction secondary to vascular occlusion as a less invasive approach (Holt et al. 1999). Arterial thrombosis can occur in oncologic cases due to the presence of factors involved in Virchow’s triad, including altered blood low, altered vascular integrity, and abnormalities of the coagulation/ ibrinolytic system (Wray et al. 2006). Antithrombotic therapy is generally performed in preference to arteriotomy and

includes streptokinase and recombinant tissue plasminogen activator (tPA).

Postoperative Care and Prognosis Postoperative management following venotomy and tumor thrombectomy includes management protocols appropriate for the primary disease causing the thrombus, with particular emphasis on monitoring for hemorrhage and hypotension. Reported postoperative complications for adrenalectomy with or without thrombectomy include dyspnea, hemoperitoneum, ventricular arrhythmias, anuric acute renal failure, and coagulopathies (Kyles et al. 2003). Antithrombotic agents such as low-molecular-weight heparin are recommended following vascular reconstruction to prevent thrombosis (Holsworth et al. 2004). Low-molecular-weight heparins have several advantages over unfractionated heparin, including a longer half-life, increased bioavailability, reduced need to monitor bleeding times, reduced incidence of bleeding, and a lower incidence of heparininduced thrombocytopenia (Hull and Pineo 1993; Duplaga et al. 2001; Mischke et al. 2001). Signs of caval obstruction should be observed for resolution following caval thrombectomy. The integrity of the operated vessel can be assessed via ultrasound and/or a nonselective angiogram performed approximately one week after surgery (Holsworth et al. 2004). Tumor thrombectomy has been reported not to negatively impact morbidity or survival times in dogs with adrenal tumors (Kyles et al. 2003) and is recommended in conjunction with adrenalectomy when tumor thrombi are present. A more recent study (Barrera et al. 2013), however, identi ied a higher perioperative mortality rate for adrenalectomy for tumors that invade the caudal vena cava, particularly if invasion is extensive, compared to tumors that did not invade the caudal vena cava. Partial occlusion of the vena cava is feasible for small locally invasive tumors. More extensive adrenal tumors with caval invasion, however, require a greater degree of surgical invasiveness and complete in low occlusion, resulting in a greater degree of cardiovascular compromise and higher short-term mortality rate (Barrera et al. 2013).

Figure 9.15 (a) Adrenal mass with caval thrombus. The thrombus is being manipulated caudally to place a Rumel tourniquet cranial to it. (b) Rumel tourniquets have been placed prior to cavotomy. (c) A cavotomy has been performed and the thrombus (black arrows) is being “milked out” of the vena cava (white arrow).

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10 Reproductive System Maurine J. Thomson and Tara A. Britt

Female Reproductive System Biopsy Techniques Presurgical biopsy of ovarian or uterine masses is rarely indicated, as surgical resection remains the de initive treatment option and is unlikely to be in luenced by the biopsy results. In fact, transabdominal needle biopsies of the ovary are not recommended as ovarian tumors readily implant on peritoneal surfaces. Abdominocentesis can be safely performed to con irm a malignant effusion, and evidence of epithelial cells can prompt investigation for an ovarian tumor (Klein 2007; Bertazzolo 2012). Histopathological examination of vulvar and vaginal masses can be readily performed via a surgical biopsy of the protruding mass. Masses that are more cranial and intraluminal can be biopsied with the assistance of vaginoscopy. Cranial and extraluminal vaginal masses can be biopsied through a perineal approach. Mammary tumors in dogs are rarely biopsied before de initive surgery, as the type of surgery is usually determined by the size of the lesion, regardless of benign or malignant disease. Fine needle aspirates (FNA) can be performed to exclude lipoma or mast cell tumors, which also occur in this region. Two studies support using FNA to differentiate benign vs. malignant tumors of the mammary gland in dogs (Cassali et al. 2007; Simon et al. 2009). Feline mammary tumors are malignant in about 85% of cases. Because the de initive surgery for malignant tumors in cats is a wider resection (bilateral radical mastectomy) than canine mammary tumors, biopsy of the mammary lesion before attempting the de initive surgery is imperative in cats.

Diagnostic Imaging

Ultrasound is the most readily available and sensitive tool for imaging ovarian and uterine tumors. Benign ovarian masses are more likely to be cystic, with more solid lesions likely to be malignant (Diezbru et al. 1998). Most benign ovarian and uterine tumors will be localized, and readily amenable to surgical resection. Evidence of ascites may be seen with ovarian carcinomas and usually indicates metastatic spread via transcoelomic implantation. Imaging of vaginal tumors can be done with vaginoscopic examination, retrograde vaginography, and urethrocystography. Advanced imaging such as computed tomography (CT) or magnetic resonance imaging (MRI) can be useful to provide images of the primary tumor, particularly vaginal tumors where ultrasound is limited, and to determine the extent of metastatic disease for malignant tumors. Thoracic radiographs or CT are used to determine any evidence of pulmonary metastasis, though abdominal ultrasound or CT can also determine involvement of abdominal metastases.

Ovarian Tumors Surgery is indicated as the best treatment option for ovarian and uterine tumors. Ovariohysterectomy (OHE) is recommended but oophorectomy can be performed. A standard OHE is performed other than if adhesions are present, such as omental adhesions, they are resected en bloc with the tumor and not “peeled off” from the tumor. Benign masses may grow up to 16 cm, and extreme care should be taken to prevent rupture of the mass during surgical removal (Figure 10.1). Adenomas and adenocarcinomas may be bilateral, requiring bilateral resection. All serosal surfaces, including omental and intestinal, should be carefully examined for evidence of metastatic disease and biopsied where indicated.

Histologic Tumor Types Ovarian tumors are uncommon in dogs and cats due to early neutering in these species. They are generally classi ied as epithelial, germ cell, sex cord stromal, and mesenchymal in origin, according to the World Health Organization (WHO) classi ication. Two studies have described

the detailed histologic and immunohistochemical characteristics of canine ovarian tumors (Akihara et al. 2007; Riccardi et al. 2007). The epithelial tumors include papillary adenoma and adenocarcinoma, cystadenoma and cystadenocarcinoma, and undifferentiated carcinoma. The epithelial tumors account for 40–50% of ovarian tumors (Patnaik and Greenlee 1987). Most epithelial tumors are malignant, with about 50% having metastasized to other organs at the time of diagnosis (Patnaik and Greenlee 1987; Infante et al. 1998). Many also show clinical signs of bilateral alopecia and abnormal estrus cycles as a result of altered hormonal levels (Infante et al. 1998). Germ cell tumors include dysgerminomas, teratomas, and teratocarcinomas, comprising about 10% of ovarian tumors. Approximately 50% of teratocarcinomas have metastasized at the time of diagnosis. Sex cord stromal tumors are the most commonly reported ovarian tumors and include granulosa cell tumors, thecomas, and luteomas. Granulosa cell tumors are the most common of the stromal tumors. Granulosa cell tumors are usually unilateral and benign and may produce estradiol or progesterone, resulting in clinical signs of persistent estrus, vulvar swelling and discharge, and alopecia (Johnson et al. 2001). About 20% are associated with metastases. They have also been associated with endometrial polypoid adenomyomatosis (Zanghi et al. 2007). Hyperestrogenemia can also result in bone marrow suppression, with associated leukopenia, thrombocytopenia, and anemia (Pluhar et al. 1995). This can be reversible with surgical resection and blood transfusions.

Figure 10.1 Ovarian tumor. These tumors can grow very large, and extreme care should be taken to prevent rupture of the mass during removal. Arrow points to uterine horn. Source: Image courtesy of Dr. Phil Thomas.

Prognosis Survival outcomes are only rarely reported in the veterinary literature. The prognosis for solitary tumors completely excised is good, regardless of histopathology. In a study of 16 cases of ovarian tumors, 81% had a favorable outcome and 19% died or were euthanized due to their disease (Kusy et al. 2005). Prognosis for metastatic disease is poor.

Adjuvant Therapy

In the presence of metastatic disease, chemotherapy appears to lengthen survival times, with platinum-based protocols being the most effective (Klein 2007), although long-term prognosis remains poor. Intracavitary use of cisplatin has been described as useful in palliating malignant effusions associated with ovarian adenocarcinomas (Moore et al. 1991; Olsen et al. 1994). About 80% of ovarian carcinomas express the COX-2 enzyme, and so the use of piroxicam may be warranted (Borzacchiello et al. 2007).

Uterine Tumors Surgery Treatment for uterine tumors is surgical resection via OHE and removal of metastatic foci if possible. Standard celiotomy and OHE are performed. Omental adhesions, if present, are excised en bloc with the tumor as opposed to being “peeled off.”

Histologic Tumor Types and Prognosis Uterine neoplasms are uncommon in small animals due to the incidence of early neutering in dogs and cats. The most common histologic types are leiomyomas, ibroleiomyomas, leiomyosarcomas, adenomas, adenocarcinomas, and ibromas. Of the mesenchymal tumors, leiomyomas represent 85–90% of reported cases, and leiomyosarcomas represent about 10% (Brodey and Roszel 1967; Withrow and Susaneck 1986). Leiomyomas are typically slow growing and noninvasive. Hereditary multifocal renal cystadenocarcinomas and nodular dermato ibrosis of German shepherd dogs may also be associated with uterine leiomyomas in this breed (Moe and Lium 1997). Leiomyosarcomas are the most common malignant tumor, and adenocarcinomas are only rarely reported (Murphy et al. 1994). Many tumors are incidental indings at surgery or necropsy, though malignant masses may cause ascites, anorexia, vaginal discharge, and concurrent pyometra with enlargement of the uterus (Murphy et al. 1994).

Prognosis for leiomyomas is excellent as surgery is curative for benign lesions. The prognosis for leiomyosarcomas is good if there is no evidence of metastatic disease (Withrow and Susaneck 1986). The prognosis for adenocarcinomas remains guarded due to the high metastatic potential (Moe and Lium 1997).

Adjuvant Therapy The role of chemotherapy and radiation has not been investigated in small animals after surgery for malignant tumors.

Vaginal and Vulvar Tumors Surgery Leiomyomas and other benign smooth muscle tumors are hormone dependent so conservative resection combined with OHE is normally curative. It is recommended to insert a urinary catheter prior to any surgery involving the vagina or vestibule to prevent inadvertent trauma to the urethra. Benign lesions on a pedicle can be ligated directly with a crushing suture, or a trans ixation suture for wider pedicles.

Episiotomy If visualization is poor, exposure can be greatly improved by performing a dorsal episiotomy. The bitch is placed in sternal recumbency, with the tail elevated and secured to the dorsal midline region with tape or towel clamps. A purse-string suture of 3-0 nylon is placed around the anus, and the vulvar area is clipped and prepared for surgery (Figure 10.2). A urinary catheter is placed to maintain visualization of the urethra. The blunt end of a scalpel handle or noncrushing forceps are placed in the dorsal aspect of the vestibule to allow tissue stabilization, and an incision is made dorsally, toward the ventral aspect of the anus. Hemorrhage is usually profuse and controlled with cautery and ligation. Gelpi retractors or noncrushing forceps are placed to improve visibility and maintain retraction. After identi ication of the base of the tumor, the mass is excised or the pedicle is ligated. Extraluminal leiomyomas can often be approached via a dorsal episiotomy and

removed via blunt dissection. These masses are usually well encapsulated and poorly vascularized, and they are quite amenable to blunt dissection (Figure 10.3). The vaginal mucosa from where the tumor was excised is closed with either interrupted or continuous 3-0 absorbable sutures. The episiotomy is closed with a three-layer closure. The mucosa is apposed with continuous or interrupted 3-0 absorbable sutures, the subcutaneous layers with 3-0 continuous absorbable sutures. The skin is routinely closed with 3-0 nylon (Mathews 2001). Vulvovaginectomy Vulvovaginectomy and perineal urethrostomy as described by Bilbrey et al. (1989) can be performed for more in iltrative and extensive lesions, such as malignancies (Figure 10.4). Dogs are placed in sternal recumbency and a purse-string suture is placed in the anus. The area is clipped from the base of the tail to the ventral aspect of the vulva and laterally to the midthigh area. A urinary catheter is inserted. A fusiform incision is made in the skin around the vulva, dorsally extending halfway between the vulva and anus. Tissue is sharply dissected from the labia and vestibule, and hemorrhage is controlled with cautery and ligation. The constrictor vestibuli and constrictor vulvae muscles are sharply dissected from the vestibule, and the dorsal labial branches of the ventral perineal artery are ligated. The catheterized urethra is dissected free and transected where it enters the ventral loor of the vestibule. Stay sutures are placed in the urethra to aid caudal retraction. Further dissection is performed cranial to the vagina by sharp dissection of the ischiocavernosus and ischiourethralis muscles and passing between the paired levator ani muscles to the level of the cervix. The vaginal and uterine arteries and their branches are ligated. The vagina can be transected caudal to the cervix in intact bitches or can be removed with the cervix and stump of the uterus in spayed bitches. Intact bitches should also have an OHE performed concurrently (Nelissen and White 2012; Ogden et al. 2020). The deep tissues are apposed with 2-0 absorbable interrupted sutures. The transected urethra is retracted caudally via the stay sutures and the distal end spatulated. The subcutaneous tissues are closed with 3-0 absorbable suture material and the skin with 3-0 nylon. The urethral mucosa is sutured to the skin with 4-0 nylon or absorbable suture, approximately

4 cm ventral to the anus. The procedure has low morbidity, and urinary continence is preserved. Postoperative complications can involve mild urine scalding, urinary tract infection, and mild stress incontinence. Exposure of the ventral aspect of the vagina and urethra can be achieved via a sagittal pubic osteotomy as described by Davies and Read (1990a) (see Chapters 7 and 11). Vaginal/vestibular tumors that involve the urethral papilla or that require removal of the urethral papilla to attain complete margins can be removed with the vaginourethroplasty technique (see Chapter 11). An alternative technique is to make two approaches (Nelissen and White 2012): one with the dog is dorsal recumbency and a ventral midline laparotomy is performed to access the caudal abdomen. An OHE is performed in intact females. The cranial aspect of the vagina is dissected free, while carefully preserving the ureters, the vasculature and innervation to the bladder, and the urethra. The dissection is continued as far caudally as possible. The laparotomy is closed, and the dog is repositioned in sternal recumbency with the pelvic limbs extended caudally over the edge of the table to make the second approach. A perineal approach as described earlier is performed and the vagina is removed (Nelissen and White 2012). Different levels of vaginectomy and vulvovaginectomy are possible (Ogden et al. 2020). The different levels have been described as vulvovaginectomy, complete vaginectomy, and subtotal vaginectomy (Figure 10.5) (Ogden et al. 2020). When a complete or subtotal vaginectomy is performed, a fullthickness circumferential incision of the vaginal wall is made at the junction of the vagina with the vestibule immediately cranial to the urethral ori ice or more cranial (Nelissen and White 2012).

Figure 10.2 Use of episiotomy to improve exposure of vaginal resection. A urinary catheter is placed to maintain visualization of the urethra. (a) Noncrushing forceps are placed in the dorsal aspect of the vestibule to allow tissue stabilization. (b) An incision is made dorsally, toward the ventral aspect of the anus. (c) Gelpi retractors or noncrushing forceps are placed to improve visibility and maintain retraction. A urinary catheter is placed in the urethra. (d) Closure of the episiotomy is achieved with a three-layer closure. Source: Photograph courtesy of Dr. Phil Thomas.

Figure 10.3 Vaginal leiomyoma. (a) These tumors can grow quite large. Arrow points to opening of vulva. Vulva is being distorted ventrally from the presence of the mass. (b) These tumors are often easily removed with blunt dissection. Source: Photograph courtesy of Dr. Phil Thomas.

Figure 10.4 (a) Perivaginal dissection for vulvovaginectomy. Dissection is performed medial to the lateral ligaments of the bladder. (bA) The vagina is removed through the perineal incision. (bB) The urethra is pulled through the perineal incision with stay sutures. (bC) After dorsal spatulation, the mucosa of the urethra is sutured to the skin. Source: Reproduced with permission from Bilbrey, S.A., S.J. Withrow, M.K. Klein, et al. 1989. Vulvovaginectomy and perineal urethrostomy for neoplasms of the vulva and vagina. Vet Surg 18:450–453.

Figure 10.5 Illustration of the extent of the excision and the tissues removed (in red) with the different procedures: (a) vulvovaginectomy, (b) total vaginectomy, and (c) partial (or subtotal) vaginectomy. The illustrations show an intact female and therefore an ovariohysterectomy is also performed. Source: Illustrated by Kip Carter.

Histologic Tumor Types Vaginal tumors are the second most frequently reported tumors of the female reproductive system, following mammary tumors (Brodey and Roszel 1967; Murphy et al. 1994; Lana et al. 2007). Most are benign leiomyomas arising from the smooth muscle of the vestibule of the vagina (Kydd and Burnie 1986). They can arise intraluminally or extraluminally, appearing as a perineal mass. Intraluminal tumors are often attached by a pedicle and appear to be hormone dependent. Transmissible venereal tumors (TVTs) most commonly occur on the external genitalia in endemic regions, appearing as a cauli lower-like lesion (Rogers et al. 1998). Leiomyosarcoma is the most frequently reported malignant tumor, although adenocarcinoma, squamous cell carcinoma, hemangiosarcoma, and mast cell tumors can also be seen (Brodey and Roszel 1967; Withrow and Susaneck 1986). Large benign tumors often appear externally through the vulva after straining, particularly during estrus (Klein 2007). Another differential diagnosis for a mass protruding from the vulva in a dog during estrus is vaginal edema (formally recognized as vaginal hyperplasia). Wide-based tumors are more likely to be malignant, whereas those associated with a pedicle are usually benign (Withrow and Susaneck 1986). Urinary tract carcinomas can also protrude or invade cranially or caudally from the urethral papilla to involve the vagina and vestibule (Magne et al. 1985; Davies and Read 1990b; Norris et al. 1992) (see Chapter 11). Mast cell tumors occur on the vulva and require resection with 2–3 cm margins (or proportional margins, see Chapter 4) and a tissue plane deep.

Prognosis

Reported complications of vaginectomy and vulvovaginectomy include rectal perforation intraoperatively, infection and dehiscence of the urethrostomy site, inability to empty the bladder, urinary incontinence, urine scald, urinary tract infection, perineal hernia development, and dyschezia (Nelissen and White 2012; Ogden et al. 2020). Urinary incontinence developed in 29% of dogs postoperatively with 14% remaining incontinent two months postoperatively (Ogden et al. 2020). Surgery is almost always curative for benign lesions. Surgical resection of leiomyosarcomas can have a good prognosis with surgery, though resection of transitional or squamous cell carcinoma arising from the urethra is often associated with a poor outcome due to local recurrence or metastases (Magne et al. 1985; Bilbrey et al. 1989; Davies and Read 1990b; Norris et al. 1992). Mast cell tumors of the vulva tend to be associated with a higher metastatic rate than those of the limbs and trunk. Ultrasound staging of abdominal nodes, liver, and spleen should be performed prior to surgery for dogs with a mast cell tumor.

Adjuvant Therapy Adjunct chemotherapy can be used for mast cell tumors of the vulva following surgery. Transitional cell tumors (TCCs) arising in the urethra and extending into the vagina can be treated with piroxicam and mitoxantrone, as in the treatment of bladder TCC (see Chapter 11), though insuf icient data are available for dogs with urethral/vaginal tumors treated with chemotherapy to allow any assessment of an improved survival time.

Tumors of the Clitoris Only carcinomas have been reported as tumors of the clitoris in dogs (Verin et al. 2018). In a study of six primary canine clitoral carcinomas, cytologic indings were consistent with malignant epithelial neoplasia of apocrine gland origin (Verin et al. 2018). Hypercalcemia was present in two of these dogs. In the one dog where the parathyroid hormonerelated peptide (PTHrP) was measured, it was found to be elevated. Canine clitoral carcinomas presented clinicopathologic features

resembling apocrine gland anal sac adenocarcinomas with neuroendocrine characteristics, and 2 of 6 neoplasms were considered as carcinomas with neuroendocrine differentiation (Verin et al. 2018). Surgical excision appears to be the treatment of choice for clitoridal tumors. Even with metastasis to regional lymph nodes, long-term survival is possible (over 400 days) although this is based on very few dogs (Verin et al. 2018). The prognosis should remain guarded. All clitoral masses in one study were irm, nodular, hyperemic, and effaced the normal clitoral structure extending to the clitoral fossa (Verin et al. 2018). Therefore, surgical excision requires excision beyond the clitoris itself. An episiotomy is performed dorsally (perineotomy) to gain better access and the clitoridal mass is removed with a portion of the vestibular wall surrounding it, removing, in essence, the clitoridal fossa en bloc with the clitoris.

Canine Mammary Tumors Surgery Surgery is the treatment of choice for all mammary tumors, except patients with in lammatory carcinoma or distant metastatic disease. The type and extent of surgery depend on the size of the tumor, number of masses, and invasiveness into underlying tissues.

Lumpectomy In dogs, lumpectomy or nodulectomy is performed for small masses that are super icial and entails removing a margin of about 1 cm of skin and surrounding mammary tissue.

Mammectomy Mammectomy or single mastectomy is the removal of a gland and is indicated for centrally located tumors in a gland greater than 1 cm or showing invasiveness into surrounding skin or abdominal fascia. The region to be resected can be delineated with a surgical skin marker, removing skin and surrounding tissue with a 1–2 cm margin around

the tumor. Deep dissection is performed down to the external abdominal muscle fascia. If adherent to the abdominal fascia, this is also removed, along with abdominal musculature if required.

Regional Mastectomy Regional mastectomy: Glands 1, 2, and 3 (cranial thoracic, caudal thoracic, and cranial abdominal gland, respectively) and glands 3, 4, and 5 (cranial abdominal, caudal abdominal, and inguinal gland, respectively) have major lymphatic connections between them and are often removed together for larger masses occupying this region or if multiple masses are located in adjacent glands. The inguinal lymph node is closely associated with the ifth mammary gland and is usually removed with it. The axillary nodes are dif icult to access, rarely involved, and only removed if enlarged or cytologically positive (Lana et al. 2007).

Complete Mastectomy Complete unilateral or bilateral mastectomy is the removal of all glands as a single unit. This can be performed for dogs with extensive disease. Staging of a bilateral mastectomy where a unilateral mastectomy is performed on either side 3–6 weeks apart is better tolerated than a one-stage bilateral procedure in dogs. An elliptical skin incision is made around the entire chain to be excised, removing skin and surrounding tissue with a 1–2 cm margin around the tumors. Deep dissection is performed down to the external abdominal muscle fascia. If adherent to the abdominal fascia, this is also removed, along with abdominal musculature if required. The caudal super icial epigastric artery and veins are identi ied at the level of gland 5, and they are isolated, ligated, and divided. Closure is achieved with a continuous or interrupted suture of 3-0 or 2-0 absorbable material in one or two layers, and skin closure with 3-0 nonabsorbable material. Use of walking sutures can be helpful closing the mastectomy site to address the tension and can decrease seroma formation along with reducing acute postoperative pain (Travis et al. 2018).

Bilateral Removal of Mammary Glands 4 and 5

Bilateral removal of mammary glands 4 and 5 can be reconstructed with the use of lank fold laps, as described by Hunt (1995) (Figure 10.6). Dogs are placed in dorsal recumbency, and the skin is prepared on the ventral abdomen and thigh region bilaterally. The tumor is resected with adequate margins, including skin and fat down to the level of the abdominal fascia. Abdominal fascia or musculature is also removed if the tumor is adherent to deeper tissues. Hemorrhage is controlled with cautery, hemoclips, and ligation as required. The caudal super icial epigastric arteries and veins usually need to be ligated. The lank folds are pulled away from the thigh and incised from the sti le toward the lank, leaving the base attached over the lank region. The medial and lateral aspects of the elevated lank fold are gently dissected apart to create a U shape of skin that is pivoted into position. The donor site is closed with one to two layers of 3-0 absorbable suture material, and 3-0 nylon interrupted sutures in the skin. The laps are elevated bilaterally if required and sutured together over the ventral abdominal defect. An active suction drain can be placed before closure and sutured in place. Closure of the ventral abdominal defect is achieved in two layers, with continuous or interrupted 3-0 absorbable sutures in the subcutaneous tissue and 3-0 interrupted nylon in the skin. An Elizabethan collar is applied, and the active suction drain is usually maintained for 24–48 hours, depending on the amount of serum collected. Animals vary in the amount of loose skin available over the lank fold region. Postoperative activity is restricted for 10 days, and the complication of the donor site breaking down is possible if vigorous activity is allowed. Animals return to normal ambulation after healing is complete.

Figure 10.6 Bilateral caudal regional mastectomy in the dog reconstructed with lank fold laps as described by Hunt. (a, b) The tumor is resected with adequate margins, including skin and fat down to the level of the abdominal fascia. (c) The lank folds are pulled away from the thigh and incised from the sti le toward the lank, leaving the base attached over the lank region. The lank fold on the right side has been pivoted over the caudal abdominal defect. The point of the lap that was close to the sti le in its orthotopic position has been sutured close to the vulva in its heterotopic position. The donor site is closed by advancing the skin at the caudal aspect of the limb cranially covering the medial aspect of the limb. (d) The laps have been elevated bilaterally and sutured together on midline over the ventral abdominal defect. Source: Images courtesy of Dr. Julius Liptak.

Prognosis Based on Extent of Surgery In previous studies in dogs, the extent of surgery was not associated with differences in survival time or local recurrence rate (MacEwen et al. 1985; Allen and Mahaffey 1989). In a more recent study, 58% of dogs developed a new tumor in the ipsilateral remaining glands after a regional mastectomy had been performed (Stratmann et al. 2008). The authors of this study argued that this was evidence to recommend performing a unilateral mastectomy. However, all dogs in this study were sexually intact and not spayed at the time of the initial regional mastectomy. This might have affected the likelihood of developing a new tumor.

OHE and Mammary Tumors The role of OHE in the prevention of mammary tumors is widely accepted (Withrow and Susaneck 1986). The risk of developing a malignant mammary tumor compared to a sexually intact dog is 0.5% if the OHE is performed before the irst heat cycle, 8% if OHE is performed between the irst and second heat cycles, and 26% if OHE is performed between the second heat and 2.5 years of age, after which there is no reduction in the risk (Schneider et al. 1969). Following a systematic review of the literature, however, it was determined that the evidence demonstrating OHE reduces the risk of tumor development was weak (Beauvais et al. 2012). The role of OHE in the treatment of mammary tumors is controversial. The advantage of OHE at the time of resection of mammary tumors is unclear. Sorenmo et al. (2000) showed a survival bene it for those dogs treated with OHE at the time of mammary tumor removal or two years prior to presentation, compared to those intact or spayed longer than two years prior to presentation. However, three other studies did not show any survival advantage with OHE at the time of presentation (Yamagami et al. 1996; Morris et al. 1998; Philibert et al. 2003). Chang et al. (2005) did show a survival bene it with OHE at the time of mammary tumor removal, and this was more signi icant for dogs with complex carcinoma. Given the fact that mammary carcinomas in dogs constitute a heterogeneous disease, the bene icial effect of OHE is likely to present for only certain dogs, dependent on some intrinsic factors of the tumors. Based on one

prospective randomized study of dogs with mammary carcinoma, dogs with grade 2, estrogen receptor-positive tumors, or with increased peri-surgical serum 17β-estradiol concentration, represent a subset of dogs with mammary carcinomas likely to bene it from OHE (Kristiansen et al. 2016). It was suggested that peri-surgical serum 17βestradiol concentration can be used as an easily available marker to identify dogs that might bene it from OHE. (Kristiansen et al. 2016).

Inflammatory Mammary Carcinoma Surgery is contraindicated for in lammatory carcinoma. These tumors are poorly differentiated carcinomas with extensive lymphatic involvement, edema, and marked in lammatory reaction. They grow and metastasize very rapidly, with patients often in disseminated intravascular coagulation at the time of presentation (Withrow and Susaneck 1986; Marconato et al. 2009).

Histologic Types and Prognosis About one-half of mammary tumors in dogs are benign and the other half are malignant, and about one-half of the malignant tumors will metastasize throughout the course of the disease (50-50 percent rule). Benign tumors are frequently less than 1 cm and malignant tumors frequently >2 cm. A histological progression from benign to malignant with increasing tumor size has been documented in dogs (Sorenmo et al. 2009, 2011; Gedon 2020). Gedon’s (2020) study also demonstrated progression from malignant to more highly malignant carcinoma with larger tumors. Complications occurred in 17% of dogs following mammary tumor removal in one study (Evans et al. 2021). High body weight and undergoing bilateral mastectomy were associated with increased odds of complications. Dogs undergoing chain mastectomy that did not receive antimicrobials postoperatively had higher risk of developing complications. Dogs undergoing concurrent OHE or ovariectomy had decreased odds of complications (Evans et al. 2021). Benign mammary tumors are cured with surgical resection. Factors that confer a worse prognosis for canine malignant mammary tumors

are masses greater than 2 cm, invasive or ulcerated masses, tumors present longer than six months, positive lymph nodes for neoplastic cells, poorly differentiated or anaplastic carcinoma, in lammatory carcinoma, lack of estrogen receptors, high Ki67, invasion into the vascular or lymphatic system, and incomplete surgical margins (Hellman et al. 1993; Philibert et al. 2003; Chang et al. 2005; Lana et al. 2007; Tran et al. 2016). Factors that do not affect prognosis are age, number of tumors, glands involved, and the type of surgery (unless incompletely resected). Philibert et al. (2003) found the prognosis of malignant tumors based on histologic type was a median survival time (MST) of 2.5 months for anaplastic carcinoma vs. 21 months for adenocarcinoma. When comparing histologic grade of canine mammary tumors, 81% of dogs with noninvasive malignant tumors were free of disease 2 years after surgery, compared to only 3% of those with vascular or lymphatic invasion (Chang et al. 2005). Chang et al. (2005) also found that dogs with lymph node-positive disease or distant metastases had an MST of 6 months compared to greater than 80% alive at 2 years for dogs with no evidence of metastases. In this study tumors greater than 5 cm, or present longer than six months, had a higher incidence of spread to regional lymph nodes. Szczubial and Lopuszynski (2011) showed that dogs with lymph node-positive disease had an average survival time of 6-8 months compared to >18 months if lymph nodes were clear. In a recent paper of 94 dogs with malignant mammary tumors, independent predictors of survival time were clinical stage, lymphatic invasion, ulceration, and completeness of surgical margins. MSTs for patients with lymphatic invasion was 179 days vs. 1098 without, presence of ulceration was 11 days vs. 443 days without ulceration, complete surgical margins were 1098 days vs. 68 days for those without clean margins (Tran et al. 2016). Completeness of margins was still signi icant with patients with lymphatic invasion, reinforcing the role of surgery as the mainstay of treatment for canine mammary tumors. In Chocteau et al.’s (2019a) study, a histological staging system was used where histopathological size, stromal invasion, lymphovascular invasion, and lymph node assessment were used. In this cohort of 433 dogs, stage 0 was carcinoma in situ, and MST was not reached. Stage 1 was a tumor 1700

days. Stage 2 were tumors >2 cm but no lymphovascular invasion with MST > 1180 days. Stage 3a is tumor 2 cm, lymphovascular invasion and MST 163 days. This histological grading system was signi icant for tumor recurrence and survival time. In this study, the completely excised tumor rate was only 58%. The probability of death within 1 year was 3% for carcinoma in situ, 14% for stage 1, 24% for stage 2, 55% for stage 3a, and 68% for stage 3b (Chocteau et al. 2019a).

Adjunct Therapy The role of chemotherapy following surgery for human breast cancer is well established but has still not been fully established in dogs. In a small prospective study of 31 dogs with mammary tumors, 19 received surgery only, and 12 received surgery plus either doxorubicin or docetaxel. There was no statistical difference in survival times between the two groups, although there was a tendency to longer survival in the chemotherapy-treated group (Simon et al. 2006). Large prospective clinical trials are needed to fully establish the role of adjuvant chemotherapy in dogs with malignant mammary tumors. Interestingly, in one study desmopressin improved the disease-free interval and survival time in dogs with malignant mammary gland tumors removed surgically (Hermo et al. 2008). In a study comparing 58 surgically treated dogs with malignant mammary carcinoma to 36 which received surgery and chemotherapy, no statistical improvement in survival time for dogs with lymphatic invasion or lymph node-positive disease was shown with adjuvant chemotherapy (Tran et al. 2016).

Feline Mammary Tumors Surgery Complete unilateral or bilateral mastectomy is the recommended surgical method for the treatment of feline malignant mammary tumors as it signi icantly reduces the chance of local recurrence and provides the best survival (MacEwen et al. 1984; Novosad et al. 2006; Gemignani

et al. 2018). This technique is the method of choice regardless of the size of the tumor. Currently available data support performing a complete bilateral mastectomy in all cats (Novosad et al. 2006; Geminagni 2018). The inguinal lymph nodes are routinely removed with the gland 4 (most caudal glands; cats have four glands in each chain), although the axillary nodes are only removed if enlarged or positive for metastatic spread of the tumor (Figure 10.7). The cat is placed in dorsal recumbency, and the skin of the entire ventral and ventrolateral thorax and abdomen is prepared. A sterile surgical marker is used to delineate the region to be resected, encompassing all skin and subcutaneous tissue around all mammary glands, down to the level of the thoracic and abdominal musculature. If there is tumor adherent to muscle ventrally, this is also removed en bloc with the tumor. Closure is achieved with a continuous or interrupted suture of 3-0 absorbable material in one or two layers and skin closure with 3-0 nonabsorbable material. Use of walking sutures can be helpful closing the mastectomy site to address the tension and to decrease seroma formation (Lopez et al. 2020). A fentanyl patch can be placed 24 hours prior to surgery, and adequate analgesia is provided postoperatively. These cats are often uncomfortable for 24–48 hours after surgery until some degree of skin stretching occurs, and analgesia is extremely important in their postoperative recovery period. Flank fold laps as described above for the dog can also be used for cats. Many cats can have a complete bilateral mastectomy performed as a single procedure, but in some cats, it needs to be staged 3–6 weeks apart where a complete unilateral mastectomy is performed sequentially. Obese cats or cats with very large tumors are typically the ones for which a staged bilateral mastectomy is required. In order to determine before surgery if the bilateral procedure is feasible, the skin lateral to each mammary chain (and 2–3 cm lateral to the tumors) is picked up and pulled toward the ventral midline to see if it meets (this might have to be done under anesthesia in some cats). If the skin lateral to each chain meets on midline, then a bilateral mastectomy as a single procedure can be performed.

Figure 10.7 Bilateral mastectomy in the cat. (a) The cat is placed in dorsal recumbency (cranial toward top of picture), and the skin of the entire ventral and ventrolateral thorax and abdomen is prepared. A sterile surgical marker is used to delineate the region to be resected. (b) All the mammary glands, including skin and subcutaneous tissue around all mammary glands, have been excised. The tumor was adherent to fascia caudally, and fascia was removed en bloc with the tumor (arrow). (c) Closure has been performed by suturing skin over ventral midline. Source: Images courtesy of Dr. Julius Liptak.

OHE and Mammary Tumors OHE confers protection to developing mammary carcinoma in cats (Hayes et al. 1981; Misdorp et al. 1991; Overley et al. 2005). In one study, OHE cats had 0.6 of the relative risk of intact females for developing mammary carcinoma (Hayes et al. 1981) while in another study OHE accounted for a 70% risk reduction for developing mammary carcinoma (Misdorp et al. 1991). Cats spayed prior to 6 months of age had a 91% reduction in the risk of mammary carcinoma

development compared with intact cats. Those spayed prior to 1 year had an 86% reduction in risk (Overlay et al. 2005).

Histologic Tumor Types and Prognosis In one study of complete mastectomy, complications occurred in 19.7% of cats treated with unilateral mastectomy, 35.7% of cats treated with staged bilateral mastectomy, and 40.6% of cats treated with singlesession bilateral mastectomy. Complications were signi icantly more likely to occur in cats undergoing bilateral (staged and single session) vs. unilateral mastectomy (Gemignani et al. 2018). However, the difference in complication rates between single session bilateral mastectomy and staged bilateral mastectomy was not signi icant. Complications included infection, dehiscence, seroma, abdominal hernia, respiratory distress, seizure, and esophageal stricture. Two cats died in the immediate postoperative period; 1 cat experienced cardiac arrest after unilateral mastectomy, and one cat experienced respiratory failure attributed to excessive wound closure tension after singlesession bilateral mastectomy (Gemignani et al. 2018). Feline mammary tumors are malignant in over 85% of cases, with the majority being adenocarcinoma. A histological grading system of 1-3 indicates welldifferentiated, moderately differentiated, and poorly differentiated disease. Tumor size and lymphatic invasion are prognostic factors that consistently affect survival time for feline mammary tumors (MacEwen et al. 1984; Ito et al. 1996; Hahn and Adams 1997; Viste et al. 2002; Skorupski et al. 2005). In one study, MST without lymphatic invasion was 863 days vs. 195 days for those cats with lymphatic invasion. Cats with tumors greater than 3 cm have reported survival times of 4–12 months, those with 2–3 cm tumors have survival times of 15–24 months, and those smaller than 2 cm have an MST greater than 3 years (Ito et al. 1996; Viste et al. 2002). Two studies demonstrated signi icantly improved survival times with the use of bilateral mastectomy with MST of 917 days vs. 428 days for those with a regional mastectomy and 348 days for unilateral mastectomy (Novosad et al. 2006) and median survival of 1140 days for cats treated with bilateral complete mastectomy vs. 473 days for cats treated with unilateral complete mastectomy (Gemignani et al. 2018). Surgical margins are prognostic for local progression (Gemignani et al. 2018). In

2014, Mills et al. assessed the application of a modi ied histological grading system which included lymphovascular invasion, nuclear form, and a greater variation in mitotic rate. Grade 1 was considered lowgrade carcinoma, grade 2 was intermediate grade, and grade 3 was high-grade carcinoma. Of the 97 cats in this study, tumor diameter was not a signi icant factor overall, though tumor diameter greater than 3 cm was associated with shorter overall survival times. Histological grade was predictive of survival with grade 1 having an MST of 31 months, grade 2 being 14 months, and grade 3 being 8 months. The MSTs of cats with solid or cribriform carcinoma were 8–10 months compared to 21 months for tubulopapillary subtype. Mitotic count (62) and nuclear characteristics were inversely related to survival times. Mitotic index of >62 was associated with MST of 9 months vs. 18 months if 3 ml/kg/min, whereas dogs with one kidney have a GFR >1.5 ml/kg/min (Urie et al. 2007). Serum creatinine concentration can increase post unilateral nephrectomy (mean of 1.22 mg/dl pre vs. 1.66 mg/dl post) and serum phosphorus concentration can decrease but both remain within the normal range in healthy canine kidney donors (Urie et al. 2007). Blood urea nitrogen (BUN) and urine speci ic gravity do not change signi icantly after nephrectomy in healthy kidney donors (Urie et al. 2007). In another study of dogs having a unilateral nephrectomy for renal disease, mean serum creatinine concentration at least six months after nephrectomy was 2.2 mg/dl (Gookin et al. 1996). In total, 43% of dogs became azotemic 17 days to 69 months after the nephrectomy but for each dog, azotemia could be explained on the basis of prerenal factors, progression of preexisting renal disease, or acquired renal disease unrelated to nephrectomy (Gookin et al. 1996). Complications of nephrectomy include oliguria and organ laceration, need for blood transfusion within 24 hours of the surgery, and pancreatitis (Gookin et al. 1996). Serum creatinine concentrations also increase in feline kidney donors but values remain in the normal range on average (1.36 mg/dl pre nephrectomy and 1.71 mg/dl post nephrectomy) (Lirtzman and Gregory 1995). Rarely, tumor extending down the renal vein toward the vena cava is seen during surgery. These “tumor thrombi” are not usually adherent to the vein walls and can be gently milked toward the kidney to allow an encircling ligature to be placed around the renal vein. If the thrombus occupies the full extent of the vein and enters the vena cava, then it can be managed in a fashion similar to an adrenal tumor thrombus extending down the phrenicoabdominal vein (see Chapter 13, endocrine system); that is, a Satinsky clamp can be placed around the

insertion of the renal vein into the vena cava, a venotomy performed at the renal vein–cava junction, and the kidney-renal vein-thrombus complex removed en bloc. The venotomy is then repaired with a simple continuous pattern of 5/0 polypropylene suture.

Histologic Tumor Types and Prognosis Bilateral tumors have been reported at a rate of 4% (Bryan et al. 2006). The kidneys can also be a site of metastasis (e.g. melanoma), so full staging is important. In a study of 82 dogs (Bryan et al. 2006), 49 had carcinomas, 28 had sarcomas, and 5 had nephroblastomas. Although only 16% of dogs had evidence of pulmonary metastasis on thoracic radiographs at diagnosis, 77% had metastatic disease at the time of death. Median survival time for dogs with carcinomas was 16 months (range 0–59 months), for dogs with sarcomas 9 months (range 0–70 months), and for dogs with nephroblastomas 6 months (range 0–6 months). In a report of 14 dogs with renal hemangiosarcoma (Locke and Barber 2006), one dog had pulmonary metastasis at diagnosis, all dogs underwent nephrectomy, and 4 of 14 dogs also received adjunctive chemotherapy. Median survival time of all dogs was 278 days (range 0–1005 days). These results indicated that renal hemangiosarcoma in dogs may have a better prognosis when compared to dogs with hemangiosarcoma in splenic, cardiac, or retroperitoneal locations (Locke and Barber 2006). Leiomyoma of a kidney is a rare diagnosis in dogs (Laluha et al. 2006). In another study of dogs that had nephrectomy for renal cell carcinoma, mitotic index (MI) was found to be an independent prognostic variable (Edmondson et al. 2015). Median survival for dogs with an MI >30 was 187 days compared with 1184 days for dogs with an MI of 10 cm) at the time of diagnosis (Straw et al. 1992; Bray et al. 2014). Survey radiographs usually do not provide suf icient detail to determine the degree of tumor involvement of the pelvic bones to appropriately plan the surgical approach. CT is the preferred imaging modality for pelvic tumors because they provide superior detail and a cross-sectional perspective that aides in planning the surgical approach and resection (Figures 16.15a and b). MRI provides better soft tissue detail and is recommended for preoperative imaging of soft tissue tumors such as injection-site sarcomas and soft tissue sarcomas. A minimum of 2 cm lateral margins and one fascial plane for deep margins has been recommended for most tumors, but wider margins should be considered with more aggressive tumors (e.g. injection site sarcomas where 5 cm lateral margins and two fascial layers for deep margins may provide better local tumor control [Phelps et al. 2011]). MRI can provide better soft tissue detail than CT, but there are no currently studies to determine whether either modality is superior for surgical planning.

Surgical Options Each individual patient will have a unique presentation in terms of tumor type, location, and extent, so the surgical technique will differ

depending on the presentation (Kramer et al. 2008; Bray et al. 2014). In humans, the term “external hemipelvectomy” is used to describe a procedure that also includes amputation of the pelvic limb, while “internal hemipelvectomy” is used when the limb is preserved (Ham et al. 1997; Beck et al. 2008). By using this nomenclature, there are six major categories for hemipelvectomy in the dog (Figure 16.16) (Bray 2014). Total External Hemipelvectomy Total external hemipelvectomy involves removal of the ipsilateral pelvic limb and hemipelvis to the level of the pubic symphysis (Figure 16.16a). The ilial wing is elevated at the sacroiliac junction. Partial sacrectomy (up to one-third of the sacral body) may also be performed if necessary. This may be considered for tumors affecting the ilium, ischium, or pubis where resection of the entire skeletal compartment is necessary. Caudal External Hemipelvectomy Caudal external hemipelvectomy involves removal of the ipsilateral pelvic limb, acetabulum, and ischium wing, extending from just caudal to the sacroiliac joint and medially to the level of the pubic symphysis (Figure 16.16b). This approach preserves a small section of the ilial wing and the site of origin for the sartorius muscle, which is ideal for the closure of the abdominal wall. This approach may be considered for soft tissue tumors located caudal to the femur (e.g. within the lexor muscles) or for peripheral nerve sheath tumors. There is also good access to the entire lumbosacral nerve plexus and intervertebral foramen with this approach. Cranial External Hemipelvectomy Cranial external hemipelvectomy involves removal of the ipsilateral pelvic limb, acetabulum, and ilial wing, extending to the level of the pubic symphysis (Figure 16.16c). This approach is ideal for soft tissue tumors located cranial to the femur (i.e. within the extensor muscles). This approach preserves the site of origin of the semimembranosus and semitendinosus muscles, which may be used for closure of the abdominal defect.

Figure 16.15 (a) Transverse CT images of a hemangiosarcoma of the proximal femur in a dog with extension along the ilium (short blue arrow) and acetabulum (long blue arrow). In this case, the medial osteotomy should be performed at the level of the pubic symphysis (short white arrow). (b) Computed tomography image of low-grade chondrosarcoma (CSA) involving the right ilial wing and ilial body.

Figure 16.16 Hemipelvectomy techniques. External pelvectomy entails amputation of the ipsilateral pelvic limb, whereas internal hemipelvectomy enables functional limb sparing. (a) Total external hemipelvectomy; (b) caudal external hemipelvectomy; (c) cranial external hemipelvectomy; (d) cranial internal hemipelvectomy (iliectomy); (e) caudal internal hemipelvectomy (ischiectomy); (f) middle internal or external hemipelvectomy (acetabulectomy, shown as external version in igure since limb is amputated). Although option B is perhaps the most common technique, consideration of tumor location and local invasiveness are important in surgical planning. Source: Reproduced with permission from Bray, J.P. 2014. Hemipelvectomy: Modi ied surgical technique and clinical experiences from a retrospective study. Vet Surg 43:19–26.

Cranial Internal Hemipelvectomy Cranial internal hemipelvectomy (Figure 16.16d), or iliectomy, is reserved for tumors con ined to the surface of the ilial wing or sartorius muscle. This approach can potentially be performed without requiring

amputation of the pelvic limb, depending on the local extent of the tumor (Oramas et al. 2020). Caudal Internal Hemipelvectomy Caudal internal hemipelvectomy (Figure 16.16e), or ischiectomy, is reserved for tumors con ined to the ischium or semimembranosus and semitendinosus muscles. This approach can potentially be performed without requiring amputation of the pelvic limb, depending on the local extent of the tumor (Gilman et al. 2020). Middle Internal or External Hemipelvectomy Middle internal or external hemipelvectomy, or acetabulectomy, involves removal of the femoral head and acetabulum, often involving amputation of the ipsilateral limb (Figure 16.16f). This approach is best reserved for tumors con ined to the coxofemoral joint without extension into the surrounding tissues. This approach has been described in the cat for management of fracture malunion causing fecal obstipation (Kasa and Kasa 1986). Acetabulectomy can be performed without requiring amputation of the pelvic limb provided the tumor is con ined completely to the coxofemoral joint, though some gait effects may be observed similar to femoral head ostectomy. Acetabulectomy without limb amputation has been reported in dogs for pelvic fractures following trauma (Alexander and Carb 1979).

Surgical Preparation Knowledge of the regional anatomy is essential given the proximity of the pelvic bones to vital structures such as the urethra and rectum. To aid in intraoperative identi ication of these structures, the urethra should be catheterized and the placement of a syringe case into the rectum has been described (Kramer et al. 2008). A purse-string suture should be placed to minimize contamination of the surgical ield. Perioperative intravenous antibiotics should be administered throughout the procedure (cefazolin, 22 mg/kg every 1.5–2.0 hours). Hemipelvectomy is a major surgery with the potential for signi icant hemorrhage (Straw et al. 1992; Bray et al. 2014; Barbur et al. 2015). With the compartmental approach to the dissection described below,

the mid-body transection of muscles is minimized (Bray 2014). Nevertheless, severe hemorrhage requiring transfusion or aggressive volume support may arise despite anatomic knowledge and sound surgical technique being followed due to the proximity to large vessels. Preparation of the patient for a potential blood transfusion should be made prior to surgery by performing a cross-match or blood typing as appropriate for blood bank facilities available in the hospital. Anesthesia management should include consideration for multi-modal preemptive analgesia (Pascoe 2000). This may include systemic opioids, in combination with either morphine and/or lidocaine epidural. Non-steroidal anti-in lammatory drugs may be used at the discretion of the surgeon and patient comorbidities. Local nerve blocks (with bupivacaine) at the time of transection may also be considered. Finally, placement of a wound diffusion catheter may allow the provision of local pain relief in the immediate postoperative period (Abelson et al. 2009). The use of liposome-encapsulated bupivacaine can also be used for prolonged (72 hours) analgesia.

Surgical Technique The goal of surgery should be to complete excise the neoplasm with at least one intact fascial plane about the entire circumference of the tumor. The compartmental approach described allows muscles to be removed en bloc, including their sites of skeletal insertion. This strategy addresses the potential spread of the micro-metastatic satellite nodules contained within an ill-de ined anatomic boundary around the tumor and minimizes the morbidity associated with extensive muscular transection. The following description outlines the dissection necessary for a total external hemipelvectomy or caudal external hemipelvectomy (options A and B). Some extrapolation of the fundamental principles may be required if other variations of hemipelvectomy are required, and close consultation of an anatomic text is usually necessary. Hemipelvectomy is typically performed in lateral recumbency (Figure 16.17a); however, oblique positioning may be helpful for en bloc excision of sciatic nerve root tumors requiring concurrent hemilaminectomy. When making the skin incision, consideration should be given to preserving suf icient

skin for closure without compromising the complete resection of the tumor and for excising biopsy tracts (Figure 16.17b). Medial Dissection The dissection begins medially, with a curvilinear incision extending along the medial thigh from the inguinal fold to the ischium. The sartorius muscle (both cranial and caudal bellies) is transected at the level of the sti le and elevated en bloc from the limb, preserving its attachment on the ilial wing. Penetrating vascular structures are ligated as necessary. Once elevated, the muscle should be wrapped in a salinesoaked swab and retained in the wound. The medial thigh muscles (adductor, gracilis, and pectineus) are incised on the midline down to the level of the pubic symphysis (Figure 16.17c). There is a faint fascial aponeurosis that de ines the midline at this site. The abdominal muscles are incised as they insert on the pubis and retracted cranially, elevating the muscle from the ilial wing until the iliopsoas muscle is visible and the ventral surface of the ilial wing is palpable. The abdominal muscle is retracted cranially from the pubis using self-retaining retractors. The femoral artery and vein are followed to their bifurcation with the external iliac artery and vein, double ligated, and divided. Individual inguinal vascular branches may also need to be ligated. The iliopsoas muscles are then isolated and transected with a scalpel blade. Where possible, this should be performed as close to the tendinous insertion on the femoral neck. The ventral surface of the ilial wing is exposed with periosteal elevators. Lateral Dissection A curvilinear skin incision is now made on the lateral surface of the thigh, joining the previous medial incisions. The skin is elevated proximally to expose the lumbar fascia dorsal to the coxofemoral joint. Dissection now continues caudally around the ischium, between the semitendinosus and ischiocavernous muscles, staying medial to the sacrotuberous ligament. The muscles of the pelvic diaphragm (levator

ani and lateral coccygeus) should be preserved on the medial aspect of the dissection. The super icial gluteal muscle is transected along its length close to its dorsal origin. The lumbar fascia may also be incised cranially to expose the middle gluteal muscle.

Figure 16.17 (a) Intraoperative photograph of dog with a large proximal femoral hemangiosarcoma being treated by total hemipelvectomy. A surgical marking pen outlines at least 3 cm skin margins around the biopsy tract. Not visible from this perspective is the medial aspect, where more skin was preserved for closure. (b) Following the skin incision where a ≥3 cm margin was measured around the biopsy tract and underlying tumor. A urethral catheter is being placed to help identify and protect this structure during the procedure. (c) The musculature originating from the pubic symphysis has been sharply elevated to prepare the osteotomy site on the symphysis (long arrow) with an oscillating saw. A periosteal elevator (notched arrow) has been placed under the anticipated osteotomy site to help protect the underlying urethra. The inset shows the pubic symphysis following osteotomy (short arrow). (d) A wide osteotome is used to disarticulate through the sacroiliac joint taking care not to fracture the sacrum (unless this is intended to obtain a wider surgical margin). (e) The medial aspect of the hemipelvis following disarticulation of the sacroiliac joint. The long arrow points to the osteotomized pubic symphysis, the short arrow to the ilial wing, the white notched arrow the portion of the pubic symphysis remaining with the dog, and the blue notched arrow the abdominal wall. (f) Image of the medial aspect of the excised tumor and associated limb. The large hemangiosarcoma is seen expanding the soft tissues ventral to the pubic symphysis (notched arrow) and the short arrow points to the articular surface of the scaroiliac joint. (g) Postoperative photograph of a dog treated with hemipelvectomy and amputation. Note how the medial skin was preserved (arrow) and lifted dorsally to close the defect. This was done because more extensive lateral skin excision was required to remove a biopsy tract en bloc with the hemipelvectomy. Source: Images courtesy of Dr. Stephen Withrow.

Limb Amputation If a total hemipelvectomy is being performed, the sacrum can be exposed and the ilium elevated by inserting an osteotome at the sacroiliac joint and separating with a mallet (Figure 16.17d). If necessary, a small ventral edge of ilium can be osteotomized to preserve the origin of the previously elevated sartorius muscle so it can

be used for closure. Alternatively, the medial gluteal muscle can be partially elevated to allow the ilium to be osteotomized with an oscillating saw immediately caudal to the sacroiliac joint. The pubic symphysis is osteotomized with an oscillating saw or osteotome and mallet. As the limb is gently elevated from the body, the remaining medial muscle attachments will be exposed and can be carefully incised (Figure 16.17e). The internal obturator muscle may be an important medial barrier for some tumors that have penetrated into the pelvic canal via the obturator foramen (Figure 16.17f). In these cases, care needs to be taken to ensure the tumor capsule is not breached and the internal obturator muscle is removed en bloc with the amputated limb. With the limb free of muscular attachments, it will now be tethered by nerve branches only. These nerves can be transected close to the limb in most cases, but the pudendal nerve branches, which are located more caudally, should be preserved where possible. Prior to transection, the nerve sheath should be injected with a long-acting local anesthetic (e.g. a mixture of lidocaine and bupivacaine or liposomeencapsulated bupivacaine) proximal to the site of transection (Pascoe 2000). For peripheral nerve sheath tumors, transection should be performed a minimum of 2–5 cm proximal to any grossly abnormal tissue. If required, each nerve branch can be traced to the level of the intervertebral foramen at L6, L7, and S1. Closure Prior to closure, the wound should be lavaged and hemostasis checked. The sartorius muscle can be unwrapped from its moist swab and secured to the surrounding tissues to seal the exposed abdomen and pelvic canal. If insuf icient autogenous tissue exists to successfully close the body wall, a prosthetic mesh may be needed. The subcutaneous tissues and skin are then closed routinely (Figure 16.17g). Surgical Variations When tumors originate from the caudal aspect of the pelvis and cross the pubic midline, it may be necessary to perform osteotomies through the obturator foramen on the opposite side to obtain a wide enough

margin. In these cases, greater care must be taken to protect the urethra and rectum from iatrogenic trauma (Bray 2014). Anecdotally, up to a third of the sacrum (through the sacral foramina) can be safely excised if the tumor invades across the sacroiliac joint. However, a limited laminectomy window or pediculectomy should be performed for en bloc excision of nerve root tumors extending into the spinal canal due to the risk of vertebral fracture at this site.

Postoperative Complications Potential complications include hemorrhage and hematoma formation, wound dehiscence, incisional hernia formation, seroma formation, infection, obstipation, pressure point sores, urethral and rectal trauma or dysfunction, and tumor recurrence (Straw et al. 1992; Kramer et al. 2008; Bray et al. 2014; Barbur et al. 2015). However, complications are usually infrequent. Postoperative recovery is similar to pelvic limb amputations and is typically associated with few concerns (Alexander and Carb 1979; Kasa and Kasa 1986; Straw et al. 1992; Kramer et al. 2008; Bray et al. 2014; Barbur et al. 2015).

Functional Outcome Clinical function following hemipelvectomy should be similar to that following pelvic limb amputation and is in luenced by the patient size, itness, and agility. Larger patients may bene it from some supportive walking for the irst three to four days until they gain con idence and coordination (Alexander and Carb 1979; Kasa and Kasa 1986; Straw et al. 1992; Kramer et al. 2008; Bray et al. 2014).

Cosmetic Outcome The cosmetic results for hemipelvectomy are also similar to pelvic limb amputation. In cases where the ischiatic tuberosity is preserved, it may be optimal to leave some muscular tissue and its nerve supply intact to prevent the development of a decubital ulcer. Similarly, because the scrotum will become exposed and subject to trauma, castration at the time of surgery is recommended (Bray et al. 2014).

Prognosis The outcome for dogs following hemipelvectomy is similar to that expected for the histological diagnosis of the tumor, as reported elsewhere in this chapter, with some distinctions. In one study, the median survival times for chondrosarcoma (1232 days), osteosarcoma (533 days), and soft tissue sarcoma (373 days) were not statistically different, with high rates of local tumor recurrence or metastatic disease impacting long-term outcome for all malignant tumors (Bray et al. 2014). Metastatic disease was a common cause of death after hemipelvectomy, occurring in 47% of 83 dogs. The 12-month survival rate was approximately 50% for dogs with malignant mesenchymal tumors (i.e. hemangiosarcoma, osteosarcoma, chondrosarcoma, soft tissue sarcoma, etc.). On multivariate analysis, there were no factors of signi icance that were predictive of improved survival or disease-free interval (Bray et al. 2014). There is limited data on the survival of cats following hemipelvectomy (Straw et al. 1992; Bray et al. 2014). The outcomes for 16 cats were reported in one study (Bray et al. 2014), with cats having a signi icantly longer survival time compared to dogs and a 75% 1-year survival rate. No statistical difference in survival was found between cats with chondrosarcoma, osteosarcoma, and soft tissue sarcoma, but the individual numbers of each tumor type were low. Clean resection margins were associated with statistically signi icant improved mean survival time (1965 days compared to 198 days). Metastatic disease was less common than in the dog, developing or being suspected in only 12.5% of cats, both with osteosarcoma. The median disease-free interval for local recurrence for all tumor types was 105 days (Bray et al. 2014).

Scapulectomy Applicable Tumors and Patient Selection Osteosarcoma is the most common tumor of the scapula in dogs, accounting for up to 75% of all scapular tumors and 13% of all axial OSA (Liu et al. 1977; Knecht and Priester 1978; Heyman et al. 1992;

Hammer et al. 1995; Dickerson et al. 2001; Montinaro et al. 2013). Chondrosarcoma, FSA, HSA, and liposarcoma have also been reported to involve the scapula (Liu et al. 1977; Sylvestre et al. 1992; Kirpensteijn et al. 1994; Trout et al. 1995; Erdem and Pead 2000; Norton et al. 2006; Montinaro et al. 2013). Lameness is the most common presenting sign, while a visible swelling is evident in up to 33% of dogs (Montinaro et al. 2013). Radiographic changes are consistent with other bone tumors, with a mixed pattern of lytic and productive changes most common (Figures 16.18(a and b) (Kirpensteijn et al. 1994). However, due to positioning dif iculties and superimposition of the body wall, the extent of the disease may be dif icult to determine. In these cases, CT (Figure 16.19a) or nuclear scintigraphy (Figure 16.19b) are useful for determining the location and extent of scapular involvement. In addition, a concurrent CT scan of the thoracic cavity can be performed for evaluation of pulmonary metastasis (Waters et al. 1998; Nemanic et al. 2006; Eberle et al. 2011; Armbrust et al. 2012).

Figure 16.18 (a) and (b) The radiographic changes in dogs with primary tumors of the scapula are consistent with other bone tumors. Note the mixed pattern of lytic and blastic changes in the proximal scapula in both of these dogs with an osteosarcoma of the scapula (yellow arrows). Computed tomography is preferred for imaging the scapula because positioning and superimposition of the body wall and soft tissues can make interpretation of radiographs of the scapula dif icult.

Figure 16.19 (a) A CT scan of a dog with a primary osteosarcoma of the scapula (yellow arrow). Computed tomography scans provide more detailed information than radiographs regarding the degree of bone involvement, extension into adjacent soft tissues, and surgical planning. An additional advantage is that helical CT scans are more sensitive for the detection of pulmonary metastases than high-detail three-view thoracic radiographs. (b) Nuclear scintigraphy of a dog with a primary scapular osteosarcoma (yellow arrow). Note that the tumor extends to the glenoid and hence partial scapulectomy is not possible. Nuclear scintigraphy can be used for both surgical planning (to determine surgical whether partial or total scapulectomy is indicated, and surgical margins if partial scapulectomy is possible) and to scan for secondary metastatic or synchronous bone lesions. A bone biopsy is rarely indicated for de initive diagnosis prior to surgery because the vast majority of scapular tumors are malignant and knowledge of tumor type will not change the surgical approach. However, the prognosis for scapular OSA and HSA is guarded and adjuvant chemotherapy is recommended for both of these scapular tumors (Kirpensteijn et al. 1994; Trout et al. 1995; Erdem and Pead 2000; Norton et al. 2006). A ine needle aspirate, core aspirate, or bone biopsy should be performed if the tumor type will change the willingness of the owner to pursue curative-intent treatment because of either a poorer prognosis or the need for adjuvant chemotherapy.

As described previously, clinical staging tests include high-detail threeview thoracic radiographs, and preferably breath-hold thoracic helical CT scans for evaluation of pulmonary metastasis (Waters et al. 1998; Wrigley 2000; Nemanic et al. 2006; Eberle et al. 2011; Armbrust et al. 2012), and whole-body bone scintigraphy or survey radiographs for bone metastasis (LaRue et al. 1986; Forrest and Thrall 1994; Jankowski et al. 2003; Dernell et al. 2007; Montinaro et al. 2013). Scapulectomy is not recommended if there is evidence of distant metastasis.

Preoperative Margin Assessment Scapular tumors should be resected with a minimum of 3 cm margins (Trout et al. 1995). The extent of bone tumor involvement is most accurately determined using CT scans (Figure 16.19a) (Davis et al. 2002; Sugiura et al. 2002; Karnik et al. 2012), while this involvement is overestimated by radiographs, nuclear scintigraphy (Figure 16.19b), and MRI (Leibman et al. 2001; Davis et al. 2002; Wallack et al. 2002). The use of imaging techniques that overestimate the degree of bone involvement may be preferable because complete resection of the bone tumor is more likely (Leibman et al. 2001). CT scans and/or nuclear scintigraphy are recommended for determining surgical margins because both imaging modalities are also used in the diagnosis and clinical staging of dogs with scapular tumors.

Surgical Technique Subtotal (or partial) or total scapulectomy is recommended for the surgical treatment of non-metastatic scapular tumors. Limb amputation is an alternative to scapulectomy, but scapulectomy is preferred because limb function can be preserved. Scapulectomy is performed through a lateral approach to the scapular spine. If a biopsy has been performed, then the biopsy tract should be excised en bloc with the bone tumor and all involved soft tissues. The trapezius and omotransversarius muscles are dissected close to their origins on the scapula, as are the acromial and spinous heads of the deltoideus muscle, but greater margins may be required depending on the location of the tumor (Kirpensteijn et al. 1994; Trout et al. 1995; Montinaro et al. 2013). The scapula is retracted laterally to permit deep dissection of

the serratus ventralis muscle from the medial surface of the scapula. The brachial plexus and axillary artery and vein should be preserved during deep dissection. If required, the suprascapular and subscapular nerves are identi ied, infused with 0.2–0.5 ml of bupivacaine, and then transected (Kirpensteijn et al. 1994). For subtotal scapulectomy, the infraspinatus, supraspinatus, and subscapularis muscles are tranescted at the level of the planned osteotomy (Montinaro et al. 2013). For total scapulectomy, the coracobrachialis, teres minor, infraspinatus, supraspinatus, and subscapularis tendons are then transected from their insertions on the humerus (Kirpensteijn et al. 1994; Montinaro et al. 2013). The teres major and long head of the triceps muscles are incised from their insertions on the caudal scapula (Kirpensteijn et al. 1994; Montinaro et al. 2013). For subtotal scapulectomy, an osteotomy is performed at or proximal to the scapular neck to preserve the glenoid cavity and origin of the biceps tendon (Figures 16.20 and 16.21a). The osteotomy should be performed a minimum of 3 cm from the distal aspect of the tumor, as determined by bone scintigraphy or CT scans. For total scapulectomy, the glenohumeral joint capsule is incised and disarticulated. The scapula is then removed with the attached infraspinatus, supraspinatus, and supscapularis muscles (Figures 16.21b and c) (Kirpensteijn et al. 1994; Trout et al. 1995; Montinaro et al. 2013). For dogs treated with total scapulectomy, limb function may be improved by tenodesis of the biceps tendon to the proximal humerus with either bone screws or mattress sutures to the remaining joint capsule (Figure 16.22) (Kirpensteijn et al. 1994).

Figure 16.20 A distal scapular osteotomy (arrow) for partial scapulectomy has been performed with an oscillating saw in a dog with a scapular osteosarcoma. The osteotomy should be performed a minimum of 3 cm distal to the distal aspect of the tumor, as determined by CT scans or nuclear scintigraphy.

Figure 16.21 Postoperative specimens following partial scapulectomy (a) and total scapulectomy ([b], lateral aspect, and [c], medial aspect with the subscapularis muscle incised to expose the osteosarcoma lesion). Following partial scapulectomy, the omotransversarius, trapezius, serratus ventralis, and rhomboideus muscles can be attached to the distal aspect of the remaining scapula with nonabsorbable suture material through predrilled holes on the edge of the scapula segment (Kirpensteijn et al. 1994; Montinaro et al. 2013). Alternatively, the supraspinatus, infraspinatus, deltoid, and long head of the triceps can be sutured to the serratus ventralis, omotransversarius, and trapezius muscles without direct attachment to the scapular segment (Figures 16.23a and b) (Kirpensteijn et al. 1994; Trout et al. 1995; Montinaro et al. 2013). This is done so that the muscles cover the scapular segment and minimize dorsal displacement of the scapula during weight bearing on the limb. A closed-suction drain can be used in the subcutaneous space (Trout et al. 1995), but is rarely indicated because seroma formation is an uncommon postoperative complication. The subcutaneous tissue and skin are closed routinely.

Figure 16.22 Tenodesis of the biceps tendon to the proximal humerus has been performed with a screw and spiked washer following total scapulectomy. Although the effect of this is unknown, tenodesis may improve postoperative lameness in dogs following total scapulectomy.

Figure 16.23 (a) The soft tissue defect following partial scapulectomy. (b) The defect has been closed primarily with apposition of the supraspinatus, infraspinatus, deltoid and long head of the triceps to the serratus ventralis, omotransversarius and trapezius muscles. Following total scapulectomy, the long head of the triceps muscle is sutured over the humeral head to the deltoid, omotransversarius, and trapezius muscles (Kirpensteijn et al. 1994; Montinaro et al. 2013). The trapezius muscle is sutured to the serratus ventralis muscle (Kirpensteijn et al. 1994; Trout et al. 1995; Montinaro et al. 2013). The subcutaneous tissue and skin are closed routinely.

Cosmetic and Functional Outcome The postoperative outcome following scapulectomy improves with time. In a report of 42 dogs treated with partial to total scapulectomy, there was no difference in limb use between dogs treated with partial, subtotal, and total scapulectomy (Montinaro et al. 2013). Increasing

body weight had a signi icant negative effect on limb use in the irst 14 days, but not at later time intervals (Montinaro et al. 2013). Analgesia and physiotherapy are important to maximize postoperative recovery and ameliorate lameness following both subtotal and total scapulectomy. In one study, the proportion of dogs with good to excellent limb function improved with time and physiotherapy with 22% of dogs having good to excellent limb function at 2 weeks, 39% at 1 month, 72% at 2 months, and 100% at 3 months (Montinaro et al. 2013). In other studies, the extent of scapulectomy affected the degree of postoperative lameness with postoperative limb use less predictable following total scapulectomy (Kirpensteijn et al. 1994) and recovery times are subjectively longer in comparison to subtotal scapulectomy. Limb use is often good to excellent for dogs treated with subtotal scapulectomy because the scapulohumeral joint is stabilized by the preservation of the acromial head of the deltoid muscle and distal portions of the infraspinatus and supraspinatus muscles, and the range of motion of the shoulder is maintained by the brachiocephalicus and latissimus dorsi muscles (Kirpensteijn et al. 1994; Trout et al. 1995; Erdem and Pead 2000; Norton et al. 2006). For these reasons, total scapulectomy should only be performed in cases where the tumor involves the distal scapula or where adequate surgical margins cannot be attained without excision of the glenoid (Kirpensteijn et al. 1994).

Prognosis In one study of 42 dogs treated with scapulectomy for various primary tumors of the scapula, the overall disease-free interval was 204 days and the median survival time was 246 days (Montinaro et al. 2013). Local tumor recurrence was either con irmed or suspected in 3 dogs (7%) and pulmonary metastasis was diagnosed in 67% of dogs followed up with three-view thoracic radiographs (Montinaro et al. 2013). The only identi ied prognostic factor was the administration of adjuvant chemotherapy, where median survival times were 107 dogs for dogs treated with surgery alone and 269 days for dogs treated with surgery and chemotherapy (Montinaro et al. 2013). The median survival times for dogs with OSA, CSA, and STS were 246 days, not reached (with a mean survival time of 108 days), and 413 days, respectively (Montinaro et al. 2013). In other smaller studies,

individual survival times were usually greater than 2 years for dogs with scapular CSA (Heyman et al. 1992; Kirpensteijn et al. 1994; Hammer et al. 1995; Trout et al. 1995; Erdem and Pead 2000; Dickerson et al. 2001; Norton et al. 2006). Scapular OSA has similar biologic behavior to other appendicular OSA with a high metastatic rate, and hence adjuvant chemotherapy is recommended (Heyman et al. 1992; Hammer et al. 1995).

Ulnectomy Applicable Tumors and Patient Selection Osteosarcoma is the most common tumor of the ulna in dogs (Straw et al. 1991a; Liptak et al. 2004a; Sivacolundhu et al. 2013). Lameness is the most common presenting sign (Straw et al. 1991a). Radiographic changes are consistent with other bone tumors, with a mixed pattern of lytic and productive changes most common (Figure 16.24a) (Straw et al. 1991a; Sivacolundhu et al. 2013). The majority of ulnar sarcomas are located in the distal aspect of the ulna, but the central and proximal third of the ulna can also be involved (Sivacolundhu et al. 2013).

Figure 16.24 (a) Lateral preoperative radiograph of a dog with an osteosarcoma in the distal ulna (arrow). (b) Immediate postoperative lateral radiograph following partial ulnectomy. Note that the styloid process has been resected and no reconstruction was required. This dog was clinically sound the day following ulnectomy. (c) Intraoperative photo of a dog with a distal ulnar osteosarcoma following osteotomy 3 cm proximal to the most proximal extent of the tumor (arrow); UL, ulnaris lateralis. (d) The tendon of the ulnaris lateralis muscle has been retracted to allow disarticulation of the styloid process from the ulnar notch (UN) of the distal radial metaphysis and removal of the ulnar bone segment. A bone biopsy is rarely indicated for de initive diagnosis prior to surgery because the vast majority of ulnar tumors are malignant and knowledge of tumor type will not change the surgical approach. However, a ine needle aspirate, core aspirate, or bone biopsy should be performed if the tumor type will change the willingness of the owner to pursue curative-intent treatment because of either a poorer prognosis with a malignant tumor or the need for adjuvant chemotherapy for OSA.

As described previously, clinical staging tests include high-detail threeview thoracic radiographs and preferably breath-hold thoracic helical CT scans for evaluation of pulmonary metastasis (Waters et al. 1998; Wrigley 2000; Nemanic et al. 2006; Eberle et al. 2011; Armbrust et al. 2012), and whole-body bone scintigraphy or survey radiographs for bone metastasis (LaRue et al. 1986; Forrest and Thrall 1994; Jankowski et al. 2003; Dernell et al. 2007; Montinaro et al. 2013).

Preoperative Margin Assessment Ulnar tumors should be resected with a minimum of 3 cm margins (Trout et al. 1995). The extent of bone tumor involvement is most accurately determined using CT scans (Davis et al. 2002; Sugiura et al. 2002; Karnik et al. 2012), while this involvement is overestimated by radiographs, nuclear scintigraphy, and MRI (Leibman et al. 2001; Davis et al. 2002; Wallack et al. 2002). The use of imaging techniques that overestimate the degree of bone involvement may be preferable because complete resection of the bone tumor is more likely (Leibman et al. 2001). CT scans and/or nuclear scintigraphy are recommended for determining surgical margins because both imaging modalities are also used in the diagnosis and clinical staging of dogs with ulnar tumors. Evidence of radial involvement should be carefully evaluated. While this is rare (Sivacolundhu et al. 2013), involvement of the adjacent radius would necessitate either curative-intent treatment options (such as forequarter amputation, traditional limb-sparing surgery, or stereotactic radiosurgery) or conversion to palliative options (such as palliative radiation, bisphosphonates, and/or analgesic drugs).

Surgical Technique Ablative limb-sparing surgery of the ulna can also be performed successfully provided the tumor is located in the mid-to-distal part of the bone (Figure 16.24a) (Straw et al. 1991a; Liptak et al. 2004b; Sivacolundhu et al. 2013). Ulnectomy can be performed without subsequent reconstruction of the ulna (Figure 16.24b) (Straw et al. 1991a; Liptak et al. 2004b; Sivacolundhu et al. 2013). A lateral approach is made to the ulna. The soft tissues, including the tendons of

the lateral digital extensor and ulnaris lateralis muscles, are preserved if there is no evidence of adhesions or invasion. The lateral digital extensor and ulnaris lateralis muscles are retracted cranially and caudally, respectively, to expose the ulna. The ulna is osteotomized a minimum of 3 cm from the proximal (or, if appropriate, distal) extent of the tumor, as determined by preoperative imaging or the gross tumor, whichever is greater (Figure 16.24c). Care is taken not to score the radius during ulnar osteotomy as radial fractures have resulted from such scoring. For distal tumors, it is often necessary to remove the entire styloid process. In these cases, disarticulation of the styloid process from the ulnar notch of the radius (Figure 16.24d) or removal of a portion of the ulnar notch on the lateral aspect of the radial metaphysis, without entering the radiocarpal joint, is required for removal of the ulnar bone segment. This should be done carefully as an iatrogenic intraoperative fracture is possible. Despite the disruption of the lateral collateral ligament, stabilization is typically not required following resection of the styloid process in dogs (Figure 16.24b) (Straw et al. 1991a; Sivacolundhu et al. 2013). However, in cats, excision of the styloid process results in disruption of the carpal joint, and either prosthetic reconstruction of the lateral collateral ligament or pancarpal arthrodesis is required following distal ulnar resections. If the proximal ulnar osteotomy must be performed proximal to the interosseous ligament, then stabilization of the remaining proximal ulna to the radius is necessary to prevent distraction of the proximal ulna by the triceps muscles during ambulation or radial head luxation. This is typically achieved by placing cortical bone screws from the ulna to the radius in a caudal-to-cranial direction or, alternatively and preferentially, cerclage wires can be used. Screws engaging the ulna and radius are prone to backing out or breaking. A bone tunnel can be created in the ulna from lateral to medial, at the same level of just distal to the radial head, and the wire is passed through the bone tunnel instead of going around the ulna caudally. This helps prevent the wire from slipping. Forequarter amputation or stereotactic radiosurgery may be required for proximal ulnar tumors.

Cosmetic and Functional Outcome

The postoperative outcome following ulnectomy is usually very good to excellent with near-normal to normal limb use in the author’s experience.

Prognosis In one study of 12 dogs with ulnar OSA treated with ulnectomy, the local recurrence rate was 63.5% and the median survival time was 8.5 months (Straw et al. 1991a). In a more recent study, the median disease-free interval was 437 days and the median survival time was 463 days (Sivacolundhu et al. 2013). No dog developed local recurrence in this latter study and 50% of the 30 dogs developed metastasis to the lungs and/or other bone. The only prognostic factor was histologic subtype, where dogs with telangiectatic OSA had a signi icantly decreased median survival time (208 days compared to 463 days) (Sivacolundhu et al. 2013).

Limb‐sparing Surgery Applicable Tumors and Patient Selection Limb-sparing candidates are dogs that are either not suitable for amputation (such as a dog with neurologic disease or severe clinical orthopedic disease) or, more commonly, have an owner who declines amputation (Straw and Withrow 1996; Dernell 2003; Liptak et al. 2004b; Dernell et al. 2007). Clinical staging tests include palpation and possibly aspiration of the regional lymph nodes, high-detail three-view thoracic radiographs or breath-hold thoracic helical CT scans for evaluation of pulmonary metastasis (Waters et al. 1998; Wrigley 2000; Nemanic et al. 2006; Dernell et al. 2007), and whole-body bone scintigraphy for bone metastasis (LaRue et al. 1986; Forrest and Thrall 1994; Jankowski et al. 2003; Dernell et al. 2007) or PET/CT. Dogs with non-metastatic appendicular primary bone tumors are candidates for limb-sparing surgery. However, only tumors in the distal radius are readily amenable to limb salvage because orthopedic function following pancarpal arthrodesis is usually good (Dernell 2003; Lesser 2003). Limb-sparing

surgery is not frequently performed for tumors in other locations because of poor postoperative orthopedic function following arthrodesis of joints, such as the shoulder, hock, and sti le (Huber et al. 1998; Kuntz et al. 1998a; Lesser 2003). However, limb salvage for proximal tibial, distal femoral, and proximal femoral tumors may become more commonplace as total sti le and total hip replacement techniques are adapted for oncologic surgery and joint preservation (Liptak et al. 2005b). Finally, good limb-spare candidates should have irm tumors with a de inable soft tissue compartment, minimal extension into adjacent soft tissues, no evidence of a pathologic fracture, and less than 50% of the length of the bone involved (Figure 16.25) (Straw and Withrow 1996; Dernell 2003; Liptak et al. 2004b; Dernell et al. 2007). Furthermore, they should have no evidence of pyoderma and have good cardiac, renal, and bone marrow function. Dogs with ill-de ined and edematous adjacent soft tissue are less ideal candidates, particularly those with 360° involvement (Figures 16.26a and b). Pathologic fracture is a relative contraindication for limb-sparing surgery, particularly if minimally displaced, because the dispersement of tumor cells into the surrounding tissues may increase the risk of local tumor recurrence (Dernell 2003; Liptak et al. 2004b; Dernell et al. 2007). However, one study concluded that pathologic fractures did not increase the risk of local recurrence, but this was based on a small number of cases (Mitchell et al. 2016), and the role of local chemotherapy and/or adjunctive radiation therapy in minimizing the risk of local tumor recurrence needs to be de ined.

Figure 16.25 Photograph of a Great Dane considered a good candidate for limb-sparing surgery. On palpation the lesion was irm, well-de ined with minimal involvement of the surrounding soft tissue structures. The two small black arrows point to biopsy stab incisions used to obtain needle core biopsies on the medial aspect of the limb. The white arrow on the lateral aspect points to the mildly expansile lesion in the distal radial metaphysis.

Preoperative Margin Assessment Primary appendicular bone tumors are usually con ined to the tumor pseudocapsule, and a marginal excision is usually adequate to completely dissect the tumor away from the surrounding skin. Other soft tissue, such as muscle bellies and tendons, should be resected with 2–3 cm margins if possible (Dernell 2003; Liptak et al. 2004b; Dernell et al. 2007). Margins of bone should be a minimum of 3 cm when excising the bone segment (Dernell 2003; Liptak et al. 2004b; Dernell et al. 2007). The extent of tumor involvement in the bone can be assessed by survey radiographs, nuclear scintigraphy, CT, or MRI scans.

Figure 16.26 Lateral (a) and caudal (b) aspect of the distal radius of a poor candidate for limb-sparing surgery. Note the edematous, circumferential nature of the lesion in the surrounding soft tissues.

Figure 16.27 Craniocaudal radiographic image of a good candidate for limb-sparing surgery of the distal radius. The lesion is relatively small, well-de ined and there is no evidence of intra-articular involvement, pathologic fracture, or proximal intramedullary extension beyond 50% of the length of the bone. There is a discrepancy in the literature whether radiography underestimates or overestimates the proximal extent of distal radial OSA lesions in dogs (Figure 16.27) (King et al. 1980; Parchman et al. 1989; Lamb et al. 1990; Leibman et al. 2001). Nuclear scintigraphy overestimates the degree of tumor involvement by up to 14% (Figures 16.28a and b) (Leibman et al. 2001; Wallack et al. 2002). CT scans also overestimate the intramedullary extent of tumors by up to 27% (Davis et al. 2002; Wallack et al. 2002; Karnik et al. 2012). MRI is useful for determining the intramedullary extent of tumors on T1-weighted images and overestimate this involvement by only 3%, and soft tissue involvement with contrast-enhanced images (Figure 16.29) (Wallack et al. 2002). Overestimation of the proximal extent of the tumor may decrease the risk of incomplete excision, but it also may incorrectly exclude a dog as a suitable candidate for limb-sparing surgery if the extent of tumor involvement exceeds 50% of the length of the bone (Leibman et al. 2001).

Surgical Technique Tumor Resection A full limb preparation is performed including clipping the entire foot. A strict aseptic technique is practiced for the duration of the procedure. Intravenous antibiotics (cefazolin, 22 mg/kg) are administered at least 60 minutes prior to the time of skin incision (Hagen et al. 2020), every 1.5–2 hours throughout the procedure, and then every 6–8 hours for the next 24 hours (Dernell 2003; Dernell et al. 2007). The limb is covered with a barrier such as a stockinette, iodinated adhesive dressing, or a combination of the two to minimize contact with the skin. It is important to have a team of surgeons and technicians that can work together to perform the procedure in an ef icient manner, adhering to strict aseptic techniques.

Figure 16.28 (a) Nuclear scintigraphy of the same dog as in Figure 16.27. Note the compact nature of the lesion con ined to the metaphyseal portion of the bone. (b) Nuclear scintigraphy of a dog deemed a poor candidate for limb-sparing surgery of the distal radius. Although scintigraphy may overestimate the extent of tumor in iltration in the bone, increased uptake of technetium can be seen extending into the proximal third of the bone which raises concern for the ability to resect the tumor with complete margins while preserving suf icient radius for bony reconstruction using standard orthopedic principles. The normal position of an osteotomy in the mid-radius is indicated by an arrow.

Figure 16.29 A T1 sagittal magnetic resonance image of a canine osteosarcoma in the distal radial metaphysis (white arrowhead). The short arrow points to the transition between pathologic (left of the arrow) and normal (right of the arrow) intramedullary tissue within the radius. The long arrow points to normal fatty bone marrow which has a white appearance on the T1 image. The notched arrow is pointing to the ulna. The dog is positioned in either lateral or dorsal recumbency. A cranial, craniolateral, or craniomedial approach is performed from the level of the elbow joint to the metacarpophalangeal joint centered over the third metacarpal distally (Dernell 2003; Dernell et al. 2007). The cephalic vein should be carefully preserved (Figure 16.30a) (Dernell et al. 2007). If a preoperative biopsy has been performed, the biopsy site is excised en bloc with the bone segment (Dernell 2003; Liptak et al. 2004b; Dernell et al. 2007). With the craniolateral approach, the deep antebrachial fascia is incised between the external carpi radialis and common digital extensor muscles, and these muscles are retracted with Gelpi retractors to expose the diaphysis of the radius and supinator and pronator muscles. These latter muscles are elevated from the proximal radius with a periosteal elevator because the limb-sparing plate usually extends on to the proximal aspect of the radius (Dernell 2003).

The dissection is continued distally to elevate the skin away from the distal radius and ulna. This peritumoral dissection is performed with great care using a combination of sharp and blunt dissection outside the tumor pseudocapsule and attempting to leave a thin layer of normal subcutaneous tissue with the tumor (Figure 16.30b) (Dernell 2003; Liptak et al. 2004b). The tumor pseudocapsule is often identi iable by the abnormal tissue color and increased vascularity from tumor vessels over the stretched fascia. The origin of the abductor pollicus longus muscle and the involved extensor muscles (extensor carpi radialis, common digital extensor, lateral digital extensor ± ulnaris lateralis) are transected at the level of the planned osteotomy site (Dernell 2003; Dernell et al. 2007). If necessary, transection of all four extensor muscles can be performed without compromising limb function; however, preservation of at least the ulnaris lateralis muscle is recommended to preserve some soft tissue adjacent to the implant. A transverse arthrotomy is then performed with the antebrachiocarpal joint in a lexed position (Figure 16.30c). The joint capsule margin should be maximized distally by incising the joint capsule closer to the radiocarpal bone than the distal radius (Dernell 2003; Dernell et al. 2007). Following the transverse arthrotomy, the articular surface of the distal radius should be inspected for evidence of pathologic fracture (Figure 16.30d). If there is evidence of a pathologic fracture, then conversion of the surgery into a limb amputation should be considered because the risk of local tumor recurrence may be increased. Alternatively, the radiocarpal, ulnar carpal, and a portion of the accessory carpal bone can be removed to obtain a wider distal margin. If there is no evidence of pathologic fracture, the arthrotomy is extended laterally to the level of the ulna and then medially to divide the medial collateral ligament (Figures 16.30c and e). This necessitates transection of the extensor carpi radialis tendon at its insertion distally. With a sharp osteotome and mallet, a small portion of the medial aspect of the ulna is shaved off in a distal-to-proximal direction (the lateral two-thirds of the distal ulna is preserved while the medial third of the distal ulna is resected with the radius to minimize the risk of local tumor recurrence) (Dernell 2003; Dernell et al. 2007). If the ulna is to be resected en bloc with the radius, then the joint capsule incision continues laterally, and the lateral collateral ligament is divided.

Figure 16.30 (a) The cephalic vein (arrow) should be preserved if possible to maintain venous drainage from the distal limb and minimize the risk of postoperative complications. (b) An intraoperative photograph showing marginal excision along the tumor pseudocapsule (arrow) and an osteotomy of the proximal radius a minimum of 3 cm distant to the proximal extent of the osteosarcoma based on preoperative imaging studies (arrowhead). Wider soft tissue margins are preferable if possible, especially of biopsy tracts, but this is not always possible. (c) A transverse arthrotomy is performed with the antebrachiocarpal joint in a lexed position (cadaver specimen, limbsparing course, University of Missouri. Source: Image courtesy of Dr. Jimi Cook). (d) A pathologic fracture through the distal radial articular surface (arrow). The joint should be inspected for such lesions, and, if present, conversion to limb amputation should be considered because of the increased risk of tumor cell seeding and local tumor recurrence. Source: Image courtesy of Dr. Charles Kuntz. (e) Intraoperative photograph of a distal radial osteosarcoma following a marginal dissection around the visible portion of the tumor (arrowhead). Great care was taken to insure that the tumor pseudocapsule was left intact. Proximal to the tumor, a radial osteotomy is being performed in the mid-diaphyseal portion of the radius (short arrow) with an oscillating bone saw. It is important that the osteotomy is transverse in both the craniocaudal and medial to lateral planes. The disarticulated radial epiphysis is shown by the long arrow. (f) Craniocaudal radiographic projection of an excised distal radial osteosarcoma specimen. The arrowhead points to the proximal radial osteotomy site, the short arrow to the presumptive proximal extent of the tumor, and the small notched arrow points to the articular surface of the distal radius. This specimen was submitted for radiographic interpretation intraoperatively to evaluate the proximal margin in better detail than can be achieved with preoperative radiographs. Once the specimen radiograph has been interpreted to have been excised with a comfortable margin, closure of the tissues is commenced. (g) The radiocarpal (short arrow) and ulnar carpal (notched arrow) bones are osteotomized with either an oscillating or sagittal saw to remove the articular cartilage and provide a lat surface for allograft or endoprosthetic contact.

An incision is then made in the medial fascia caudal to the radius at the approximate level of the planned radial osteotomy site. Digital examination of the tissues caudal to the distal radius is performed to insure an intact tumor pseudocapsule adjacent to the lexor muscles. The osteotomy site in the mid-radius is then determined by measuring the predetermined desired margin from the antebrachiocarpal joint or by holding the implant (e.g. endoprosthesis) over the distal radius as a reference and marking the radius with electrocautery. A transverse osteotomy is performed with an oscillating saw at the desired level of the radial diaphysis (attempting to avoid damage to the caudal

interosseous artery if an ulnar-based limb-salvage technique is to be utilized for reconstruction) (Figure 16.30e). Care should be taken to insure that the osteotomy is truly transverse, as it will determine contact of the implant with the host bone. The fascial dissection is continued along the medial aspect of the bone to the level of the antebrachiocarpal joint, preserving the noncontiguous lexor muscles. Large vessels are ligated or hemoclipped and the caudal joint capsule is transected to complete the disarticulation (Dernell 2003; Dernell et al. 2007). When the distal ulna is removed en bloc with the radius, the level of the ulnar osteotomy is typically performed at the same level of the radial osteotomy. Alternatively, the ulnar osteotomy can be stair-stepped by performing it 2–3 cm distal to the radial osteotomy. The excised tumor containing bone is then submitted for a specimen radiograph to evaluate surgical margins prior to closure (Figure 16.30f) (Dernell 2003; Dernell et al. 2007). A curette or Volkman spoon is then used to collect a marrow sample from the cut edge of the remaining proximal radius for histopathologic evaluation of margins (Dernell 2003; Dernell et al. 2007). The proximal aspect of the radial and ulnar carpal bones is then osteotomized with an oscillating saw to provide a lat surface for the distal aspect of the radial implant (e.g. cortical allograft or endoprosthesis) (Figure 16.30g). A true arthrodesis can be performed by debriding articular cartilage from all of the carpal bones and packing cancellous bone graft into the joint spaces; however, this is now felt to be unnecessary because complete bony fusion is not needed for stable limb function over the life-span of most dogs with appendicular OSA. Cortical Allograft The use of a massive cortical allograft for the reconstruction of the distal radius is historically the most commonly performed technique for limb salvage in dogs and is still preferred by some surgeons (LaRue et al. 1989; Kirpensteijn et al. 1998; Morello et al. 2001; Dernell 2003; Dernell et al. 2007). A transverse osteotomy is performed across the distal aspect of the allograft to remove the articular cartilage and to

create a lat surface to abut the radiocarpal bone (Dernell 2003; Dernell et al. 2007). A second osteotomy is then performed at the proximal aspect of the graft to match the allograft length to that of the radial defect. A curette is used to ream out the marrow cavity in preparation for illing the intramedullary canal with bone cement (polymethylmethacrylate [PMMA]). The limb-sparing bone plate is then temporarily ixed to the cortical allograft with one to two cortical bone screws (one distal and one proximal or one centrally), with the cortical allograft positioned immediately proximal to the distal 3.5/4.5 mm plate hole for the radial carpal bone (Figure 16.31a). The bone screws are then removed and the intramedullary canal of the cortical allograft is illed with amikacin (1000 mg)-impregnated PMMA (Dernell 2003; Dernell et al. 2007). The addition of PMMA signi icantly improves cortical allograft strength and reduces screw loosening (Kirpensteijn et al. 1998). As the PMMA starts to harden, the cortical bone screws are reinserted to secure the limb-sparing bone plate to the cortical allograft. The allograft and bone plate are then placed into the defect and the plate secured with cortical bone screws, loading two screws on either side of the allograft to compress the allograft rigidly into place, to the proximal radius, radial carpal bone, and third metacarpal bone (Figure 16.31b) (Dernell 2003; Dernell et al. 2007). A supplemental orthogonal 2.7 mm bone plate applied medially has also been described to minimize mechanical complications associated with ixation of a cortical allograft for limb-sparing surgery (Renwick and Scurrell 2013). A minimum of 80% of the metacarpal bone should be covered by the plate to minimize the risk of metacarpal fracture (Séguin et al. 2003; Pooya et al. 2004).

Figure 16.31 (a) Intraoperative photograph of the medial aspect of an allograft (notched arrow) just prior to implantation. A single screw (arrowhead) is being used to secure the plate to the allograft. (b) Following illing of the allograft with antibiotic impregnated bone cement, the allograft was secured into the radial defect and compressed (2 mm on each end by use of a 4.5 mm broad dynamic compression plate). The short arrow points to the interface between the radiocarpal bone and distal end of the allograft and the long arrow points to the interface between the remaining proximal radius and proximal end of the allograft. Endoprosthesis An endoprosthesis (Veterinary Orthopedic Implants) was developed by Dr. Charles Kuntz as an alternative to cortical allografts. The advantages of the endoprosthesis include avoidance of some of the logistical factors involved with cortical allografts (such as bone harvesting and maintaining a bone bank) and shorter operative times due to its readyto-implant nature (Liptak et al. 2004b, 2006a, 2006b). The radial

endoprosthesis was originally manufactured as a solid construct of lengths of 122 and 145 mm (Figure 16.32a). Several modi ications have been made, including a shorter endoprosthesis (98 mm), discontinuation of the 145 mm endoprosthesis, endoprostheses compatible with a locking limb-sparing plate, and coating the ends of the endoprosthesis with hydroxyapatite to improve osseous integration of the endoprosthesis with host bone (Figure 16.32b).

Figure 16.32 (a) Photograph of the irst-generation 122 mm radial endoprosthesis and hybrid limb-sparing bone plate. (b) Photograph of the second-generation 98 mm radial prosthesis. Note the shorter length and hollowed out sections of the endoprosthesis. The third-generation endoprosthesis has hydroxyapatite-coated ends to promote bony ingrowth and biologic ixation and is now compatible with a hybrid limb-sparing locking plate to improve biomechanical ixation. Both were developed in an effort to overcome construct failures in the proximal radius. In Figure 16.36a, the proximal aspect of the limbsparing bone plate has been cut to a length appropriate for the dog based on preoperative radiographs. In Figure 16.35b, the plate has not been cut. These images also illustrate how the endoprosthesis can either be placed directly proximal to the solid portion of the plate over the carpal bones or just proximal to the irst hole proximal to the solid portion. Sliding the plate more proximal in the latter example allows a screw to be placed into the radiocarpal bone. (c) An intraoperative image of a irst-generation endoprosthesis used to reconstruct the bony defect in the distal antebrachium following resection of an osteosarcoma. Note the 10° bend at the endoprosthesis-radial carpal bone junction and the lack of gap formation at the endoprosthesis-host bone interfaces. Minimizing gap formation at these interfaces decreases strain and the risk of construct failure. Also, note that the distal aspect of the limb-sparing plate covers >80% of the metacarpal bone, which is necessary to minimize the risk of metacarpal bone fracture. Biomechanical testing has shown the endoprosthesis to be superior to cortical allografts in a cadaveric model loaded to failure (Liptak et al. 2006b). In that study, limbs were initially cycled from 30 to 100% of body weight to simulate a clinical setting, but there was no evidence of failure in any of the four pilot limbs tested after 100 000 cycles. As a result, the limbs were loaded to failure. Endoprosthesis constructs had signi icantly greater yield load, energy at yield, and ultimate load when compared to limbs reconstructed with a cortical allograft (Liptak et al. 2006b). In the same study, the impact of ulnar resection was also examined. Preservation of the ulna did increase the load to yield and ultimate failure by 41 and 29%, respectively, in limbs reconstructed with cortical allografts, compared to 12 and 13% for endoprosthesis constructs (Liptak et al. 2006b). However, this was not signi icant and

there were no signi icant differences in stiffness, yield load and energy, and ultimate load and energy at failure with preservation or resection of the ulna in either of the constructs (Liptak et al. 2006b). The clinical implications of this inding are important. For dogs being treated with limb-sparing techniques that do not utilize the ulna for replacement of the radius (as opposed to techniques that do utilize the ulna such as the ulnar rollover technique [Séguin et al. 2003, 2017; Pooya et al. 2004]), resection of the ulna en bloc with the tumor-bearing radius would simplify the surgery because separation of the distal radius from the ulnar styloid process without disrupting the tumor pseudocapsule can be dif icult. This could reduce the rate of local recurrence, which is typically 8–28%, but has been reported as high as 60% (LaRue et al. 1989; Morello et al. 2001; Withrow et al. 2004; Liptak et al. 2006a; Séguin et al. 2017). It can also be dif icult to determine whether there is ulnar involvement in some cases, and costly imaging such as MRI is sometimes necessary to determine ulnar involvement. With less concern for ulnar involvement, routine en bloc resection of the ulna could be performed in questionable cases without the use of advanced imaging. While these results provide some insight into the importance of ulnar preservation, further evaluation is needed to con irm these cadaveric acute loading indings. In one study, preservation or removal of the ulna was not associated with an increased rate of implantassociated complications with the metal endoprosthesis technique (Mitchell et al. 2016). For application of the endoprosthesis, some surgeons bend the limbsparing plate to 10° at the level of the carpal joint, while others do not bend the limb-sparing plate (Figure 16.32c) (Liptak et al. 2006a). The limb-sparing plate is then coupled to the endoprosthesis using speci ic machined screws, and the construct is placed into the defect, taking care to ensure that contact between the metal and host bone is maximized at both interfaces. It is important that there is no or minimal gap formation between the implant-host bone interfaces (distally at the radial carpal bone and proximally at the radius) because gap formation signi icantly increases strain and the risk of implant failure (unpublished results). Once satis ied with contact and rotational orientation, the limb-sparing bone plate is secured to the host bone. Distally, the plate is typically secured to the third metacarpal bone;

however, the fourth metacarpal can be used as an alternative to achieve optimal rotation of the manus. For most large breed dogs, 3.5 mm cortical bone screws are used in the proximal radius and radial carpal bone, and 2.7 mm cortical bone screws are used in the metacarpal bone (Liptak et al. 2006a). For giant breeds, 4.5 mm cortical screws should be considered in the proximal radius and 3.5 mm screws distally in the metacarpal bone. For the majority of cases, locking screws are preferred to cortical screws to potentially minimize the risk of mechanical failure of the construct. A minimum of 80% of the metacarpal bone should be covered by the plate to minimize the risk of metacarpal fracture (Séguin et al. 2003; Pooya et al. 2004). The surgical site is lavaged copiously with sterile isotonic saline. Many surgeons insert a closed suction drain from the proximal aspect of the elbow into the surgical wound (Liptak et al. 2006a; Dernell et al. 2007). For closure, the pronator, supinator, and extensor muscle bellies are approximated with absorbable mono ilament suture. Finally, the subcutaneous tissues and skin are closed routinely, taking care to maximize apposition of the dermal edges and preserve the cephalic vein. Postoperative radiographs are evaluated for implant position, including a minimum of four bicortical screws in the proximal radius that are not penetrating the ulna (because pronation and supination of the antebrachium may increase the risk of screw loosening), good contact at the implant-host bone interfaces, and that the distal screws in the third or fourth metacarpal bone are well aligned and the plate is covering at least 80% of the length of the metacarpus (Figures 16.33a– c) (Séguin et al. 2003; Liptak et al. 2006a; Dernell et al. 2007). The limb is then bandaged with a soft-padded wrap and changed daily until incisional drainage has ceased. The closed suction drain is typically removed within 24 hours of surgery.

Cosmetic and Functional Outcome The cosmetic outcome of radial limb-sparing is very good. Aside from lacking the ability to lex the antebrachiocarpal joint, many clients do not appreciate that the limb has been altered. In the absence of complications, limb function is good to excellent in most dogs (LaRue et

al. 1989; Morello et al. 2001; Dernell 2003; Liptak et al. 2006a; Dernell et al. 2007; Séguin et al. 2017, 2019); however, complications are reported in up to 96% of dogs (Mitchell et al. 2016; Wustefeld-Janssens et al. 2020).

Potential Complications Infection is the most frequent complication encountered with limbsparing surgery (Figure 16.34a) (LaRue et al. 1989; Dernell et al. 1998b; Kirpensteijn et al. 1998; Morello et al. 2001; Lascelles et al. 2005; Liptak et al. 2006a; Mitchell et al. 2016; Séguin et al. 2017, 2019; Wustefeld-Janssens et al. 2020). The etiology of infection is multifactorial with proposed factors including extensive soft tissue resection with the vascular compromise to a poorly perfused site, poor soft tissue coverage, implantation of large orthopedic implants, nonvascularized bone (cortical allograft), possibly immunogenic cortical bone, and administration of local and/or systemic chemotherapy (Dernell et al. 1998b). Infection occurs in 30–78% of dogs with a median time to infection of 75 days (LaRue et al. 1989; Dernell et al. 1998b; Kirpensteijn et al. 1998; Morello et al. 2001; Lascelles et al. 2005; Liptak et al. 2006a; Mitchell et al. 2016; Séguin et al. 2017, 2019; Wustefeld-Janssens et al. 2020). It was hoped that the all-metal nature of the endoprosthesis would reduce the risk of infection or at least make infections easier to resolve than with cortical allografts; however, infection rate and severity of the infection are comparable to that of the allograft (Figure 16.34b) (Liptak et al. 2006a; Mitchell et al. 2016). A number of different bacterial organisms have been cultured with monomicrobial and polymicrobial infections occurring in approximately 50% of cases each (Dernell et al. 1998b). Initially, infections are treated with culture-directed antibiotics, isotonic saline lavages, and wet-to-dry bandages. If unresponsive or recurrent, then antibiotic-impregnated beads (PMMA or absorbable calcium sulfate) can be surgically implanted adjacent to the infection site (Figure 16.34c) (Dernell et al. 1998b). Limb amputation is a salvage procedure for the management of dogs with uncontrollable infections. In a recent study of 192 dogs treated with limb-sparing surgery (WustefeldJanssens et al. 2020), amputation was performed in 17 dogs with surgical site infections. Dogs treated with secondary amputation had a

median survival time of 205 days after limb amputation, and 97% of these dogs had good functional outcomes (Wustefeld-Janssens et al. 2020). On the positive side, the infection has been associated with an increase in survival time, with dogs with infected limbs living nearly twice as long as those with non-infected limbs (Lascelles et al. 2005; Liptak et al. 2006a).

Figure 16.33 (a) Lateral radiographic projection of a distal radial allograft 14 months after surgery. Radiographic union with the proximal radius and radiocarpal bone is evident (the proximal and distal bone interfaces are marked by the short and long arrows, respectively). A broken screw (arrowhead) is seen in one of the carpal bones. Bone cement can also be seen illing the intramedullary portion of the allograft (notched arrow). (b) Lateral radiographic projection of a 122 mm long irst-generation radial endoprosthesis immediately following surgery. This hybrid limb-sparing plate allows the use of either 3.5 mm or 4.5 mm cortical screws (in this case 3.5 mm) and either 3.5 mm or 2.7 mm cortical screws distally (in this case, six 2.7 mm screws and two 3.5 mm screws that were used to replace stripped 2.7 mm screws). The proximal and distal metal-bone interfaces are marked by the short and long arrows, respectively. A small portion of the distal medial aspect of the ulnar styloid (arrowhead) was excised en bloc along with the radius to improve the chances of a complete excision. (c) Lateral radiographic projection of a 98 mm long secondgeneration prosthesis secured with a locking hybrid limb-sparing plate with seven 3.5 mm locking screws in the proximal radius and seven 2.7 mm standard screws in the third metacarpal bone. Due to concern for ulnar involvement, the distal third of the ulna was excised along with the radius. In addition, due to concern regarding proximity of the tumor to the radiocarpal joint, the radiocarpal and ulnar carpal bones were excised en bloc along with the radius to obtain a wider distal margin. Simultaneous excision of the radiocarpal bone necessitates a partial ostectomy of the accessory carpal bone (notched arrow). The shorter 98 mm endoprosthesis used in this case allowed for two additional screws to be placed in the proximal radius when compared to that of the 122 mm long endoprosthesis which would have only allowed placement of ive screws. Implant failure occurs in approximately 40% of cases but is catastrophic in up to 18% of cases (Figures 16.35a–d) (Liptak et al. 2006a; Mitchell et al. 2016; Séguin et al. 2017, 2019; WustefeldJanssens et al. 2020). Implant failure is commonly caused by cycling associated with everyday activity. Bone cement injection into the intramedullary canal of cortical allografts increases screw pullout

strength and reduces the incidence of screw loosening, implant failure, and allograft fracture (Kirpensteijn et al. 1998). Dogs that developed a construct failure after limb-sparing surgery were reported to have a survival advantage that was independent of infection (Liptak et al. 2006a). In dogs with either a cortical allograft or endoprosthesis limb spare, those with construct failure had a median survival time of 685 days compared with dogs without construct failure that had a median survival time of 322 days. Further investigation into the mechanism of this survival advantage is warranted. Management of a construct failure depends on the nature of the failure. It is relatively common to replace loose or broken screws with larger screws (for nonlocking plates) and culture at the time of surgery. Catastrophic failure may require complete revision, use of an alternative limb-sparing technique (e.g. bone transport osteogenesis) or amputation (WustefeldJanssens et al. 2020).

Figure 16.34 (a) A photograph of a dog with a severe postoperative infection following limb-sparing surgery with a cortical allograft. The infection has resulted in loss of overlying skin with exposure of both the cortical allograft and limb-sparing plate. A previous effort to close the skin wound with stented sutures is evident. (b) A severe postoperative infection following limb-sparing surgery with an endoprosthesis resulting in skin loss and exposure of the limb-sparing plate. The rate and severity of infections are similar between cortical allografts and endoprostheses. (c) The dog in Figure 16.37b did not respond to culture-directed antibiotics and was successfully treated with antibiotic-impregnated polymethylmethacrylate beads (arrows). Note that this dog has two limb-sparing plates. A second plate was applied approximately two weeks after the original surgery to treat a fracture that occurred along the screws in the proximal radius.

Figure 16.35 (a) A postoperative radiograph following limb-sparing surgery with an endoprosthesis. There is loosening of one of the screws in the proximal radius (arrow). The majority of so-called implant failures are incidental indings and do not require further treatment. (b) Catastrophic failure of an endoprosthesis limb-sparing surgery with all screws in the proximal radius breaking and resulting in loss of construct stability. Catastrophic failures occur in approximately 10% of limb-sparing surgeries and require further revision. (c) Postoperative lateral radiographic projection of a distal radial limb-spare one day after surgery. A fracture is visible (long arrow) propagating along the screw holes in the proximal radius. (d) The same dog following revision surgery with a longer 4.5 mm broad plate and a supplemental 2.7 mm dynamic compression plate orthogonal to the primary plate. Local tumor recurrence is caused by incomplete resection or, more commonly, residual neoplastic cells in the soft tissue adjacent to the tumor capsule following marginal resection of the primary bone tumor (Figures 16.36a and b). The rate of local recurrence is typically 7–28%, but has been reported as high as 60% (LaRue et al. 1989; Morello et al. 2001; Withrow et al. 2004; Liptak et al. 2006a; Mitchell et al. 2016;

Séguin et al. 2017, 2019; Wustefeld-Janssens et al. 2020); however, this rate may be reduced to less than 15% with the use of locally released chemotherapy agents, such as cisplatin from open-cell polylactic acid biodegradable implants (not commercially available) and appropriate case selection (Withrow et al. 2004). Local recurrence may either have no effect or a negative impact on survival time, depending on how the owner handles the information (Liptak et al. 2004b). Local recurrence can be managed with a second limb-sparing surgery, amputation (Wustefeld-Janssens et al. 2020), or palliative radiation therapy.

Figure 16.36 (a) Local tumor recurrence in the distal antebrachium of a dog following limb-sparing surgery with an endoprosthesis and preservation of the ulna. Note the hollowed appearance of the styloid process consistent with bone lysis caused by a recurrent tumor (arrow). (b) Local tumor recurrence causing lytic destruction of the radial carpal bone (arrow) in a dog following limb-sparing surgery with an endoprosthesis. This dog presented with a pathologic fracture prior to limb-sparing surgery, but the owners declined limb amputation and wished to proceed with limb-sparing surgery.

Alternative Limb‐Sparing Techniques A number of limb-sparing alternatives to cortical allografts have been described over the years. The initial approach is the same with resection of the bone tumor and contiguous tissue with appropriate margins, but the technique to reconstruct the subsequent radial defect differs. Radial Autografting Reconstruction with a radial autografting can be performed with either autoclaving, irradiation, or pasteurization (Buracco et al. 2002; Yamamoto et al. 2002; Morello et al. 2003; Liptak et al. 2004c, 2004d; Boston et al. 2007). Pasteurization involves a submersion of the tumorcontaining bone segment in a sterile water bath at 65 °C for 40 minutes (Figure 16.37) (Buracco et al. 2002; Morello et al. 2003). Both autoclaving and pasteurization result in complete thermal necrosis of the tumor. An advantage of pasteurization over autoclaving is that the lower temperature does not destroy proteins such as bone morphogenetic proteins (Buracco et al. 2002; Morello et al. 2003). Preservation of such proteins may facilitate the incorporation of the graft into the host bone to a greater degree than autoclaving.

Figure 16.37 Lateral postoperative radiograph of a pasteurized autograft for a distal radial canine osteosarcoma. The distal half of both the radius and ulna were excised, pasteurized, and then secured back into the defect with a limited contact dynamic compression bone plate. Source: Images courtesy of Dr. Paolo Buracco.

Ulnar Autografting Ulnar autografting techniques include the use of an ipsilateral vascularized ulnar transposition graft, also called the ulnar rollover technique (Séguin et al. 2003, 2017) and free grafting of the contralateral ulna via microvascular anastomosis (Walsh et al. 2000; Hodge et al. 2011). With the ulnar transposition technique, transverse osteotomies are made in the ulna, one 1–2 mm distal to the level of the radial osteotomy, and the distal osteotomy is made at the level of the isthmus proximal to the facet that articulates with the radius (Figures 16.38a and b). It is important during the process of the procedure to preserve the blood supply and soft tissue envelope of the distal ulna (caudal interosseous artery and vein, abductor pollicus longus, pronator quadratus, and ulnar head of the deep digital lexor muscles) (Séguin et al. 2003). A bone plate is then used to stabilize the autograft similarly to that of an allograft. The advantages of this technique are that there is no distant donor site morbidity, the replacement bone is autologous, and that the graft is vascularized, making it less likely to become infected and possibly speed healing (Séguin et al. 2003). In a study of 27 limbs in 26 dogs treated with the ulnar rollover technique (Séguin et al. 2017), the viability of the ulnar graft was able to be determined in 20 limbs with 85% viable and 15% nonviable. In this study, the overall complication rate was 74.1% with infection in 44.4%, biomechanical failure in 55.6%, and local tumor recurrence in 11.1% of limbs. Limb function was considered good to excellent in 63.0% of limbs (Séguin et al. 2017). In a clinical study of eight dogs treated with vascularized ulnar bone grafts, infection was reported in 62.5% of dogs, implant loosening in 37.5% of dogs, and implant failure in 12.5% of dogs (Hodge et al. 2011). Lateral Manus Translation

A modi ication of the ulna rollover technique, termed lateral manus translation, has been reported in 18 dogs (Séguin et al. 2019). Rather than osteotomizing the ulna and rolling the ulnar segment into the radial defect, the manus is translated laterally (Figure 16.39a) and stabilized with a standard limb-sparing plate from the proximal radius to the third metacarpal bone, thus bridging the radial defect, and a string-of-pearls plate contoured along the lateral aspect of the ulna to the dorsal aspect of the fourth metacarpal bone (Figures 16.39b and c). In the 18 dogs treated with this technique, the overall complication rate was 67% with 10 dogs developing surgical site infections, 6 dogs with biomechanical complications, and local tumor recurrence in 4 dogs (Séguin et al. 2019).

Figure 16.38 (a) Illustrations of the ulna roll-over technique. Proximal and distal osteotomies are performed in the ulna and the ulna is rolled into the radial defect and secured with a bone plate to the proximal radius and third metacarpal bone. The success of this procedure relies on preservation of the soft tissue envelope around the ulna consisting of the caudal interosseous artery and vein, abductor pollicus longus, pronator quadratus, and ulnar head of the deep digital lexor muscles. Source: Reproduced with permission from Seguin, B., Walsh, P.J., Mason, D.R., et al. 2003. Use of an ipsilateral vascularized ulnar transposition autograft for limb-sparing surgery of the distal radius in dogs: An anatomic and clinical study. Vet Surg 32:69–79. (b) Lateral radiograph showing the ulnar rollover procedure 471 days postoperatively. The ulnar graft (between arrows) has healed to the radius and carpus. Source: Picture courtesy Dr. Bernard Séguin.

Bone Transport Osteogenesis Bone transport osteogenesis (BTO) is an innovative technique resulting in the gradual replacement of the excised distal radius with regenerate bone via a process called distraction osteogenesis. The phenomenon of distraction osteogenesis was described many years ago by a Russian surgeon named Gabriel Ilizarov. This technique has been used to reconstruct distal radial bone defects following resection of distal radial and tibial OSA (Tommasini Degna et al. 2000; Rovesti et al. 2002; Ehrhart 2005). The transportation of a bone segment across a bone defect using distraction osteogenesis is called longitudinal BTO (Figures 16.40a–d) (Tommasini Degna et al. 2000; Rovesti et al. 2002; Ehrhart 2005). The main advantages of BTO are that the bone is autogenous and highly vascular (Matsuyama et al. 2005), resistant to infection, and, following ixator removal, requires no permanent implants (Ehrhart 2005). It has been used as a primary limb-sparing technique or for salvaging other failed and/or infected limb salvage procedures (Tommasini Degna et al. 2000; Rovesti et al. 2002; Ehrhart 2005). The main disadvantage is the length of time the animal spends in the circular ixator frame. The distraction time depends on the size of the defect, with a mean distraction time of 123 days (range, 66–150 days) until docking and a mean of 205 days (range, 90–350 days) until frame removal (Tommasini Degna et al. 2000; Ehrhart 2005). A modi ication, referred to as double BTO, uses simultaneous longitudinal transport of two contiguous bone segments at different rates, thus allowing the defect to be illed in less time than compared with a single transport segment. Double BTO has been used in a dog with OSA of the distal aspect of the tibia and the 11 cm defect required 92 days of distraction (at an effective distraction rate of 1.5 mm/day) and 162 days until frame removal (Rovesti et al. 2002). Transverse BTO, involving medial transport of the distal ulna into the radial defect, has been described to decrease distraction and frame times in a cadaveric model and single live normal research dog (Jehn et al. 2007). With transverse BTO, a longitudinal osteotomy is performed in the ulna starting at the level of the radial osteotomy and extending down to the distal aspect of the styloid process. The medial half of the remaining ulna is then transported medially across the radial defect to the level of the medial aspect of the remaining radius proximally and the

radiocarpal bone distally. Unlike longitudinal BTO, the distraction distance is not dependent on the amount of bone removed with transverse BTO but rather the medial-to-lateral width of the radius. Theoretically, because the distraction distance is considerably shorter with transverse BTO than for longitudinal BTO, the time to ixator removal may be shorter (Jehn et al. 2007). This technique has yet to be reported in a clinical case.

Figure 16.39 (a) Illustrations of the lateral manus translation technique. Rather than osteotomizing the ulna, the ulna is preserved and the manus is translated laterally. Source: Illustration courtesy Dr. Bernard Séguin. Postoperative lateral (b) and dorsoventral (c) radiographs of a limb-sparing case using the lateral manus translation technique. Note the radial defect has been bridged with a standard limb-sparing plate from the proximal radius to the third metacarpal bone, and a string-of-pearls plate has been contoured to ix the lateral aspect of the radius to the dorsal aspect of the fourth metacarpal bone. Source: Reproduced with permission from Séguin, B., Walsh, P.J., Ehrhart, E.J., et al. 2019. Lateral manus translation for limb-sparing surgery in 18 dogs with distal radial osteosarcoma in dogs. Vet Surg 48 :247–256.

Figure 16.40 Radiographs showing bone transport osteogenesis (BTO) to ill a large bone defect resulting from excision of a distal radial osteosarcoma in a dog. The radiographic series shows the immediate postoperative appearance (a), the half-way point for bone transport at 5 weeks (b), the regenerate bone forming in the wake of docked transport segment at 16 weeks (c), and consolidation of the regenerate bone at 36 weeks at the time of removal of the circular external ixator (d). Source: Reproduced with permission from Ehrhart, N. 2005. Longitudinal bone transport for treatment of primary bone tumors in dogs: Technique description and outcome in 9 dogs. Vet Surg 34:24–34.

Intraoperative Extracorporeal Radiation Intraoperative extracorporeal radiation has been used for limb-sparing surgery in a small number of dogs with appendicular OSA (Huber et al. 2000; Liptak et al. 2004c, 2004d; Boston et al. 2007). This technique

involves an osteotomy proximal or distal to the tumor (depending on the anatomic site of the tumor; e.g. the osteotomy is made proximal to a distal radial tumor and distal to a proximal humeral tumor) and dissection of normal tissues from the tumor bone segment while preserving the adjacent joint capsule and supporting ligamentous structures (e.g. collateral ligaments). The neurovascular bundle, muscle, skin are held away from the affected bone, and the tumorcontaining bone segment is rotated approximately 90° out of the wound bed (Liptak et al. 2004c; Boston et al. 2007). The bone tumor segment is then irradiated with a single dose of 70 Gy. Collimation of the beam is performed so that approximately 1 cm of bone at the osteotomy site is spared to allow healing of the osteotomy site following internal ixation with either a bone plate, interlocking nail, or combination of the two. The advantage of this technique is that arthrodesis of the adjacent joint is not typically necessary (which is the major limiting factor to the success of limb-sparing in sites other than the distal radius and ulna) (Liptak et al. 2004c; Boston et al. 2007). Of the initial 14 cases reported, limb function was good in the immediate postoperative period; however, 50% of dogs required revision within 5–9 months of surgery, including four limb amputations (Liptak et al. 2004c). Additionally, local recurrence and infection were reported in four dogs each. In situ radiation of the distal femur and any tibial tumor can be performed without osteotomy. In distal radial cases, the collapse of the subchondral bone and subsequent implant failure has been observed (Boston et al. 2007). Thus transcarpal plating to the third metacarpal bone is recommended to span the subchondral bone of the distal radius and prevent collapse. Further evaluation, as well as technique modi ication, is required before this procedure can be recommended (Huber et al. 2000; Liptak et al. 2004c, 2004d; Boston et al. 2007). Transcutaneous Amputation Prosthesis Transcutaneous amputation prosthesis involves partial amputation of the limb for a distal primary bone tumor. The amputated segment of the limb is then replaced with a prosthesis, including a prosthetic foot, attached to either an intramedullary (Fitzpatrick et al. 2011) or extramedullary prosthesis (Figures 16.41a–d). The biologic challenge

with this technique is the promotion of skin ingrowth into the prosthesis to prevent skin recession and subsequent infection (Fitzpatrick et al. 2011). Design of the prosthetic foot can be an orthopedic challenge and revisions of the prosthetic foot design are often required before a suitable result is obtained. Patient‐Specific Implants: Computer Design and 3D Printing Recent advances in computer-aided design (CAD) and threedimensional (3D) printing techniques have the potential to revolutionize the ield of tissue engineering, particularly in the area of endoprosthetics (Razi et al. 2012; Sing et al. 2016;Wang et al. 2016). The process of 3D printing, or more precisely additive manufacturing (AM), allows complex 3D objects to be created literally “dot-by-dot” from a computer-generated model (Imanishi and Choong 2015; Sing et al. 2016). The advantage of AM technology is the freedom from design constraints of conventional manufacturing processes, where the need for a precise mold or tooling apparatus can restrict implant production to a more generic design that must it a wide range of patient presentations (Sing et al. 2016; Wang et al. 2016). With AM, complex and patient-speci ic 3D geometries can be fabricated whilst keeping build time and costs to a realistic level.

Figure 16.41 A dog with a tarsal osteosarcoma treated with partial amputation at the level of the distal tibia and extramedullary transcutaneous prosthesis. (a) Preoperative lateral radiograph showing an advanced osteolytic lesion of the tarsus which was later diagnosed as an osteosarcoma. (b) Intraoperative photo following partial amputation at the level of the distal tibia and ixation of the extramedullary transcutaneous prosthesis to the tibia. (c) Lateral postoperative radiograph of the extramedullary transcutaneous prosthesis. (d) The irst iteration of the prosthetic foot one day postoperatively. In addition to ingrowth of skin into the skin-prosthesis interface, design of the prosthetic foot is one of the challenges of this technique and this prosthetic foot required further revision before the dog could walk without lameness. The process of powder bed fusion allows the fabrication of orthopedic implants from different biocompatible materials such as 316L stainless steel, titanium-6-aluminium-4-vanadium (Ti6Al4V), and cobalt-

chromium (CoCr) (Sing et al. 2016). Powder bed fusion uses an energy source to melt and fuse particles of metal powder at precise points as determined by a computer design. When the selective melting of one layer is completed, the building platform is then lowered by a predetermined distance before another layer of powder is applied. This process is repeated until the entire 3D structure is complete (Figure 16.42). Selective laser melting (SLM) or electron beam melting (EBM) have been used for the creation of orthopedic implants, each utilizing a different energy source and different build conditions (Razi et al. 2012; Van der Stok et al. 2013; Parthasarathy 2014; Harrysson et al. 2015; Sing et al. 2016; Wang et al. 2016). Titanium and its alloys are rapidly becoming the materials of choice for biomedical implants due to many favorable properties (Razi et al. 2012; Sing et al. 2016). Titanium has excellent biocompatibility, strength-toweight ratio, and osteointegrative properties. These properties can be further exploited with the AM process by incorporation of a designdependent porosity into the structural component of the implant (Razi et al. 2012; Sing et al. 2016; Wang et al. 2016). A porous implant can be engineered to have an elastic modulus that more closely mimics the actual properties of bone (Razi et al. 2012; Liu et al. 2013; Parthasarathy 2014; Wang et al. 2016). The porous scaffold also enables vascular and cellular ingrowth into the implant, such that new bone tissue will ultimately form directly on to the implant surface. This potential for complete integration of the implant into the host tissues (i.e. osteointegration) is a “holy grail” for human biomedical implants because integration minimizes the potential for infection and implant failure, which can be devastating for the patient (Verran and Whitehead 2005). The optimal geometry and architecture of the scaffold structure to support osteointegration along a length of a large defect remain unknown, but current components use an average pore size of 400–600 μm and a volume porosity of 75–85%. Various surface topologies and coatings may also in luence the extent of osteointegration (Sing et al. 2016).

Figure 16.42 Advances in 3D printing techniques have the potential to revolutionize the ield of endoprosthetics. (a) and (b) Using CT data, models of the bones are created in silico. A personalized endoprosthesis-implant is designed to replace the distal aspect of the radius that will be excised. Source: Images courtesy Anatolie Timercan and Dr. Vladimir Brailovski. (c) and (d) The endoprosthesis-implant is 3D-printed by laser powder bed fusion of a titanium alloy. (e) endoprosthesis-implant in the limb at surgery. (f) and (g) Postoperative radiographs of the limb. Source: Images (c)–(g) courtesy Bernard Séguin.

In human surgery, custom-designed implants are rapidly gaining acceptance and have been utilized in a variety of situations, particularly craniofacial reconstruction and joint reconstruction (Parthasarathy 2014; Imanishi and Choong 2015). Due to the precise geometric it of the custom implant, surgical complexity and operating times are reduced, both of which should lead to lower rates of infection and faster recovery times. The veterinary experiences with CAD/AM of orthopedic implants have largely mirrored those of the human ield, with custom-designed implants being utilized initially to manage complex medical problems (Liska et al. 2007; Harrysson et al. 2015). Publications are largely

limited to isolated case reports and media releases, indicating the current novelty of the technology. In oncology patients, implants have been developed for the mandible, distal radius, and distal tibia with good clinical function reported (Figures 16.41a–d and 16.42b–c) (Bray et al. 2017; Liptak et al. 2017; Fitzpatrick and Guthrie 2018; Choi et al. 2019; Séguin et al. 2020). If these initial forays continue to af irm the promise of improved patient outcomes through reduced implant failure and infection rates, it is likely this technology will play an increasingly important role for veterinary patients in the future. In a inite element model of customized canine limb salvage endoprostheses and cutting guides, surgical time was estimated to be reduced by up to 50% with a possible reduction in the risk of construct failure (Timercan et al. 2019). Microwave Ablation Microwave ablation is a non-surgical limb-sparing technique. In microwave ablation, microwaves are used to create an electromagnetic ield that forces oscillation and rotation of polar molecules, such as water, at two to ive billion times per minute. The resultant increased kinetic energy creates heat, which is evenly distributed through the tissue and kills tumor cells within the zone of ablation by heating tissues to greater than 55 °C to induce acute coagulative necrosis (Salyer et al. 2020). The local effects of microwave ablation have been investigated in six dogs with a median tumor necrosis of 55% and no intraoperative or periprocedural complications up to 2 days postablation (when limb amputation was performed) (Salyer et al. 2020). The results of this pilot study suggest microwave ablation is a feasible technique for limb salvage in dogs. Limb Shortening Resection of the bone tumor with arthrodesis of the remnant of the radius to the carpus has been reported in one dog (Boston and Skinner 2018). This limb salvage technique was intended to shorten the limb but avoid the common complications associated with reconstructive limb-sparing techniques. The limb function was very good.

Digit‐Metacarpus‐Metatarsus Amputation Patient Selection Tumors of the foot can originate from osseous or soft-tissue structures. Squamous cell carcinoma (SCC) and malignant melanoma are the most commonly reported canine digit tumors, although soft tissue sarcoma (STS), OSA, synovial cell sarcoma, mast cell tumor (MCT), HSA, plasmacytoma, and benign neoplasms, and pyogranulomatous in lammation have also been reported (O’Brien et al. 1992; Gambin et al. 1995; Marino et al. 1995; Henry et al. 2005; Liptak et al. 2005a; Wobeser et al. 2007a). Digit SCC usually only involves a single digit, but multiple digit SCC has been reported (Henry et al. 2005; Wobeser et al. 2007a). Digit tumors are rare in cats, but the majority are malignant. Squamous cell carcinoma is the most frequently diagnosed digit neoplasia in cats, while malignant FSA, OSA, HSA, and giant cell tumor of bone have also been reported. Other tumors include metastatic pulmonary carcinomas, benign MCT and hemangioma, and nonneoplastic in lammation (Wobeser et al. 2007b). A visible mass, with or without lameness, is the most common presenting sign for animals with a digit tumor (Figures 16.43a and b) (Marino et al. 1995; Henry et al. 2005). Radiographs of the affected paw are recommended (Figures 16.44a–c). Bone lysis is more commonly associated with malignant tumors, but this inding is not pathognomonic because osteolysis can also be observed in dogs with pododermatitis and benign tumors (Marino et al. 1995; Voges et al. 1996; Henry et al. 2005). Moreover, the absence of bone involvement does not preclude a neoplastic disease because bone changes are frequently not associated with digit MCT, solitary plasmacytoma, STS, and sebaceous gland adenocarcinoma (Voges et al. 1996). A ine needle aspirate, core aspirate, or bone biopsy is recommended for the de initive diagnosis of a digit tumor, to exclude non-neoplastic diseases, and to determine skin margins for surgical resection. Clinical staging consists of the evaluation of the regional lymph nodes and three-view thoracic radiographs or thoracic CT. The metastatic risk is moderate for digit SCC and OSA, and high for malignant melanoma

(Marino et al. 1995; Henry et al. 2005). The regional lymph nodes should be palpated in all cases, but ine needle aspiration or incisional or excisional biopsy is recommended for dogs with digit melanoma based on a high incidence of nodal metastasis in palpably normal lymph nodes in dogs with oral malignant melanoma (Williams and Packer 2003).

Figure 16.43 (a) A squamous cell carcinoma of the digit in a dog. Note the typical large, ulcerated appearance. (b) A mast cell tumor of the interdigital webbing. Except for squamous cell carcinoma and malignant melanoma, most soft tissue tumors of the digits do not have underlying bone involvement on radiographs.

Figure 16.44 Lateral and dorsopalmar/plantar radiographs should be taken of the affected paw. A spectrum of radiographic changes may be observed, such as soft tissue opacity without underlying bone involvement, such as in this dog with a digit squamous cell carcinoma (a); to a bone lesion with a mixed lytic-blastic pattern (b) or lytic pattern (c), such as in these two dogs with primary osteosarcomas of the metacarpus. Cats and dogs with primary, non-metastatic tumors are good candidates for digit amputation, although digit amputation can also be performed for the de initive treatment of benign and non-neoplastic masses and as a palliative procedure in animals with either painful or infected tumors. Digit amputation is not recommended for cats with acrometastasis from primary lung tumors because, anecdotally, digit amputation does not palliate pain associated with digit metastasis or prolong survival time.

Preoperative Margin Assessment Similar to other appendicular bone tumors, tumors of the manus and pes with bone involvement should be resected with a minimum of 3 cm margins in the affected bone, which typically involves the entire bone

(Gambin et al. 1995; Marino et al. 1995; Henry et al. 2005; Liptak et al. 2005a). Skin margins are determined by tumor type. The extent of bone tumor involvement is most accurately determined using CT scans (Davis et al. 2002; Sugiura et al. 2002; Karnik et al. 2012), while this involvement is overestimated by radiographs, nuclear scintigraphy, and MRI (Leibman et al. 2001; Davis et al. 2002; Wallack et al. 2002). The use of imaging techniques that overestimate the degree of bone involvement may be acceptable because complete resection of the bone tumor may be more likely (Leibman et al. 2001).

Surgical Technique The surgical options for the management of tumors of the digit, metacarpus, and metatarsus include digit, partial foot amputation, and limb amputation. There is no signi icant difference in local recurrence rate between these surgical techniques (Henry et al. 2005), but local recurrence is signi icantly more likely with incomplete excision (Marino et al. 1995). Hence, the least aggressive technique which will achieve complete surgical resection is recommended. Amputation of one or two digits (digit and partial foot amputation, respectively) provides adequate local tumor control for benign and malignant neoplasms con ined to the nail bed, distal phalanges, and bones of the metacarpus or metatarsus (Marino et al. 1995; Henry et al. 2005; Liptak et al. 2005a). Limb amputation is rarely indicated for tumors of the digit, metacarpus, or metatarsus unless these tumors are extensive and involve more than two digits or extend beyond the proximal metacarpal or metatarsal bones. For digit or partial paw amputation, the distal limb is clipped and aseptically prepared. This can be dif icult because of the digits, nail beds, and pads (Probst and Millis 2003). The animal is placed in either lateral or dorsal recumbency. A tourniquet can be used prior to the initial skin incision to aid in intraoperative hemostasis (Probst and Millis 2003); however, this is not often required. The skin incision is an inverted Y-shape with the stem of the Y extending along the dorsal aspect of the affected digit and metacarpal or metatarsal bone, and the arms of the Y extending from the dorsal incision around the medial and lateral aspects of the base of the digit and meeting on the palmar

(thoracic limb) or plantar (pelvic limb) aspect of the digit (Figure 16.45a) (Probst and Millis 2003). If the second or ifth digits are being amputated, then the Y-shaped incision can be positioned medially or laterally, respectively, rather than dorsally (Figure 16.45b). The skin incision should be performed with appropriate lateral margins, depending on the tumor type (Liptak et al. 2005a). Following the skin incision, the digital arteries and veins are cauterized, ligated, or clipped. For digit amputations in the thoracic limb, the interosseous muscles are sectioned, tendons of the common and lateral digital extensors and super icial and deep digital lexors are transected, and branches of the dorsal and palmar common digital and metapodial artery and vein are either ligated or cauterized at the planned level of amputation (Liptak et al. 2005a). Similarly, for pelvic limb digits, the interosseous muscles are sectioned, tendons of the long and lateral digital extensors and super icial and deep digital lexors are transected, and branches of the dorsal and plantar metatarsal and common digital artery and vein are either ligated or cauterized at the planned level of amputation (Figure 16.45c) (Wobeser et al. 2007a). The digit should be amputated as high as possible. Depending on the location and extent of the tumor as assessed with preoperative imaging, the level of amputation should either be the distal aspect of the metacarpal or metatarsal bone or at the carpometacarpal or tarsometatarsal joint. A high-speed burr, oscillating saw, or bone cutters can be used to perform the osteotomy of the proximal metacarpus or metatarsus (Figure 16.45d) (Probst and Millis 2003; Liptak et al. 2005a); more distal amputations may result in postoperative lameness because of weight bearing on the distal end of the amputated digit (Muir and Pead 1998). For disarticulation of either the metacarpophalangeal or metatarsophalangeal joints, the joint capsule and collateral and sesamoidean ligaments are incised with a scalpel blade. The proximal margins of the amputated digit are inked and the sample submitted for histopathologic evaluation (Figure 16.45e). The interosseous muscles are apposed and the subcutaneous and skin are closed routinely (Figures 16.45f and 16.46a–c) (Probst and Millis 2003; Liptak et al. 2005a).

Figure 16.45 (a) An inverted Y-shape incision is made with the stem of the Y extending along the dorsal aspect of the metacarpus or metatarsus, and the arms of the Y extending from the distal aspect of the stem and wrapping around the medial and lateral aspects of the digit to meet on the palmar (metacarpus) or plantar (metatarsus) aspect of the digit. (b) For second or ifth digits, the inverted Y-shaped incised is based either medially or laterally rather than dorsally. (c) The interosseous muscles and associated ligaments are transected at the level of the planned osteotomy, and the relevant vessels ligated, in a dog with a primary metatarsal osteosarcoma. (d) The high metatarsal amputation is being performed with a high-speed burr in the dog in (c) with a primary metatarsal osteosarcoma. (e) The proximal margin has been inked for histopathologic examination following high amputation of the metatarsus in the dog in (c) and (d) with a metatarsal osteosarcoma. (f) The resultant defect following amputation of the digit is closed in three layers: interosseous muscles, subcutaneous tissue, and skin. A padded bandage is used for 7–10 days postoperatively to protect the paw and prevent splaying of the digits and disruption of the surgical site (Probst and Millis 2003; Liptak et al. 2005a). A Mason metasplint can also be used to provide additional protection of the surgical site following thoracic limb digit amputations (Liptak et al. 2005a). Exercise should be restricted for 2–4 weeks.

Cosmetic and Functional Outcome

Limb function is usually very good to excellent following amputation of one to two digits, even with excision of one or both of the weightbearing third or fourth digits. In one study of 33 dogs in which single digit amputation was performed for various diseases and trauma, 40% had minor short-term (≤14 days) complications, such as dehiscence with or without infection, and 25% had long-term (>14 days) complications, which mainly consisted of intermittent lameness (Kaufmann and Mann, 2013). Short-term complications were signi icantly more likely following digit amputation in the pelvic limb; however, body weight, the digit amputated (weight bearing versus nonweight bearing), number of digits amputated (one or two), and the level of amputation did not have a signi icant effect on either short- or longterm outcome (Kaufmann and Mann, 2013).

Figure 16.46 The postoperative appearance following amputation of the fourth digit and metacarpal bone for a metacarpal osteosarcoma (a), amputation of the ifth digit for a digit melanoma (b), and partial foot amputation of the weight-bearing third and fourth digits for an extraskeletal soft tissue osteosarcoma (c). Limb function is also good to very good following partial foot amputation, including amputation of both weight-bearing digits. In a small series of 11 dogs treated with partial foot amputation, lameness resolved after a median of 37 days in eight dogs (range, 1–180 days) and improved but persisted as a mild lameness in the remaining three dogs (Liptak et al. 2005a; Kaufmann and Mann, 2013).

Prognosis

The prognosis following digit amputation is dependent on the tumor type. In lammatory and benign tumors can be cured with complete surgical excision. For dogs with SCC, the metastatic rate is 5–29%, with the lymph nodes and lungs the most common sites (O’Brien et al. 1992; Marino et al. 1995; Henry et al. 2005; Wobeser et al. 2007a; Belluco et al. 2013). The median survival time is 26 months or greater, with 1- and 2-year survival rates of 50–95% and 18–74%, respectively (O’Brien et al. 1992; Marino et al. 1995; Henry et al. 2005; Wobeser et al. 2007a). An aggressive surgical approach is recommended because local tumor recurrence is signi icantly more likely with marginal or incomplete resection (Marino et al. 1995). Tumor location is also important as SCC arising from the subungual region has a signi icantly better prognosis than SCC arising from other areas of the digit (Marino et al. 1995). De novo SCC development in other digits has been reported in up to 22% of dogs (Belluco et al. 2013). The prognosis for dogs with digit melanoma is dif icult to determine because 50% are benign melanocytic nevi and 50% are malignant melanoma. Melanocytic nevi, similar to most dermal melanomas, are cured with surgical excision alone. However, malignant melanoma of the digit has a local recurrence rate of 14–30% and a metastatic rate of 50–71%, especially to the regional lymph nodes and lungs (Marino et al. 1995; Wobeser et al. 2007a). The median survival time for dogs with digit malignant melanoma is 12 months with 1- and 2-year survival rates of 44–66% and 11–22%, respectively (Marino et al. 1995; Henry et al. 2005; Wobeser et al. 2007a). The combination of digit amputation and xenogeneic murine tyrosinase DNA vaccine for dogs with digit melanoma resulted in an overall median survival time of 476 days with a 63% 1-year survival rate (Manley et al. 2011). The presence of metastasis at diagnosis and clinical stage were prognostic. The median survival times for dogs with metastasis and no metastasis at presentation were 105 days and 533 days, with 48% 2- and 3-year survival rates in dogs with no metastasis at presentation (Manley et al. 2011). The median survival times for dogs with stages I, II, III, and IV digit melanoma were >952 days, >1093 days, 321 days, and 76 days, respectively (Manley et al. 2011).

The prognosis for dogs with digit MCT is similar to cutaneous MCT in other locations, with a median survival time of 20 months and 1- and 2year survival rates of 75–88% and 63%, respectively (Marino et al. 1995; Wobeser et al. 2007a). Median survival times of dogs with OSA of the digits, metacarpus, or metatarsus following digit amputation, with or without chemotherapy, range from 466 to 687 days (Gambin et al. 1995; Tremolada et al. 2020). Chemotherapy is recommended for dogs with OSA, synovial cell sarcoma, and high-grade MCT of the digits, while immunotherapy with a commercially available melanoma vaccine is recommended for dogs with digit melanoma (Manley et al. 2011). An effective chemotherapy protocol for SCC has not been identi ied, but protocols involving platinum drugs, doxorubicin, and/or non-steroidal anti-in lammatory drugs should be considered.

Vertebral Tumors Patient Selection Osteosarcoma is the most common vertebral tumor and accounts for up to 16% of all axial OSA (Knecht and Priester 1978; Morgan et al. 1980; Heyman et al. 1992; Hammer et al. 1995; Dernell et al. 2000). Other primary vertebral tumors include CSA, FSA, HSA, osteochondroma (or multiple cartilaginous exostosis), and plasma cell tumors (solitary plasmacytoma or multiple myeloma) (Knecht and Priester 1978; Morgan et al. 1980; Doige 1987; Heyman et al. 1992; Hammer et al. 1995; Rusbridge et al. 1999; Dernell et al. 2000). Soft tissue tumors, particularly histiocytic sarcomas, can secondarily involve the vertebrae. Carcinomas (mammary and thyroid glands, bladder, and prostate) and sarcomas (appendicular OSA and visceral HSA) can also metastasize to one or more vertebrae, especially the thoracic and lumbar vertebrae (Morgan et al. 1980; Dernell et al. 2000). A thorough physical examination should be performed to identify possible occult primary tumors. Pain and neurologic de icits are the two most common signs in dogs with vertebral tumors (Morgan et al. 1980; Dernell et al. 2000; Dixon et

al. 2019). Neurologic de icits are caused by compression of nerve roots or the spinal cord (Morgan et al. 1980; Dernell et al. 2000). Neurologic signs are typically slowly progressive, but pathologic fracture will cause an acute deterioration in neurologic function. A neurologic scoring system has been devised and is prognostic for outcome and survival in dogs treated surgically: 1 is pain only, 2 is weakness, 3 is ataxia and loss of conscious proprioception, and 4 is paresis or paralysis (Dernell et al. 2000). A spectrum of radiographic changes is observed in dogs with vertebral tumors. These changes can be dif icult to detect due to inconsistent vertebral shape and superimposition of overlying ribs and soft tissue (Morgan et al. 1980). Cortical lysis with vertebral body collapse is a characteristic inding in primary vertebral tumors (Figures 16.47a and b), but a late event in metastatic tumors (Morgan et al. 1980; Dernell et al. 2000). Skip and multiple tumors are reported in up to 25% of dogs with primary vertebral OSA and can be dif icult to differentiate from metastatic tumors (Morgan et al. 1980). Osteochondromas are wellcircumscribed benign lesions that frequently involve the dorsal spinal elements, such as the dorsal lamina and spinous process, rather than the vertebral body (Figure 16.48) (Doige 1987). Other imaging techniques include myelography, CT and MRI scans, and nuclear scintigraphy (Figures 16.49a–c) (Kippenes et al. 1999).

Figure 16.47 (a) A lateral radiograph of a dog with an osteosarcoma of the sixth lumbar vertebra. Note the lytic changes in the vertebral body, lamina, and articular processes. (b) A lateral projection of a myelogram in a dog with osteosarcoma of the fourth thoracic vertebra. Note the vertebral body is collapsed in a cranial-to-caudal direction relative to the adjacent third and ifth thoracic vertebra. Myelographic changes include the collapse of the subarachnoid space and unilateral or asymmetric displacement of the spinal cord (Figures 16.47a and 16.49a) (Morgan et al. 1980). Advanced imaging provides the most accurate information for evaluating the degree of vertebral involvement but differentiating intra- and extradural involvement can be dif icult (Kippenes et al. 1999). Advanced imaging is also important for determining the resectability of the tumor and either surgical or radiation therapy planning. Nuclear scintigraphy can be bene icial in identifying the location of single and multiple lesions but cannot differentiate multifocal OSA from multiple metastatic lesions. Furthermore, most plasma cell tumors are photophenic due to marked osteolysis and minimal new bone production. A biopsy is required for a de initive diagnosis but is infrequently required because the vast majority of vertebral tumors are malignant and knowledge of tumor type will not change the recommended treatment options. However, if a plasma cell tumor is suspected, then a biopsy may be appropriate because plasma cell tumors can be treated effectively with radiation therapy rather than surgical resection. Open

biopsy via laminectomy is contraindicated in people because contamination of the epidural space increases the risk of local tumor recurrence (Boriani et al. 1997). A transpedicular approach, with the subsequent illing of the defect with bone cement or CT-guided bone biopsy, is preferred if a biopsy is to be performed (Boriani et al. 1997). Staging for distant metastasis includes three-view thoracic radiographs and perhaps CT scans. Whole-body bone scans should be performed because synchronous or metastatic lesions are reported in up to 25% of dogs with vertebral OSA (Morgan et al. 1980).

Figure 16.48 A lateral radiograph of a dog with an osteochondroma arising from the dorsal spinous processes of the fourth and ifth thoracic vertebrae. Osteochondromas typically arise from the dorsal lamina or spinous processes.

Figure 16.49 Advanced imaging modalities provide more accurate information on the degree of vertebral involvement and extension into adjacent soft tissues, surgical resectability, and surgical and/or radiation planning. (a) A ventrodorsal projection of a myelogram in a dog with an osteosarcoma of the sixth cervical vertebra. The tumor is displacing and compressing the spinal cord toward the right side of the spinal canal. (b) A sagittal CT image of the same dog in Figure 16.49a showing that the osteosarcoma lesion affects the left lateral vertebral body, pedicle and lamina from zones 1 to 5 (see Figure 16.50). (c) A contrast-enhanced MRI of the same dog in Figures 16.49a and b shows that the tumor extends into the adjacent cervical musculature.

Surgical Technique The treatment options for the management of vertebral tumors in dogs include surgical resection and/or stabilization, radiation therapy, and chemotherapy. The majority of reported treatments in cats and dogs are palliative (Dernell et al. 2000; Rossmeisl et al. 2006; Roynard et al. 2016; Dixon et al. 2019), with few reported curative-intent treatments reported in veterinary medicine (Chauvet et al. 1999; Nakata et al. 2017; Liptak et al. 2019). The curative-intent options in human oncology depend on whether the tumor is benign, malignant, or metastatic, whether the tumor has been completely or incompletely excised, and the metastatic potential of the tumor. Various staging systems have been described for the surgical management of vertebral tumors in people, and these may also be applicable for dogs with vertebral tumors. These staging systems involve dividing the vertebra into 12 equal zones, similar to a clock face, and then basing the type of surgical resection on the number of zones affected by the tumor and whether the tumor is benign or malignant (Figure 16.50a) (Boriani et al. 1997). Based on this surgical staging system, there are three major types of en bloc excision: vertebrectomy, sagittal resection, and resection of the dorsal lamina (Boriani et al. 1997). The surgical approach is dependent on the location (cervical, thoracic, lumbar, or sacral) and extent of the tumor, and these approaches are described in detail elsewhere (Piermattei and Johnson 2004).

Figure 16.50 (a) The Weinstein-Boriani-Biagnini (WBB) Surgical Staging System for vertebral tumors. The transverse extension of the vertebral tumor is described by 12 radiating zones (1–12 in clockwise order) and ive concentric layers (A–E) from the paravertebral extraosseous compartments to dural involvement. (b) En bloc excision of vertebral body tumors is possible if at least one pedicle is free from tumor (zones 4–8 or 5–9). (c) En bloc sagittal excision of eccentric vertebral tumors (vertebral body, pedicle and/or transverse process) is possible if the tumor does not extend beyond zones 3–5 or 8–10. Sagittal resections are limited to cervical tumors because a combined ventral and dorsal approach is required for en bloc excision. Source: Reproduced with permission from Boriani, S., Weinstein, J.N., and Biagini, R. 1997. Primary bone tumors of the spine: Terminology and surgical staging. Spine 22:1036–1044.

Vertebrectomy is recommended for centrally located tumors with one pedicle free from the tumor (i.e. zones 4–8 or 5–9) (Figure 16.50b). Vertebrectomy can be performed in one or two stages, with two-stage procedures preferred in most cases. A dorsal approach is used for resection of the annulus ibrosus and dorsal longitudinal ligament, hemostasis of the epidural venous plexus, and stabilization; while a ventral approach is used for hemostasis of the segmental vessels, cranial and caudal diskectomies, en bloc removal of the vertebral body, and reconstruction and stabilization (Boriani et al. 1997). Stabilization techniques include dynamic compression plates, multiple-level Harrington rod ixation, wire ixation of facets and spinous processes, interbody fusion, and acrylic ixation (Boriani et al. 1997). Piecemeal total vertebrectomy has been reported in a dog with vertebral FSA (Chauvet et al. 1999) and a cat with a vertebral OSA (Nakata et al. 2017), and total en bloc vertebrectomy in one dog with an invasive FSA (Figure 16.51) (Liptak et al. 2019). Sagittal resection is recommended for eccentrically located tumors in the vertebral body, pedicle, or transverse process (i.e. zones 3–5 or 8– 10) (Figure 16.50c) (Boriani et al. 1997). A two-stage combined dorsal and ventral approach, as described above, permits access to 300° of the vertebra (Figure 16.52) (Boriani et al. 1997). The nerve root or roots are transected as necessary. The margins for sagittal resection and vertebrectomy are one zone away from the tumor margins (Boriani et al. 1997). Dorsal lamina resection is indicated for tumors in which the pedicles are not involved (i.e. zones 10–3) (Boriani et al. 1997). A wide dorsal laminectomy is recommended, but surgical resection is often marginal, and stabilization may be required if the articular facets are excised bilaterally (Figures 16.53a–c). Dorsal lamina resections should be combined with adjuvant radiation therapy to maximize local tumor control. Although surgical resection with vertebrectomy is rarely feasible in dogs, dorsal decompression can provide meaningful palliation in dogs with localized dorsal tumors (Boriani et al. 1997; Dernell et al. 2000). Radiation therapy, either with palliative or curative-intent, can be bene icial in dogs with vertebral tumors (Dernell et al. 2000; Swift and

LaRue 2018; Dixon et al. 2019). The role of chemotherapy is unknown, even in dogs with vertebral OSA, as most dogs are euthanized due to the local tumor rather than metastatic disease (Dernell et al. 2000). Chemotherapy and radiation therapy are recommended for the treatment of dogs with multiple myeloma. In people with primary vertebral OSA, the best results are achieved when wide excision, or marginal excision and adjuvant radiation therapy, combined with chemotherapy (Boriani et al. 1997; Ozaki et al. 2002).

Figure 16.51 A total en bloc multiple segment vertebrectomy of T9 to T12 has been performed in a dog with an invasive myxosarcoma. This was done through a combined dorsal and intrathoracic approach, including ive ribs. The vertebral segment was reconstructed with customized, three-dimensional printed, modular titanium implants.

Prognosis In one study, the median survival time for dogs with malignant vertebral tumors was 135 days, and survival time was not signi icantly in luenced by preoperative neurologic score, tumor type (OSA or FSA),

primary or metastatic disease, anatomic location (cervical, thoracic or lumbar), chemotherapy, or radiation therapy (Dernell et al. 2000). In another study of 22 dogs with vertebral OSA, the median progressionfree survival time was 120 days (Dixon et al. 2019). In contrast to the earlier study, dogs with cervical OSA (median survival time 42 days) had a signi icantly worse outcome than dogs with either thoracic (median survival time 79 days) or lumbar OSA (median survival time 153 days). Furthermore, dogs treated with a combination of surgical decompression, radiation therapy, and chemotherapy had signi icantly longer survival times (median survival time 261 days) than dogs treated with surgery alone (median survival time 42 days) (Dixon et al. 2019). Although not signi icant, the neurologic score can provide useful information as dogs with a preoperative score of 1 had a survival time of 330 days compared with 120 days if the neurologic score was greater than 1 (Dernell et al. 2000). Furthermore, dogs with a post-treatment neurologic score of 1 or 2 were 12 times more likely to survive than dogs with a post-treatment score of 3 or 4 (Dernell et al. 2000). Curative-intent radiation therapy provides a signi icant improvement in survival time when compared with palliative radiation, with survival times of 150 and 15 days, respectively (Dernell et al. 2000). In a small study of nine dogs with either primary or metastatic vertebral OSA treated with stereotactic radiation therapy, the median survival time was 139 days and there were no differences in outcomes with different neurologic scores or between dogs with primary and metastatic OSA (Swift and LaRue 2018). In people with vertebral OSA, a poor prognosis is seen with large, metastatic, and sacral tumors (Ozaki et al. 2002).

Figure 16.52 An en bloc sagittal resection has been performed in a dog with an osteosarcoma of the sixth cervical vertebra (see Figure 16.55). A combined dorsal and lateral (pictured) approach was used for excision. A dorsal laminectomy was performed from the dorsal approach and removal of the vertebral body and subsequent stabilization using pins and polymethylmethacrylate was performed from the lateral approach.

Figure 16.53 (a) A contrast-enhanced MRI of a dog with an osteosarcoma arising from the base of the dorsal spinous process and dorsal lamina of the second thoracic vertebra. (b) A dorsal lamina resection, with preservation of the articular facets, was performed for marginal excision of the tumor. (c) The excised specimen showing the tumor arising from the dorsal lamina and base of the dorsal spinous process. This dog was also treated with full-course adjuvant radiation therapy and was euthanized 11 months postoperatively because of local tumor recurrence.

Joint Tumors Patient Selection

Joint tumors are usually primary and malignant (McGlennon et al. 1988; Vail et al. 1994; Whitelock et al. 1997; Craig et al. 2002; Fox et al. 2002). Synovial cell sarcoma was considered the most common tumor of the canine joint (McGlennon et al. 1988; Vail et al. 1994), but recent evidence suggests that other soft tissue sarcomas of periarticular tissue are more prevalent, and immunohistochemistry is required to differentiate these tumor types (Whitelock et al. 1997; Craig et al. 2002; Moore 2014). Other joint tumors include histiocytic sarcoma, synovial myxoma and myxosarcoma, osteosarcoma, chondrosarcoma, ibrosarcoma, hemangiosarcoma, liposarcoma, rhabdomyosarcoma, and undifferentiated sarcoma (Whitelock et al. 1997; Craig et al. 2002, 2010). Synovial cell sarcomas are malignant tumors arising from mesenchymal cells within tenosynovial tissue of joints, bursa, and tendon sheaths (McGlennon et al. 1988). The sti le, elbow, shoulder, carpal, tarsal, and hip joints are most commonly involved, in decreasing order (McGlennon et al. 1988). Metastasis to the regional lymph nodes and lungs is reported in up to 32% of dogs at diagnosis and in 41–54% of dogs during the course of disease (McGlennon et al. 1988; Vail et al. 1994; Whitelock et al. 1997; Craig et al. 2002; Fox et al. 2002). Arguably, the true biologic behavior of synovial cell sarcomas is not well documented given that most data come from studies performed prior to differentiating synovial cell sarcomas and histiocytic sarcomas (McGlennon et al. 1988; Vail et al. 1994; Whitelock et al. 1997; Fox et al. 2002). Because the most common tumor of the canine joint is histiocytic sarcoma (Craig et al. 2002), it is likely that earlier studies on synovial cell sarcomas included a substantial number of dogs with histiocytic sarcomas, but it was not known that immunohistochemistry was required to differentiate these from synovial cell sarcomas. Periarticular or articular histiocytic sarcomas are a variation of localized histiocytic sarcomas in which the sarcoma arises from the tissues adjacent to the joint or within the joint, respectively (Moore 2014). Articular histiocytic sarcoma is more common than periarticular histiocytic sarcoma in both cats and dogs (Craig et al. 2002; Moore 2014). The sti le and elbow joints are most commonly affected, but any joint can be involved (Craig et al. 2002). Rottweilers may be

predisposed as more than 50% of cases in one study were reported in this breed (Craig et al. 2002). The development of periarticular histiocytic sarcoma has been associated with previous joint disease in dogs (van Kuijk et al. 2013; Manor et al. 2018). Typically, dogs have lameness, joint pain, and synovial effusion. Biopsy is required for a de initive diagnosis. Analysis of synovial luid is usually consistent with chronic, low-grade in lammation, and neoplastic cells are rarely identi ied. Large core biopsies, using either a Jamshidi needle or open wedge, are suf icient to establish a diagnosis and histologic grade. Dogs with suspected joint tumors should be clinically staged with the interrogation of regional lymph nodes and joint and three-view thoracic radiographs. If histiocytic sarcoma has been diagnosed, then abdominal ultrasonography is also recommended to differentiate localized from disseminated histiocytic sarcoma (Skorupski et al. 2009; Moore 2014). Radiographs of the affected joint will often reveal a soft tissue opacity adjacent to the affected joint (Figure 16.54). Mineralization of the soft tissue mass is occasionally seen in humans but rarely in dogs. Bone involvement is observed in 11–100% of cases and can either be smooth and well delineated, due to pressure necrosis from the expansile mass, or permeative to punctate lysis as a result of bony invasion (Figure 16.55) (McGlennon et al. 1988; Vail et al. 1994; Whitelock et al. 1997; Craig et al. 2002; Fox et al. 2002).

Treatment Limb amputation is the recommended treatment for cats and dogs with a histologically con irmed joint tumor (McGlennon et al. 1988; Vail et al. 1994; Whitelock et al. 1997; Craig et al. 2002; Fox et al. 2002; Liptak et al. 2004f). The technical aspects of amputation of the thoracic and pelvic limb are described earlier in this chapter. Local recurrence is common after conservative excision of synovial cell sarcomas and has also been reported with relative frequency in the stump of the amputation site (McGlennon et al. 1988). The role of radiation therapy and chemotherapy is unknown, but responses to

doxorubicin and radiation therapy have been reported (Tilmant et al. 1986; Vail et al. 1994).

Figure 16.54 A lateral radiographic projection of the tibiotarsal joint in a cat with a synovial cell sarcoma. Note the soft tissue opacity dorsal to the tibiotarsal joint with no evidence of bone involvement.

Figure 16.55 A ventrodorsal radiographic projection of the pelvis in a dog with a synovial cell sarcoma of the coxofemoral joint. Note the lysis of the femoral head, femoral neck and greater trochanter, and acetabulum secondary to bone invasion by the tumor. Histiocytic sarcomas may respond to radiation therapy (Skorupski et al. 2007, 2009; Gibbons et al. 2011). Chemotherapy is recommended for dogs with histiocytic sarcoma because of the high metastatic potential of these tumors, with up to 91% of dogs developing metastatic disease (Vail et al. 1994; Craig et al. 2002; Skorupski et al. 2007, 2009).

Prognosis The overall median survival time for dogs with synovial cell sarcoma is 31.8 months (Craig et al. 2002). Dogs with evidence of metastatic disease to either regional lymph nodes or lungs have a worse prognosis with a median survival time of less than 6 months. Treatment type is also prognostic for both local tumor control and survival. Following conservative excision, the median disease-free interval and survival time are 4.5 months and 455 days, respectively. In comparison, the median disease-free interval and survival time are 30 months and 840 days, respectively, following treatment with limb amputation (McGlennon et al. 1988; Vail et al. 1994; Fox et al. 2002). Histologic grade is also prognostic because the median survival time for dogs with grade I synovial cell sarcoma is not reached and greater than 48 months, grade II is 36 months, and grade III only 7 months (Vail et al. 1994). The median survival times for other joint tumors in dogs following surgery alone are 5.3 months for histiocytic sarcoma, 30.7 months for synovial myxoma, and 3.5 months for other sarcomas (Craig et al. 2002). However, the combination of limb amputation and chemotherapy with cyclonexyl-chloroethyl-nitrosourea (CCNU/lomustine) may be bene icial in dogs with localized histiocytic sarcoma of the joint because the median survival time with this protocol is 568 days (Skorupski et al. 2007, 2009). Regional and distant metastasis are common in dogs with joint sarcomas, being reported in 50–91% of dogs with histiocytic sarcoma and 100% of dogs with other types of joint sarcomas (Craig et al. 2002; Skorupski et al. 2007). While

the presence of metastasis is a negative prognostic indicator for dogs with periarticular histiocytic sarcoma following treatment with surgery with or without chemotherapy, median survival times were still relatively long for dogs with metastatic disease (253 days, compared to 980 days for dogs without evidence of metastatic disease) (Klahn et al. 2011).

Muscle Tumors Patient Selection Primary muscle tumors are rare in cats and dogs. Hemangiosarcoma is the most common primary muscle tumor in dogs, although others include rhabdomyosarcoma and rhabdomyoma, in iltrating and intermuscular lipoma, histiocytic sarcoma, malignant lymphoma, and mast cell tumor (Roth 1990; Bergman et al. 1994; Ward et al. 1994; Cooper and Valentine 2002; Bulakowski et al. 2008). Intramuscular Hemangiosarcoma Subcutaneous and intramuscular HSA accounts for 13–47% of all HSA lesions (Bulakowski et al. 2008). Hematology and a coagulation pro ile are recommended because of the risk of anemia, thrombocytopenia, and localized and systemic bleeding disorders such as disseminated intravascular coagulation (Ward et al. 1994). Metastasis at the time of diagnosis is rare, but because of the metastatic potential of HSA in dogs, particularly to the spleen, liver, and heart, clinical staging with abdominal ultrasound, echocardiography, and three-view thoracic radiographs or abdominal and thoracic CT is recommended (Bulakowski et al. 2008). Rhabdomyosacroma Rhabdomyomas and rhabdomyosarcomas are primary tumors of striated muscle (Cooper and Valentine 2002). They are very rare and account for less than 0.001% of all canine tumors (Cooper and Valentine 2002). Immunohistochemistry (especially myoglobin and alpha-sacromeric actin) and perhaps electron microscopy are required

for de initive diagnosis (Cooper and Valentine 2002). Immunohistochemistry with myogenin and MyoD1 can be helpful to provide a diagnosis (Tuohy et al. 2021). In people, rhabdomyosarcomas are classi ied as embryonal, botryoid, alveolar and pleomorphic. This classi ication scheme has prognostic importance, with botryoid rhabdomyosarcoma having the best outcome and alveolar rhabdomyosarcoma having the worst outcome (Cooper and Valentine 2002). There is currently insuf icient information in the veterinary literature to know if this classi ication scheme has similar prognostic signi icance in animals. Furthermore, the revision of the human classi ication system is being considered because of discoveries in the molecular pathogenesis and genomes of human rhabdomyosarcoma (Caserto 2013). Histologically, the majority of rhabdomyosarcomas in dogs are classi ied as embryonal despite occurring in adult dogs, although younger dogs are more commonly reported with embryonal retrobulbar rhabdomyosarcoma (Scott et al. 2016). There is a possible predilection for muscles of the head region, including the tongue, although they can also affect head and neck sites not typically associated with skeletal muscle (such as the hard palate and larynx) (Cooper and Valentine 2002; Scott et al. 2016). They have also been reported to arise in the myocardium and urinary bladder. These tumors are locally invasive and have a moderate metastatic potential. Reported sites of metastasis include the lungs, liver, kidney, spleen, and adrenal glands (Cooper and Valentine 2002). Infiltrative Lipoma In iltrative lipomas are benign but locally aggressive and in iltrate normal muscle, fascia, nerve, myocardium, joint capsule, and bone (Gleiser et al. 1979; McChesney et al. 1980; Bergman et al. 1994; McEntee et al. 2000). In iltrative lipomas may have a predilection for the extremities (Gleiser et al. 1979; McChesney et al. 1980; Bergman et al. 1994), but the abdominal and thoracic wall, head, and perianal region have also been reported (Gleiser et al. 1979). Cytology and histopathology are consistent with a benign process with welldifferentiated adipocytes and no evidence of anaplasia or other characteristics of malignancy (Bergman et al. 1994).

Advanced imaging is recommended to determine the extent of the tumor and plan the surgical approach. CT scans are useful in determining the extent of disease in most cases (Figure 16.56), but differentiating normal fat from in iltrative lipoma can be dif icult (McEntee and Thrall 2001). MRI has better soft tissue detail and is probably preferable to CT scans for the local staging of dogs with intramuscular tumors like in iltrative lipomas.

Figure 16.56 A CT scan of a dog with an in iltrative lipoma of the thoracic wall. Advanced imaging is recommended for dogs with in iltrative lipomas, and other intramuscular tumors, to determine the extent of disease and assist in surgical planning. Intermuscular Lipoma Intermuscular lipomas are usually located between the semitendinosus and semimembranosus muscles and extend along the full length of the thigh. They can also occur between the semitendinosus and biceps femoris muscles, vastus lateralis and biceps femoris muscles, and deep

to the sartorius muscle (Thomson et al. 1999; Case et al. 2012). In one study, an equal distribution of intermuscular lipomas was reported in the thoracic and pelvic limbs, with intermuscular lipomas of the thoracic limb located between the super icial and deep pectoral muscles, serratus ventralis and subscapularis muscles, omotransversarius and subscapularis muscles, and antebrachial lexor muscles (Case et al. 2012). The most common clinical sign is a large and luctuant to irm mass in the caudal thigh (Thomson et al. 1999), although lameness and abduction of the limb are also relatively common (Case et al. 2012). Muscle Pseudotumors Muscle pseudotumors are non-neoplastic masses that form within skeletal muscle and mimic tumors (Cooper and Valentine 2002). Broadly, this may include any reactive or degenerative process that results in a tumor-like growth in skeletal muscle. These include myositis ossi icans and musculoaponeurotic ibromatosis (desmoid tumor) (Layton and Ferguson 1987; Dueland et al. 1990; Cooper and Valentine 2002). These tend to be discrete but also recur following marginal excision (Layton and Ferguson 1987; Dueland et al. 1990; Cooper and Valentine 2002).

Surgical Technique Hemangiosarcoma, Rhabdomyosarcoma and Infiltrative Lipoma For all primary muscle tumors other than intermuscular lipoma, an aggressive surgical approach is required to prevent local tumor recurrence. The margins of resection have not been determined for in iltrative lipomas, but 3 cm margins are prudent considering their in iltrative behavior. A similar approach is recommended for primary intramuscular sarcomas (HSA or rhabdomyosarcoma) (Figure 16.57). These margins should be based on palpation and advanced imaging (Figure 16.58a). If the tumor is contained within a muscle belly, then the affected muscle should be excised (Figure 16.58b). Intraoperative hemorrhage is common, particularly in dogs with intramuscular HSA, and hence hemostasis is important.

Figure 16.57 Surgical planning for a dog with a hypodermal hemangiosarcoma. These tumors should be excised with 3 cm lateral margins and a minimum of one fascial layer for deep margins. Advanced imaging is recommended to determine both the lateral and deep extents of the tumor prior to surgical excision.

Figure 16.58 (a) A CT scan of a dog with an intramuscular mast cell tumor of the vastus lateralis. (b) An intraoperative image of the intramuscular mast cell tumor being excised en bloc with the biopsy tract. Reconstruction was not required following excision because normal limb function can be maintained with the remaining quadriceps muscle. Source: Images courtesy of Dr. Sarah Boston.

If the affected muscle is not essential for normal function, then this muscle can be excised without reconstruction. However, if the muscle is integral to normal function, then reconstruction may be required. Muscle can be reconstructed with either a muscle lap (for instance, the latissimus dorsi muscle lap in the thoracic limb and the semitendinosus muscle lap in the pelvic limb [Figures 16.59a–d]), or using a combination of mesh, porcine submucosa, and suture material. Radiation therapy may have a role in the treatment of dogs with in iltrative lipomas, preferably as an adjunct following incomplete excision (McEntee et al. 2000). Intermuscular Lipoma Surgical treatment involves extirpation of the mass. With the dog in either lateral or dorsal recumbency, an incision is made along the caudal aspect of the thigh over the swelling (Figures 16.60a–e) (Thomson et al. 1999; Case et al. 2012). The semitendinosus and semimembranosus muscle bellies are separated using blunt dissection

to expose the lipomatous mass. The mass can usually be separated from the surrounding tissue using a combination of blunt dissection and digital extrusion (Thomson et al. 1999). The sciatic nerve is deep to the mass and should be identi ied and protected during dissection (Thomson et al. 1999). A closed-suction drain in inserted into the tumor excision site because the large dead space is prone to the development of seromas (Thomson et al. 1999).

Figure 16.59 (a) An intraoperative image of a hemangiosarcoma arising from the Achilles tendon. The biopsy tract has been excised en bloc and the distal aspect of the Achilles tendon has been transected (arrow). (b) The Achilles tendon is required for normal function of the pelvic limb and hence needs to be reconstructed. In this case, the semitendinosus muscle (arrow) has been elevated from the ischium and re lected distally for reconstruction of the Achilles tendon. (c) Tension has been established with biotenodesis screws and suture material (arrows) spanning from the distal femur to the calcaneus. (d) The semitendinosus muscle (arrow) is wrapped around the suture material and sutured to the remaining cuff of the distal Achilles tendon to reconstruct the Achilles tendon.

Prognosis Intramuscular Hemangiosarcoma

In three studies investigating hypodermal HSA, local recurrence was reported in 25–50% and metastasis in 43–73% of dogs (Hammer et al. 1991; Ward et al. 1994; Bulakowski et al. 2008). Adjuvant radiation therapy does not improve local tumor control in dogs with incompletely excised intramuscular HSA; hence the surgeon should attempt to achieve complete resection rather than plan for incomplete excision and adjuvant radiation therapy (Bulakowski et al. 2008). The role of chemotherapy is controversial. The median survival time for ive dogs with intramuscular HSA treated with surgical excision alone was 309 days (Ward et al. 1994). In two studies of dogs with hypodermal HSA treated with surgery and adjuvant doxorubicin, the median survival times were 273 and 425 days (Hammer et al. 1991; Bulakowski et al. 2008). Furthermore, the median disease-free interval and survival time were signi icantly shorter for dogs with intramuscular HSA compared to subcutaneous HSA (Bulakowski et al. 2008). However, despite these results, full-course chemotherapy using doxorubicin-based protocols and/or metronomic chemotherapy is recommended for dogs with intramuscular HSA because of the high potential for metastatic disease (Ward et al. 1994). Rhabdomyosarcoma The prognosis for dogs with rhabdomyosarcoma is dif icult to determine because of so few reported cases. However, disease-free intervals and survival times have been encouraging in the cases treated with surgery and adjunctive radiation and/or chemotherapy (Senior et al. 1993; Block et al. 1995; Lascelles et al. 1998; Takiguchi et al. 2002; Ueno et al. 2002; Saulnier-Troff et al. 2008; Tuohy et al. 2021). Embryonal rhabdomyosarcomas may be more invasive and have a moderate potential for metastasis (Cooper and Valentine 2002). Rhabdomyomas have been described in the pinna of four female cats, and surgical excision was curative in all cats (Roth 1990).

Figure 16.60 (a) The typical appearance of an intermuscular lipoma in a dog with a large mass in the caudal aspect of the thigh. (b) After a caudal approach to the thigh, the semitendinosus and semimembranosus muscles are separated to expose the lipoma. (c) The intermuscular lipoma is removed using a combination of blunt dissection and digital extrusion, taking care to identify and preserve the sciatic nerve. (d) and (e) To prevent seroma formation, a closed-suction or Penrose drain is inserted into the dead space. Infiltrative Lipoma In iltrative lipomas do not metastasize, but local recurrence occurs in 36–50% of dogs treated with surgery alone with a median disease-free interval of 239 days and 67% of dogs disease-free at 12 months in two studies (McChesney et al. 1980; Bergman et al. 1994). The 1-year survival rate was 83% (Bergman et al. 1994). In another study of 13

dogs treated with radiation therapy, the median survival time was 40 months; however, only one of these dogs was euthanized because of their in iltrative lipoma (McEntee et al. 2000). Recurrence was not noted in four dogs treated with adjuvant radiation therapy following incomplete surgical excision (McEntee et al. 2000). Hence, if an in iltrative lipoma is not completely excised, adjuvant radiation therapy should be used to minimize the risk of local tumor recurrence. Intermuscular Lipoma Intermuscular lipomas do not metastasize, and local recurrence is rare following surgical treatment (Thomson et al. 1999; Case et al. 2012).

Adjunctive Therapies Applicable Tumors The following discussion will focus on adjuvant therapy (chemotherapy and radiation therapy) for musculoskeletal tumors, including OSA, CSA, synovial cell sarcoma, and localized histiocytic sarcoma. Osteosarcoma and Chemotherapy Osteosarcoma is the most common malignant appendicular bone tumor in dogs, and median survival times following limb amputation alone ranges from 103 to 175 days with 6-, 12- and 24-month survival rates of 45–52%, 11–21%, and 0–4%, respectively (Mauldin et al. 1988; Shapiro et al. 1988; Straw et al. 1991b; Spodnick et al. 1992; Thompson et al. 1992). Chemotherapy after amputation targets micrometastatic disease and signi icantly increases both the time to developing gross metastasis and overall survival time. The most commonly reported chemotherapy protocols are doxorubicin (30 mg/m2 every 2–3 weeks for ive treatments) and/or a platinum-based drug, such as cisplatin (70 mg/m2 every 3 weeks for 4–6 treatments and administered with an aggressive saline diuresis protocol to prevent cisplatin-induced nephrotoxicity) or carboplatin (300 mg/m2 every 3 weeks for 4–6 treatments) (Mauldin et al. 1988; Shapiro et al. 1988; Kraegel et al. 1991; Straw et al. 1991b; Berg et al. 1992, 1995; Thompson and Fugent

1992; Bergman et al. 1996; Chun et al. 2000, 2005; Liptak et al. 2001; Bailey et al. 2003; Kent et al. 2004; Moore et al. 2007; Bacon et al. 2008; Phillips et al. 2009; Saam et al. 2011; Selmic et al. 2014a; Frimberger et al. 2016). There is no difference in survival times if chemotherapy is started preoperatively, intraoperatively, or up to 3 weeks postoperatively (Berg et al. 1995, 1997); however, one study showed unacceptable chemotherapy-related toxicities if the chemotherapy protocol was started 2 days after limb amputation (DeRegis et al. 2003). One study showed a lower proportion of dogs with chemotherapy-related adverse effects when treated with single-agent carboplatin compared to single-agent doxorubicin (Selmic et al. 2014a). Dual-agent chemotherapy protocols have more recently been investigated, but these combinations do not appear to offer any survival advantage compared to single-agent protocols (Liptak et al. 2001; Bailey et al. 2003; Kent et al. 2004; Chun et al. 2005; Bacon et al. 2008; McMahon et al. 2011; Skorupski et al. 2016). Median disease-free intervals and median survival times with single- and dual-agent protocols following limb amputation are 73–257 days and 104–413 days, respectively, with 1- and 2-year survival rates of 33–65% and 16– 28%, respectively (Mauldin et al. 1988; Shapiro et al. 1988; Kraegel et al. 1991; Straw et al. 1991b; Berg et al. 1992, 1995; Thompson and Fugent 1992; Bergman et al. 1996; Chun et al. 2000, 2005; Liptak et al. 2001; Bailey et al. 2003; Kent et al. 2004; Moore et al. 2007; Bacon et al. 2008; Phillips et al. 2009; Saam et al. 2001; Selmic et al. 2014a; Frimberger et al. 2016; Skorupski et al. 2016). One study of 50 dogs with appendicular OSA treated with limb amputation and either six doses of single-agent carboplatin or three doses each of alternating carboplatin and doxorubicin showed a signi icantly longer disease-free interval (425 days compared to 135 days) in dogs treated with singleagent carboplatin (Skorupski et al. 2016). A single continuous subcutaneous infusion of carboplatin (300 mg/m2 total dose over 3–7 days) was reported in 17 dogs following either amputation or limbsparing surgery (Simcock et al. 2012); adverse events were reported in 10 dogs and 7 dogs developed local infections. The median survival time in these dogs was 365 days and there were no associations between survival time and other factors such as postoperative infection (Simcock et al. 2012). In a follow-up to this study, 45 dogs with

appendicular OSA were treated with the same protocol and the overall median survival time was only 196 days (Santamaria et al. 2019). Maintenance therapy with metronomic chemotherapy following fullcourse chemotherapy has also been investigated, but no survival advantage was reported, and there was a signi icantly higher rate of adverse events in dogs treated with combination therapy compared to carboplatin alone (Bracha et al. 2014; London et al. 2015; Matsuyama et al. 2018). The rate of local recurrence of osteosarcoma after limb-sparing in dogs is typically 20–28%, but has been reported as high as 60% (LaRue et al. 1989; Morello et al. 2001; Withrow et al. 2004; Liptak et al. 2006a; Mitchell et al. 2016). Incomplete excision is a prognostic factor for local recurrence (Withrow et al. 2004). One study investigated whether inserting a biodegradable cisplatin-containing implant (OPLA-Pt) into the limb-spare site at the time of surgery would decrease the rate of local recurrence (Withrow et al. 2004). Eighty dogs with OSA were enrolled, split into equal groups (blinded) to receive OPLA with cisplatin or OPLA without cisplatin. Overall, local tumor recurrence was diagnosed in 37 dogs (46.3%), including 13 dogs in the OPLA-Pt group (32.5%) and 24 dogs in the control group (60%). The difference in the local recurrence rate was not signi icant (p = 0.071); however, dogs in the OPLA-Pt group were 53.5% less likely to experience local recurrence than dogs in the control group (Withrow et al. 2004). Following an incomplete resection, the time to local recurrence was signi icantly longer for dogs in the OPLA-Pt group (median of 282 days versus 172 days for the control group, p = 0.01) (Withrow et al. 2004). Another study examined the role of using subcutaneous OPLA-Pt following limb amputation (Mehl et al. 2005). One hundred and ive dogs underwent limb amputation for appendicular OSA, with 39% of dogs being treated with a single surgical implantation of OPLA-Pt sponge between muscle bellies during the closure of the limb amputation site, and the remaining 61% of dogs received two treatments with the insertion of a second OPLA-Pt sponge under the surgical wound 4 weeks after limb amputation. There were no signi icant differences in either disease-free interval or survival times

between these two groups and no detectable advantage to giving a second dose of local delivery cisplatin (Mehl et al. 2005). Osteosarcoma and Immunotherapy Postoperative infection after limb-sparing surgery signi icantly improves median metastasis-free intervals and median survival times (Lascelles et al. 2005; Liptak et al. 2006a; Culp et al. 2014). Interestingly, surgical site infections following limb amputation did not result in a signi icant difference in either median DFI or median survival time compared to amputated dogs without a surgical site infection (Hans et al. 2018). In one study, the median survival time for dogs with a non-infected limb-sparing surgery was 289 days compared to a median survival time of 685 days for dogs with an infected limbsparing surgery (Liptak et al. 2006a). Dogs without a postoperative infection were 2 (Lascelles et al. 2005) to 25 times (Liptak et al. 2006a) more likely to die as a result of their tumor than dogs with a postoperative infection. A similar inding has been reported in people with surgically treated OSA (Jeys et al. 2007). The mechanisms responsible for these prolonged metastasis-free intervals and survival times have not been elucidated, but an upregulation of either cellmediated or humoral antitumor activity has been proposed (Lascelles et al. 2005). The combination of immunotherapy with chemotherapy has been investigated in the adjunctive management of dogs with appendicular OSA following limb amputation. The administration of liposomeencapsulated muramyl tripeptide phosphatidylethanolamine (L-MTPPE) after completion of cisplatin chemotherapy signi icantly increased median survival times (14.4 months compared to 9.8 months), but median survival times were not signi icantly increased if L-MTP-PE was administered concurrently with cisplatin chemotherapy (Kurzman et al. 1995). In a pilot study of 18 dogs with spontaneous appendicular OSA, a recombinant Listeria monocytogenes vaccine expressing a chimeric human HER2/neu fusion protein was administered if dogs had no evidence of metastatic disease after being treated with either limb amputation or limb-sparing surgery and four doses of adjuvant

carboplatin (Mason et al. 2016). Adverse effects of the vaccine were low grade and transient on the day of administration. The vaccine-induced antigen-speci ic interferon-gamma responses against HER2/neu in 15 dogs within 6 months of treatment. The median DFI and median survival time were 615 days and 956 days, respectively, with 1-, 2-, and 3-year survival rates of 78, 67, and 56%. These results were signi icantly better than the historical control group of 18 dogs (treated with amputation and adjuvant chemotherapy with no evidence of metastasis at the end of their chemotherapy course) with a median survival time of 423 days and 1-, 2-, and 3-year survival rates of 55, 28, and 22% (Mason et al. 2016). In another pilot study, 14 dogs with appendicular osteosarcoma were treated with amputation and vaccine-enhanced adoptive T-cell treatment with cytokine boost (Flesner et al. 2020). Vaccine-enhanced adoptive T-cell treatment with cytokine boost combines autologous tumor vaccine with activated cellular therapy and interleukin-2. Toxicities were minimal. The median DFI and median survival time were 213 days and 415 days, respectively, with 5 dogs surviving >730 days. Osteosarcoma and Radiation Therapy Radiation therapy can be used for palliation and curative-intent in the management of dogs with appendicular OSA. Palliative radiation therapy is used most commonly for pain relief in dogs with appendicular OSA that are not surgical candidates for limb amputation (because of concurrent disease or stage III disease with skeletal metastasis) or if an owner has declined curative-intent therapy. The goal of palliative radiation therapy is to provide relief of speci ic clinical signs (decrease the pain and lameness associated with OSA) while resulting in minimal, if any, radiation-induced acute adverse effects. A number of different palliative radiation protocols have been described including 8–10 Gy once weekly for 4 weeks (McEntee et al. 1993; Bateman et al. 1994; Thrall and LaRue 1995; McEntee 1997; Ramirez et al. 1999; Green et al. 2002; Mueller et al. 2005) and two consecutive 8– 10 Gy fractions (Knapp-Hoch et al. 2009; Pagano et al. 2016; Duffy et al. 2018). Radiation therapy reduces local in lammation, minimizes pain,

slows the progression of metastatic lesions, and improves the quality of life in dogs and humans with primary and metastatic lesions (McEntee et al. 1993; Bateman et al. 1994; Thrall and LaRue 1995; McEntee 1997; Ramirez et al. 1999; Anderson and Coia 2000; Green et al. 2002; Mueller et al. 2005; Mayer and Grier 2006; Coomer et al. 2009; KnappHoch et al. 2009; Weinstein et al. 2009; Pagano et al. 2016). A 50–93% response rate is reported with the median onset of response 2–14 days after initiation of radiation therapy and median duration of response 53–130 days (McEntee et al. 1993; Bateman et al. 1994; Thrall and LaRue 1995; McEntee 1997; Ramirez et al. 1999; Green et al. 2002; Mueller et al. 2005; Knapp-Hoch et al. 2009; Pagano et al. 2016). The duration of response is signi icantly improved when less than 50% of the bone is involved and with OSA located in the proximal humerus (Ramirez et al. 1999; Green et al. 2002), although OSA located in the distal radius has also been reported as a favorable site (Knapp-Hoch et al. 2009). Higher cumulative doses, higher intensity of treatment, and the addition of chemotherapy to palliative radiation protocols improve both response rate and duration of response (McEntee 1997; Ramirez et al. 1999; Green et al. 2002; Oblak et al. 2012). The increased survival times reported with the combination of palliative radiation therapy and chemotherapy were based on small numbers of dogs; however, in a more recent study comparing 43 dogs treated with palliative radiation therapy alone and 43 dogs treated with palliative radiation therapy with metronomic lomustine, there was no difference in median survival time (154 days without and 184 days with metronomic lomustine) (Duffy et al. 2018). Palliative radiation therapy is not associated with acute effects and thus does not affect the quality of life (McEntee et al. 1993; Bateman et al. 1994; Thrall and LaRue 1995; McEntee 1997; Ramirez et al. 1999; Green et al. 2002; Knapp-Hoch et al. 2009). Late effects are uncommon but can be seen with high doses per fraction and high total cumulative doses. Repeat radiation for palliative-intent has been described in dogs and humans with minimal adverse effects and a bene icial response in both pain control and survival time (Ramirez et al. 1999; Morris 2000). The median survival time for dogs treated with palliative radiation is 122–313 days (McEntee et al. 1993; Bateman et al. 1994; Thrall and LaRue 1995; McEntee 1997; Ramirez et al. 1999; Green et al. 2002; Knapp-Hoch et al. 2009). Radiopharmaceuticals, such

as samarium, have been used for the palliation of primary and metastatic bone lesions but are expensive and not readily available (Lattimer et al. 1990; Milner et al. 1998). Despite previously being thought to be a radiation-resistant tumor, some reports detail signi icant tumor necrosis in OSA after radiation therapy (Withrow et al. 1990, 1993; Powers et al. 1991). These reports have served as the basis for investigating radiation therapy for curativeintent purposes. Until recently, no curative-intent radiation therapy strategies existed for dogs with appendicular OSA. Since 2004, investigative curative-intent radiation therapy for canine OSA has been described with either curative-intent full-course fractionated external beam protocol (Walter et al. 2005), single megadose radiation therapy as part of an intraoperative extracorporeal irradiation limb-sparing procedure (Liptak et al. 2004c; Boston et al. 2007), and as part of stereotactic radiosurgery (SRS) protocol (Farese et al. 2004; Coomer et al. 2009; Kubicek et al. 2016; Nolan et al. 2020; Martin et al. 2021). With any of these curative-intent strategies, radiation therapy is delivered for local tumor control, and chemotherapy is administered for control of the metastatic disease. Fractionated radiation therapy is commonly used in veterinary medicine but has only been reported with limited success for the treatment of canine OSA. In one study, nine dogs were treated with a Monday-through-Friday protocol, with most dogs receiving 3 Gy per fraction (range, 3–5 Gy) and a total radiation dose of 57 Gy (range, 48–57 Gy). All dogs responded to radiation therapy, and 50% of dogs showed no progression of their local disease based on radiographs and clinical signs before death or the end of the study. The median local control time was 196 days, and the median survival time was 209 days (Walter et al. 2005). These results did not show a substantial improvement over reported palliative protocols and, although treatments were well tolerated, no substantial local disease control or survival bene it was evident. Chemotherapeutic agents, such as cisplatin or carboplatin, are often used in conjunction with de initive radiation therapy for proposed control of metastatic disease and chemical radiopotentiation, but their ef icacy has not been investigated (Heidner et al. 1991; Lana et al. 1997, 2004; Walter et al. 2005).

Recently, moderate radioresistance of canine OSA cell lines was found in vitro. All OSA cell lines studied displayed a relatively low alpha-tobeta ratio and high survival fraction at 2 Gy (Fitzpatrick et al. 2008). Such indings may explain why OSAs may not respond well to conventional fractionated radiotherapy protocols and suggest that larger doses per fraction are needed to induce greater tumor cell kill. Thus, radiation treatment options that deliver large doses per fraction while sparing normal surrounding tissue may be more effective in achieving local tumor control (Farese et al. 2004; Coomer et al. 2009; Kubicek et al. 2016; Nolan et al. 2020; Martin et al. 2021). Stereotactic Radiosurgery/Radiation Therapy (SRS or SRT) Conventional radiation therapy relies on the use of fractionated protocols to minimize damage to surrounding healthy tissues (Farese et al. 2004). Conversely, SRS uses multiple, non-coplanar beams of radiation that are stereotactically focused on the target to deliver the entire radiation dose in a single treatment. Stereotactic radiosurgery minimizes damage to healthy surrounding tissues by relying on the extreme accuracy of radiation delivery to a tumor and a steep dose gradient between the tumor and the surrounding normal tissues. The major bene its of this technique over fractionated protocols include fewer anesthetic episodes and a greater biologic effect on tumor cells (Farese et al. 2004). Stereotactic radiosurgery has been reported in human and veterinary patients for the treatment of intracranial abnormalities and, more recently, appendicular OSA (Farese et al. 2004; Coomer et al. 2009; Kubicek et al. 2016; Nolan et al. 2020; Martin et al. 2021). Pretreatment preparation involved the placement of a targeting array and contrastenhanced CT images. In the irst OSA cases treated with SRS (Farese et al. 2004; Kubicek et al. 2016), treatment plans were initially designed to surround the entire contrast-enhanced region with the 20 Gy isodose line. Since these early cases, a better understanding of the extent of radiation doses that can be tolerated by the surrounding tissues (i.e. skin) has resulted in the use of increased doses such that the periphery of the lesion is covered with the 30–35 Gy isodose line and the center receives approximately 60 Gy (Coomer et al. 2009). This plan is suitable

for proximal humeral tumors, but the proximity of the skin to the outer surface of the bone in the distal radius location makes safe delivery of these doses possible only when the diseased tissue is mostly con ined to the intramedullary portion of the bone. Following localization via the targeting array and infrared camera system, the area of interest is positioned under the isocenter of the linear accelerator, and radiation therapy is performed (6 MV). Immediately following treatment, the localizing array, biteplate, and associated pins are removed, and the dog recovered from anesthesia. Carboplatin (300 mg/m2) is infused intravenously over 20 minutes immediately after completing SRS to potentiate the antitumor effects of radiation and to treat micrometastatic disease. Adjunctive chemotherapy (single-agent carboplatin or alternating doxorubicin and carboplatin) is continued for treatment of micrometastatic disease (Farese et al. 2004; Kubicek et al. 2016). In this report, the survival time for treated cases treated was 363 days (Farese et al. 2004). The median overall survival time was between 290 and 350 days in more recent studies (Kubicek et al. 2016; Nolan et al. 2020; Martin et al. 2021). An additional advantage of SRS is that it can be applied to almost any bone. Dogs have been treated with lesions in the distal radius, proximal and distal ulna, proximal humerus, proximal and distal tibia, proximal and distal femur, and skull. Tumor-associated lameness improved in 84% of dogs, with a maximum improvement within a median of 3 weeks post-treatment and a median duration of lameness improvement of 6 months (Martin et al. 2021). Skin-related effects include alopecia, desquamation, leukotrichia, and hyperpigmentation. Skin desquamation is typically observed three to four weeks after therapy and resolves over the following four weeks. Because the size and shape of the tumor are different with every case, the amount and distribution of radiation delivered are customized for each patient. Case selection is important for the success of SRS because the success rate for long-term control is determined by the size and extent of the lesion (Farese et al. 2004). Smaller lesions with minimal bone lysis and contained within the bone cortices allow greater coverage without injuring the skin. Pathologic fracture can occur following SRS because there is minimal bone regeneration following irradiation, and radiation affects the

vascularity of bone and results in the bone becoming more brittle (Farese et al. 2004; Covey et al. 2014; Kubicek et al. 2016; Martin et al. 2021). In a recent study, the fracture-free rates at 3, 6, and 9 months following SRS were 73, 44, and 38%, respectively; and the median times to fracture were 4.2 months in dogs with subchondral bone involvement and 16.3 months in dogs without subchondral bone involvement (Kubicek et al. 2016). In another study, 41% of dogs had a fracture after SRT, and the risk of fracture was >50% for dogs that lived more than 333 days (Martin et al. 2021). Surgical repair of pathologic fracture subsequent to SRS has been reported in six dogs, with ive of these dogs subsequently developing infections (Covey et al. 2014). To prophylactically manage the risk of post-radiation fracture or treat pathologic fractures, a strategy of SRS and concurrent surgical stabilization of the irradiated bone was reported in 18 dogs (Boston et al. 2017). Unfortunately, major complications were reported 88% of dogs, and hence this approach was not recommended. Alternative management strategies are being investigated in animal models, such as increasing bone stock and strength by treating with zoledronic acid and parathyroid hormone (Curtis et al. 2016). These indings demonstrate a need for improved patient selection for this procedure. For these reasons, smaller lesions with minimal bone lysis are less likely to develop post-treatment pathological fractures. In contrast, larger lesions with an extensive outer soft tissue component are more dif icult to treat effectively with SRS. Preoperative bone biopsy is not recommended since several treated cases have developed pathologic fractures through bone biopsy tracts approximately six months following SRS. If SRS is being considered as a treatment option, then ine needle aspiration rather than needle core biopsy is recommended for diagnostic purposes. Interestingly, an orthotopic model of canine osteosarcoma and SRS has been developed in rats which could allow for evaluation of treatments, in combination with SRS, which may reduce the rate of pathologic fractures such as bisphosphonates, radioprotectants, and parathyroid hormone (Schwartz et al. 2013). This model could also allow the evaluation of adjunctive therapies that could also enhance the anti-tumor effects of radiation (Schwartz et al. 2013).

Bisphosphonates Bisphosphonates are drugs that speci ically inhibit osteoclast function and can have direct anti-neoplastic properties. The most commonly used bisphosphonates in dogs have been pamidronate and zoledronate. They can be used on their own, mostly as palliation for pain or as an adjuvant to radiation therapy and/or chemotherapy. Pamidronate used by itself provided pain alleviation for over 4 months in 28% of dogs (Fan et al. 2007), whereas zoledronate used by itself provided durable improved limb function for over 4 months in 50% of dogs (5 out of 10 dogs) (Fan et al. 2008). Osteosarcoma and Metastatectomy Distant metastasis is the life-limiting event in the majority of dogs with appendicular OSA treated with curative intent. After the diagnosis of metastatic disease, median survival times range between 18 and 66 days (Ogilvie et al. 1993; Boston et al. 2006; Saam et al. 2011; Turner et al. 2017). For dogs with pulmonary metastasis, there is no difference in survival times between untreated dogs and dogs treated with chemotherapy or tyrosine kinase inhibitors (Ogilvie et al. 1993; Kim et al. 2017; Laver et al. 2018). In contrast, metastatectomy of pulmonary lesions can provide both palliation of clinical signs associated with hypertrophic osteopathy (Liptak et al. 2004e) and longer survival times (O’Brien et al. 1993; Turner et al. 2017). Criteria for pulmonary metastatectomy were established in one retrospective study of 36 dogs: metastasis-free interval ≥300 days and less than three metastatic lesions (O’Brien et al. 1993). In this study, the median disease-free intervals following pulmonary metastatectomy were 128 days for dogs with an initial metastasis-free interval ≥300 days and 58 days for dogs with a metastasis-free interval 275 days and less than three lung lesions) had a signi icantly longer median survival time (232 days) and lower hazard of tumor-related death (0.3) than dogs not treated with metastatectomy (49 days). Dogs with metastasis to sites other than the lungs had a signi icantly greater hazard of death than dogs with lungs as the irst and only site of metastasis. Video-

assisted microwave ablation of a metastatic lung lesion has been reported in one dog as an alternative to open metastatectomy (Mazzaccari et al. 2017). Chondrosarcoma Chondrosarcoma is the second most common primary bone tumor in dogs and has a low to moderate metastatic rate (Brodey et al. 1959, 1963, 1974; Brodey and Riser 1969; Ling et al. 1974; Liu et al. 1977). It is generally considered slow to metastasize and the lungs are the most common metastatic location (Popovitch et al. 1994; Waltman et al. 2007; Farese et al. 2009). While not considered a radiation-sensitive tumor, some clinical response has been seen with coarse fraction protocols (Popovitch et al. 1994; Lana et al. 1997, 2004; Dernell et al. 2007). There are no reports of chemotherapy showing a signi icant survival, or local disease control, bene it in dogs or humans, but luoroquinolones have been proposed as a possible adjunctive treatment in people with CSA because of their antichondrocytic effects (Mulhaupt et al. 2001). Synovial Cell Sarcoma Synovial cell sarcomas originate from either the joint capsule or tendon sheaths. They have a moderate to a high metastatic rate depending on tumor grade (Vail et al. 1994). Up to 32% of cases have metastatic disease at the time of diagnosis and 54% by the time of euthanasia (Vail et al. 1994), with lymph nodes and lungs being the most common metastatic locations. Limb amputation is typically recommended and as proximal as possible to prevent stump recurrence (Dernell et al. 2007). There is little information regarding the usefulness of adjuvant therapy (chemotherapy and radiation), but doxorubicin-based protocols have been suggested for non-metastatic grade II and III tumors (Tilmant et al. 1986; Vail et al. 1994). One dog was treated with radiation therapy alone and did not have evidence of tumor recurrence two years after radiotherapy (Vail et al. 1994). Both chemotherapy and radiation therapy warrant further investigation for the treatment of dogs with synovial cell sarcoma. Localized Histiocytic Sarcoma

Histiocytic sarcoma is an aggressive neoplasm of dendritic cells with metastasis to the local lymph nodes and lungs reported in 70–91% of dogs (Affolter and Moore 2000, 2002; Skorupski et al. 2009). In one study of 16 dogs with localized histiocytic sarcoma treated with surgery and CCNU, the median disease-free interval was 243 days, and the median survival time was 568 days. Two dogs developed local recurrence, and 50% developed metastatic disease (Skorupski et al. 2009).

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17 Ethics and Surgical Limits of Surgical Oncology Julius M. Liptak

Introduction Surgical oncology is a discipline reliant on excellent communication skills with clients and referring veterinarians. The irst issue concerning client communication is delivering the bad news that their pet has cancer, especially with all the negative connotations associated with cancer and death. It is normal for human patients, and presumably owners of cancer-bearing pets, to struggle with the news that they have been diagnosed with cancer. Clinicians need to be cognizant of the owner’s feelings and emotional state, and present the news with empathy, understanding, and honesty (Shaw 2020). Other useful recommendations include the use of empathic expression, active listening, and the use of a variety of media in discussing information with owners, including prompt sheets and online resources (Shaw 2020). Some institutions and practices have on-site counselors to facilitate these conversations with owners, particularly owners who are having a dif icult time in coping with the diagnosis of cancer, need assistance in the decision-making process, require support during the treatment of their pet, or identify owners who may be suicidal. When communicating with owners, it is important that the clinician clearly communicate with the owner and check that they understand the information being presented. Some owners may have unrealistic expectations of the longevity and cure following treatment. In human oncology, patient understanding and awareness of the information presented is often limited with frequent misunderstandings about prognosis, the chance of cure, expected survival, and aims of treatment (Shaw 2020). This is understandable considering that many owners are just coping with the news that their pet has cancer and then are expected to process all the information regarding the cancer type, treatment options, and prognosis. Hence it is important that the clinician ensures that the owner understands the information or schedule a second appointment to discuss treatment options and prognosis once the owner has processed the news regarding their pet’s diagnosis. Clients need to be educated about the cancer type (potential causes, biologic behavior, and prognosis), clinical staging tests, and treatment options (surgery, radiation therapy, chemotherapy, and alternative therapies). Without this knowledge, a client cannot make an informed decision on the best treatment option for them and their pet. Owners can also feel empowered by being involved in the decision making for their pet, as do people with cancer (Shaw 2020). Finally, speci ically pertaining to surgical oncology, client communication is essential when discussing potential complications of treatment, operating on dif icult or potentially terminal cases, and considering radical or new procedures. For instance, when operating on a dog with a ruptured splenic mass and hemoabdomen, the surgeon should

always discuss with the owner prior to surgery their preference for euthanasia on the table or recovering a dog if metastatic disease is diagnosed intraoperatively. One of the exciting aspects of surgical oncology is that we occasionally attempt surgeries that are infrequently or have never been performed. When contemplating such a surgery, the surgeon must honestly communicate with the client about the rarity of these procedures and that the outcome is often unknown.

Surgical Limits Present-day surgical oncology has bene ited from the experiences (and mistakes) of many of the forefathers of veterinary surgical oncologists. They have de ined what is and is not possible based on their experiences at a time when surgery was used to treat every oncology case because the other oncology disciplines were in their infancy and less well accepted. However, some of the surgical procedures previously thought of as impossible or inadvisable are now being reinvestigated because of advancements in imaging, anesthesia, analgesia and intensive care, and changes in the expectations of owners and their tolerance of less than perfect cosmetic and functional outcomes. So what are the limits of surgical oncology? The answer is not decisive as the question can be considered from anatomic, functional, and ethical points of view, and perhaps also from a cosmetic perspective.

Anatomic Limits So what can a cat or dog live without? Table 17.1 includes many of the anatomic structures that a cat or dog can live without. There are not many organs or structures that otherwise healthy cats and dogs really need. But, because it can be done does not necessarily mean it should be done and we should always strive to do more good than harm to our patients. The bene its of a surgical procedure should be weighed against its risks when assessing whether a surgical procedure is feasible and viable. These bene its and risks which should be considered include functional and cosmetic outcomes and the likelihood of tumor control.

Functional Limits Functional outcome is essential when considering the feasibility of certain surgical procedures. Anatomically, and even functionally, there are many organs and structures that cats and dogs can live without. But what are the functional limits of what we can resect? While the functional limits are being pushed to greater limits with advancements in medical management and also the tolerance of owners to less than perfect postoperative results, there are some procedures which result in unacceptable functional outcomes. For instance, total pancreatectomy results in dif icult postoperative management and a poor quality of life. Postoperatively, these dogs require management of diabetes mellitus, pancreatic insuf iciency, maldigestion and malabsorption, and short survival times (Rosin et al. 1972; Yoshizawa et al. 1976). So what surgical procedures are limited by their poor and unacceptable functional results? The list is actually very short but includes:

Total laryngectomy (or permanent tracheostomy) in cats (not dogs) Total pancreatectomy (Rosin et al. 1972; Yoshizawa et al. 1976) Bilateral nephrectomy Resection of >60% lung volume? (Liptak et al. 2004; Majeski et al. 2016; Wavreille et al. 2016) Resection of seven or more ribs? (Liptak et al. 2008) There are surgical procedures which do have questionable functional outcomes, but these outcomes are more of an inconvenience for owners and rarely involve intensive medical management postoperatively. Furthermore, these procedures are becoming increasingly more acceptable as our medical knowledge and technical skill improve. For instance, total unilateral mandibulectomy in cats results in good tumor control but the median time to return to voluntary eating is two to four weeks, and some cats will never voluntarily eat and groom again (Northrup et al. 2006). However, we can provide good nutrition to these cats by feeding them through gastrostomy tubes. Ultimately, the decision to proceed with such surgeries is dependent on the owner and their willingness to manage their cat or dog following surgery. Communication is essential in surgical oncology and only with a thorough discussion of the surgical procedure and its complications and outcome can an owner make an informed decision about the care of their pet. There are some procedures which have traditionally been avoided based on early unrewarding experiences, such as total cystectomy (Saeki et al. 2015) and total prostatectomy (Bennett et al. 2018). However, some surgeons are performing these procedures again because owner expectations have changed with time. For both of these procedures, the major surgical complication is urinary incontinence (Saeki et al. 2015; Bennett et al. 2018). Incontinence is more of an inconvenience than a poor functional outcome. Nowadays, owners are much more prepared to manage an incontinent dog. Surgical oncologists should not be limited by a technically feasible procedure if the owner is well informed and consenting, if animals do not require extensive, complicated, and prolonged postoperative management, and if tumor control is good following surgery. Then there are some procedures which have always been quite well accepted, but their functional outcome is less than perfect. While these procedures are technically feasible and animals may be able to function well without these organs or structures, there are other factors and limitations which need to be considered. Again, the decision to proceed with these surgical procedures is dependent on the judgment of a well-informed and educated owner. For instance, a total laryngectomy is possible in a dog, but that dog can never be allowed to swim again, otherwise, they will drown. This may be acceptable for some owners, but not for owners of a hunting dog or a dog that loves to swim. Some mandibulectomy and maxillectomy procedures can affect the ability of a dog to eat and play. While this is often temporary, such outcomes are unacceptable to some owners and perfectly acceptable to other owners. Another classic example is limb amputation. Limb amputation has a de inite social stigma, but cats and dogs can function very well following limb amputation (Dickerson et al. 2015). With improvements in analgesia, it is uncommon for a large breed dog not to walk out of the hospital on three legs the day after surgery. However, the median time to maximal recovery following limb amputation is

four weeks (Kirpensteijn et al. 1999) and some animals will have some decrease in their level of activity. While this decrease in activity is often only mild, many owners will not elect to proceed with limb amputation because of the real or perceived functional results.

Table 17.1 Anatomic structures or organs that can be sacri iced acutely in dogs and cats. Some of this information is based on the literature whereas some is based on the author’s and editors’ experience, which can be argued is anecdotal. Not all dogs or cats will be able to tolerate this extent of resection. This list is not exhaustive.

System

Organ or Anatomic Structure

Alimentary

Maxilla

Mandible

How Much Can Comments Be Resected, or What Can the Dog or Cat Live Without? Total unilateral maxillectomyorbitectomy (Wallace et al. 1992); Radical maxillectomy: bilateral to the level of PM2-PM3, including en bloc nasal planectomy (Lascelles et al. 2004).

Radical mandibulectomy: total unilateral mandibulectomycontralateral rostral mandibulectomy (Boston et al. 2020). Tongue Total glossectomy (Dvorak et al. 2004; Buelow and Marretta 2011; Culp et al. 2013). Esophagus Up to 20% of the cervical esophagus and 50% of the thoracic esophagus (Saint and Mann 1929; Macmanus et al. 1950).

Chaptera

6 Oral tumors

6 Oral tumors

Total glossectomy not 6 Oral tumors recommended in cats.

Circumferential 7 Alimentary partial myotomy may tract reduce anastomotic tension and allow resection of greater lengths of esophagus without dehiscence (Muangombut et al. 1974).

System

Organ or Anatomic Structure

How Much Can Be Resected, or What Can the Dog or Cat Live Without?

Stomach

75%

Comments

Chaptera

Percent amount of stomach that can be excised without concern for postoperative morbidity has not truly been established. Location excised within the stomach is likely key. Preservation of the lower esophageal sphincter and pylorus allows a better quality of life. Total gastrectomy has been reported in a single case report (Sellon et al. 1996). Up to 85% Short bowel (Guthbertson et syndrome can occur al. 1970; Yanoff et with resection of al. 1992)