Veterinary surgical oncology 9780470963210, 0470963212

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Veterinary Surgical Oncology

Veterinary Surgical Oncology Simon T. Kudnig, BVSc, MVS, MS, FACVSc, Diplomate ACVS Melbourne Veterinary Specialist Centre Glen Waverley, Victoria, Australia

Bernard Séguin, DVM, MS, Diplomate ACVS Associate Professor College of Veterinary Medicine Oregon State University Corvallis, Oregon USA

Illustrations by Dave Carlson

A John Wiley & Sons, Inc., Publication

This edition first published 2012 © 2012 by John Wiley & Sons, Ltd. Wiley-Blackwell is an imprint of John Wiley & Sons, formed by the merger of Wiley’s global Scientific, Technical and Medical business with Blackwell Publishing. Registered office: John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, UK Editorial offices: 2121 State Avenue, Ames, Iowa 50014-8300, USA The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, UK 9600 Garsington Road, Oxford, OX4 2DQ, UK For details of our global editorial offices, for customer services and for information about how to apply for permission to reuse the copyright material in this book please see our Website at www.wiley.com/ wiley-blackwell. Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by Blackwell Publishing, provided that the base fee is paid directly to the Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923. For those organizations that have been granted a photocopy license by CCC, a separate system of payments has been arranged. The fee codes for users of the Transactional Reporting Service are ISBN-13: 978-0-8138-0542-9/2012. Designations used by companies to distinguish their products are often claimed as trademarks. All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners. The publisher is not associated with any product or vendor mentioned in this book. This publication is designed to provide accurate and authoritative information in regard to the subject matter covered. It is sold on the understanding that the publisher is not engaged in rendering professional services. If professional advice or other expert assistance is required, the services of a competent professional should be sought. Library of Congress Cataloging-in-Publication Data Veterinary surgical oncology / [edited by] Simon T. Kudnig, Bernard Séguin ; illustrations by Dave Carlson.    p. ; cm.   Includes bibliographical references and index.   ISBN-13: 978-0-8138-0542-9 (hardcover : alk. paper)   ISBN-10: 0-8138-0542-2 (hardcover : alk. paper)   I.  Kudnig, Simon T.  II.  Séguin, Bernard, 1968–   [DNLM:  1.  Neoplasms–surgery.  2.  Neoplasms–veterinary.  3.  Surgery, Veterinary–methods.  SF 910.T8]   LC classification not assigned   636.089'7–dc23 2011032156 A catalogue record for this book is available from the British Library. Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books. Set in 10.5 on 12.5 pt Minion by Toppan Best-set Premedia Limited

Disclaimer The publisher and the author make no representations or warranties with respect to the accuracy or completeness of the contents of this work and specifically disclaim all warranties, including without limitation warranties of fitness for a particular purpose. No warranty may be created or extended by sales or promotional materials. The advice and strategies contained herein may not be suitable for every situation. This work is sold with the understanding that the publisher is not engaged in rendering legal, accounting, or other professional services. If professional assistance is required, the services of a competent professional person should be sought. Neither the publisher nor the author shall be liable for damages arising herefrom. The fact that an organization or Website is referred to in this work as a citation and/or a potential source of further information does not mean that the author or the publisher endorses the information the organization or Website may provide or recommendations it may make. Further, readers should be aware that Internet Websites listed in this work may have changed or disappeared between when this work was written and when it is read.

1  2012

To my wife Narelle, my parents Philip and Judy, my brother Martin, and my sister Mandy for their unending support and understanding, and to my daughter Samantha for the joy and perspective on life you have brought. S.K. To my wife Lisa, my parents Gisèle and René, and my brother Jean-François for their encouragement, support, and love and to my children Alexandre and Gabrielle, for being my inspiration and teaching me so much more. B.S. To Dr. Stephen J. Withrow for teaching us, among many other things: “Success is the ability to move forward in the face of failure.” S.K. and B.S.

Contents

List of Contributors Preface

ix xiii

  1

Principles of Surgical Oncology Nicole Ehrhart, William T.N. Culp

  2

Multimodal Therapy Tania A. Banks

15

  3

Interventional Oncology William T.N. Culp

35

  4

Skin and Subcutaneous Tumors Stewart Ryan, Erik G.H. Wouters, Sebastiaan van Nimwegen, Jolle Kirpensteijn

55

  5

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

87

  6

Oral Tumors 119 Julius M. Liptak, B. Duncan X. Lascelles

  7

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

  8

3

179

  9

Cardiovascular System Simon T. Kudnig, Eric Monnet

329

10

Reproductive System Maurine J. Thomson, Tara A. Britt

341

11

Urinary Tract Nicholas J. Bacon, James P. Farese

365

12

Eyelids, Eye, and Orbit B. Duncan X. Lascelles, Michael Davidson

383

13

Endocrine System Bernard Séguin, Lisa Brownlee, Peter J. Walsh

405

14

Hemolymphatic System Christine C. Warzee

443

15

Nervous System Elaine R. Caplan

465

16

Musculoskeletal System Julius M. Liptak, William S. Dernell, James P. Farese, Deanna R. Worley

491

Index

569

Respiratory Tract and Thorax 273 Marina Martano, Sarah Boston, Emanuela Morello, Stephen J. Withrow

vii

List of Contributors

Sara A. Ayres, DVM, DVSc, Diplomate ACVS Surgeon, Simcoe Veterinary Surgical Referral Ontario, Canada Head and Neck Tumors Nicholas J. Bacon, MA, VetMB, CertVR, CertSAS, Diplomate ECVS, Diplomate ACVS Clinical Assistant Professor, Surgical Oncology University of Florida College of Veterinary Medicine Gainesville, Florida, USA Urinary Tract Tania A. Banks, BVSc, FACVSc Lecturer, Small Animal Surgery The School of Veterinary Science, The University of Queensland Gatton Campus, QLD, Australia Multimodal Therapy Alimentary Tract: Pancreas Sarah Boston, DVM, DVSc, Diplomate ACVS Assistant Professor, Small Animal Surgery (Surgical Oncology) Department of Clinical Studies Ontario Veterinary College, University of Guelph, Guelph, ON, Canada Respiratory Tract and Thorax: Chest Wall Tumors, Laryngeal Tumors, Tracheal Tumors Tara A. Britt, VMD, Diplomate ACVS Veterinary Surgical Services Veterinary Referral Center of Colorado Englewood, CO, USA Reproductive System: The Male Lisa Brownlee, DVM, MS, Diplomate ACVIM (Internal Medicine) Assistant Professor, Department of Clinical Sciences College of Veterinary Medicine, Oregon State University Corvallis, OR, USA Endocrine System

Paolo Buracco, DVM, Diplomate ECVS Professor of Veterinary Surgery School of Veterinary Medicine 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 Elaine R. Caplan, DVM, Diplomate ACVS, Diplomate ABVP Texas Veterinary Oncology, Capital Area Veterinary Specialists, Inc. Austin, TX, USA Nervous System Ryan P. Cavanaugh, DVM, Diplomate ACVS Staff Surgeon, VCA Alameda East Veterinary Hospital Denver, CO, USA Alimentary Tract: Stomach, Liver and Gall Bladder, Pancreas, Small Intestine William T.N. Culp, VMD, Diplomate ACVS Assistant 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; Associate Dean and Director of Veterinary Medical Services College of Veterinary Medicine, North Carolina State University Raleigh, NC, USA Eyelids, Eye, and Orbit ix

x  List of Contributors

William S. Dernell, DVM, MS, Diplomate ACVS Professor and Chair, 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 Associate Professor, Surgical Oncology, Department of Small Animal Clinical Sciences College of Veterinary Medicine, University of Florida Gainesville, FL, USA Urinary Tract Musculoskeletal System Jolle Kirpensteijn, DVM, PhD, Diplomate ACVS, Diplomate ECVS Professor, Surgery, Department of Clinical Sciences of Companion Animals Faculty of Veterinary Medicine, Utrecht University Utrecht, The Netherlands Skin and Subcutaneous Tumors: Skin Tumors General Principles, Soft Tissue Sarcomas Simon T. Kudnig BVSc, MVS, MS, FACVSc, Diplomate ACVS Staff Surgeon, Melbourne Veterinary Specialist Centre Melbourne, Victoria, Australia Cardiovascular System B. Duncan X. Lascelles, BSc, BVSc, PhD, CertVA, DSAS(ST), Diplomate ECVS, Diplomate ACVS Professor of Surgery and Pain Management, Surgery Section and Comparative Pain Research Laboratory 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 Specialist Small Animal Surgeon, Alta Vista Animal Hospital Ottawa, Ontario, Canada Head and Neck Tumors Oral Tumors Musculoskeletal System Marina Martano, DMV, PhD Assistant Professor of Veterinary Surgery School of Veterinary Medicine, University of Turin Grugliasco (TO), 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 Assistant Professor of Veterinary Surgery School of Veterinary Medicine, University of Turin Grugliasco (TO), Italy Respiratory Tract and Thorax: Lung. Stewart Ryan, BVSc, MS, Diplomate ACVS Assistant Professor, Musculoskeletal and Surgical Oncology, Department of Clinical Sciences College of Veterinary Medicine and Biomedical Sciences Colorado State University Fort Collins, CO, USA Skin and Subcutaneous Tumors: Skin Tumors General Principles, Mast Cell Tumors Bernard Séguin, DVM, MS, Diplomate ACVS Associate Professor, Department of Clinical Sciences College of Veterinary Medicine, Oregon State University Corvallis, OR, USA Endocrine System Maurine J. Thomson, BVSc, FACVSc Specialist, Surgical Oncologist Veterinary Specialist Services, Springwood Centre Underwood, Qld, Australia Reproductive System: The Female

List of Contributors  xi

Sebastiaan van Nimwegen, DVM, PhD Department of Clinical Sciences of Companion Animals 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 Assistant Professor, Surgical Oncology, Department of Clinical Sciences College of Veterinary Medicine and Biomedical Sciences, Colorado State University Fort Collins, CO, USA Musculoskeletal System

Peter J. Walsh, DVM, MVetSc, Diplomate ACVS Veterinary Specialty Group West Sacramento, CA, USA Endocrine System

Erik G.H. Wouters, DVM Department of Clinical Sciences of Companion Animals Faculty of Veterinary Medicine, Utrecht University Utrecht, The Netherlands Skin and Subcutaneous Tumors: Skin Tumors General Principles, Soft Tissue Sarcomas

Christine C. Warzee, DVM, Diplomate ACVS Assistant Professor, Surgical Oncology Center for Comparative Oncology, College of Veterinary Medicine Michigan State University East Lansing, MI, USA Hemolymphatic System Stephen J. Withrow, DVM, Diplomate ACVS, Dipomate ACVIM (Oncology) University Distinguished Professor, Surgical Oncology, Department of Clinical Sciences College of Veterinary Medicine and Biomedical Sciences, Colorado State University Fort Collins, CO, USA Respiratory Tract and Thorax: Metastasectomy for Sarcomas

Preface

This book is the result of the collaboration between many contributors who belong to the Veterinary Society of Surgical Oncology (VSSO). At its inception, the impetus to write this book was to help fulfill the goals of the VSSO, which include “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 officers, and graduated veterinarians and veterinary surgeons” (www. vsso.org/aims.html). The field of surgical oncology has greatly expanded in recent years. The creation of the VSSO reflects this growth. The idea of the VSSO was the brainchild of Dr. Steve Withrow. Dr. Withrow is, for many of us, the pioneer of surgical oncology in veterinary medicine, and he instituted the first fellowship in veterinary surgical oncology in 1988. Many of the original members of the VSSO are graduates of the fellowship. Under the leadership of Dr. Julius Liptak, the VSSO was officially created in 2006. In the first year of the VSSO, there were less than 30 members, whereas at the time of publication there are more than 235. Members are from North America, Europe and the United Kingdom, Australia and New Zealand, and Asia. The American College of Veterinary Surgeons (ACVS) has announced that it will recognize further training and expertise in certain fields of surgery, one of which is oncologic surgery. This is affirmation of the expanding body of knowledge in surgery in general as well as that focusing on a certain field is necessary to remain the most proficient. The recognition of advanced training in a field will best promote continued development of novel ideas that will increase our understanding of the diseases and their treatment. We hope this textbook will serve as a repository of knowledge for anyone with an interest in surgical oncology to use and to build upon in the future.

The emphasis of this book is on the surgical aspect of treating small animals afflicted by cancer. This book is not meant to be a full review of small animal oncology as there are several excellent existing textbooks doing so. For instance, this book was not meant to be a comprehensive review of how to diagnose the diseases. Rather, we wanted to concentrate on the surgical procedures, such as those that are not well covered in the literature. Our goal is to assist decision making and to cover controversies in the field. The reader is expected to have a basic knowledge of general surgical principles and surgical techniques. We are indebted to all the contributors for their remarkable contributions. The excellence of the chapters is to their credit and not ours, but any errors are our responsibility. We want to thank Erin Gardner, Erica Judisch, Nancy Turner, Erin Magnani and Susan Engelken from Wiley-Blackwell for their assistance and patience during this whole process, which was for the most part new to both of us. We also want to thank Jane Loftus for copy-editing the chapters; and Dave Johnson and Lorie Kennerly from the Information Technology Services at the College of Veterinary Medicine, Oregon State University, for their assistance when needed. We also thank Jill Bartlett from Oregon State University and Jean-François Séguin for their technical assistance with some of the figures. We need to thank our colleagues, house officers, students, and staff for their support and the motivation they supplied. And most importantly, we thank our families who by extension and default have lived through the creation of this book. Without their support and understanding, this would not have been possible. We hope you find this book helpful in your practice and education and welcome any comments you may have. Simon T. Kudnig and Bernard Séguin

xiii

Veterinary Surgical Oncology

1 Principles of surgical oncology Nicole Ehrhart, William T.N. Culp

Cancer treatment is a rapidly changing and evolving area involving the use of 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 cancer 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 significantly 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. These surgeons have expertise in selecting surgical treatment options in combination with other forms of cancer treatment, as well as knowledge of the benefits and risks associated with a multidisciplinary approach beyond that which can be mastered within a 3-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 the last 14 years. With the development of new treatments such as small molecule inhibitors, gene therapy, and new forms of radiation, 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 the pet owners before surgery is initiated. The efficacy of surgical therapy in any patient with cancer is heavily dependent upon the surgeon’s global under-

standing 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 before 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 owners with enough information to help them make an informed choice regarding the best treatment plan 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 insufficiency, hepatic disease, or osteoarthritis may limit or change specific 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 flat-coated retriever with a femoral bony lesion noted on radiographs that has been referred

Veterinary Surgical Oncology, First Edition. Edited by Simon T. Kudnig, Bernard Séguin. © 2012 by John Wiley & Sons, Ltd. Published 2012 by John Wiley & Sons, Ltd.

3

4  Veterinary Surgical Oncology

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 and concomitant disease Staging diagnostics such as a complete blood count, chemistry profile, urinalysis, thoracic radiographs, and abdominal ultrasound are essential components for the preoperative assessment of veterinary oncology 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 to provide 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 difficult anatomical 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 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 beneficial adjunct to surgery. In human cases of osteosarcoma, neoadjuvant chemotherapy is commonly used prior to surgery and local tumor response (as measured by percentage of tumor necrosis) has been shown to be associated with increased survival. A recent veterinary study showed that neoadjuvant chemotherapy with prednisone administered to a group of dogs with intermediate grade mast cell tumors resulted in tumor size reduction; surgical excision of very large

mast cell tumors or tumors that were in an anatomical 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 to allow a less aggressive surgical margin. Further study is needed to assess the benefit 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 field, 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 fibroblasts and blood vessels (Séguin et al. 2005). Even so, surgery in previously irradiated fields 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 field should be discussed at length prior to deciding if neoadjuvant radiation is warranted.

Surgical Planning Fine-needle aspirate Fine-needle aspiration is often the most minimally invasive technique for obtaining critical information about a newly identified mass prior to surgery. The accuracy of a fine-needle aspirate depends on many factors, including the tumor type, location, and amount of inflammation. Overall sensitivity and specificity of cytology has been reported to be 89% and 100%, respectively (Eich et al. 2000; Cohen et al. 2003). Imaging tools such as ultrasound and fluoroscopy can increase the chance of obtaining a diagnostic sample.

Principles of Surgical Oncology  5

In most patients, a fine-needle aspirate of cutaneous or subcutaneous lesions can be obtained with no sedation and a minimal amount of discomfort. Fine-needle aspiration has been compared to histopathological samples in several studies. In a recent study of the correlation between cytology generated from fine-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% specific for diagnosing neoplasia (Ghisleni et al. 2006). The goal of fine-needle aspiration is to differentiate between an inflammatory or neoplastic process, and if neoplastic, whether the tumor is benign or malignant. In some cases, the specific tumor type can be determined (e.g., mast cell tumor). In other cases, the class of tumor may be identified (e.g., sarcoma), but the specific diagnosis requires histopathology (e.g., chondrosarcoma versus osteosarcoma). The overall purpose of performing the fine-needle aspiration is to guide the staging diagnostics (where to look for metastasis or paraneoplastic diseases) and surgical dose. For example, a fine-needle aspirate of a mass showing normal adipocytes would indicate that the mass is not inflammatory; rather, it is a neoplastic process and is benign (lipoma). Based on the knowledge of the biological behavior of this tumor we would perform no other staging tests and prescribe a minimal surgical dose (marginal resection). Alternatively, if the fine-needle aspirate of a mass indicated carcinoma cells, we would be prompted to perform more advanced staging (three-view thoracic radiographs, abdominal ultrasound, lymph node aspirates) and would prescribe a larger surgical dose. Fine-needle aspiration of internal organs can also be performed and may be helpful in guiding diagnostic and treatment choices. Image guidance should be used when obtaining tissue from fine-needle aspirations of masses within a body cavity. Aspirates of lung and other thoracic organs can be performed safely in most cases. In one study, fine-needle aspiration of lung masses had a sensitivity of 77% and a specificity of 100% (DeBerry et al. 2002). The aspiration of cranial mediastinal masses is beneficial, as thymomas can be diagnosed by cytology (Rae et al. 1989; Atwater et al. 1994; Lana et al. 2006). Cytological 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 a fine-needle aspirate sample. Thymomas will contain both CD4+ and CD8+ lymphoctyes, 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 fineneedle 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 fineneedle aspiration of hepatic neoplasia (Wang et al. 2004). In cases of suspected splenic hemangiosarcoma, fine-needle aspiration is generally not recommended, as an accurate diagnosis is unlikely due to the abundance of blood-filled cavities. Additionally, complications may include severe bleeding from the aspiration site. Fineneedle aspiration of splenic neoplasia such as lymphoma and mast cell tumors is often diagnostic (Hanson et al. 2001). Other tumors in which fine-needle aspiration has been used to obtain diagnostic information include gastrointestinal tumors and bony tumors. The accuracy of fine-needle aspiration in the diagnosis of gastrointestinal neoplasia is often dependent on the type of neoplasia present. For instance, fine-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 specificity of the diagnosis is similar among these neoplastic diseases with fine-needle aspiration (Bonfanti et al. 2006). In a recent report, ultrasound-guided fine-needle aspiration of osteosarcoma lesions was found to have a sensitivity of 97% and specificity of 100% for the diagnosis of a sarcoma (Britt et al. 2007). Another study found that cytology after fine-needle aspiration agreed with incisional and excisional biopsies of bony lesions in 71% of cases (Berzina et al. 2008). As with any procedure, fine-needle aspirates are not without risk. In certain cases, bleeding or fluid 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 fine-needle aspiration 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 can cause massive 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 fine-needle aspiration,

6  Veterinary Surgical Oncology

it remains an effective, inexpensive, and valuable tool in the preoperative planning process. Biopsy Clinicians often use the term biopsy as a nonspecific description of obtaining a tissue sample for histopathological interpretation. For this reason, we will designate biopsy procedures into two major categories: pretreatment biopsy (tissue obtained before treatment initiation) or posttreatment biopsy (tissue obtained at the time of definitive tumor resection). We will also give examples of specific biopsy techniques. All biopsy procedures, whether pretreatment or posttreatment, should be carefully planned with several factors in mind. These factors include known patient comorbidities, anatomical location of the mass, differential diagnoses, biopsy technique, eventual definitive treatment, and any neoadjuvant or 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 do not need general anesthesia. Instrumentation includes a needle core biopsy instrument (automated or manual), no. 11 scalpel blade, local anesthetic, and a 22-gauge 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 bupivicaine. 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 fired, and the instrument is withdrawn. The 22-gauge 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 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 The punch biopsy 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. Instrumentation includes a punch biopsy instrument, no. 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 bupivicaine. For cutaneous masses, an incision is not necessary. For subcutaneous masses, make an incision in the skin over the mass to allow a better sample to be procured. 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, use 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 sufficient to close the incision. The same procedure can be performed on visceral organs. Incisional (wedge) biopsy The incisional biopsy technique is effective for masses in all locations and generates a larger sample for histopathological 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 definitive 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. Obtaining a representative sample of the mass is the most important principle to consider. It is also important to obtain a sample that is deep enough and that contains the actual tumor, rather than just the fibrous 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. Instrumentation includes a no. 11 or no. 15 scalpel blade, local anesthetic, Metzenbaum scissors, forceps, suture, and hemostats. A gelpi retractor or similar selfretaining 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 parallel

Principles of Surgical Oncology  7

incisions are started superficially 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 suture. Posttreatment biopsy (excisional biopsy) The approach to an excisional biopsy varies 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, a fine-needle aspirate should be obtained to discern if a given mass is inflammatory 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 remains after fine-needle aspiration, 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 using a wide excision. If it is deemed that an excisional biopsy can be performed while leaving this option, an excisional biopsy may be considered. Once an excision is performed, the local anatomy is forever altered; both deep and wide tissue planes to the tumor are invaded, providing the opportunity for 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 first 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 (e.g., lipoma), this margin is minimal or even intralesional. In other cases (e.g., soft tissue sarcoma), the margin should be much 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 definitive 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 definitive 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 anatomical 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 using 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 decalcification 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. 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 no. 11 scalpel blade and a Jamshidi needle. 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. Lymph node biopsy Treatment and biopsy of lymph nodes in neoplastic disease remains controversial (Gilson 1995). Removing

8  Veterinary Surgical Oncology

a lymph node or performing an incisional biopsy of a lymph node can aid in staging the patient and assist in determining prognosis or treatment options. The surgical oncologist should have a thorough knowledge of the anatomical location of the probable draining lymph node for a mass in a particular location. The excisional biopsy of superficial lymph nodes such as the mandibular, 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 no. 10 or no. 15 scalpel blade, Metzenbaum scissors, forceps, suture, and suture scissors. 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 superficial tissue overlying the lymph node is bluntly and sharply dissected. The lymph node capsule is then grasped with the forceps and blunt 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. Endoscopic biopsy Esophagoscopy, gastroscopy, duodenoscopy, and colonoscopy are routinely performed in veterinary medicine as minimally invasive techniques to attain biopsy tissue from the gastrointestinal tract. Biopsies attained during these procedures are generally smaller than that which 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 underused modalities, but successful procurement of kidney, bladder, liver, spleen, adrenal gland, pancreas, stomach, intestine, and lung biopsies have been described by 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 per-

formed by minimally invasive techniques (Fagotti et al. 2007). 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 field. Surgeons should avoid contact with 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 flaps can assist in closure (Soderstrom and Gilson 1995; Aiken 2003). 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 field. 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 field as these fluids may be widely dispersed throughout the subcutaneous space during movement. To decrease the risk of recurrence after tumor resection, there are several techniques 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 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 essential that a new set of instruments, gloves, and possibly drapes be used 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

Principles of Surgical Oncology  9

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 fit 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 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 definition “dirty” or incomplete. The surgical techniques used to remove tumors define the type and magnitude of intended surgical margin. When tumors are removed using an intracapsular technique, dissection occurs within the dimensions of the tumor and residual microscopic disease always remains (Soderstrom and Gilson 1995). Marginal excision refers to tumors excised with a 1 cm or less cuff of normal tissue surrounding the mass. Marginal excision may be quite appropriate for certain tumors such as lipomas but is often not sufficient for malignant tumors (Ehrhart and Powers 2007). Wide excision refers to tumors removed with 1–3 cm of normal tissue in all directions, including a deep margin. To achieve wide excision, the mass needs to be removed en bloc and the pseudocapsule and reactive zone should be completely contained within a cuff of normal tissue. Because dissection for a wide excision is intracompartmental, it is distinguished from a radical excision. A radical excision is considered an excision of normal tissue surrounding the mass of greater than 3 cm or the entire anatomical compartment (e.g., amputation). Extracompartmental excision is defined by a plane of excision beyond the anatomical compartment considered to have a cancer-resistant tissue barrier (Soderstrom and Gilson 1995). Special focus is usually placed on mast cell tumors and soft tissue sarcomas when considering surgical margins. These tumor types generally have a bulky mass that is easily palpable; however, microscopic projections

of tumor cells extend out from the main tumor bed (Séguin et al. 2001; Murphy et al. 2004; Ehrhart 2005). These tendrils of tumor cells need to be considered preoperatively so that a proper surgical dose can be determined. Historically, 3 cm margins were recommended for excision of mast cell tumors and soft tissue sarcomas. Recently, though, studies have shown that 2 cm margins are sufficient for complete excision of 91%–100% of grade 2 mast cell tumors (Simpson et al. 2004; Fulcher et al. 2006). Recommendations for surgical margins around soft tissue sarcomas, however, continue to be at least 3 cm (Aiken 2003; Ehrhart 2005; Liptak and Forrest 2007). In many cases, the deep margin of a tumor excision can be less than 2–3 cm from the tumor if removal of one tissue plane deep to the last tissue plane the tumor touches is achieved. For example, if the tumor is freely moveable in the subcutaneous tissue of the thigh, removal of the fascia lata as the deep margin will often be sufficient to achieve a clean margin. On the other hand, if the tumor is attached to the fascia lata, a muscle plane deep to this layer must be removed to achieve a clean margin. Unfortunately, the true definition of a “fascial plane” is lacking in medicine, and specific guidelines remain elusive (Fasel et al. 2007). While to some authors the definition of fascia has included adipose tissue, this concept is not universally supported (Fasel et al. 2007). A current definition of fascia is considered “sheaths, sheets, or other dissectible connective tissue aggregations visible to the unaided eye” (Wendell-Smith 1997; Fasel et al. 2007). Furthermore, fascia can be “considered as gross structures enveloping and/or supporting other formations” (Fasel et al. 2007). These definitions support the removal of a deep layer of connective tissue (not including adipose tissue) when considering a deep margin. When an incomplete margin is noted on histopathological evaluation, the surgeon must decide on the next appropriate course of action. Options include intensive monitoring for recurrence, reexcision, and chemotherapy and radiation therapy. Both human and veterinary studies support early reexcision of a surgical wound bed when an incomplete margin is achieved during the primary surgery (Raney et al. 1982; Gibbs et al. 1997; Bacon et al. 2007). The goal during a reexcision surgery is to achieve tumor-free margins. Therefore, the entire wound bed must be treated as a dirty site and must be completely removed with a margin of normal tissue around it so that all tumor cells and microscopic extensions previously left in the patient will be removed. This always requires a more extensive surgery than the original surgical attempt.

10  Veterinary Surgical Oncology

Palliative and cytoreductive surgery The decision to perform a palliative or cytoreductive surgery is often a difficult one, and the surgeon needs to educate the client and referring veterinarian about the risks and benefits of such surgery. Piecemeal removal (debulking) of a mass should generally only be performed when the mass is physically causing obstruction or altering function. There is little advantage to debulking otherwise, unless the removal results in only microscopic amounts of disease left behind. Palliation of symptoms caused by obstructive masses by removing most of or portions of large masses can temporarily improve quality of life in some cases. This should be performed only when necessary as excessive bleeding can often occur and dehiscence is very common.

Postoperative Considerations Tissue marking As discussed above, following an excisional biopsy, the surgical margins of the mass should be clearly indicated in some way so that the histopathologist can accurately evaluate the mass for complete excision. Several methods have been proposed to do this, including specialized sectioning techniques, suture markers, inking, and the submission of adjacent tissue as a separate sample (Rochat et al. 1992; Mann and Pace 1993; Seitz et al. 1995). Inappropriate sectioning can result in neoplastic cells being noted at the cut margin, and a false-positive result can occur. Sutures can be used to mark a particular area of interest or for tumor orientation, but sutures need to be removed before sectioning to prevent microscopic artifact (Mann and Pace 1993). A sample of tissue surrounding the surgical wound can also be submitted for evaluation. However, this increases the size of the wound bed, and added expense may be seen due to the submission of extra biopsy samples. In general, the marking of tumor margins with inks or dyes is recommended. Several types of inks and dyes have been evaluated, including merbromin, laundry bluing, India ink, alcian blue, typists’ correction fluid, commercial acrylic pigments, and artists’ pigment in acetone (Rochat et al. 1992; Mann and Pace 1993; Seitz et al. 1995; Chiam et al. 2003). Alcian blue has been shown to be the best marking material; however, india ink and commercial kits (Davidson Marking System, IMEB Inc., San Diego, CA) are reasonable alternatives (Seitz et al. 1995). One of the benefits of the commercial kits is that multiple colors are provided. When using these kits, all the margins can be marked in different colors, but at a minimum, the lateral margin can be marked in one color and the deep margin in a different color. Yellow, black, and blue are considered the best

colors to use, whereas red and green are less ideal (Seitz et al. 1995). Guidelines for fixation of surgical tissue specimens Small biopsy samples should be placed in fixative immediately to prevent drying of the sample. Early fixation will initiate changes in the sample that will prevent autolysis and bacterial alteration of the sample (Stevens et al. 1974). In large biopsy submissions, the sample should be sliced evenly to allow more complete fixation (Dernell and Withrow 1998; Ehrhart and Withrow 2007). Many fixatives, including formalin, Bouin’s fluid, chilled isopentane, Zenker’s fluid, and glutaraldehyde have been described in veterinary medicine (Osborne 1974; Stevens et al. 1974), but in general, 10% buffered formalin is sufficient for almost all biopsies. A biopsy sample should be fixed in formalin in a 1:10 solution of tissue to formalin (Ehrhart and Withrow 2007). Frozen sections The use of frozen sections is common in human medicine. (Lessells and Simpson 1976; Kaufman et al. 1986). Frozen sections generate an accurate diagnosis in greater than 97% of human biopsy samples (Lessells and Simpson 1976; Kaufman et al. 1986). The process requires highly trained personnel and equipment specific to the procedure, and thus veterinary facilities that have the capability are limited (Ehrhart 1998). In one veterinary study, the accuracy of frozen sections in determining a specific diagnosis was 83% (Whitehair et al. 1993). In that same study, frozen sections were able to make a determination between neoplastic and nonneoplastic diseases in 93% of cases (Whitehair et al. 1993). Wound healing The veterinary oncology patient has several risk factors that may increase the frequency of complications associated with wound healing (Cornell and Waters 1995). Nutritional compromise and concomitant disease can be treated to improve the outcome of wound healing, but other factors such as tumor type and completeness of surgical excision have to be considered as well. Neoadjuvant and adjuvant therapies such as chemotherapy, radiotherapy, and antiangiogenic medications have also been documented to impair wound healing (Devereux et al. 1979; Cornell and Waters 1995; te Velde et al. 2002; Séguin et al. 2005). Proper surgical technique as described above can be employed to decrease the chance of wound complications. Regular communication with the patient’s owner

Principles of Surgical Oncology  11

both before and after surgery will help to preemptively prepare for complications or aid in rapid identification and intervention when complications arise. Prevention of self-trauma should be routinely discussed with the owner, and methods of prevention such as bandaging or having the patient wear an Elizabethan collar should be included in the postoperative care. Adjuvant therapy The time to discuss the potential need for adjuvant therapy in a tumor patient is prior to any surgical intervention. This allows owners to make informed choices and to better prepare for the financial burden, time required, and potential complications associated with this type of therapy. Failing to properly prepare the client for these additional treatments and the benefits and challenges unique to each one may leave the patient’s owner feeling overwhelmed, underinformed, and may expose the patient to unnecessary morbidity or delay in treatment. Chemotherapy in the adjuvant setting is generally administered after wound healing has been completed. Experimentally, it has been shown that administering certain types of chemotherapy before or at the same time as surgery may retard wound healing (Shamberger et al. 1981; de Roy van Zuidewijn et al. 1986; Lawrence, Talbot et al. 1986; Lawrence, Norton, et al. 1986). By the time a patient is ready for suture or staple removal, a wound is generally healed sufficiently, and chemotherapy may be administered. The results of the biopsy will also be accessible at a similar time, and these can help to guide chemotherapeutic recommendations. Radiation therapy may be administered preoperatively or postoperatively. In general, radiation therapy will slow wound healing. In cases where radiation is administered either before or after surgery, it is important to ensure that there is minimal tension on the wound closure. This requires careful planning prior to and during the initial surgery. In some cases, if local flaps require extensive dissection in areas away from the tumor bed and outside the proposed radiation field, it may be better to delay primary closure until it is known if tumor margins are clean. This will help prevent seeding of tumor cells along the dissection planes where the flap will be raised. In postoperative patients who require radiation therapy but have wound complications such as infection or dehiscence, it is often better to try to manage the wound complication before beginning radiation. This may not always be possible, as tumor remaining in the wound may prevent wound healing. In these cases, it may be necessary to go forward with radiation in an open wound setting. In many cases, once acute effects have resolved, the wound can be closed. In these

cases, strict adherence to the “no skin tension” rule is imperative. While certain basic concepts of surgery will remain static for the treatment of neoplasia, pursuit of better options for our patients will require that the surgical oncologist be able to adapt. It is hoped that the desire for improved outcomes will continue to improve the lives of our patients as well as their owners. Prolonging a quality of life for veterinary patients and advising their owners appropriately about the options that we have to offer should remain our goal as advances in therapy occur.

References Aiken, S.W. 2003. Principles of surgery for the cancer patient. Clin Tech Small An P 18:75–81. Atwater, S.W., B.E. Powers, R.D. Park, et al. 1994. Thymoma in dogs: 23 cases (1980–1991). J Am Vet Med Assoc 205:1007–1013. Bacon, N.J., W.S. Dernell, N. Ehrhart, et al. 2007. Evaluation of primary re-excision after recent inadequate resection of soft tissue sarcomas in dogs: 41 cases (1999–2004). J Am Vet Med Assoc 230:548–554. Barnes, R.F., C.L. Greenfield, D.J. Schaeffer, et al. 2006. Comparison of biopsy samples obtained using standard endoscopic instruments and the harmonic scalpel during laparoscopic and laparoscopicassisted surgery in normal dogs. Vet Surg 35:243–251. Berzina, I., L.C. Sharkey, I. Matise, et al. 2008. Correlation between cytologic and histopathologic diagnoses of bone lesions in dogs: A study of the diagnostic accuracy of bone cytology. Vet Clin Path 37:332–338. Bonfanti, U., W. Bertazzolo, E. Bottero, et al. 2006. Diagnostic value of cytologic examination of gastrointestinal tract tumors in dogs and cats: 83 cases (2001–2004). J Am Vet Med Assoc 229: 1130–1133. Britt, T., C. Clifford, A. Barger, et al. 2007. Diagnosing appendicular osteosarcoma with ultrasound guided fine-needle aspiration: 36 cases. J Small Anim Pract 48:145–150. Chiam, H.W., P.G. Maslen, and G.J. Hoffman. 2003. Marking the surgical margins of specimens: Commercial acrylic pigments are reliable, rapid and safe. Pathology 35:204–206. Cohen, M., M.W. Bohling, J.C. Wright, et al. 2003. Evaluation of sensitivity and specificity of cytologic examination: 269 cases (1999–2000). J Am Vet Med Assoc 222:964–967. Cornell, K. and D.J. Waters. 1995. Impaired wound healing in the cancer patient: Effects of cytotoxic therapy and pharmacologic modulation by growth factors. Vet Clin N Am-Small 25:111–131. DeBerry, J.D., C.R. Norris, V.F. Samii, et al. 2002. Correlation between fine-needle aspiration cytopathology and histopathology of the lung in dogs and cats. J Am Anim Hosp Assoc 38:327–336. Dernell, W.S. and S.J. Withrow. 1998. Preoperative patient planning and margin evaluation. Clin Tech Small An P 13:17–21. De Roy van Zuidewijn, D.B.W., T. Wobbes, T. Hendriks, et al. 1986. The effect of antineoplastic agents on the healing of small intestinal anastomoses in the rat. Cancer 58:62–66. DeRycke, L.M.J.H., J.J. van Bree, and P.J.M. Simoens. 1999. Ultrasoundguided tissue-core biopsy of liver, spleen and kidney in normal dogs. Vet Radiol Ultrasoun 40:294–299. Devereux, D.F., L. Thibault, J. Boretos, et al. 1979. The quantitative and qualitative impairment of wound healing by adriamycin. Cancer 43:932–938.

12  Veterinary Surgical Oncology Drixler, T.A., E.E. Voest, T.J.M.V. van Vroonhoven, et al. 2000. Angiogenesis and surgery: From mice to man. Eur J Surg 166:435–446. Eich, C.S., J.G. Whitehair, S.D. Moroff, et al. 2000. The accuracy of intraoperative cytopathological diagnosis compared with conventional histopathological diagnosis. J Am Anim Hosp Assoc 36:16–18. Ehrhart, E.J. and B.E. Powers. 2007. The pathology of neoplasia. In Small Animal Clinical Oncology, 4th edition, pp. 54–67. Stephen Withrow and David Vail, editors. Philadelphia: Saunders. Ehrhart, N. 1998. Principles of tumor biopsy. Clin Tech Small An P 13:10–16. Ehrhart, N. 2005. Soft-tissue sarcomas in dogs. J Am Anim Hosp Assoc 41:241–246. Ehrhart, N.P. and S.J. Withrow. 2007. Biopsy principles. In Small Animal Clinical Oncology, 4th edition, pp. 147–153. Stephen Withrow and David Vail, editors. Philadelphia: Saunders. Fagotti, A., F. Fanfani, R. Longo, et al. 2007. Which role for pre-treatment laparoscopic staging? Gynecol Oncol 107:S101– S105. Fasel, J.H., J.C. Dembé, and P.E. Majno. 2007. Fascia: A pragmatic overview for surgeons. Am Surgeon 73:451–453. Fulcher, R.P., L.L. Ludwig, P.J. Bergman, et al. 2006. Evaluation of a two-centimeter lateral surgical margin for excision of grade I and grade II cutaneous mast cell tumors in dogs. J Am Vet Med Assoc 228:210–215. Ghisleni, G., P. Roccabianca, R. Ceruti, et al. 2006. Correlation between fine-needle aspiration cytology and histopathology in the evaluation of cutaneous and subcutaneous masses from dogs and cats. Vet Clin Path 35:24–30. Gibbs, C.P., T.D. Peabody, A.J. Mundt, et al. 1997. Oncological outcomes of operative treatment of subcutaneous soft-tissue sarcomas of the extremities. J Bone Joint Surg Am 79:888–897. Gilson, S.D. 1995. Clinical management of the regional lymph node. Vet Clin N Am-Small 24:149–167. Hanson, J.A., M. Papageorges, E. Girard, et al. 2001. Ultrasongoraphic appearance of splenic disease in 101 cats. Vet Radiol Ultrasoun 42:441–445. Kaufman, Z., S. Lew, B. Griffel, et al. 1986. Frozen-section diagnosis in surgical pathology. A prospective analysis of 526 frozen sections. Cancer 57:377–379. Lana, S., S. Plaza, K. Hampe, et al. 2006. Diagnosis of mediastinal masses in dogs by flow cytometry. J Vet Intern Med 20:1161– 1165. Lansdowne, J.L., E. Monnet, D.C. Twedt, et al. 2005. Thoracoscopic lung lobectomy for treatment of lung tumors in dogs. Vet Surg 34:530–535. Lawrence, W.T., T.L. Talbot, and J.A. Norton. 1986. Preoperative or postoperative doxorubicin hydrochloride (adriamycin): Which is better for wound healing? Surgery 100:9–13. Lawrence, W.T., J.A. Norton, A.K. Harvey, et al. 1986. Doxorubicininduced impairment of wound healing in rats. J Natl Cancer Inst 76:119–126. Lessells, A.M. and J.G. Simpson. 1976. A retrospective analysis of the accuracy of immediate frozen section diagnosis in surgical pathology. Br J Surg 63:327–329. Liptak, J.M., W.S. Dernell, N. Ehrhart, et al. 2004. Canine appendicular osteosarcoma: Diagnosis and palliative treatment. Comp Cont Educ Pract 26:172–183. Liptak, J.M. and L.J. Forrest. 2007. Soft tissue sarcomas. In Small Animal Clinical Oncology, 4th edition, pp. 425–454. Stephen Withrow and David Vail, editors. Philadelphia: Saunders. Magne, M.L. 1995. Oncologic applications of endoscopy. Vet Clin N Am-Small 25:169–183.

Mann, F.A. and L.W. Pace. 1993. Marking margins of tumorectomies and excisional biopsies to facilitate histological assessment of excision completeness. Semin Vet Med Surg 8:279–283. McEntee, M.C. 2006. Veterinary radiation therapy: review and current state of the art. J Amer Anim Hosp Assoc 42:94–109. Moore, L.E. 2003. The advantages and disadvantages of endoscopy. Clin Tech Small An P 18:250–253. Murphy, S., A.H. Sparkes, K.C. Smith, et al. 2004. Relationships between the histological grade of cutaneous mast cell tumours in dogs, their survival and the efficacy of surgical resection. Vet Rec 154:743–746. Nyland, T.G., S.T. Wallack, and E.R. Wisner. 2002. Needle-tract implantation following US-guided fine-needle aspiration biopsy of transitional cell carcinoma of the bladder, urethra, and prostate. Vet Radiol Ultrasoun 43:50–53. Ogilvie, G.K. 1998. Interventional nutrition for the cancer patient. Clin Tech Small An P 13:224–231. O’Reilly, M.S., T. Boehm, Y. Shing, et al. 1997. Endostatin: An endogenous inhibitor of angiogenesis and tumor growth. Cell 88:277–285. Osborne, C.A., V. Perman, and J.B. Stevens. 1974. Needle biopsy of the spleen. Vet Clin N Am-Small 4:311–316. Osborne, C.A. 1974. General principles of biopsy. Vet Clin N AmSmall 4:213–232. Powers, B.E., S.M. LaRue, S.J. Withrow, et al. 1988. Jamshidi needle biopsy for diagnosis of bone lesions in small animals. J Am Vet Med Assoc 193:205–210. Rae, C.A., R.M. Jacobs, and C.G. Couto. 1989. A comparison between the cytological and histological characteristics in thirteen canine and feline thymomas. Can Vet J 30:497–500. Raney, R.B., A.H. Ragab, F.B. Ruymann, et al. 1982. Softtissue sarcoma of the trunk in childhood. Cancer 49:2612– 2616. Rawlings, C.A., E.W. Howerth, S. Bement, et al. 2002. Laparoscopicassisted enterostomy tube placement and full-thickness biopsy of the jejunum with serosal patching in dogs. J Am Vet Med Assoc 63:1313–1319. Rochat, M.C., F.A. Mann, L.W. Pace, et al. 1992. Identification of surgical biopsy borders by use of India ink. J Am Vet Med Assoc 201:873–878. Roth, L. 2001. Comparison of liver cytology and biopsy diagnoses in dogs and cats: 56 cats. Vet Clin Path 30:35–38. Séguin, B., N.F. Leibman, V.S. Bregazzi, et al. 2001. Clinical outcome of dogs with grade-II mast cell tumors treated with surgery alone: 55 cases (1996–1999). J Am Vet Med Assoc 218:1120–1123. Séguin, B., D.E. McDonald, M.S. Kent, et al. 2005. Tolerance of cutaneous or mucosal flaps placed into a radiation therapy field in dogs. Vet Surg 34:214–222. Seitz, S.E., G.L. Foley, and S.M. Maretta. 1995. Evaluation of marking materials for cutaneous surgical margins. Am J Vet Res 56: 826–833. Shamberger, R.C., D.F. Devereux, and M.F. Brennan. 1981. The effect of chemotherapeutic agents on wound healing. Int Adv Surg Oncol 4:15–58. Simpson, A.M., L.L. Ludwig, S.J. Newman, et al. 2004. Evaluation of surgical margins required for complete excision of cutaneous mast cell tumors in dogs. J Am Vet Med Assoc 224:236–240. Soderstrom, M.J. and S.D. Gilson. 1995. Principles of surgical oncology. Vet Clin N Am-Small 25:97–110. Stanclift, R.M. and S.D. Gilson. 2008. Evaluation of neoadjuvant prednisone administration and surgical excision in treatment of cutaneous mast cell tumors in dogs. J Am Vet Med Assoc 232:53–62.

Principles of Surgical Oncology  13 Stevens, J.B., V. Perman, and C.A. Osborne. 1974. Biopsy sample management, staining, and examination. Vet Clin N Am-Small 4:233–253. Te Velde, E.A., E.E. Voest, J.M. van Gorp, et al. 2002. Adverse effects of the antiangiogenic agent angiostatin on the healing of experimental colonic anastomoses. Ann Surg Oncol 9:303–309. Vaden, S.L. 2005. Renal biopsy of dogs and cats. Clin Tech Small An P 20:11–22. Wang, K.Y., D.L. Panciera, R.K. Al-Rukibat, et al. 2004. Accuracy of ultrasound-guided fine-needle aspiration of the liver and cytologic

findings in dogs and cats: 97 cases (1990–2000). J Am Vet Med Assoc 224:75–78. Wendell-Smith, C.P. 1997. Fascia: An illustrative problem in international terminology. Surg Radiol Anat 19:273–277. Whitehair, J.G., S.M. Griffey, H.J. Olander, et al. 1993. The accuracy of intraoperative diagnoses based on examination of frozen sections. Vet Surg 22:255–259. Wykes, P.M., S.J. Withrow, and B.E. Powers. 1985. Closed biopsy for diagnosis of bone lesions in small animals. J Amer Anim Hosp Assoc 21:489–494.

2 Multimodal therapy Tania A. Banks

The key to success for the effective management of many cancers in animals today and in the future lies in employing a multipronged attack. Multimodal therapy requires not only a sound understanding of the strengths and weaknesses of each modality used, the tumor’s response to each treatment modality, and an accurate understanding of the various specific toxicities and interactions but also—and most importantly—a cooperative, communicative, interactive, and integrated team. The traditional trilogy in the oncology arsenal, surgery, radiation, and chemotherapy, remains the essence of the current mainstream multimodal protocol using a combination of some or all. The best outcomes will be realized when the multimodal therapy is planned and coordinated. The surgeon talks to and collaborates with the radiation oncologist while involving the medical oncologist from the outset as well. This also includes empowerment and involvement of the pet’s owners and family. These protocols are costly and time-consuming, and they require tweaking and adjustment throughout the course of treatment. A healthy client–doctor relationship is born from careful consultation with all specialists and the owner. All specialists must know the animal’s status and special situation as well knowing the owner. This way nothing is “lost in translation” and confidence is maintained, resulting in a strong sense of trust. Over the years, a volume of experiences has amassed and provided the wisdom to make these firm recommendations: plan, cooperate, and communicate. The surgeon, who operates on an animal with a solid tumor, then refers to a radiation oncologist to “mop up” residual disease has likely done the animal a disservice. Upfront surgical and radiation therapy planning minimizes surgical morbidity and minimizes normal tissue radia-

tion injury while maximizing the efficacy of the union of modalities. In the following sections the technology of multimodal therapy is presented in some detail using specific tumor settings to illustrate them. Underscoring this technology is the philosophy of this introduction and it cannot be overstated: the effective management of cancer in patients is a team event. Surgery remains the mainstay for treating many types of cancer in pets, and the value of a competent surgical oncologist cannot be understated. The type of surgical mind-set, specific knowledge, and technical prowess required is a specialized skill. Such a surgeon appreciates and can deliver what is required to expertly attempt a surgical cure or completely change tack for a palliative or diagnostic approach and employ other modalities synergistically. Radiation therapy as an addition to the available treatment options allows a greater scope and choice of therapy in many instances. Examples of tumors commonly treated with radiation include certain oral tumors, nasal tumors, brain tumors, mast cell tumors, and soft tissue sarcomas. Radiation can be used with palliative (e.g., to palliate bone pain with primary appendicular osteosarcoma) or curative intent and be used on its own or with surgery. For example, radiation can be used with surgery to treat a solid tumor in a location where wide clean 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, fixation, and exact location of mass; plan the radiation field size and shape; determine how to spare normal tissue and include a large enough field; meet the owners; discuss complications, costs, expected outcome;

Veterinary Surgical Oncology, First Edition. Edited by Simon T. Kudnig, Bernard Séguin. © 2012 by John Wiley & Sons, Ltd. Published 2012 by John Wiley & Sons, Ltd.

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16  Veterinary Surgical Oncology

etc. The surgeon’s role in this setting is a delicate, minimal surgery with intent to preserve blood and oxygen supply to the tissue to increase the effectiveness of radiation. A marginal resection to remove all the 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 curative-intent 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 fine, nonirritating (inert) suture material in minimal amounts, obliteration of dead space in the wound, avoidance of tension, postoperative 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 field. 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 field. Radiation can be used postoperatively (as in the above scenario) or preoperatively or intraoperatively, depending on tumor type and location. Sources of radiation therapy include megavoltage (>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, multileaf collimators, custommade blocks, etc. 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 mast cell tumors and hemangiosarcomas. In this setting the surgeon needs to involve the medical oncologist prior to surgery. Chemotherapy also can prolong life postoperatively by addressing systemic metastasis; the classic example is appendicular osteosarcoma in dogs. Chemotherapy can be used immediately postoperatively 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). Bisphosphonates concentrate within areas of active bone remodeling and induce osteoclast apoptosis, which is of therapeutic benefit 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. 2007). Other therapies that can be combined with more traditional therapies such as surgery, radiation, and chemotherapy include gene therapy, immunotherapy, and photodynamic therapy (PDT). Molecular and targeted therapies show great potential. These therapies include gene therapy (e.g., viral and nonviral vectors); targeting signal transduction that regulates cell growth, differentiation, survival, and death (e.g., via inhibition of protein kinase); RNA (ribonucleic acid) interference (the use of double-stranded RNA to cause posttranscriptional gene silencing); antiangiogenic factors (including metronomic chemotherapy and cyclo-oxygenase-2 inhibitors); and telomerase (enzyme that maintains telomeres or the protective structures at ends of chromosomes). Ninety-five percent of all canine cancers are associated with telomerase activity, whereas almost all normal cells have no telomerase activity (Argyle et al. 2007). Embolization treatments include “bland arterial embolization” (without chemotherapy) and chemoembolization (embolization with chemotherapeutic agents) that can be used as 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. 2002). There are several experimental studies of embolization treatments in healthy dogs, including chemoembolization with gemcitabine (Granov et al. 2005), carboplatin (Chen et al. 2004), 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. 2002) and decreased primary tumor size in a dog with a soft tissue sarcoma (Sun et al. 2002). A thinking surgical oncologist is always aware of the animal as a whole and how the behavior of the

Multimodal Therapy  17

specific cancer in the specific patient influences the surgeon’s role. The surgeon is cognizant of paraneoplastic syndromes, appropriate imaging and staging prior to and during surgery, appropriate supportive and follow-up care, and how various modalities can be used

synergistically to achieve maximal outcome with minimal morbidity. Tables 2.1, 2.2, and 2.3 outline various treatment modalities and published outcomes of these treatments for various types of cancers in dogs and cats.

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), vitamin A–related synthetic retinoids. Cryosurgery is used for small lesions, and there are partial responses with piroxicam in dogs. For curative-intent radiation therapy (RT), median survival time (MST) is approximately 8–20 months. Curative-intent RT followed by surgical debulk (13 dogs) has MST of 47 months (Adams et al. 1987; Adams et al. 1998; Adams et al. 2005; Lana et al. 2004; McEntee et al. 1991; Nadeau et al. 2004; Theon et al. 1993). 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). Palliative 3D conformal RT (38 dogs) has overall median progression-free interval of 10 months (Buchholz et al. 2009). Chemotherapy alone (small numbers of dogs) is investigational (Hahn, Knapp, et al. 1992; Langova et al. 2004). Radiation sensitizers (some investigational) is generally not better than RT alone. Other treatments include brachytherapy, immunotherapy, cryotherapy, and PDT (all investigational) (Lucroy, Long, et al. 2003; MacEwen et al. 1977; Thompson et al. 1992; White et al. 1990; Withrow 1982). Transitional cell carcinoma (TCC) (dogs): Bladder/urethra: Surgery includes debulk, stent, bypass (e.g., prepubic cystostomy catheter for palliation if obstructed). Rarely is there complete excision. Nephrectomy is performed if one ureter is obstructed; if both ureters are obstructed, there is no benefit to surgery. Debulking surgery alone for bladder TCC has MST of 109 days (Lengerich et al 1992). One dog treated with resection of proximal urethra and bladder neck and bilateral ureteroneocystostomy and adjuvant chemotherapy for bladder survived 580 days (Saulnier-Troff et al. 2008). Radiation: Complications of urinary incontinence and cystitis occurs with whole-bladder intraoperative radiation (Walker and Breider 1987; Withrow et al. 1989). Coarse fractionation external beam radiation (with mitoxantrone-piroxicam) showed no benefit over mitoxantrone-piroxicam chemotherapy alone (Poirier, Forrest et al. 2004). 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). Medical: Mitoxantrone-piroxicam combination with minimal toxicity has a MST of 291 days (Henry et al. 2003). For piroxicam alone, palliative MST is 195 days (20% alive after 1 year) (Mutsaers et al. 2002). Concurrent antibiotics are commonly needed. PDT: PDT is currently under investigation (Lucroy, Ridgway et al. 2003; Ridgway and Lucroy 2003). Prostatic carcinoma: Prostatectomy is performed for early stage disease confined to prostate capsule (but there is a high rate of urinary incontinence) (Basinger et al. 1989; Hardie et al. 1984). Other treatment modalities include transurethral-resection (TUR) (electrosurgical and investigational; relieves urethral obstruction, but 2 of 3 dogs had perforated urethra) (Liptak, Brutscher et al. 2004); 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); NSAIDs (MST 6.9 months in 16 dogs, compared to 0.7 months with no cancer therapy in 15 dogs) (Sorenmo, Goldschmidt, et al. 2004); intraoperative prostatic radiation (MST for 10 dogs was 114 days) (Turrel 1987a); PDT (investigational) (Lucroy, Bowles et al. 2003; L’Eplattenier et al. 2008); and palliative radiation for skeletal metastasis. (Continued )

Intranasal Carcinoma

Transitional Cell Carcinoma (urogenital)

Table 2.1.  (Continued ) Neoplasia

Researched Treatment Options and Outcomes

Solitary Primary Lung Mass

Surgery (lung lobectomy) is performed. All adjuvant chemotherapy is investigational at this stage: systemic chemotherapy (vinorelbine) (Poirier, Burgess et al. 2004); inhalational chemotherapy (Hershey et al. 1999; Vail et al. 2000); intrapleural chemotherapy for malignant pleural effusion (Moore, Kirk et al. 1991). Resection is done if possible (about 70%), along with chemotherapy (Aronsohn 1985; Atwater et al. 1994; Willard et al. 1980; Martin et al. 1986, especially if concurrent with megaesophagus relating to a poor surgical candidates); radiation therapy has complete to partial responses, and many also received concurrent surgery or chemotherapy (Hitt et al. 1987; Kaser-Hotz et al. 2001; Smith et al. 2001). Treatment of concurrent myasthenia gravis is accomplished with immunosuppressive and or anticholinesterase therapy, H2 blockers, other supportive care. Intestinal: Modalities include surgery with wide margins (at least 5 cm); adjuvant doxorubicin chemotherapy in cats with colonic adenocarcinoma (Slaweinski et al. 1997); intracavitary chemotherapy for carcinomatosis (Moore, Kirk et al. 1991); adjuvant doxorubicin chemotherapy in dogs (Paoloni et al. 2002); piroxicam palliative for rectal tubulopapillary polyps if unresectable or as alternative to surgery (Knottenbelt et al. 2000). Surgery for primary tumor and regional (sublumbar) lymph nodes (repeated surgical removal of metastatic lesions may afford prolonged survival) (Hobson et al. 2006); debulking and omentalization of sublumbar nodes when nonresectable (Hoelzler et al. 2001); adjuvant radiation for local tumor and nodal metastasis; systemic chemotherapy (various protocols) (Goldschmidt and Zoltowski 1981; Williams et al. 2003; Turek et al. 2003; Ross et al. 1991; Bennett et al. 2002). Surgery is the treatment of choice, except for inflammatory carcinoma or if distant metastasis is present. Surgery includes nodulectomy, mammectomy, regional mastectomy, unilateral or bilateral mastectomy, and also lymph node removal for staging. The surgical choice depends on benign versus malignant, size, number, and species (cat versus dog). In cats, adequate surgical treatment combined with adjuvant chemotherapy may be of benefit to prolong survival time over surgery alone. In one paper, the MST of cats that received surgery and doxorubicin was 448 days, and the median disease-free interval (DFI) was 255 days (Novosad et al. 2006). There is no known proven effective adjuvant chemotherapy protocol for malignant or metastatic mammary tumors in dogs. Some preliminary studies show promise; in 14 dogs with stage III disease (T3 N0 M0) and 2 dogs with stage IV disease (any T N1 M0), half had cyclophosphamide and 5-FU, and half had regional mastectomy alone. The dogs receiving adjuvant chemotherapy had improved survival and disease-free interval (Karayannopoulou et al. 2001). Another study showed adjuvant gemcitabine chemotherapy postsurgery in dogs had no benefit (Marconato et al 2008). Doxorubicin and cyclophosphamide or cisplatin has some antitumor effect against mammary adenocarcinoma. Doxorubicin is associated with partial response with duration of 12 and 16 months in 2 dogs with metastatic mammary adenocarcinoma (Hahn, Richardson et al. 1992). Doxorubicin increases membrane viscosity and lipid hydroxyperoxide, and this effect is increased with concurrent medroxyprogesterone acetate (Pagnini et al. 2000). Doxorubicin has better efficacy than platinum drugs, and carboplatin and cisplatin have the same efficacy in mammary tumor cell culture; efficacy is not affected by cell type (adenocarcinoma, solid, mixed cell) (Simon et al. 2001). Piroxicam plus radiation therapy has produced best results with inflammatory carcinoma. In 44 human patients with inflammatory breast carcinoma, an 81% response rate was achieved with combination therapy (fluorouracil, doxorubicin, cyclophosphamide, mastectomy, and adjuvant paclitaxel) (Cristofanilli et al. 2001). Adjuvant chemotherapy is investigational, considered if poor prognostic factors are present (e.g., large, lymph node–positive, invasive, high grade), and administered after complete surgical removal (Lana et al. 2007).

Thymoma

Intestinal

Anal Sac Adenocarcinoma (see Figure 2.1)

Mammary

18

Table 2.1.  (Continued ) Neoplasia

Salivary Gland Carcinoma

Ear Carcinoma

Ovarian Carcinoma

Uterine Carcinoma Insulinoma

Thyroid Carcinoma

Hyperthyroid Cats

Researched Treatment Options and Outcomes Immunomodulation appears ineffective to date (Lana et al. 2007). Ovariohysterectomy early in life is preventative. Ovariohysterectomy as part of treatment is still not proven clearly to be of benefit (Fowler et al. 1974; Brodey et al. 1983; Morris et al. 1998; Yamagami et al. 1996; Sorenmo, Shofer et al. 2000). Tamoxifen is not recommended (Morris et al. 1993). Surgery is used for aggressive removal where possible, along with adjuvant radiation if there is incomplete resection (Carberry et al. 1987; Hammer et al. 2001; Evans and Thrall 1983; Carberry et al. 1988), and chemotherapy (investigational). Surgery is used (conservative if benign, radical if malignant, resectable, and no metastases) (Marino et al. 1994; Marino et al. 1993; London et al. 1996). Radiation is used as an alternative to surgery if unresectable or as adjuvant to incomplete resection (Theon et al. 1994); PDT used for local disease. Ovariohysterectomy: Intracavitary cisplatin for malignant effusion (Moore, Kirk et al. 1991; Olsen et al. 1994). Platinum drugs with tamoxifen used in metastatic human ovarian tumors. Hectate-b significantly reduces tumor burden (Gawronska et al. 2002). Chemotherapy has potential to prolong life in animals with metastatic ovarian cancer. Uterine adenocarcinoma in cats: Treatment is ovariohysterectomy. Role and effectiveness of radiation and chemotherapy is unknown. Modalities include surgery (resection primary, staging, debulking metastases), frequent feeds, prednisolone, streptozotocin, diazoxide, and octreotide (Feldman and Nelson 2004; Leifer et al. 1986; Tobin et al. 1999; Robben et al. 1997; Moore et al. 2002). Dogs: Mobile thyroidectomy (Carver et al. 1995; Klein et al. 1995; Panciera et al. 2004), fixed/ nonresectable radiation therapy treatment of choice 80% for 1-year survival, 72% for 3-year survival (Theon et al. 2000). 131I thyroid ablation can give prolonged survival in dogs with nonresectable thyroid carcinoma, with local/regional tumor MST at 839 days and MST 366 days for metastasis (Adams et al. 1995; Panciera et al. 2004; Peterson et al. 1989; Turrel et al. 2006; Worth et al. 2005). Chemotherapy is considered as adjuvant treatment for nonresectable primary or large primary carcinoma (>27 cm3), bilateral disease, or for gross metastatic disease) (Theon et al. 2000; Jeglum and Whereat 1983; Fineman et al. 1998; Post and Mauldin 1992; Ogilvie et al. 1991; Hammer et al. 1994; Gallick et al. 1993; Leav et al. 1976). Boron neutron capture therapy is investigational (Pisarev et al. 2006). Multinodular adenomatous hyperplasia (70%–75%), solitary benign adenomas (20%–25%), malignant carcinomas (1%–3%) (Bailey and Page 2007). 131I thyroid ablation is treatment of choice: oral antithyroid medication, topical methimasole to pinna, thyroidectomy (Padgett 2002; Flanders 1999), ultrasound-guided percutaneous ethanol injections (Wells et al. 2001), ultrasound-guided percutaneous radiofrequency ablation (Mellary et al. 2003). Preoperative scintigraphy is ideal (Bailey and Page 2007).

19

(a)

(b)

(c)

Figure 2.1.  (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. (Courtesy of Mary-Kay Klein)

20

Table 2.2.  Round cell. Neoplasia

Researched Treatment Options and Outcomes

Mast Cell Tumor

Marginal surgery with adjuvant radiation results in 85%–95% 2-year control for stage 0, grade I or II (Turrel et al. 1988; Al-Sarraf et al. 1996; Frimberger et al. 1997; LaDue et al. 1998). Other modalities include marginal surgery with adjuvant chemotherapy (vinblastine and prednisolone; see Figure 2.2) (Davies et al. 2004), surgery with curative intent (2–3 cm margins depending on grade) (Simpson et al. 2004), vinblastine-prednisolone chemotherapy as adjuvant to surgery for high risk (mucous membrane origin, node positive, high-grade) (Thamm et al. 2006). Chemotherapy may also be used for dogs with multiple cutaneous mast cell tumors. 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). A recent paper suggested dogs with a mitotic index (MI; number of mitoses per 10 high-power fields) is prognostic, with animals with MI = 0 not reaching median survival, animals with MI between 1 and 7 with MST of 18 months, and dogs with MI > 7 with a MST of 3 months (Elston et al. 2009). A higher MI may help identify which subset of grade II mast cell tumors would benefit from adjuvant chemotherapy. Other chemotherapy agents include lomustine, vincristine, prednisolone/ cyclophosphamide/vinblastine, cyclophosphamide/vincristine/prednisolone/hydroxyurea (Elmslie 1997; McCaw et al. 1997; Rassnick et al. 1999; Davies et al. 2004; Thamm et al. 1999; Gerritsen et al. 1988), vinorelbine (Grant et al. 2008), inhibitors of tyrosine kinase (SU11654), both direct antitumor and antiangiogenic activity (London et al. 2003; Liao et al. 2002). 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 confidently attained because of mass location or size or both (Stanclift and Gilson 2008). Multiple myeloma treatment modalities include chemotherapy using melphalan and prednisolone standard, as well as cyclophosphamide, CCNU, chlorambucil, doxorubicin, vincristine (Matus et al. 1986; MacEwen and Hurvitz 1977; Hanna 2005; Drazner 1982; Brunnert et al. 1992; Osborne et al. 1968; Gentilini et al. 2005; Fan et al. 2002; Vail 2007); surgery (stabilization of pathological fractures; see Figure 2.3) (Vail 2007; Banks et al. 2003) with or without adjuvant radiation therapy, bisphosphonates (Vail 2007); tyrosine kinase– inhibitor therapy SU11654 (London et al. 2003). Extramedullary treatment modalities (cutaneous) include conservative surgical resection (can add chemotherapy if local recurrence or incomplete margins) (Rusbridge et al. 1999; Kryiazidou et al. 1989). Radiation alone for stable solitary osseous plasmacytoma (MacEwen et al. 1984; Rusbridge et al. 1999; Meis et al. 1987). Surgery plus radiation for solitary osseous plasmacytoma resulting in an unstable long-bone fracture or surgery with or without radiation for solitary osseous plasmacytoma resulting in neurological compromise (Vail 2007). Various chemotherapy protocols (Boyce and Kitchell 2000; Carter et al. 1987; Cotter and Goldstein 1983; Garrett et al. 2002; Greenlee et al. 1990; Khanna et al. 1998; Keller et al. 1993; MacEwen et al. 1981; MacEwen et al. 1987; Morrison-Collister et al. 2003; Mutsaers et al. 2002; Myers et al. 1997; Page et al. 1992; Postorino et al. 1989; Stone et al. 1991; Valerius et al. 1997; Zenman et al. 1998) immunotherapy (investigational) (MacEwen et al. 1985; Crow et al. 1977; Jeglum et al. 1988; Steplewski et al. 1990; Rosales et al. 1988; Jeglum 1996); radiation therapy for whole body (localize stage I or stage II disease for nasal or CNS lymphoma, palliation of local disease) (Vail and Young 2007); bone marrow transplantation and staged half-body radiation after remission with induction of chemotherapy—both investigational (Williams et al. 2004; Gustavson et al. 2004)—or surgery for solitary lymphoma (early stage I) or solitary extranodal, or splenectomy for massive splenomegaly due to lymphosarcoma (Moldovanu et al. 1966; Brooks et al. 1987) or surgery for obstructive or ruptured gastrointestinal lymphoma (Marks 2001).

Plasma Cell Tumor

Lymphoma

21

(a)

(b)

Figure 2.2.  (A) Terrier breed dog with concurrent multiple mast cell tumors and previous history of having had several other mast cell tumors removed. (B) Same dog as (A), with tumor in a poor prognostic location (prepuce). This dog was treated with multiple marginal resections and adjuvant chemotherapy.

(a)

(b)

Figure 2.3.  (A) Multiple myeloma causing a pathological fracture of T12, treated with surgical stabilization and adjuvant chemotherapy. (B) Same dog as in (A), with surgical stabilization of a subsequent pathological fracture of the humerus. This dog survived approximately 8 months due to a combination of surgery and chemotherapy.

22

Table 2.3.  Mesenchymal. Neoplasia

Researched Treatment Options and Outcomes

Soft Tissue Sarcoma (Schwannoma, neurofibroma, peripheral nerve sheath tumor, etc.)

Surgery, wide margins, with curative intent (Baez et al. 2004; Banks, Straw et al. 2003; Banks, Straw et al. 2004; Dernell, Withrow et al. 1998; Kuntz et al. 1997; Posterino et al. 1988), surgery-marginal resection with adjuvant radiation (Evans 1987; Forrest et al. 2000; Graves et al. 1988; McKnight et al. 2000); systemic chemotherapy of possible benefit for highly anaplastic tumors but as yet unproven for grade III soft tissue carcinomas (Selting et al. 2000). Marginal resection and localized cisplatin chemotherapy into wound bed (OPLA-Pt/ Atrigel) as yet still investigational (Banks and Straw 2003). Metronomic chemotherapy (continuous low-dose chemotherapy) with cyclophosphamide and piroxicam significantly increased disease-free interval for incompletely resected soft tissue sarcomas compared to control dogs (Elmslie et al. 2008). Surgery (Davidson et al. 1997; Hershey et al. 2000; Kuntz CA unpublished data; Lidbetter et al. 2002; McEntee and Page 2001); surgery and radiation therapy (Cohen et al. 2001; Cronin et al. 1998; Bregazzi et al. 2001; Kobayashi et al. 2002), chemotherapy (Barber et al. 2000; Poirier et al. 2004; Bregazzi et al. 2001); immunotherapy (Jourdier et al. 2003; Kent 1993; King et al. 1995; Quintin-Colonna et al. 1996). Careful surgical dissection (peeling out), excellent prognosis (Thomson et al. 1999). Aggressive surgical resection, adjuvant radiation if margins incomplete (McEntee and Thrall 2001). Wide surgical resection with clean margins yields good prognosis (Baez et al. 2004). Adjuvant radiation if incomplete resection. Surgery, usually debulking, pericardiectomy for palliation (surgical or thoracoscopic), intracavitary and/or intravenous chemotherapy (Closa et al. 1999; Dunning et al. 1998; Jackson et al. 1999; Kerstetter et al. 1997; Moore, Kirk et al. 1991; Stepien et al. 2000; Seo et al. 2007; Sparkes et al. 2005; Spugnini et al. 2008). Early metastasis a concern even if complete resection achieved (Liptak and Brebner 2006). Surgery, chemotherapy, radiation therapy (all investigational, as very little reported) (Itoh et al. 2004). Surgery (high amputation is treatment of choice because local recurrence is higher with marginal or wide resection) (Vail et al. 1994); chemotherapy may be of benefit if sarcoma is high grade and there is no metastasis, or if the node is positive (Vail et al. 1994; Tilmant et al. 1986). Adjuvant radiation for incomplete excision investigational. Surgical resection with wide margins is treatment of choice (Lascelles et al. 2003; Schwarz et al. 1991a; Schwarz et al. 1991b; White 1991); if not resectable with clean margins, surgery and radiation therapy (unreported) or radiation therapy alone (palliative) (Thrall 1981). Systemic chemotherapy has no known benefit. For histologically low-grade, biologically high-grade oral fibrosarcoma, prognosis depends upon early diagnosis and aggressive treatment. Prolonged survival can be achieved in some dogs with surgery, radiotherapy alone, surgery and radiotherapy, and radiotherapy and local hyperthermia (Ciekot et al. 1994). For local disease, surgery with wide clean margins (Kudnig et al. 2003; Ramos-Vara et al. 2000; Kosovsky et al. 1991; Wallace et al. 1992; Schwarz et al. 1991a; Schwarz et al 1991b; Overly et al. 2001; MacEwen et al. 1986; Harvey et al. 1981; Hahn et al. 1994); repeat surgery with wide margins or adjuvant radiation therapy if margins incomplete; radiation therapy alone (Freeman et al. 2003; Bateman et al. 1994; Blackwood and Dobson 1996; Theon et al. 1997; Turrel 1987b; Proulx et al. 2003; Farrelly et al. 2004). Regional lymph node metastasis treatment includes surgery and or radiation therapy; chemotherapy (partial responses) (Kudnig et al. 2003; Overly et al. 2001; Rassnick et al. 2001; Page et al. 1991); immunotherapy (investigational) (Alexander et al. 2006; Bergman, Camps-Palau et al. 2003; Bergman, MacEwen et al. 2003; Bergman et al. 2004; Dow et al. 1998; Elmslie et al. 1994; Elmslie et al. 1995; MacEwen et al. 1999; Moore et al. 1991; Quintin-Colonna et al. 1996).

Vaccine-Associated Sarcomas in Cats

Intermuscular Lipoma Infiltrative Lipoma Liposarcoma Mesothelioma

Lymphangiosarcoma Synovial Cell Sarcoma

Oral Fibrosarcoma

Oral Melanoma

(Continued )

23

Table 2.3.  (Continued ) Neoplasia

Researched Treatment Options and Outcomes

Cutaneous Melanoma

Surgical excision is treatment of choice (Bolon et al. 1990; Aronsohn and Carpenter 1990); chemotherapy shows little response (Ogilvie et al. 1991; Moore 1993; Gillick and Spiegle 1987; Rassnick et al. 2001); hyperthermia and intralesional cisplatin/carboplatin (Theon et al. 1991) and PDT (Cheli et al. 1987; Dougherty et al. 1981) have short-lived responses. Radiation therapy likely to be of use if melanoma not surgically excisable (Vail and Withrow 2007). Immunomodulation is investigational (Hogge et al. 1999; Dow et al. 1998; Hajduch et al. 1997; Quintin-Colonna et al. 1996; Alexander et al. 2006; MacEwen et al. 1999; Bergman et al. 2006; Bianco et al. 2003; Gyorffy et al. 2005). Surgery (amputation/limb-spare) (Vasseur 1987; Berg et al. 1992; LaRue et al. 1989; Thrall et al. 1990; Withrow et al. 1993; Morello et al. 2003; Buracco et al. 2002; Ehrhart 2005; Tomamassini et al. 2000; Ehrhart et al. 2002; Rovesti et al. 2002; Seguin et al. 2003; Pooya et al. 2004; Liptak, Dernell, et al. 2004; Huber et al. 2000); hemipelvectomy (Straw et al. 1992); partial scapulectomy (Trout et al. 1995; Kirpensteijn et al. 1994); ulnectomy (Straw et al. 1991). Local chemotherapy as adjuvant to limb-sparing (OPLA-Pt) reduced local recurrence rate (Straw et al. 1994; Withrow et al. 2004). Local chemotherapy (isolated limb perfusion) (Van Ginkel et al. 1995) as adjuvant to limb-sparing (investigational); radiation therapy to primary site (palliative as alternative to amputation/limb-spare) (McEntee et al. 1993; Ramirez et al. 1999; Mueller et al. 2005; Green et al. 2002; Heidner et al. 1991); adjunctive to limb-spare (Thrall et al. 1990; Withrow et al. 1993), radioisotopes (Milner et al. 1998; Aas et al. 1999); chemotherapy (various protocols) adjuvant to limb-spare or amputation (clear benefit) (Thompson and Fugent 1992; Bergman et al. 1996; Berg et al. 1995; Berg et al. 1997; Kent et al. 2004); chemotherapy neoadjuvant to limb-sparing to downstage disease presurgery (Withrow et al. 1993; O’Brien et al. 1996); chemotherapy as an adjuvant to palliative radiation (role unclear) (Walter et al. 2005). Surgery as cure of local disease, prolonged survival if local disease cured (MST 14 months even if metastasis present at diagnosis) (Dernell, Straw et al. 1998). If surgical removal not possible, consider surgical debulk plus adjuvant radiation therapy (Straw et al. 1989). Wide surgical excision significantly improves survival. Median survival time is 540 days treated with amputation alone (Popovitch et al. 1994); chest wall resection MST 1,080 days (Pirkey-Ehrhart et al. 1995); wide surgical excision for nonnasal sites MST of 3,097 days and did not reach MST (Waltman et al. 2007); and MST 979 days for 25 dogs with appendicular chondrosarcoma treated with amputation alone, although grade was found to be prognostic (Farese et al. 2009). Debulking and adjuvant radiation therapy if location is not amenable to curative resection, to radiation alone (Popovitch et al. 1994; Lana et al. 1997), or have objective responses to coarse fraction radiation alone (Dernell 2007). Metastasis still occurs in about 25%, even after surgical resection. Grade may be prognostic for survival (Waltman et al. 2007; Farese et al. 2009). Dogs: Stage I surgery (MST 780 days), stage II and III surgery (and adjuvant doxorubicin chemotherapy should be considered) (Ward et al. 1994). Twenty-one dogs with subcutaneous (17) and intramuscular (4) hemangiosarcomas, with adequate local tumor control and no metastasis at presentation, were treated with adjuvant doxorubicin. Five dogs also received adjuvant radiation therapy. The MST for subcutaneous HSA was 1,189 days and for intramuscular was 272.5 days (Bulakowski et al 2008). Cats: Wide surgical excision (metastasis occurs less frequently than dogs, but adjuvant chemotherapy may have a role, depending on the case) (Miller et al. 1992; Kraje et al. 1999; McAbee et al. 2005). Radiation therapy is considered adjuvantly if incompletely resected local disease.

Appendicular Osteosarcoma

Multilobular Osteochondrosarcoma Chondrosarcoma

Cutaneous Hemangiosarcomas (HSA)

24

Multimodal Therapy  25 Table 2.3.  (Continued ) Neoplasia

Researched Treatment Options and Outcomes

Visceral HSA

Surgery (e.g., splenectomy) (Spangler and Culbertson 1992; Spangler and Kass 1997; Brown et al. 1985; Sorenmo, Baez, et al. 2004; Prymak et al. 1988); adjuvant chemotherapy of various types can be considered for splenic hemangiosarcomas, with median survival times of 141–179 days reported (Ogilvie et al. 1996; Hammer et al. 1991; Sorenmo, Duda, et al. 2000; Sorenmo, Baez et al. 2004; Sorenmo, Samluk, et al. 2004; Sorenmo et al. 1993; Vail et al. 1995). Immunotherapy (Vail et al. 1995) and angiogenic therapy are investigational (Sorenmo, Duda, et al. 2000). Localized (skin/subcutis): Aggressive surgery with clean margins (Affolter and Moore 2002); adjuvant radiation therapy if incomplete resection; adjuvant chemotherapy (unknown role but likely to be warranted due to high metastatic potential) (Liptak and Forrest 2007). Disseminated/malignant histiocytosis: Chemotherapy can give durable partial responses but is generally unrewarding (Skorupski et al. 2003). Prognosis good with complete surgical resection.

Histiocytic Sarcomas

Uterine Leiomyoma and Leiomyosarcoma in Dogs Vaginal and Vulval Tumors

Most are benign (leiomyoma and fibroma in cat, leiomyoma and lipoma in dog).

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32  Veterinary Surgical Oncology Spugnini, E.P., S. Crispi, A. Scarabello, et al. 2008. Piroxicam and intracavitary platinum-based chemotherapy for the treatment of advanced mesothelioma in pets: Preliminary observations. J Exp Clin Cancer Res 19(27):6. Stanclift, R.M. and S.D. Gilson. 2008. Evaluation of neoadjuvant prednisone administration and surgical excision in treatment of cutaneous mast cell tumors in dogs. J Am Vet Med Assoc 232:53–56. Stepien, R.L., N.T. Whitley, and R.R. Dubielzig. 2000. Idiopathic or mesothelioma-related pericardial effusion: Clinical findings and survival in 17 dogs studied retrospectively. J Small Anim Pract 41:342–347. Steplewski, Z., C. Rosales, K.A. Jeglum, et al. 1990. In vivo destruction of canine lymphoma with adjuvant canine monoclonal antibodies. In Vivo 4:231–234. Stone, M.S., M.A. Goldstein, and S.M. Cotter. 1991. Comparison of two protocols for induction of remission in dogs with lymphoma. J Am Anim Hosp Assoc 27:315–321. Straw, R.C., R.A. LeCouteur, B.E. Powers et al. 1989. Multilobular osteochondrosarcoma of the canine skull: 16 cases (1978–1988). J Am Vet Med Assoc 195:1764–1749. Straw, R.C., S.J. Withrow, E.B. Douple, et al. 1994. The effects of cisdiamminedichloroplatinum II released from D,L,-polylactic acid implanted adjacent to cortical allografts in dogs. J Orthop Res 12:871–877. Straw, R.C., S.J. Withrow, and B.E. Powers. 1991. Primary Osteosarcoma of the ulna in 12 dogs. J Am Anim Hosp Assoc 27:323–326. Straw, R.C., S.J. Withrow, and B.E. Powers. 1992. Partial or total hemipelvectomy in the management of sarcomas in seven dogs and two cats. Vet Surg 21:183–188. Sun, F., J. Hernandez, J. Ezquerra, et al. 2002. Angiographic study and therapeutic embolization of soft-tissue fibrosarcoma in a dog: Case report and literature. J Am Anim Hosp Assoc 38(5):452–457. Thamm, D.H., E.A. Mauldin, and D.M. Vail. 1999. Prednisolone and vinblastine chemotherapy for canine mast cell tumor: 41 cases (1992–1998). J Vet Int Med 13:491–497. Thamm, D.H., M.M. Turek, and D.M. Vail. 2006. Outcome and prognostic factors following adjuvant prednisolone/vinblastine chemotherapy for high-risk canine mast cell tumor: 61 cases. J Vet Med Sci 68:581–587. Theon, A.P., P.Y. Barthez, B.R. Madewell, et al. 1994. Radiation therapy of ceruminous gland carcinoma in dogs and cats. J Am Vet Med Assoc 205:566–569. Theon, A.P, B.R. Madewell, M.F. Harb, et al. 1993. Megavoltage irradiation of neoplasms of the nasal and paranasal cavities in 77 dogs. J Am Vet Med Assoc 202:1469–1475. Theon, A.P., B.R. Madewell, A.S. Moore, et al. 1991. Localised thermocisplatin therapy: A pilot study in spontaneous canine and feline tumors. Int J Hyperthermia 7:881–892. Theon, A.P., S.L. Marks, E.S. Feldman, et al. 2000. Prognostic factors and patterns of treatment failure in dogs with unresectable differentiated thyroid carcinomas treated with megavoltage irradiation. J Am Vet Med Assoc 216:1775. Theon, A.P., C. Rodriguez, and B.R. Madewell. 1997. Analysis of prognostic factors and patters of failure in dogs with malignant oral tumors treated with megavoltage irradiation. J Am Vet Med Assoc 210:778. Thompson, J.P., N. Ackerman, J.R. Bellah , et al. 1992. 192Iridium brachytherapy, using an intracavitary afterload device, for treatment of intranasal neoplasms in dogs. Am J Vet Res 53:617–622. Thompson, J.P. and M.J. Fugent. 1992. Evaluation of survival times after limba amputation, with and without subsequent administration of cisplatin, for treatment of osteosarcoma in dogs: 30 cases (1979–1990). J Am Vet Med Assoc 200:531–533.

Thomson, M.J., S.J. Withrow, W.S. Dernell, et al. 1999. Intermuscular lipomas of the thigh region in dogs: 11 cases. J Am Anim Hosp Assoc 35:165–167. Thrall, D.E. 1981. Orthovoltage radiotherapy of oral fibrosarcomas in dogs. J Am Vet Med Assoc 172:159–162. Thrall, D.E., S.J. Withrow, B.E. Powers, et al. 1990. Radiotherapy prior to cortical allograft limb-sparing in dogs with osteosarcoma: A dose response assay. Int J Rad Onc Biol Phys 18:1354–1357. Tilmant, L.L., N.T. Gorman, N. Ackerman, et al. 1986. Chemotherapy of synovial cell sarcoma in a dog. J Am Vet Med Assoc 188:530–532. Tobin, R.L., R.W. Nelson, M.D. Lucroy, et al. 1999. Outcome of surgical versus medical treatment of dogs with beta cell neoplasia: 39 cases (1990–1997). J Am Vet Med Assoc 215:226. Tomamassini, M., N. Ehrhart, A. Ferretti, et al. 2000. Bone transport osteogenesis for limb salvage following resection of primary bone tumors: Experience with 6 cases (1991–1996). Vet Comp Orthop Trauma 23:43–51. Trout, N.J., M.M. Pavletic, and K.H. Kraus. 1995. Partial scapulectomy for the management of sarcoma in three dogs and two cats. J Am Vet Med Assoc 207:585–587. Turek, M.M., L.J. Forrest, W.M. Adams, et al. 2003. Postoperative radiotherapy and mitoxantrone for anal sac adenocarcinoma in the dog: 15 cases (1991–2001). Vet Comp Oncol 1:94–104. Turrel, J.M. 1987a. Intraoperative radiotherapy of carcinoma of the prostate gland in ten dogs. J Am Vet Med Assoc 190:48–52. Turrel, J.M. 1987b. Principles of radiation therapy. In Veterinary Cancer Medicine. GH Thielen and BR Madewell editors. Philadelphia: Lea and Febiger. Turrel, J.M., B.E. Kitchell, L.M. Miller, et al. 1988. Prognostic factors for radiation treatment of mast cell tumors in 85 dogs. J Am Vet Med Assoc 226:1368–1374. Turrel, J.M., M.C. McEntee, B.P. Burke, et al. 2006. Sodium iodide I 131 treatment of dogs with nonresectable thyroid tumors: 39 cases (1990–2003). J Am Vet Med Assoc 15:229:542–548. Vail, D.M. 2007. Plasma cell tumors. In Withrow & MacEwen’s Small Animal Clinical Oncology, 4th edition, pp. 769–784. S.J. Withrow and D.M. Vail, editors. St Louis: Saunders. Vail, D.M., A.E. Hershey, and A.S. Moore. 2000. Efficacy of adjuvant inhalational chemotherapy following surgical cytoreduction in dogs with spontaneously arising node positive primary lung cancer. Proceedings Annual Meeting of American Association for Cancer Research, San Francisco, (abstract 1272). Philadephia: American Association for Cancer Research. Vail, D.M., E.G. MacEwen, I.D. Kurzman, et al. 1995. Liposomeencapsulated muramyl tripeptide phosphatidylethanolamine adjuvant immunotherapy for splenic haemangiosarcoma in the dog: A randomised multi-institutional clinical trial. Clin Cancer Res 1:1165–1170. Vail, D.M., B.E. Powers, D.M. Getzy, et al. 1994. Evaluation of prognostic factors for dogs with synovial cell sarcoma: 36 cases (1986– 1991). J Am Vet Med Assoc 205:1300–1307. Vail, D.M. and K.M. Young. 2007. Canine lymphoma and lymphoid leukaemia. In Withrow & MacEwen’s Small Animal Clinical Oncology, 4th edition, pp. 699–733. S.J. Withrow and D.M. Vail, editors. St Louis: Saunders. Vail, D.M. and S.J. Withrow. 2007. Tumors of the skin and subcutaneous tissues. In Withrow & MacEwen’s Small Animal Clinical Oncology, 4th edition, pp. 375–401. S.J. Withrow and D.M. Vail, editors. St Louis: Saunders. Valerius, K.D., G.K. Ogilvie, C.H. Mallinckrodt, et al. 1997. Doxorubicin alone or in combination with asparaginase, followed by cyclophosphamide, vincristine, and prednisolone for treatment of

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3 Interventional oncology William T.N. Culp

Interventional radiology (IR) is a specialty that uses different imaging modalities to direct minimally invasive diagnostic and therapeutic procedures. IR has become a well-established and integral speciality in human medicine and is rapidly growing in veterinary medicine. The influx of IR techniques in veterinary medicine allows veterinary clinicians the ability to offer patients advanced treatment options that were previously unavailable. Interventional oncology (IO) is a subspecialty of IR that is focused on the treatment of oncologic disease. When performing IO procedures, it is essential for the veterinary clinician to have a firm grasp of different imaging modalities and basic surgical procedures, as surgically approaching blood vessels is often neces­sary. IO procedures such as vascular stenting, intra­arterial chemotherapy, and transarterial embolization/ chemoembolization are performed intravascularly, and specialized sheaths, guidewires, and catheters are needed for these interventions. Nonvascular diseases such as malignant obstructions and effusions can also be treated with IO techniques and involve the placement of stents and long-term catheters. Many of the current applications of IO in veterinary patients are palliative; in these cases, the primary goal is to improve quality of life while causing minimal morbidity. IO can also provide treatment options in cases that were previously considered untreatable. Reports on the use of IO in veterinary patients are limited, but investigation of IO applications in human medicine offers insight into the vast benefits that this expanding specialty can offer for our veterinary patients. A systematic discussion of the imaging, instrumentation, and techniques involved in IO will be discussed below.

Imaging A complete knowledge of the vascular anatomy is mandatory for performing vascular interventions. Additionally, the interventional radiologist should have a thorough understanding of the imaging modalities and contrast agents that are used to perform IO procedures. While imaging modalities such as fluoroscopy, computed tomography, and magnetic resonance imaging are commonly employed by veterinary clinicians, the use of these modalities for IO treatments is largely unreported, aside from isolated case reports and small case series. Modalities Stenting procedures can be performed solely with digital radiography, although fluoroscopy is superior as it allows for real-time evaluation of the anatomy. Fluoroscopy is mandatory when performing IO procedures that require vascular interventions. A fluoroscopy unit (Carm) with specifications including digital subtraction, road-mapping ability, collimation, and low patient radiation dosing are ideal. Ceiling mounting should be pursued when possible, and the C-arm should have the ability to acquire complex oblique views. Newer units allow the interventional radiologist to perform image acquisition and most other C-arm operations at the bedside, eliminating the need for an assistant to perform these tasks in a control room. While angiography performed with fluoroscopic guidance allows for excellent evaluation of the direction and velocity of blood flow, the images obtained are in two-dimensional planes and only display the lumen of the vessel (Green and Parker 2003). Computed tomographic angiography (CTA) and magnetic resonance

Veterinary Surgical Oncology, First Edition. Edited by Simon T. Kudnig, Bernard Séguin. © 2012 by John Wiley & Sons, Ltd. Published 2012 by John Wiley & Sons, Ltd.

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angiography (MRA) are rapidly developing imaging modalities that have certain advantages over fluoroscopy, including noninvasive angiographic image acquisition, less patient postprocedure discomfort, and volumetric and cross-sectional image analysis (Green and Parker 2003; Hellinger and Rubin 2006; Thornton and Grist 2006). The volumetric and cross-sectional image analysis that is obtained with CTA and MRA allows vessels to be evaluated in multiple directions with a single scan, whereas several images and injections of contrast are necessary to gain the same information using fluoroscopy (Hellinger and Rubin 2006). Advances are being made that allow CTA and MRA to be performed simultaneously with interventional techniques, which may result in more efficient and accurate IO procedures in the future (Ladd et al. 2000; Hellinger and Rubin 2006; Thornton and Grist 2006; Kos et al. 2008). Ultrasound has many applications in IR. Many of the disease processes that may require IO treatments can be diagnosed by ultrasonography. In dogs, hepatocellular carcinoma, a tumor commonly treated by chemoembolization and radiofrequency ablation in humans (Okusaka et al. 2009; Hiraoka et al. 2010), is easily identified by abdominal ultrasound (Liptak, Dernell et al. 2004). In one study of dogs with hepatocellular carcinoma, diagnosis of a hepatic mass was made with ultrasound in 93.5% of cases (Liptak, Dernell et al. 2004). Other tumors that may require an IO treatment, such as urethral, colonic, and thyroid neoplasia, can also be evaluated by ultrasound (Hume et al. 2006; Weisse et al. 2006; Barber 2007). In a recent case series of dogs with masses obstructing hepatic venous outflow, masses were often identified by ultrasonography (Schlisksup et al. 2009). In addition to the diagnostic utility of ultrasound, this modality is regularly employed in humans to aid in obtaining vascular access (to initiate the Seldinger technique) during performance of IR procedures (Longo et al. 1994; Dodd et al. 1996; Ahmad et al. 2008; Arthurs et al. 2008). Ultrasound can also be used to perform procedures, including the placement of drainage catheters, percutaneous biopsies, percutaneous ethanol injection of hepatic neoplasia, and radiofrequency ablation (Longo et al. 1994; Dodd et al. 1996; Solbiati 1998). Contrast agents Contrast agents are required components of most intravascular procedures and many stenting procedures. The predominant contrast agents used for angiography include iodinated agents, gadolinium-based agents, and carbon dioxide (Ehrmann et al. 1994; Moresco et al. 2000; Spinosa et al. 2000; Spinosa et al. 2001; Brown et al. 2003; Namasivayam et al. 2006; Bui et al. 2007). Iodinated contrast agents are available in both ionic and nonionic forms; nonionic agents are less osmolar than

their ionic counterparts (Singh and Daftary 2008). Severe reactions are reported to occur with similar incidence among all iodinated contrast agents, but mild and moderate contrast reactions occur more commonly with the use of higher osmolality iodinated contrast agents (Singh and Daftary 2008). Nephrotoxicity is a major potential complication associated with the use of iodinated contrast agents and has become the third most common cause of acute renal failure in humans (Akgun et al. 2006). The most commonly used iodinated contrast agents are the nonionic monomers such as iohexol, iopromide, iopamidol, and ioversol (Dickinson and Kam 2008). Gadolinium-based contrast agents and CO2 are used most commonly in patients who have had a previous adverse reaction to an iodinated contrast agent and in those patients with an increased risk for development of nephrotoxicity (Moresco et al. 2000; Spinosa et al. 2000; Spinosa et al. 2001; Dickinson and Kam 2008), although some recent studies have reported nephrotoxicity in association with gadolinium contrast usage (Akgun et al. 2006; Ergün et al. 2006). Agents such as gadopentetate dimeglumine, gadodiamide, gadoteridol, and gadoversetamide are the most readily available gadolinium-based contrast agents (Akgun et al. 2006) and are used when previous CO2 usage has resulted in a suboptimal study due to bowel gas artifacts or as a supplement to CO2 angiography (Spinosa et al. 2000; Spinosa et al. 2001). Gadolinium-based contrast agents produce less detailed contrast studies as compared with iodinated agents and are therefore less useful for angiography during IR procedures (Spinosa et al. 2000). When using gadolinium-based contrast agents, digital subtraction angiography is recommended to compensate for the less detailed study that is otherwise obtained (Spinosa et al. 2000). To outline a hollow viscus such as the esophagus, urethra, and colon, substances such as barium and iodinated contrast agents have been used (Hume et al. 2006; Weisse et al. 2006; Farese et al. 2008). In a recent study of esophageal tumors in dogs, barium sulfate was found to be useful in identifying mass location (Farese et al. 2008). In dogs, iodinated contrast agents have been used to evaluate urethral obstructions prior to urethral stenting (Weisse et al. 2006). Additionally, an iodinated contrast agent was used prior to colonic stenting to delineate colonic obstructions secondary to adenocarcinoma in cats (Hume et al. 2006).

Instrumentation and Implants Access needles Traditional hypodermic needles or over-the-needle catheters (Figure 3.1) can be used to puncture vessels

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(a)

(b)

(c)

(d)

Figure 3.1.  Interventional oncology instrumentation. From left to right: (A) 18-gauge over-the-needle catheter (left), 22-gauge overthe-needle catheter (right). (B) 0.035-inch hydrophilic guidewire. (C) Dilator and vascular access sheath. (D) Catheter with angled-tip.

when obtaining vascular access using the Seldinger technique (Seldinger 1953). The size of the access needle used determines the wire size that can be introduced through the needle and into the vessel. The standard venous access needle is an 18-gauge needle, which accepts guidewires up to 0.38 inches in diameter (Braun 1997). A 21-gauge needle is considered to be a micropuncture needle and allows for introduction of guidewires up to 0.018 inches in diameter (Braun 1997; Valji 2006). Guidewires Selection of a particular guidewire (Figure 3.1) is dictated by the size of access needle that has been placed, the technique to be performed, and the vessel(s) to be selected. Most guidewires are available in three standard lengths: 150 cm, 180 cm, and 260 cm (Braun 1997). Alternative lengths of 60 cm, 125 cm, and 145 cm have been reported, but these are not readily available (Valji 2006; Kipling et al. 2009). The standard diameters of most guidewires are 0.035 and 0.038 inches. Smaller gauge wires of 0.014 and 0.018 inches are used when microcatheters and smaller (micropuncture) vascular

access needles are used (Braun 1997; Valji 2006; Kipling et al. 2009). There are a few primary principles that must be adhered to when using guidewires. First, most guidewires contain a hydrophilic coating made of polytetrafluoroethylene that needs to be primed with saline to allow for smooth passage through the lumen that has been selected (Braun 1997; Kipling et al. 2009). When sufficiently wet, the guidewire should pass easily through a catheter and allow an increased ability to perform vascular selection (Braun 1997; Kipling et al. 2009). It is essential that the guidewire remain wet during the procedure to improve guidewire function (Kipling et al. 2009). Second, the length of the selected guidewire should be at least twice the length of the catheter that is being used (Braun 1997). Third, if a guidewire is not passing easily through a vascular access needle, the needle may need to be repositioned. The wire should not be forced as the needle may be subintimal or against a sidewall (Valji 2006). Lastly, a torque device can be placed on the end of a guidewire (approximately 5–10 cm from a catheter hub that has been introduced over the guidewire) to better manipulate and steer the

38  Veterinary Surgical Oncology

guidewire (Kipling et al. 2009). These torque devices can be invaluable when passing a guidewire into vessels that are difficult to access and when crossing stenotic regions. Guidewires are also used for nonvascular stenting procedures (Hume et al. 2006; Weisse et al. 2006; Culp et al. 2007; Kipling et al. 2009). Stents that are placed through malignant obstructions are introduced over a guidewire, and the stent delivery system tapers down to the guidewire to allow for easier placement. In companion animals, 0.035-inch hydrophilic guidewires have been used to facilitate stent placement for tracheal, urethral, and colonic obstructions (Hume et al. 2006; Weisse et al. 2006; Culp et al. 2007). Sheaths The use of intravascular sheaths (Figure 3.1) is indicated when a procedure involves multiple exchanges into and out of a vessel. The sheath protects the vessel wall from damage and allows for easier passage of different catheter types. Additionally, sheaths protect the vessel from stiff intravascular devices, balloon catheters, and intravascular foreign bodies (Braun 1997; Valji 2006; Stavropoulos et al. 2006). A dilator that tapers down to a guidewire is usually present within a sheath and allows expansion of the previously made hole in the blood vessel. Sheaths contain a valve that prevents blood leakage while allowing entrance of specialized catheters, wires, stents, snares, and biopsy forceps (Snow and O’Connell 2000; Stavropoulos et al. 2006). Additionally, sheaths contain a sidearm that allows for injection of contrast, which can pass around wires and nonocclusive catheters (Snow and O’Connell 2000; Valji 2006). The French gauge of a sheath is determined by the largest gauge catheter that can fit through the sheath and represents the inner diameter of the sheath (Braun 1997; Snow and O’Connell 2000). The French size of a sheath is generally considered to be 2 French gauges smaller than the outer diameter (Valji 2006). In human medicine, sheaths have also been used for nonvascular procedures such as antegrade ureteric stenting, percutaneous transhepatic biliary drainage, and colonic stenting (Braun 1997; Snow and O’Connell 2000). The use of sheaths in urethral stenting has been described in veterinary medicine (Weisse et al. 2006; Newman et al. 2009). Some sheaths are designed with a peel-away component that is used during the placement of venous access devices and drainage catheters (Braun 1997). The peel-away component allows a device to be inserted through the sheath, and the sheath can then be removed while leaving the device in place.

Catheters When performing intravascular procedures, there are many catheter types that are available to the interventional radiologist. Decisions about which catheter is most optimal for a specific procedure is based on experience and the anatomy of the vessel that is to be selected. In human medicine, catheters with an outer diameter of 5 French (1 French = 3 mm) (Silberstein et al. 1992; Valji 2006) are chosen most commonly. (Braun 1997). This catheter size has the advantage of having good torque control and high flow rates when contrast is injected (Braun 1997). A larger catheter (6–7 French) affords the user increased control of torque (Wojtowycz 1990a; Braun 1997). Commonly used catheters are made of nylon, Teflon, or polyurethane (Wojtowycz 1990a; Valji 2006). Catheters are often categorized by the shape of the tip, with the basic catheter tip shapes being straight, pigtail, hook and angled (Braun 1997; Valji 2006). Straight catheters are commonly used for embolotherapy (delivery of a vascular occlusion agent) and for opacification of a vascular tree; however, care should be taken when injecting through a straight catheter with a single end-on hole as injury to the vessel is possible (Braun 1997). Pigtail catheters are superior for opacification, as they allow for the injection of a bolus of contrast through several small holes in the catheter, thus preventing the jet effect that may be seen with straight catheters (Wojtowycz 1990a; Braun 1997; Valji 2006). Pigtail catheters should be removed over a guidewire so that the catheter is straight during removal and therefore less likely to cause vascular damage (Wojtowycz 1990a). Hook catheters, such as the shepherd’s hook and cobra catheters, are used to catheterize vessels that have acute angled branches (Braun 1997). These visceral catheters are advanced over a guidewire to the desired location. The catheters are then allowed to reform (take on the original shape of the catheter) in a large vessel (generally aorta or vena cava) and are then gently pulled back into the lumen of the vessel selected (Braun 1997). Angled-tip catheters (Figure 3.1) are used in the selection of upwardbranching vessels; as with other catheters, a guidewire is often used to facilitate vessel selection and to maintain position once it has been established (Braun 1997). The Berenstein catheter is an example of an angled-tip catheter (Braun 1997). Similar to sheaths and guidewires, catheters can be used for nonvascular techniques. When stenting luminal obstructions, such as in the urethra or trachea, marker catheters are employed to determine appropriate stent size (Hume et al. 2006; Weisse et al. 2006; Culp et al. 2007; Newman et al. 2009). Another nonvascular

Interventional Oncology  39

oncologic use includes palliation of malignant thoracic and abdominal effusions by placing catheters for percutaneous drainage. This has been described in several human studies (Brooks and Herzog 2006; Fleming et al. 2009). Pigtail catheters are often used for draining malignant effusions since they have multiple fenestrations; a locking loop mechanism that maintains the catheter position in the desired location is also present on some pigtail catheters. When performing IO techniques, there are certain techniques and principles of catheter usage that are important to understand, namely the coaxial technique, the so-called rule of 110, and superselective catheterization with guidewire-microcatheter combination. As the size of a vessel that is being targeted for catheterization decreases, the catheter diameter must also decrease. Placement of a catheter that is too large can result in damage to the vessel wall, blood stasis with subsequent tissue ischemia, difficulty in removing the catheter, and vessel rupture (Stavropoulos et al. 2006). The coaxial technique is commonly employed to introduce progressively smaller catheters and wires to allow for superselection of vessels while minimizing the risk for development of complications. Simply stated, this technique involves placement of a smaller wire or catheter (depending on the stage of the procedure) into a catheter that is already within the blood vessel. The smaller wires and catheters share the same axis as the indwelling catheter, thus the term coaxial is used. This technique has been described in human patients undergoing selection of small vessels (Korogi et al. 1995; Tajima et al. 2008). A guide for vessel selection (particularly celiac and superior mesenteric arteries in humans) has been described and termed the “rule of 110” (Chuang 1981; Nemcek 1996). According to Chuang (1981), this rule states that “both the length and width of the catheter tip should be about 110% of the width of the aorta at the level of the artery (that is to be selected) as it branches”. The width refers to the distance between the tip of the catheter and the proximal straight limb of the catheter (Chuang 1981). If this technique is employed with a catheter of appropriate size and tip, the tip of the catheter should engage the branching vessel (i.e., celiac, cranial mesenteric, or renal artery in dogs and cats) as the catheter is pulled caudally and should subsequently enter the chosen vessel. A guidewire can be combined with a microcatheter (using the coaxial technique) to allow for superselective catheterization. To accomplish this, the guidewiremicrocatheter combination is passed through a guiding catheter to a vessel branch that is a few orders less than the desired branch (Stavropoulos et al. 2006). The guidewire-microcatheter combination is then advanced

toward the desired branch, and the guidewire is used to select the desired branch. The catheter is then immediately but gently advanced over the guidewire and into the vessel to prevent the guidewire from backing out. This should be performed in a series of steps that are slow and calculated (Stavropoulos et al. 2006). The guidewire can then be advanced further into the vessel or into a smaller branching vessel as needed. Vascular closure devices A vascular closure device is an instrument used to close the hole in a blood vessel that remains after removal of a vascular access sheath. The use of arteriotomy closure devices is well documented in human interventional cardiologic medicine; however, the use of these devices in veterinary medicine is uncommon (Meyerson et al. 2002; Koreny et al. 2004; Nikolsky et al. 2004). Historically, manual compression combined with bed rest was used to control bleeding at an arteriotomy site (Hoffer and Bloch et al. 2003). Concerns over the high rates of bleeding at these high-pressure sites spurred the development and use of devices that can be used to close vessels after a vascular IO procedure has been performed (Dauerman et al. 2007). Benefits seen with the use of closure devices have included decreased time to hemostasis and earlier ambulation (Meyerson et al. 2002; Tron et al. 2002; Hoffer and Bloch 2003; Dauerman et al. 2007). Closure devices are not universally used in human cases, however, and some studies have suggested similar or higher complication rates associated with the use of closure devices as compared to manual compression (Meyerson et al. 2002; Nikolsky et al. 2004; Dauerman et al. 2007). Vascular closure devices can be divided into two categories: passive and active (Silber 1998; Meyerson et al. 2002; Tron et al. 2002; Dauerman et al. 2007). Passive closure devices assist or enhance manual compression and do not provide immediate (75% tumor necrosis had significantly lower recurrence rates at 1 year (15%) versus dogs with 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, golden retrievers, Labrador retrievers, beagles, and schnauzers (Murphy et al. 2004; Gieger et al. 2003; Hahn et al. 2008; Hahn et al. 2004). The majority (65%–80%) of cutaneous MCTs are 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 intermediategrade MCTs have a lower metastatic potential than highgrade MCTs. The gross appearance of cutaneous MCTs is very variable, ranging from raised hairless masses to aggressive, invasive ulcerated lesions (Figure 4.4). Paraneoplastic effects can result from release of inflammatory mediators contained within the MCT cytoplasmic granules. Histamine release from cutaneous MCT can cause local effects of edema and erythema formation (Darier’s sign) that is associated with the release of vasoactive substances from MCTs (Figure 4.5). Wound healing can also be delayed due to the release of proteases. Histamine release can also cause gastrointestinal ulceration by stimulating H2 receptors on parietal cells of the stomach, which produce hydrogen chloride. Nonsteroidal anti-inflammatory drugs (NSAIDs) are contraindicated in the management of MCTs because of the increased potential for gastrointestinal ulceration. Diagnosis of MCTs Fine-needle aspiration cytology is sufficient to confirm the diagnosis of cutaneous MCTs in approximately 90% of cases but does not provide information on the tumor grade. Cytologically, MCT have large round cells with central nuclei and abundant cytoplasm. The cytoplasm contains blue to purple granules that stain with toluidine blue (Figure 4.6). Other inflammatory cells such as eosinophils and neutrophils are frequently seen mixed with the MCT cells on cytologic examination. An incisional biopsy is required to provide sufficient tissue to determine the histologic grade of cutaneous MCTs. An incisional biopsy to establish MCT grade is indicated if negative prognostic factors are present or the surgical site is not amenable to wide surgical

62  Veterinary Surgical Oncology

(b)

(a)

(c)

(e)

(d)

Figure 4.3.  Surgical en bloc resection of cutaneous tumor with planned reconstructive skin fold transposition flap. (A) Preoperative skin marking of proposed en bloc tumor excision and axial skin fold transposition flap. (B) En bloc tumor excision. (C) En bloc tumor excision completed with deep margins. (D) Transposition flap raised to close tumor resection site. (E) Completed tumor resection and reconstructive procedure closure. Images courtesy of Dr. Julius Liptak.

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 (e.g., amputation) or other therapies (e.g., radiation and/or chemotherapy) are indicated for high-grade MCTs. Drugs used for the treatment of an acute anaphylactic reaction, including histamine antagonists, corticosteroids, and epinephrine, should be available when performing an incisional biopsy of a known MST.

Clinical staging A modified version of the WHO 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,

Skin and Subcutaneous Tumors  63

(a)

(b)

Figure 4.4.  Range of cutaneous mast cell tumor appearances. (A) Ulcerated grade III MCT. (B) Grade II MCT on muzzle.

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

Figure 4.6.  Cytological appearance of canine cutaneous MCT.

and urinalysis is indicated as part of a presurgical workup for any patient with cancer. The typical path of metastatic spread is initially to the regional lymph node and then to distant sites of the spleen, liver, or bone marrow. Complete staging for cutaneous MCT includes FNA cytology of the regional lymph node, abdominal ultrasound, and thoracic radiographs. FNA cytologic examination of the regional lymph node should be done in all cases of cytologically confirmed 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 classified as clinical stage II tumors and have a poor 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). No standardized cytologic criteria exist for differentiating reactive and metastatic MCT in lymph nodes. A recent study described cytologic criteria for metastatic mast cell disease in lymph nodes and found that dogs with stage II disease had a significantly shorter survival time than dogs with stage I disease independent of grade and that dogs with grade III primary MCTs were more likely to have stage II disease (Krick et al. 2009). Abdominal ultrasonography is recommended as part of complete staging to assess the liver, spleen, and abdominal lymph nodes for metastasis. The routine aspiration cytology of normal livers and spleens is controversial. One study frequently identified mast cells in normal livers and spleens and concluded that routine aspiration cytology could not be recommended (Finora et al. 2006). Another study found that dogs with cutaneous MCTs that had cytologic evidence of

64  Veterinary Surgical Oncology Table 4.2.  WHO Clinical staging system for canine mast cell tumors. Clinical Stage

Description

0

Single tumor, incompletely excised from dermis Single tumor, confined to dermis without regional lymph node involvement Single tumor, confined to dermis with regional lymph node involvement Multiple dermal tumors or large infiltrating tumors, with or without regional lymph node involvement Any tumor with distant metastases or recurrence with metastases (including blood or bone marrow involvement)

I II III

IV

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

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). All dogs that had cytologic evidence of mast cell metastasis in the liver or spleen had abnormal ultrasonographic findings. The authors concluded that cytology of the liver and spleen was indicated as part of clinical staging for dogs with cutaneous MCTs regardless of the ultrasonographic appearance of the liver or spleen. Thoracic radiographs are included as part of the staging process to assess for thoracic lymph node enlargement or evidence of concurrent thoracic disease. Cutaneous MCTs rarely metastasize to lungs. 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 finding of mastocytemia in dogs with disease other than cutaneous MCTs (McManus 1999; LaDue et al. 1998; Endicott et al. 2007). The presence of neoplastic mast cell infiltration in the bone marrow is 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 findings or presentation for tumor regrowth, progression, or new occurrence (Endicott et al. 2007).

Preoperative imaging of the cutaneous MCT with ultrasonography, computer tomography, or MRI can facilitate definition 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 this imaging. Prognostic factors Histologic parameters Grade The most widely used grading system for canine cutaneous MCTs, 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 (Table 4.3) (Patnaik et al. 1984). 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 identified and have the widest range of biological behavior compared to the other two grades. 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 days and a metastatic rate of 55%–96% (Hume et al. 2007; Bostock 1986). There is significant variation in grading of MCTs between pathologists despite existence of a well-defined grading scheme. In one study in which 10 veterinary pathologists independently graded the same 60 cutaneous MCTs using the Patnaik grading system, agreement was 62.1% (Northrup et al. 2005). Most variation in classification was between grade I and grade II and grade II and grade III tumors. Surgeons should be aware that variation in histologic grading of MCTs exists when planning appropriate primary or adjuvant therapy. The majority of 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. Recently, mitotic index, argyrophylic nucleolar organizer regions (AgNOR), and Ki67 proliferation markers have been used to help differentiate between grade II MCTs with a poor and good prognosis to guide which patients may require close monitoring

Skin and Subcutaneous Tumors  65 Table 4.3.  Patnaik scheme for grading canine mast cell tumors. Grade

Patnaik Grade

Well differentiated

I

Intermediately differentiated

II

Anaplastic undifferentiated

III

Microscopic features • Well differentiated mast cells with clearly defined cytoplasmic borders with regular spherical or ovoid nuclei • Granules are large, deep staining, and plentiful • Cells confined to the dermis and interfollicular spaces • Cells closely packed with indistinct cytoplasmic boundaries • Nuclear/cytoplasmic ratio lower than anaplastic • Mitotic figures infrequent • More granules than anaplastic • Neoplastic cells infiltrate or replace the lower dermal and subcutaneous tissues • Highly cellular, undifferentiated cytoplasmic boundaries • Irregular size and shape of nuclei • Frequent mitotic figures • Low number of cytoplasmic granules • Neoplastic tissue replaces the subcutaneous and deep tissues

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.

and possible adjuvant therapy (Maglennon et al. 2008; Romansik et al. 2007; Scase et al. 2006).

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 significantly longer survival time than those with a MI greater than 5, regardless of histologic grade (Romansik et al. 2007).

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. In particular, identification of KIT mutations from the proliferative panel may be helpful to determine if the patient will respond to tyrosine kinase inhibitor therapy.

Proliferation indices

Size

Indicators of cellular proliferation can provide prognostic information about the likelihood of MCTs recurring locally and help differentiate the prognoses of grade II MCTs (Seguin 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 significantly associated with a shorter progressionfree interval (Gill et al. 2007). A Ki67 index of greater than 1.8% is a significantly prognostic indicator for poorer survival for grade II MCTs (Scase et al. 2006; Maglennon et al. 2008). Ki67 index is also a prognostic factor, independent of grade. The KIT protein is a tyrosine kinase receptor that is a product of the c-kit 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

Cutaneous MCT size is predictive for survival time. Dogs with grade III MCT primary tumors greater than 3 cm in maximum diameter have a shorter median survival time than those with tumors less than 3 cm diameter (Hahn et al. 2004).

Mitotic index

Breed Boxers, golden retrievers and Labrador retrievers have been identified as breeds at increased risk of developing multiple cutaneous MCTs (Thamm et al. 1999). Anatomical location MCTs located in the inguinal, perineal, or scrotal regions were previously reported to have a poorer prognosis compared to other cutaneous locations (Turrel et al. 1988). Recent studies have refuted this finding and concluded that when MCTs in these locations are treated appropriately, survival times and tumor-free intervals are equivalent to other cutaneous locations (Cahalane

66  Veterinary Surgical Oncology

et al. 2004; Sfiligoi et al. 2005). A retrospective study of 24 dogs with MCTs located in the muzzle region identified this location as a site for biologically aggressive tumors with higher regional metastatic rates than previously reported for MCTs in other sites (Gieger et al. 2003). Another study found that dogs with tumors located on the extremities had a longer tumor-free interval than dogs with MCT located on the trunk (Turrel et al. 1988). Multiple cutaneous MCT Presentation with multiple cutaneous MCTs occurs in 9–21% cases (Murphy et al. 2004; Murphy et al. 2006; Mullins et al. 2006). Boxers and older dogs are more likely to likely to present with multiple cutaneous MCTs (Kiupel et al. 2005). Multiple cutaneous MCT presentation was originally considered a poor prognostic sign. Recent studies, however have found no difference in survival times for single versus multiple cutaneous MCT (Murphy et al. 2006; Thamm et al. 1999). Dogs with multiple cutaneous MCTs have a low rate of metastasis and a good prognosis for long-term survival with adequate excision of all MCTs (Mullins et al. 2006). 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). Dogs with clinical stage 0 (i.e., single, incompletely excised local dermal tumor without regional lymph node involvement) have longer tumorfree and survival times than dogs with more extensive disease (Turrel et al. 1988). The presence of lymph node metastasis (stage II disease) carries a poorer prognosis compared to stage I disease (Murphy et al. 2006; Hume et al. 2007; Turrel et al. 1988; Krick et al. 2009). 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. 2007). The significance of clinical stage has been questioned as a reliable prognostic indicator as animals with multiple cutaneous tumors are assigned a higher clinical stage, even though these multiple tumors do not necessarily indicate metastatic disease and are not associated with a poorer outcome compared to single cutaneous MCTs (Thamm et al. 1999). Local tumor recurrence Local tumor recurrence after surgical excision is associated with a decreased overall survival time (Seguin et al. 2006).

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. If MCT disease is confined to the local cutaneous site, surgical excision is the treatment of choice. 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 therefore not be manipulated extensively during the perioperative period to avoid the risk of a degranulation reaction. Preoperative treatment with H1 blocker (diphenhydramine) and H2 blockers (cimetidine or ranitidine) and corticosteroids is strongly recommended in dogs with cutaneous MCTs that will be surgically manipulated, including biopsy, and those that show evidence of degranulation (Darier’s sign) or melena or hemoptysis associated with gastrointestinal ulcerations secondary to histamine release. Epinephrine should be available in the case of a potential anaphylactic reaction. Hypotension during surgery can be caused by mast cell degranulation and histamine release. Perioperative and intraoperative intravenous fluid therapy is indicated for circulatory support. Invasive or noninvasive blood pressure monitoring is strongly recommended. Coagulation abnormalities can occur locally at the surgical site related to heparin release, causing bleeding at the time of surgery and bruising postoperatively. Delayed wound healing can be observed after MCT excision as a result of proteolytic enzyme release and vasoactive amines from the MCT. Neoadjuvant prednisone treatment may facilitate resection when adequate surgical margins cannot be confidently attained because of mass location or size or both (Stanclift and Gilson 2008; Dobson et al. 2004). Mean reduction in MCT volume was 80.6% in 70% cases treated with neoadjuvant prednisolone. Reduction in tumor size may be related to the anti-inflammatory effect of prednisolone, reducing tumor-related inflammation 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. The determination of appropriate surgical margins should be based on tumor dimensions at initial

Skin and Subcutaneous Tumors  67

presentation rather than at post prednisolone treatment tumor size. Margins Surgical margins Wide surgical excision with adequate lateral and deep margins is the treatment of choice for most MCTs. The deep margin in particular needs to be a good-quality margin rather than a quantity margin. Fascia and collagen-dense tissues are good barriers to tumor infiltration. The deep margin should include a fascial plane deep to the tumor that has not been invaded by tumor. This margin should be removed en bloc with the tumor so that the tumor matrix is not encountered during the surgery. The surgical dogma of 3 cm lateral and one fascialplane deep margins for MCTs has been challenged recently, especially for low-grade and smaller-sized MCTs. Simpson et al. (2004) reported that a 2 cm lateral margin and a deep margin of one fascial plane appeared to be 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. A 2 cm lateral margin and one deep facial plane excision was successful in completely excising 91% of grade I and II MCTs (Fulcher et al. 2006). A similar local recurrence rate and de novo development rate was 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 are not a prerequisite for a successful long-term outcome in dogs with well-differentiated cutaneous MCTs (Murphy et al. 2004). Tumor depth has no prognostic significance. (Kiupel et al. 2005) There were no grade III tumors in these studies, so adequate margins for grade III MCTs have as yet not been determined; thus, margins 3 cm lateral and at least one fascial plane deep are recommended. 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). Anatomical site considerations Options for distal extremity MCT 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 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). Treatment of high-grade MCTs Patients with histologically confirmed high-grade MCTs should have complete staging tests performed before surgical intervention. These includes FNA cytology of the mass, incisional biopsy, regional lymph node cytology (regardless of size), and abdominal ultrasound. Postoperative recommendations Completely excised MCTs Grade I or II MCTs 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; Seguin 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. Incompletely excised MCTs Incompletely excised grade I or II MCTs have a low chance of local recurrence and low chance of metastatic spread (Seguin 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). Seguin et al. found that dogs developing local recurrence had shorter survival times than dogs without local recurrence with incompletely excised grade II MCTs (Seguin et al. 2006). Another study showed histopathological tumor-free versus non-tumor-free margins were not associated with a different frequency of tumorrelated death; however, significantly more dogs in the non-tumor-free margin group relapsed by 12 and 24 months postoperatively compared to the tumor-free margin group (Michels et al. 2002).

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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. Incompletely excised grade III MCTs have a high chance of both local recurrence and metastatic spread. These cases should receive additional local therapy (either additional surgery or radiation therapy) as well as chemotherapy (Hahn et al. 2004). Radiation therapy for MCT Radiation therapy can be used as part of multimodal therapy either as an adjunctive therapy after incomplete surgical MCT excision or as a primary treatment modality of the primary tumor and/or regional lymph node(s). Radiation is most effective and most commonly used as an adjunctive therapy after surgical removal or tumor size reduction to a microscopic level (LaDue et al. 1998). When possible, surgery should be performed prior to radiation therapy to decrease the tumor volume, as dogs treated with adjuvant radiation therapy with smaller tumor volumes have longer disease-free intervals than those with larger tumor volumes (LaDue et al. 1998; Hahn et al. 2004). The risk of systemic effects as a result of MCT degranulation is present in tumors treated with radiation of macroscopic disease, so pretreatment with prednisolone is recommended (Dobson et al. 2004). Radiation therapy is very effective at eliminating residual microscopic disease after incomplete excision of grade I and II MCTs. Local tumor control rates of 86%– 94% at 2 and 3 years are reported after adjunctive radiation therapy for incompletely excised grade II MCTs (Frimberger et al. 1997; al-Sarraf et al. 1996; Poirier et al. 2006). These rates are similar to the local tumor control rate of 89% achieved with complete surgical excision of grade II MCTs (Weisse et al. 2002). Radiation therapy for incompletely excised grade III, stage 0 MCTs, is encouraging compared to untreated incompletely excised grade III MCTs with a 1-year local control rate of 65% and 1-year survival rate of 71% (Hahn et al. 2004). If the regional lymph node is positive for MCT disease (stage II disease), radiation therapy of the affected lymph node has been advocated by some investigators to improve survival time. A study by Poirier et. al. found no difference in overall survival rate, whether the regional lymph node was prophylactically irradiated or not (Poirier et al. 2006). Palliative radiation using 4 × 8 Gy fractions at weekly intervals has been reported as a treatment option for

unresectable MCTs alone or in combination with chemotherapy (Dobson et al. 2004). Chemotherapy for MCT The use of adjuvant chemotherapy is indicated after resection of grade III MCTs because of their high metastatic rate and for metastatic and unresectable MCTs. The use of chemotherapy after incomplete resection of grade I and II MCTs is not indicated based on their lower metastatic potential. Some of the chemotherapeutic agents that have reported activity against canine MCTs are prednisolone, vinblastine, CCNU (Lomustine), vinorelbine, and chlorambucil. The response rate of macroscopic cutaneous MCTs to oral prednisolone as a single agent is reported to be 20% (McCaw et al. 1994). Most of these responses were partial responses with remission times between 10 and 20 weeks. The reported response rates for single-agent vinblastine range from 12% to 27% (Rassnick et al. 2008). Vinblastine is commonly administered to dogs at a dosage of 2.0 mg/m2. The dose can be escalated to 3.0 to 4.0 mg/m2 with neutropenia as the dose-limiting toxicity (Vickery et al. 2008; Bailey et al. 2008). CCNU (Lomustine) is an antitumor alkylating agent in the nitrosourea family. Lomustine is administered orally at a dose of 50–90 mg/m2 every 21 days. A response rate of 47% for measurable cutaneous MCTs treated with single-agent CCNU (90 mg/m2) is reported (Rassnick et al. 1999). Acute toxicities include neutropenia and thrombocytopenia. CCNU can cause a delayed, cumulative dose-related, chronic hepatotoxicity that is irreversible and can be fatal (Kristal et al. 2004). Combination chemotherapy Combination chemotherapy protocols using prednisone or prednisolone and vinblastine (Davies et al. 2004; Thamm et al. 1999; Thamm et al. 2006), CCNU and vinblastine (Cooper et al. 2009), and CCNU and prednisone (Hosoya et al. 2009) have been reported as adjuvant chemotherapy for macroscopic and microscopic cutaneous MCT disease. The rationale for combination therapy protocols is to increase local recurrence-free intervals, metastasis-free intervals, and survival times over single agent protocols. Adjuvant therapy such as prednisone and vinblastine is best employed after the initial tumor resection, rather than at the time of recurrence (Thamm et al. 1999). Deionized or hypotonic water Conflicting results have been reported on the efficacy of deionized water as an adjunctive therapy after surgical

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excision of cutaneous mast cell tumors (Brocks et al. 2008; Grier et al. 1995; Jaffe et al. 2000). A prospective, placebo-controlled, double-blinded and randomized clinical trial found that hypotonic water does not decrease the rate of local recurrence in dogs with solitary MCT after marginal surgical excision (Brocks et al. 2008). Tyrosine kinase inhibitors In dogs, 20%–30% of MCTs express a mutated form of KIT, a receptor tyrosine kinase involved in the development or progression of MCT growth and differentiation. Small-molecule tyrosine kinase inhibitors including imatinib mesylate (Gleevec), masitinib, and toceranib have shown efficacy against canine MCTs (London et al. 2009; Isotani et al. 2008; Hahn et al. 2008). Toceranib phosphate (Palladia) has recently been licensed for use in veterinary medicine for treatment of mast cell disease. The tumor should be positive for c-KIT mutations for Palladia to be potentially effective. A multicenter, placebo-controlled, randomized study recently demonstrated a 42% response rate to Palladia in dogs with grade II or III cutaneous MCTs (London et al. 2009). Ulcers of the stomach and intestine have been a common side effect of this medication (London et al. 2009). Feline cutaneous MCT Cutaneous MCT is the second most common feline skin tumor, after basal cell tumor (Miller et al. 1991). Feline cutaneous MCTs are most commonly located on the head and neck, followed by the trunk and extremities (Litster and Sorenmo 2006). Feline MCTs located on the head are less biologically active than in dogs. An increased breed incidence in Siamese cats for cutaneous MCT is reported compared to other breeds (Miller et al. 1991). Feline cutaneous MCTs have a benign biological behavior compared to canine cutaneous MCTs. The Patnaik histopathological grading scheme used for canine cutaneous MCTs is not prognostic in cats (MolanderMcCrary et al. 1998; Lepri et al. 2003). There are two forms of feline cutaneous mast cell disease, mastocytic and the less common histiocytic. The histiocytic form occurs in cats younger than 4 years old and is usually characterized by multiple nonpruritic, firm, hairless, pink subcutaneous nodules. Histiocytic MCTs generally regress spontaneously. Histologic classifications of feline cutaneous MCTs are well differentiated, poorly differentiated, or histiocytic. High mitotic activity (>4 mitoses/high-powered field) is reported as a negative prognostic indicator for feline cutaneous MCT (Lepri et al. 2003; Johnson et al. 2002).

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 mast cell tumor, 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 the visceral MCT form if disease is located in the spleen.

Mesenchymal Tumors and Melanoma Introduction This section will first evaluate the management of soft tissue sarcomas (STSs) and describe general adjunctive therapies. Specific types of STSs will then be discussed with tumor-specific treatment options. Soft tissue sarcomas Soft tissue sarcomas (STSs) are a heterogenous group of tumors that originate from connective tissues surrounding, supporting and bridging anatomical structures or tissues. STSs have similar biological behaviors, often displaying both benign and malignant characteristics. Although skin and subcutaneous tumors are the most commonly observed STSs, these sarcomas can, in principle, arise from any part of the body (Ehrhart 2005; Ettinger 2003; Kuntz et al. 1997). In general, STSs are slow-growing and locally invasive tumors, comprised mainly of spindle-shaped cells, with a low tendency for metastatic spread. The group of STSs includes wellknown tumor types such as fibrosarcoma, peripheral nerve sheath tumors (PNSTs), hemangiopericytoma, liposarcoma, myxosarcoma, and undifferentiated sarcomas (Ehrhart 2005; Gaitero et al. 2008; Liptak 2007). STSs are grouped together because histologic classification and differentiation is often complicated. The nomenclature follows classification of human STSs, based on patterns of cellular proliferation and individual cell morphology without conclusive identification of the cells of origin and is poorly standardized for animals. Some pathologists therefore prefer the term spindle cell tumors of canine soft tissue (McColl Williamson and

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Middleton 1998). Further differentiation of histologic diagnosis is reached using immunohistochemistry (Gaitero et al. 2008; Ettinger et al. 2006). The discussion pertaining to the exact histologic differentiation is not one of major clinical importance because the overall biological behavior of the STS is similar. Several important features of biological behavior that are common to all STSs include the following:

• STSs form a pseudocapsule, with the tumor cells infil• • • •

trating through the outer borders of the capsule into surrounding tissues. Local recurrence after conservative surgical excision is common. STSs metastasize in up to 20% of all cases, mainly via a hematogenous route. Macroscopic or bulky (>5 cm in diameter) STSs respond poorly to chemotherapy and radiation therapy. Histopathological grade is predictive of metastasis, and resected tumor margins predict local recurrence (Liptak et al. 2007).

Prognosis of soft tissue sarcomas The prognosis of STSs depends on tumor size, histologic grade, site, fixation to underlying structures, presence of metastasis, and completeness of removal (i.e., the surgical margins) (Ettinger 2003; Kuntz et al. 1997). The incidence of metastases in STSs is low (16 months) was significantly longer compared to incomplete excisions (9 months) (Davidson et al. 1997). Forrest et al. (2000) treated hemangiopericytoma, fibrosarcoma, and other STSs 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. STSs tumors at oral sites had a statistically significant lower median survival (540 days) as compared to other tumor sites (2,270 days). Lawrence et al. (2008) reported that coarsely frac­ tionated radiation therapy may be a reasonable pallia­ tive option for the management of canine STSs. The

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treatment protocol used single parallel opposed fields 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 field 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 STSs that have metastasized or have a high risk of metastases, such as high-grade STS, feline vaccineassociated sarcoma, and oral melanoma. Acute side effects of radiation therapy on the skin include moist desquamation and alopecia. Late effects of radiation therapy on the skin include fibrosis, 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). Chemotherapy STSs are a heterogeneous group of tumors. Because of this heterogeneity, it is hard to obtain sufficient 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 STSs is thus unclear. Chemotherapy may be beneficial 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 STSs, however, and are reported to be 15% for low-grade malignant to 41% for high-grade malignant types of cutaneous STSs. Single-agent doxorubicin, mitoxantrone, or combination protocols using vincristine, doxorubicin, and cyclophosphamide have been reported to be effective for STS (Thornton 2008). Elmslie et al. (2008) treated 30 dogs after incomplete removal of soft tissue sarcoma with continuously lowdose cyclophosphamide (10 mg/m2) and standard-dose piroxicam (0.3 mg/kg) therapy. Disease-free interval (DFI) was 410 days and 211 days, respectively, for all STSs at all sites (trunk, extremities) in treated dogs compared with 55 untreated controls. Although the median DFI was not reached for the treated dogs, it seems that the DFI was significantly prolonged (Elmslie et al. 2008; Kuntz et al. 1997; Rassnick 2003; Schlieman et al. 2006).

Immunotherapy The expression of genes encoding for immunostimulatory cytokines or tumor-associated antigens that may negatively influence tumor viability are 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 fibrosarcoma, 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 iridium-based 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 fibrosarcoma, in combination with surgery and radiotherapy, has been shown to increase the diseasefree period and survival time (Quintin-Colonna et al. 1996). 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. 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 4 weeks for three additional immunizations. Eventually four out of nine dogs remained long enough in the study to receive five or more immunizations. The five 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 five or more VEGF immunizations. Tumor microvessel density (MVD) was evaluated in biopsy specimens on week 6 and 16 of the study from these four dogs. Two of the four multiplyvaccinated dogs demonstrated a significant (>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

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immunization was capable of inhibiting tumor angiogenesis in at least half of the dogs. At this point, more research is needed to fully understand the VEGF pathway and when and how to use it. 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). Plavec et al. treated 15 dogs with unresectable STSs (2006). Total tumor radiation dose was 24 Gy, given in three 8 Gy fractions on days 0, 7, 21, or weekly. 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 (once) and bones were in the radiation field. 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 cannot prolong life for years, but rather aims to improve the quality of life for several weeks to months (Plavec et al. 2006). Specific soft tissue sarcomas Fibrosarcomas Fibrosarcomas (FSAs) are tumors derived from mesenchymal cells or fibroblasts. FSAs infiltrate 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 highgrade, 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 a highly 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 poor prognosis due to an invasive growth pattern and frequent inability of complete removal.

Peripheral nerve sheath tumors Peripheral nerve sheath tumors (PNSTs) include a variety of neoplasms including (malignant) schwannoma, neurofibroma, and neurofibrosarcoma. 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 classification of these tumors. They are locally aggressive and metastasize rarely (1,460 days) than cats that did not undergo surgery (60 days). In a study of 53 cats, subcutaneous tumors were associated with longer survival than visceral tumors, and cutaneous tumors were associated with longer survival than subcutaneous tumors. Completely excised tumors were associated with longer survival than incompletely excised tumors, and cats with incompletely excised tumors had longer survival times than those for which surgical resection was not attempted (Johannes et al. 2007; McAbee et al. 2005). In general, surgical excision is the therapy of choice in cats and dogs with cutaneous HSA. Chemotherapy

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may be a viable adjunctive therapy, especially for incompletely resected tumors. Five dogs with subcutaneous HSA treated with surgery, doxorubicin, and cyclophosphamide had a median survival time of 211 days (Sorenmo et al. 1993). Seven dogs treated with surgery, vincristine, doxorubicin, and cyclophosphamide had a median survival of 425 days (Hammer et al. 1991). A more recent study of 17 dogs with subcutaneous HSA and 4 dogs with intramuscular HSA, receiving adequate local control and doxorubicin chemotherapy, reported a median DFI and survival of 1,553 and 1,189 days for subcutaneous HSA and 266 and 273 days for intramuscular HSA, respectively. Younger age (16 versus 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 significantly 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 significant include local recurrence, presence of distant metastasis, and the number of surgeries (Cohen et al. 2001; Eckstein et al. 2009; Romanelli et al. 2008). 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 influence survival time after surgery (Cohen et al. 2001; Dillon et al. 2005; Spugnini et al. 2007). 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 (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. Recently, 57 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%. Fiftyone percent 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). A recent study of 99 cats with FISASs treated by widemargin resection, using 5 cm lateral margins and two fascial planes beneath the tumor, reported 15% recurrence and 18% distant metastasis. Adjuvant radiation therapy may improve outcome. Median DFIs after complete resection combined with radiation therapy were 405–1,110 days. Survival times after complete resection combined with radiation therapy were 476–1,290 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 a recent study, radiation therapy of residual microscopic tumor improved median DFI and survival time (20 and 30 months, respectively)

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compared to residual macroscopic tumor (4 and 7 months, respectively; Eckstein et al. 2009). 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. These results suggest that the benefit of chemotherapy is limited in the treatment of vaccine-associated sarcomas (Cohen et al. 2001).

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McEntee, M.C. and D.E. Thrall. 2001. Computed tomographic imaging of infiltrative lipoma in 22 dogs. Vet Radiol Ultrasound 42(3):221–225. McKnight, J.A., G.N. Mauldin, M.C. McEntee, et al. 2000. Radiation treatment for incompletely resected soft-tissue sarcomas in dogs. J Am Vet Med Assoc 217(2):205–210. McLaughlin, R. Jr. and A.B. Kuzma. 1991. Intestinal strangulation caused by intra-abdominal lipomas in a dog. J Am Vet Med Assoc 199(11):1610–1611. McManus, P.M. 1999. Frequency and severity of mastocytemia in dogs with and without mast cell tumors: 120 cases (1995–1997). J Am Vet Med Assoc 215(3):355–357. McSporran, K. 2009. Histologic grade predicts recurrence for marginally excised canine subcutaneous soft tissue sarcomas. Vet Pathol 46(5):928–933. Michels, G.M., D.W. Knapp, D.B. DeNicola, et al. 2002. Prognosis following surgical excision of canine cutaneous mast cell tumors with histopathologically tumor-free versus nontumor-free margins: A retrospective study of 31 cases. J Am Anim Hosp Assoc 38(5): 458–466. Mikaelian, I. and T.L. Gross. 2002. Keloidal fibromas and fibrosarcomas in the dog. Vet Pathol 39(1):149–153. Miles, J. and D. Clarke. 2001. Intrathoracic lipoma in a Labrador retriever. J Small Anim Pract 42(1):26–28. Miller, M.A., S.L. Nelson, J.R. Turk, et al. 1991. Cutaneous neoplasia in 340 cats. Vet Pathol 28(5):389–395. Molander-McCrary, H., C.J. Henry, K. Potter, et al. 1998. Cutaneous mast cell tumors in cats: 32 cases (1991–1994). J Am Anim Hosp Assoc 34(4):281–284. Moore, A.S. 2002. Radiation therapy for the treatment of tumours in small companion animals. Vet J 164(3):176–187. Morrison, W.B. and R.M. Starr. 2001. Vaccine-associated feline sarcomas. J Am Vet Med Assoc 218(5):697–702. Mukaratirwa, S., J. Chipunza, S. Chitanga, et al. 2005. Canine cutaneous neoplasms: Prevalence and influence of age, sex and site on the presence and potential malignancy of cutaneous neoplasms in dogs from Zimbabwe. J S Afr Vet Assoc 76(2):59–62. Mullins, M.N., W.S. Dernell, S.J. Withrow, et al. 2006. Evaluation of prognostic factors associated with outcome in dogs with multiple cutaneous mast cell tumors treated with surgery with and without adjuvant treatment: 54 cases (1998–2004). J Am Vet Med Assoc 228(1):91–95. Murphy, S., A.H. Sparkes, A.S. Blunden, et al. 2006. Effects of stage and number of tumours on prognosis of dogs with cutaneous mast cell tumours. Vet Rec 158 (9):287–291. Murphy, S., A.H. Sparkes, K.C. Smith, et al. 2004. Relationships between the histological grade of cutaneous mast cell tumours in dogs, their survival and the efficacy of surgical resection. Vet Rec 154 (24):743–746. Northrup, N.C., E.W. Howerth, B.G. Harmon, et al. 2005. Variation among pathologists in the histologic grading of canine cutaneous mast cell tumors with uniform use of a single grading reference. J Vet Diagn Invest 17(6):561–564. O’Brien, M.G. 2003. Skin and subcutis. In Textbook of Small Animal Surgery, 3rd edition, pp. 2359–2368. D. Slatter, editor. Philadelphia: Saunders. O’Keefe, D.A., C.G. Couto, C. Burke-Schwartz, et al. 1987. Systemic mastocytosis in 16 dogs. J Vet Intern Med 1(2):75–80. Owen L. 1980. TNM Classification of Tumors in Domestic Animals, 1980. Geneva: World Health Organization, Geneva. Pakhrin, B., M.S. Kang, I.H. Bae, et al. 2007. Retrospective study of canine cutaneous tumors in Korea. J Vet Sci 8(3):229–236.

84  Veterinary Surgical Oncology Paoletti, E., J. Taylor, B. Meignier, et al. 1995. Highly attenuated poxvirus vectors: NYVAC, ALVAC and TROVAC. Dev Biol Stand 84:159–163. Patnaik, A.K., W.J. Ehler, and E.G. MacEwen. 1984. Canine cutaneous mast cell tumor: Morphologic grading and survival time in 83 dogs. Vet Pathol 21(5):469–474. Patterson, C.C., R.L. Perry, and B. Steficek. 2008. Malignant peripheral nerve sheath tumor of the diaphragm in a dog. J Am Anim Hosp Assoc 44(1):36–40. Pavletic, M.M. 2000. Use of an external skin-stretching device for wound closure in dogs and cats. J Am Vet Med Assoc 217(3): 350–354. Pavletic, M.M. 2003. Chpt 23—Pedicle Grafts. In: Slatter, D.H. (ed.) Textbook of Small Animal Surgery. Third Edition. Philadelphia, PA: Saunders. Plavec, T., M. Kessler, B. Kandel, et al. 2006. Palliative radiotherapy as treatment for non-resectable soft tissue sarcomas in the dog—A report of 15 cases. Vet Comp Oncol 4(2):98–103. Poirier, V.J., W.M. Adams, L.J. Forrest, et al. 2006. Radiation therapy for incompletely excised grade II canine mast cell tumors. J Am Anim Hosp Assoc 42(6):430–434. Powers, B.E., P.J. Hoopes, and E.J. Ehrhart. 1995. Tumor diagnosis, grading, and staging. Semin Vet Med Surg (Small Anim) 10(3): 158–167. Quintin-Colonna, F., P. Devauchelle, D. Fradelizi, et al. 1996. Gene therapy of spontaneous canine melanoma and feline fibrosarcoma by intratumoral administration of histoincompatible cells expressing human interleukin-2. Gene Ther 3(12):1104–1112. Rassnick, K.M. 2003. Medical management of soft tissue sarcomas. Vet Clin North Am Small Anim Pract 33(3):517–531. Rassnick, K.M., D.B. Bailey, A.B. Flory, et al. 2008. Efficacy of vinblastine for treatment of canine mast cell tumors. J Vet Intern Med 22(6):1390–1396. Rassnick, K.M., A.S. Moore, L.E. Williams, et al. 1999. Treatment of canine mast cell tumors with CCNU (lomustine). J Vet Intern Med 13(6):601–605. Rassnick, K.M., D.M. Ruslander, S.M. Cotter, et al. 2001. Use of carboplatin for treatment of dogs with malignant melanoma: 27 cases (1989–2000). J Am Vet Med Assoc 218(9):1444–1448. Rohrborn, A. and H.D. Roher. 1998. Surgical aspects in the multidisciplinary treatment of soft tissue sarcomas. Praxis (Bern 1994) 87(34):1050–1060. Romanelli, G., L. Marconato, D. Olivero, et al. 2008. Analysis of prognostic factors associated with injection-site sarcomas in cats: 57 cases (2001–2007). J Am Vet Med Assoc 232(8):1193– 1199. Romansik, E.M., C.M. Reilly, P.H. Kass, et al. 2007. Mitotic index is predictive for survival for canine cutaneous mast cell tumors. Vet Pathol 44(3):335–341. Sawamoto, O., J. Yamate, M. Kuwamura, et al. 1999. A canine peripheral nerve sheath tumor including peripheral nerve fibers. J Vet Med Sci 61(12):1335–1338. Scase, T.J., D. Edwards, J. Miller, et al. 2006. Canine mast cell tumors: Correlation of apoptosis and proliferation markers with prognosis. J Vet Intern Med 20(1):151–158. Scavelli, T.D., A.K. Patnaik, C.J. Mehlhaff, et al. 1985. Hemangiosarcoma in the cat: Retrospective evaluation of 31 surgical cases. J Am Vet Med Assoc 187(8):817–819. Schlieman, M., R. Smith, and W.G. Kraybill. 2006. Adjuvant therapy for extremity sarcomas. Curr Treat Options Oncol 7(6):456– 463. Schulman, F.Y., T.O. Johnson, P.R. Facemire, et al. 2009. Feline peripheral nerve sheath tumors: Histologic, immunohistochemical, and

clinicopathologic correlation (59 tumors in 53 cats). Vet Pathol 46(6):1166–1180. Schultheiss, P.C. 2004. A retrospective study of visceral and nonvisceral hemangiosarcoma and hemangiomas in domestic animals. J Vet Diagn Invest 16(6):522–526. Seguin, B., M.F. Besancon, J.L. McCallan, et al. 2006. Recurrence rate, clinical outcome, and cellular proliferation indices as prognostic indicators after incomplete surgical excision of cutaneous grade II mast cell tumors: 28 dogs (1994–2002). J Vet Intern Med 20(4):933–940. Seguin, B., N.F. Leibman, V.S. Bregazzi, et al. 2001. Clinical outcome of dogs with grade-II mast cell tumors treated with surgery alone: 55 cases (1996–1999). J Am Vet Med Assoc 218(7):1120–1123. Seguin, B., D.E. Mcdonald, M.S. Kent, et al. 2005. Tolerance of cutaneous or mucosal flaps placed into a radiation therapy field in dogs. Vet Surg 34(3):214–222. Selting, K.A., B.E. Powers, L.J. Thompson, et al. 2005. Outcome of dogs with high-grade soft tissue sarcomas treated with and without adjuvant doxorubicin chemotherapy: 39 cases (1996–2004). J Am Vet Med Assoc 227(9):1442–1448. Sfiligoi, G., K.M. Rassnick, J.M. Scarlett, et al. 2005. Outcome of dogs with mast cell tumors in the inguinal or perineal region versus other cutaneous locations: 124 cases (1990–2001). J Am Vet Med Assoc 226(8):1368–1374. Shaw, S.C., M.S. Kent, I.K. Gordon, et al. 2009. Temporal changes in characteristics of injection-site sarcomas in cats: 392 cases (1990– 2006). J Am Vet Med Assoc 234(3):376–380. Shelly, S.M. 2003. Cutaneous lesions. Vet Clin North Am Small Anim Pract 33(1):1–46. Simon, D., D.M. Ruslander, K.M. Rassnick, et al. 2007. Orthovoltage radiation and weekly low dose of doxorubicin for the treatment of incompletely excised soft-tissue sarcomas in 39 dogs. Vet Rec 160(10):321–326. Simpson, A.M., L.L. Ludwig, S.J. Newman, et al. 2004. Evaluation of surgical margins required for complete excision of cutaneous mast cell tumors in dogs. J Am Vet Med Assoc 224(2):236–240. Sorenmo, K.U., K.A. Jeglum, and S.C. Helfand. 1993. Chemotherapy of canine hemangiosarcoma with doxorubicin and cyclophosphamide. J Vet Intern Med 7(6):370–376. Spugnini, E.P., A. Baldi, B. Vincenzi, et al. 2007. Intraoperative versus postoperative electrochemotherapy in high grade soft tissue sarcomas: A preliminary study in a spontaneous feline model. Cancer Chemother Pharmacol 59(3):375–381. Stanclift, R.M. and S.D. Gilson. 2008. Evaluation of neoadjuvant prednisone administration and surgical excision in treatment of cutaneous mast cell tumors in dogs. J Am Vet Med Assoc 232(1): 53–62. Stefanello, D., E. Morello, P. Roccabianca, et al. 2008. Marginal excision of low-grade spindle cell sarcoma of canine extremities: 35 dogs (1996–2006). Vet Surg 37(5):461–465. Stefanello, D., P. Valenti, S. Faverzani, et al. 2009. Ultrasound-guided cytology of spleen and liver: A prognostic tool in canine cutaneous mast cell tumor. J Vet Intern Med 23(5):1051–1057. Straw, R.C., S.J. Withrow, and B.E. Powers. 1992. Partial or total hemipelvectomy in the management of sarcomas in nine dogs and two cats. Vet Surg 21(3):183–188. Sugiyama, A., T. Morita, A. Shimada, et al. 2008. Primary malignant peripheral nerve sheath tumor with eosinophilic cytoplasmic globules arising from the greater omentum in a dog. J Vet Med Sci 70(7):739–742. Swaim, S.F. 2003. Chpt 24—Skin Grafts. In: Slatter, D.H. (ed.) Textbook of Small Animal Surgery. Third Edition. Philadelphia, PA: Saunders.

Skin and Subcutaneous Tumors  85 Thamm, D.H., E.A. Mauldin, and D.M. Vail. 1999. Prednisone and vinblastine chemotherapy for canine mast cell tumor—41 cases (1992–1997). J Vet Intern Med 13 (5):491–497. Thamm, D.H., M.M. Turek, and D.M. Vail. 2006. Outcome and prognostic factors following adjuvant prednisone/vinblastine chemotherapy for high-risk canine mast cell tumour: 61 cases. J Vet Med Sci 68(6):581–587. Theilen, G.H. and B.R. Madewell. 1979. Veterinary Cancer Medicine. Lea & Febiger: Philadelphia. Thornton, K. 2008. Chemotherapeutic management of soft tissue sarcoma. Surg Clin North Am 88(3):647–660, viii. Trout, N.J., M.M. Pavletic, and K.H. Kraus. 1995. Partial scapulectomy for management of sarcomas in three dogs and two cats. J Am Vet Med Assoc 207(5):585–587. Trout, N.J. 2003. Chpt 22—Principles of Plastic and Reconstructive Surgery. In: Slatter, D.H. (ed.) Textbook of Small Animal Surgery. Third Edition. Philadelphia, PA: Saunders. Turrel, J.M., J. Farrelly, R.L. Page, et al. 2006. Evaluation of stron­ tium 90 irradiation in treatment of cutaneous mast cell tumors in cats: 35 cases (1992–2002). J Am Vet Med Assoc 228(6): 898–901.

Turrel, J.M., B.E. Kitchell, L.M. Miller, et al. 1988. Prognostic factors for radiation treatment of mast cell tumor in 85 dogs. J Am Vet Med Assoc 193(8):936–940. Vail, D.M. and S.J. Withrow. 2007. Tumors of the skin and subcutaneous tissues. In Withrow & MacEwen’s Small Animal Clinical Oncology, 4th edition, pp. 375–401. S.J. Withrow and E.G. MacEwen, editors. St. Louis, MO: Saunders Elsevier. Vickery, K.R., H. Wilson, D.M. Vail, et al. 2008. Dose-escalating vinblastine for the treatment of canine mast cell tumour. Vet Comp Oncol 6(2):111–119. Ward, H., L.E. Fox, M.B. Calderwood-Mays, et al. 1994. Cutaneous hemangiosarcoma in 25 dogs: A retrospective study. J Vet Intern Med 8(5):345–348. Weisse, C., F.S. Shofer, and K. Sorenmo. 2002. Recurrence rates and sites for grade II canine cutaneous mast cell tumors following complete surgical excision. J Am Anim Hosp Assoc 38(1):71–73. Williams, J.H. 2005. Lymphangiosarcoma of dogs: A review. J S Afr Vet Assoc 76(3):127–131. Withrow, S.J. and D.M. Vail, editors. 2007. Withrow & MacEwen’s Small Animal Clinical Oncology, 4th edition. St. Louis, MO: Saunders Elsevier.

5 Head and neck tumors Sara A. Ayres, 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. This may be inaccurate, however, because it has been demonstrated that lymph node size is not an accurate predictor of metastasis in dogs with oral melanoma (Williams and Packer 2003). Furthermore, of the three regional lymphocentrums, only the mandibular lymph nodes are externally palpable (Smith 1995) and only 55% of cats and dogs with metastatic oral and maxillofacial tumors have metastasis to the mandibular lymph nodes (Smith 2002). Given these limitations, it may be prudent to biopsy these lymph nodes in all dogs with a known malignancy of the head; however this still remains controversial in veterinary medicine. Currently, lymph node aspirates are recommended for all animals with head and neck tumors, regardless of the size or degree of fixation of the lymph nodes (Williams and Packer 2003; Smith 2002). It is hoped that sentinel lymph node assessment in the near future 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 lymphoscintigraphy, intraoperative blue dyes, and intraoperative gamma probes (Lurie et al. 2006). Lymphoscintigraphy, intraoperative dyes, and contrast-enhanced ultrasonography have been described in dogs with various tumors, including head and neck cancer (Nieweg et al. 2001; Nyman et al. 2005; Worley et al. 2007).

En bloc resection of the regional lymph nodes has been described, and although the therapeutic benefit of this approach is unknown, it may provide valuable staging information (Smith 1995, 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 five lymph nodes, is located between the bifurcation of the jugular vein and division of the lingofacial 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).

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 cornified 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

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

cats involve poorly haired regions of the head and neck, such as the eyelids, pinnae, and preauricular areas (Thomson 2007; Lana et al. 1997). 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 (Withrow 2007; Thomson 2007; Dorn et al. 1971; Lana et al. 1997). 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 (Withrow 2007; Ruslander et al. 1997; Lana et al. 1997). There is no breed predisposition in cats, but there is a high incidence of nasal planum SCC in male golden and Labrador retrievers (Figure 5.1; Lascelles et al. 2000). Other tumor types include lymphoma, fibrosarcoma, mast cell tumors, malignant melanoma, hemangioma, and fibroma (Withrow 2007). Eosinophilic granulomas and immune-mediated diseases are non-neoplastic conditions involving the nasal planum that can have a similar erosive to proliferative appearance mimicking benign and malignant tumors (Withrow 2007). History and clinical signs Head and neck SCC are often chronic cancers progressing from actinic changes (crusting and erythema) to

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

carcinoma in situ lesions (noninvasive carcinoma confined to the epidermis characterized by superficial erosions and ulcers) to invasive carcinomas (deep erosive lesions; Figures 5.2 and 5.3) (Withrow 2007; Thomson 2007; Lana et al. 1997). Occasionally, nasal planum SCC may have a proliferative appearance (Thomson 2007).

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The eyelids, preauricular areas, and pinnae should also be examined carefully as up to 30% of cats have SCC in multiple head and neck locations (Withrow 2007; Vail and Withrow 2007). Diagnosis and clinical staging A deep wedge or incisional biopsy is required for definitive diagnosis of nasal planum tumors (Withrow 2007). Cytologic examination of fine-needle aspirates, impression smears, or superficial biopsies is often unrewarding because they usually reveal inflammation, ulceration, and hemorrhage, which can be present in both neoplastic and nonneoplastic lesions (Withrow 2007; Thomson 2007). Biopsies may not be required in cats with erosive or ulcerated lesions of the eyelids, preauricular area, and/or pinnae, and possibly even the nasal planum, when there is a high index of suspicion for SCC (Figure 5.2) (Thomson 2007). A deep incisional biopsy is recommended in cats with proliferative lesions, and it can be justified in all dogs and perhaps cats with any nasal planum lesion to determine histology and the depth of invasion (Withrow 2007; Thomson 2007). Advanced imaging, with either computed tomography (CT) or magnetic resonance imaging (MRI), is recommended for local staging of nasal planum tumors in 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 aspirated or ideally excised (see previous section on lymph node staging). Three-view radiographs of the thoracic cavity should be considered, but invariably show no evidence of pulmonary metastasis (Lana et al. 1997; Withrow 2007).

procedures are described in detail in the chapter on oral tumors. Surgical technique For nasal planum resection, animals are positioned in sternal recumbency with their head elevated and symmetrically positioned. Systemic analgesia with perioperative nonsteroidal anti-inflammatory drugs and opioids can be supplemented with bilateral infraorbital nerve blocks using bupivacaine (Thomson 2007). The hair (with or without whiskers) is clipped around the nasal planum and lips. Following surgical preparation and draping, the surgical margins should be demarcated 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 preferred is 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) or the preferred skin-tonasal mucosa closure using a simple interrupted suture pattern of 4-0 or 5-0 nonabsorbable suture material (Figure 5.4) (Thomson 2007).

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; Thomson 2007; Withrow 2007). Surgery provides excellent local tumor control and has several advantages compared to other treatment options, including the ability to examine surgical margins, wide availability as compared to radiation therapy and photodynamic therapy, affordability, less treatment time, and an acceptable cosmetic outcome (Lana et al. 1997). 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) (Evans et al. 1985; Lascelles et al. 2004). These

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.

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Skin-to-mucosa closure is preferred because the incidence of postoperative complications, such as stenosis of the nasal aperture, is decreased. Should the pursestring technique be used, it is recommended to leave the nasal opening larger than planned to allow some further closing of the opening by second intention healing. The deep and lateral margins of the excised nasal planum should be inked and the sample submitted for histopathological assessment of tumor type and completeness of excision. Postoperative management In the immediate postoperative period, analgesia and intravenous fluids should be continued until the animal is eating and drinking voluntarily. Cats will often not want to eat for 1–4 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 the 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-inflammatory drugs is recommended after discharge for analgesic purposes. A scab or crust usually forms over the surgical site, and this should be carefully removed at suture removal 10–14 days after surgery. Sedation may be required for suture removal.

Figure 5.5.  Cosmetic appearance 6 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. (Image courtesy of Dr. Maurine J. Thomson)

Complications Complications are uncommon. The most significant complication is stenosis of the nasal aperture. This is more common following purse-string 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, or permanent placement of stainless steel intraluminal expansile stents (Withrow 2007). The prognosis is guarded to good for cats that develop nasal stenosis. 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

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.

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

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for incompletely excised nasal planum SCC (Lascelles et al. 2000; Thomson 2007; Withrow 2007). 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 euthanatized, and the remainder were cured (Lana et al. 1997). 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 efficacy as it only protects the deeper dermal layers and not the superficial epidermis. Synthetic vitamin A derivatives, such as isotretinoin or etretinate, increase epithelial differentiation and may reverse or limit the progression of precancerous lesions (Vail and Withrow 2007). However, in one study only 1 of 15 cats with precancerous or SCC lesions responded to isotretinoin therapy (Evans et al. 1985). 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 5 mm periphery around the tumor should be rapidly frozen to −20°C and then allowed to thaw slowly. This process should be performed three times in total. The response rate to cryosurgery is dependent on tumor size and location. Response rates are better with small, superficial, 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 the fact that margins cannot be determined and the risk of local recurrence is higher than either nasal planum resection or radiation therapy. Radiation therapy Radiation can be delivered either as local or external beam therapy (Lana et al. 1997). Local radiation therapy with 90strontium plesiotherapy is indicated for cats with superficial but not deep lesions, because strontium only penetrates to a depth of 2 mm (Van Vechten and Theon 1993; Goodfellow et al. 2006). 90Strontium is administered by the local application in five fractions of 10 Gy over a 10-day period for a total dose of 50 Gy (Goodfellow et al. 2006). For appropriate lesions, tumor control is very good, with 85% of 15 cats achieving a complete response after either one (11 cats) or two (2 cats) cycles of radiation therapy. None of these cats had evidence of local recurrence after a median follow-up of 652 days (Goodfellow et al. 2006). Full-course external beam radiation therapy can be used for superficial and deep nasal planum lesions. Orthovoltage, megavoltage, and proton beam irradiation have been described (Theon et al. 1995; Lana et al. 1997; Fidel et al. 2001). Smaller and superficial 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 (Theon 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 (Theon 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. The subsequent irradiation of the tumor with a light of a wavelength that is absorbed by the photosensitizer results in the formation of oxygenfree radicals and tissue death (Roberts et al. 1991; Peaston et al. 1993; Stell et al. 2001; Buchholz et al. 2007). Similar to other nonsurgical treatment options, photodynamic therapy is recommended only for superficial 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). Complications include local

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tumor recurrence in up to 64% of cats, 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). Intralesional chemotherapy Intralesional carboplatin has been investigated in cats with SCC of the nasal planum. Twenty-three cats with advanced lesions were treated with intralesional carboplatin (100 mg/m2) resulting in a complete response rate of 73%, 1-year disease-free survival rate of 55%, and local recurrence rate of 30% (Theon et al. 1996). The combination of carboplatin with purified sesame oil reduced systemic absorption and toxicity (Theon 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 8 months in four of these cats (de Vos et al. 2004).

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 mast cell tumors (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). Diagnosis and clinical staging Definitive 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 definitive therapy because this will provide valuable information on tumor type, histologic grade, and treatment options. Biopsy options include fine-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 of the pinna. Animals are positioned in either sternal or lateral

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.

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: 1 cm margins are recommended for SCC in cats (Figure 5.8A), benign tumors in dogs, and grade I MCT; 2 cm margins for grade II MCT; and 3 cm margins for canine STS and grade III MCT (Lana et al. 1997; Ruslander et al. 1997; Simpson et al. 2004; Vail and Withrow 2007). 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

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(a)

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.

(b)

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. (Images courtesy of Dr. Maurine J. Thomson)

one or two layers with the subcutaneous tissue closed in a simple continuous pattern using absorbable monofilament suture material and the skin in either a simple interrupted or continuous pattern with nonabsorbable monofilament suture material (Figure 5.8B). Following partial pinnectomy of tumors involving the lateral or medial borders of 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 sufficient 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). Complications following pinnectomy are uncommon and include hemorrhage, wound dehiscence, and local

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.

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 to decrease the risk of local recurrence (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

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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 superficial 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).

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 deficits, 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 deficits (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 (Theon 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; Theon 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). 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; Bacon et al. 2003; Moisan and Watson 1996). 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 (Carlotti 1991; Rogers 1988; Bacon et al. 2003). Malignant tumors of dogs and cats include ceruminous gland adenocarcinoma, SCC, and carcinoma of undetermined origin (Figure 5.11). Other malignant tumors affecting dogs include round cell tumor, sarcoma, malignant melanoma, fibrosarcoma, mast cell tumor, leiomyosarcoma, plasmacytoma, and hemangiosarcoma. Benign tumors of dogs and cats include inflammatory polyps, ceruminous gland adenoma, basal cell tumor, and papillomas. Histiocytoma, plasmacytoma, benign melanoma, and fibroma have also been reported in the dog (London et al. 1996; Lucke 1987; Rogers 1988; Bacon et al. 2003; ter Haar 2006). 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, inflammatory 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 nonneoplastic masses that can involve the external ear canal of the cat (Carlotti

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(a)

(b)

Figure 5.11.  (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.

(a)

(b)

Figure 5.12.  (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 ear canal was also resected, but not included in this image.

1991; Rogers 1988). Occasionally, they will extend on to the pinna (Figure 5.12). Patients are most commonly 2–15 years of age, with multiple masses 1–5 mm in size and containing black fluid. They are black fluid-filled cysts 1–5 mm in size that can extend from the ear canal on to the pinna. They have been reported in cats 2–15 years of age. Both ears may be affected. They are best treated with surgical resection. 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 inflammatory 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. The masses can be firm or friable, pedunculated or invasive. Pedunculated masses are typically benign, and malignant masses are typically broadbased (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 identification of the mass, a fine-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 inflammatory polyps and mast cell tumors from ceruminous gland adenoma and adenocarcinoma. This differentiation is useful as inflammatory 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

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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 definitive mass removal, histopathology should be performed in all cases to confirm 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 (Theon 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 findings, such as a soft-tissue density within the tympanic cavity, osseus thickening of the bulla, and sclerosis of the petrous temporal bone, are not specific for tumor ingrowth. They could also be consistent with secondary infection or inflammation (Rogers 1988; Marino et al. 1993). In one study, the presence of these radiographic changes in dogs with ceruminous gland adenocarcinoma did not affect 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 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). 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 confined to the lateral or vertical ear canal (Figure 5.13). A CT or MRI should be done to ensure that the horizontal ear canal is not involved (Lanz and Wood 2004). 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

(a)

(b)

Figure 5.13.  (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.

with tumors involving the lateral aspect of the vertical ear canal had a lateral ear canal resection (Marino et al. 1994). Sixty-six percent of the tumors recurred, with only 2 of the 6 cats alive at 1 year. The median diseasefree 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. 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 profile 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 significant intraoperative hemorrhage. For patients with bilateral disease, it may be preferable to stage the

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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. 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 is 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 superficial to the facial nerve to prevent iatrogenic trauma, as it may be entrapped in adjacent fibrous tissue (Smeak and Inpanbutr 2005). Bipolar cautery should be used for hemostasis. The ear canal is transected at the junction of the horizontal and osseus 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 ossified (Smeak and Inpanbutr 2005). Instruments should be directed in a caudal-tocranial direction away from the facial nerve. Following removal of the ear canal, the osseus 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

filled with saline and packed with a gauze square for 5 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 ronguers in a caudodorsal-to-cranioventral direction. Do not use ronguers 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 osseus external ear canal and bulla be completely removed to prevent chronic abscessation/fistulation. 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 superficial 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

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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 2 days after surgery. An Elizabethan collar is indicated if the patient is traumatizing the incision. A modification of the above technique is recommended for animals with erect ear carriage. Using new instruments and gloves, an advancement flap 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.

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 6 hours may be more successful. There is no evidence that the local administration of anesthetic agents caused an increased incidence of facial nerve deficits 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.

Postoperative management

Complications

Patients should be treated empirically with antibiotics until culture and sensitivity results are obtained. An appropriate antibiotic is then administered for 2–4 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 Eschirichia 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-inflammatory medication and tramadol or codeine should be administered for 5 days following surgery (Lanz and Wood 2004). Local infusion of anesthetic agents, such as intraoperative splash block, nerve blocks, and by 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. 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

In the immediate postoperative period, there can be swelling of the surgery site. This, in combination with the bandage, can cause difficulty breathing, particularly in brachycephalic patients. Patients should be monitored closely and the bandage loosened or removed if there is any concern. The risk of this is higher in patients that have had concurrent bilateral TECA and LBO. 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 deficits are often permanent. Following surgery, the incidence of facial nerve paresis/ paralysis in dogs is 5%–50%, with most cases resolving within 4 weeks. The cat has a higher incidence of neurologic dysfunction when compared to the dog and a higher incidence of permanent facial nerve deficits 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 and is less likely to resolve (Matthiesen and Scavelli 1990; 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 (Bacon et al. 2003). The majority of cases resolved within 1 month.

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Hearing loss is expected in all patients following surgery. Patients with significant ear disease may have been deaf prior to surgery. Owners should be warned of this in patients with bilateral disease. When evaluated by brain stem–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 fistulous tracts (ter Haar 2006). A significant complication following surgery is the development of otitis media and a fistulous 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 osseus 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 confined 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 4 out of 8 with SCC (London et al. 1996). In a third study, local tumor control was obtained with ear canal ablation in 6 dogs, however, 2 (1 with ceruminous gland adenocarcinoma and 1 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 significantly reduced median survival time of 5.3 months, whereas those with tumors confined 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 deficits, histologic evidence of invasion, and a histologic diagnosis of SCC or carcinoma of undetermined origin versus adenocarcinoma (London et al. 1996; Bacon et al. 2003). Cats with neurologic deficits at presentation had a significantly shorter median survival time of 1.5 months compared to 15.5 months in cats without neurologic deficits. Cats with histologic evidence of invasion had a median survival time of 4 months versus 21.7 months for cats that did not have invasion. Cats with ceruminous gland adenocarcinoma lived significantly longer than cats with SCC (median of 49 months versus 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 1 year (Marino et al. 1994; Bacon et al. 2003). In another study of 15 cats, 7 had ceruminous gland adenocarcinoma; of those 7 cats, 3 were dead by 6 months (Williams and White 1992). The remaining patients had no evidence of recurrence 6 months after surgery. High mitotic index (≥3 mitotic figures per highpower field) 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 (Theon et al. 1994). CT or MRI is recommended for radiation therapy planning (Theon et al. 1994). Megavoltage radiation is

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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 (Theon 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 (Theon 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 MondayWednesday-Friday schedule (Rogers 1988; Theon 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 deficits are common, including facial nerve paralysis, Horner’s syndrome, head tilt, nystagmus, and ataxia. Patients with tumor extension into the nasopharynx may present with increased chronic nasal discharge, respiratory noise or compromise, dysphagia, and exercise intolerance (Trevor and Martin 1993; Bradley 1984; Lanz and Wood 2004; ter Haar 2006). A similar mass may also be identified 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). Papillary adenomas have been documented in the middle ear of dogs (Little et al. 1989). Aggressive

neoplasia is rare in dogs. Cholesteatoma, an epidermoid cyst, can be misinterpreted as an aggressive tumor. It is an accumulation of keratinized debris in the middle ear of dogs (Hardie et al. 2008). It is typically associated with chronic otitis externa/media. Patients with more advanced disease can present with pain opening their mouth and neurologic signs, including head tilt, facial nerve paresis, and ataxia. With CT, some patients will have marked expansion of the bulla and lysis of the squamous or petrosal portions of the temporal bone. Contrast medium enhancement has also been observed that can be confused with a neoplastic process. Preoperative biopsies may be considered (transpalatal aspirate from the expanded bulla or a ventral approach). A ventral bulla osteotomy (VBO) or TECA and LBO should be performed, with tissue from the middle ear submitted for histopathology and culture and sensitivity. Alternatively, a caudal auricular approach to the tympanic bulla for removal of a cholesteotoma 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 difficult in these patients as the epithelium is adhered to the invaginated bone. SCC is the most common tumor type in cats (Stone et al. 1983; Rogers 1988; Lane and Hall 1992). Fibrosarcoma, adenocarcinoma, and lymphosarcoma have also been documented in the middle ears of cats (Rogers 1988; Lane and Hall 1992; Trevor and Martin 1993). 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 5 cats, all had facial nerve deficits 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). Nasopharyngeal polyps (NPs) are the most common mass lesion in the feline middle ear (Rogers 1988; Lanz and Wood 2004) and should be differentiated from neoplastic conditions. They typically affect younger patients (less than 2 years of age) (Bradley 1984; Lanz and Wood 2004); however, they have been reported in patients up to 15 years of age (Rogers 1988). In one study, the mean age of cats with NP was 1.5 years (6 months–5 years) (Trevor and Martin 1993). Patients can be bilaterally affected (Trevor and Martin 1993). 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

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MRI should be interpreted with caution following surgery as scar tissue has been shown to enhance contrast 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 deficits may not resolve with surgery. Treatment

Figure 5.14.  Traction-avulsion of a nasopharyngeal polyp extending into the external ear canal of a 4-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.

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, or a visible mass. 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). NPs are typically pedunculated and can be pale gray, white, or pink (Lanz and Wood 2004) (Figure 5.14). Diagnosis Skull radiographs 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 should be performed to evaluate the bulla (Bradley 1984; Lanz and Wood 2004). The bulla is typically thickened with a fluid 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). Advanced imaging, such as CT or MRI, is particularly important in patients with neurologic deficits (Horner’s or peripheral vestibular syndrome) to assess invasion into adjacent structures. This allows for appropriate surgical planning. CT or

VBO is recommended for diseases confined to the middle and inner ear. There is good exposure of the tympanic cavity, and gravity assists drainage (Trevor and Martin 1993). 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 benefit from chemotherapy (ter Haar 2006). 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 osteostomy is performed with a Steinmann pin or burr. The opening is enlarged with rongeurs. 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 fibers 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

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Figure 5.15.  Traction-avulsion of a large nasopharyngeal polyp in a cat. Note the intratracheal urinary catheter used to insufflate 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.

case of malignant tumors as it may track neoplastic cells outside of the surgical field. 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-inflammatory medication may be given for 5 days following surgery. Thirteen percent to 83% of patients undergoing VBO have positive middle ear cultures, and antibiotics are administered for 1–4 weeks based on culture and sensitivity results (Trevor and Martin 1993). The drain is removed 1–3 days following surgery. Treatment options for NPs include traction-avulsion and VBO (Figure 5.15). 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 difficult intubation if there is a large mass in the nasopharynx. Although it is preferable to avoid it, a temporary tracheotomy may be performed. Following induction, oxygen may be administered by a small urinary catheter placed into the airway (Figure 5.15). 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 5.15). 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. Masses are removed similarly from the external ear canal (see Figure 5.14). If they are difficult to reach, a vertical incision can be made in the lateral wall of the vertical ear canal (ter Haar 2006). An incision is made in the overlying skin. The subcutaneous tissues and parotid gland are dissected from the cartilage of the lateral aspect of the vertical ear canal. A vertical stab incision is made. Stay sutures are placed cranial and caudal to the incision to facilitate exposure. Small closed hemostats are introduced into the horizontal ear canal. The polyp is then grasped as closely as possible to the osseus meatus and avulsed with rotation and traction. It should not be simply excised as it is important to remove the stalk. The middle ear is then gently lavaged with warm saline. The osseus meatus and lateral aspect of the tympanic cavity can be gently palpated with a curette to remove any additional tissue. The cartilage of the ear canal is then closed with 4-0 monofilament suture in a simple interrupted suture pattern. The subcutaneous tissues are closed similarly with a simple continuous pattern. Some authors recommend that a VBO be performed in all patients with NPs that have radiographic changes of the bulla or neurologic deficits. 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. 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), but normally resolving within 4 weeks of surgery. 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). Facial nerve paralysis and peripheral vestibular syndrome (secondary to aggressive curettage) may also occur (Trevor and Martin 1993; Lanz and Wood 2004). Hypoglossal nerve deficits have also been reported following VBO, due to

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excessive retraction (Lanz and Wood 2004). The primary nonneurologic complication is recurrence of the inflammatory polyp (6% recurrence rate has been reported following VBO). Recurrent otitis media/interna, pharyngeal swelling, and incisional drainage have also been reported (Lanz and Wood 2004). 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. Prognosis There are few published reports of outcome following surgery for neoplasia of the middle ear. A dog with papillary adenoma had a ventral bulla osteotomy and partial curettage of the middle ear. He was euthanized 2 years after surgery for chronic otorrhea (Little et al. 1989). 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, lymphosarcoma, and ceruminous gland adenocarcinoma, the mean survival time was 1.25 months (4 days to 3 months), with surgery not improving the clinical course (Trevor and Martin 1993). The patients were euthanized due to progressive or recurrent clinical signs. 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 second 13 year-old cat, an adenocarcinoma was incompletely excised, due to firm 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). In patients with NPs, a decreased recurrence rate is expected with VBO (Lanz and Wood 2004). In one study, 7 cats had no recurrence, with a mean follow-up of 17 months following VBO (range 5–36 months following surgery). In another study of 37 cats with NP,

follow-up was available for 22 cats. Recurrence occurred in 9 cats (41%) after 1–9 months (median 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 traction-avulsion 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 and colleagues (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.

Salivary Gland Tumors Salivary gland tumors are uncommon in the dog and rare in the cat. Most patients are elderly. In a review of the literature, 79 dogs and 72 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). The median age for dogs was 9 years (3–14 years) (Habin and Else 1995; Evans and Thrall 1983; Louw and Van Schouwenburg 1984; Carberry et al. 1987; Brunnert and Altman 1990; 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), 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). 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;

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Hammer et al. 2001). Of the 79 dogs reported in the literature with malignant salivary tumors, 66 (84%) were adenocarcinoma (including simple, complex, cyst, and basal cell). The remaining 13 (16%) 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 fibrous histiocytoma, malignant myoepithelioma, extraskeletal osteosarcoma, and mast cell tumor (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). Of the 72 cats reported in the literature with malignant salivary tumors, 62 (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 (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). Secondary invasion of the salivary glands has been reported with fibrosarcoma and lymphosarcoma (Spangler and Culbertson 1991). Benign tumors are rare. Adenomas and lipomatous infiltration of the mandibular and parotid salivary glands have been reported in the dog (Carberry et al. 1988; Bindseil and Madsen 1997; Brown et al. 1997). These masses are not fixed 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 7 months following surgery. Adenoma, papillary adenomas, and cystadenoma have been reported in the cat (Spangler and Culbertson 1991; Carberry et al. 1988) (Figure 5.16). 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 fineneedle aspirate alone. Histopathology is needed to make a definitive 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). Dogs have more dramatic clinical signs with a history of ptyalism, nausea, pain on opening the mouth, frequent vomiting,

(a)

(b)

(c)

Figure 5.16.  (A, B) Salivary adenoma involving the lip of a cat that was surgically excised with wide margins. (C) Postoperative appearance.

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

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(Brooks et al. 1995). In two reported feline cases treated with surgical excision alone, the patients were diseasefree 6 months and 2 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). The majority present with bilateral enlargement of the mandibular salivary glands; however, unilateral involvement and parotid salivary gland involvement have also been reported. The glands may be painful on palpation. 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. Sialoceles also present with a swelling in the ventral neck, intermandibular space, pharynx, or under the tongue and are not fixed 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 8 weeks and cats had a median duration of 4 weeks (Hammer et al. 2001). Of the 79 dogs and 72 cats reviewed in the literature, the medical records of 5 dogs and 4 cats had information regarding the duration of clinical signs. The median duration for cats was 5 weeks (3 weeks–6 months), and the median duration for dogs was 2 weeks (4 days–6 weeks) (Carpenter and Bernstein 1991; Habin and Else 1995; Wells and Robinson 1975; Carberry et al. 1987; Thomsen and Myers 1999; PérezMartínez et al. 2000; Lambrechts and Pearson 2001; Kim et al. 2008; Psalla et al. 2008). 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 floor 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 deficits (facial nerve paresis, Horner’s syndrome), and sneezing (Hammer et al. 2001; Mazzullo et al. 2005). The mass is typically unilateral, firm, nonpainful, and fixed 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, are 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). 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). Most tumors are characterized by a rapid infiltrative growth at the time of diagnosis. Metastatic disease typically involves the regional lymph nodes and lung. 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, and the brain have been reported (Habin and Else 1995). 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 nonneoplastic diseases. The cytologic findings consistent with salivary gland adenocarcinoma are well described in the literature (Militerno et al. 2005). Cytology may be difficult to interpret in cases of necrotizing sialometaplasia (Brooks et al. 1995). Incisional biopsy will yield a more definitive diagnosis. At a minimum, the mass and associated lymph nodes should be evaluated by fine-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 submandibular, prescapular, axillary, and bronchial lymph nodes have also been reported (Habin and Else 1995; Mazzullo et al. 2005). 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 osseus 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

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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 profile (±T4). Hypoglycemia has been reported in cases of salivary adenocarcinoma (Morrison 2002). Treatment 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 fixed 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. Extirpation of the ipsilateral neck can be performed with a good outcome (Withrow 2007). The sequelae may be an inability to blink the ipsilateral eyelids due to facial nerve paresis. Some authors recommend tarsorrhaphy and the use of eye drops; however, if tear production is normal, they should not be necessary. 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 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 field 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 and should be preserved if possible. For closure,

the parotidoauricularis muscle is apposed and the superficial layers closed routinely. If there is significant 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; Bartoe et al. 2007). 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. If the arch is to be replaced, holes are predrilled on either side of the proposed osteotomy sites with a 0.35 mm drill bit or K-wire. The rostral osteotomy site is just caudal to the orbital ligament. The second site is extended caudally such that it gives maximum exposure to the tumor. The osteotomy is then performed between the holes with an oscillating or sagittal saw. The orbital ligament is transected midbody, and the arch is reflected 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 fixed 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, USA) in a horizontal mattress pattern and the superficial tissues are closed routinely. An Elizabethan collar is indicated following surgery to prevent self-trauma. Complications include seroma formation, infection, facial nerve paresis, and tumor recurrence. As most of these tumors are invasive, follow-up with radiation therapy is recommended (Carberry et al. 1988). Patients have received 37–57 Gy. 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 (Hammer et al. 2001). In another report, three dogs with parotid gland adenocarcinoma received

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10 doses from an orthovoltage unit totaling 45 Gy (Evans and Thrall 1983). Side effects include transient moist dermatitis, which can be severe, and permanent hair loss and color change. If the oral cavity is within the field, the patients may experience transient mucositis. If the eye is in the field, keratoconjunctivitis sicca, and cataracts may develop months following radiation therapy. 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 79 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 (mast cell tumor) had surgery and chemotherapy, and three (metastatic parotid adenocarcinoma, invasive solid anaplastic carcinoma 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), and one was euthanized 8 months after diagnosis with a massive tumor (Sozmen et al. 2003). Of the five 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 1 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 3 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). Of the 7 cats reported in the literature, 1 cat had surgery (adenocarcinoma of a minor salivary gland) (Burek et al. 1994) with tumor recurrence at 3 months, 1 had surgical excision and radiation therapy (malignant mixed tumor of the mandibular salivary gland) (Kim et al. 2008) with pulmonary metastases at 7 weeks, 4 (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 1 (poorly differentiated tumor of the mandibular salivary gland) (Wells and Robinson 1975) was euthanized 5 months following presentation. Unfortunately, there is little data evaluating the outcome with chemotherapy. An array of protocols have 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 disease are more likely to receive chemotherapy. In people, a correlation with environmental carcinogens and the development of salivary gland tumors has been identified. It has been proposed that salivary neoplasia in animals may also have a 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 fibrosarcoma (9%) (Todoroff and Brodey 1979). Mast cell tumor and extramedullary plasmacytoma (with and without amyloid deposits) have also been reported (Lucke 1987; Brunnert and Altman 1991; Rowland et al. 1991). 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

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van der Gaag 1987; Ramos-Vara et al. 2000; Schultheiss 2006). Malignant melanoma is characterized by local infiltration 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 confirm 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 fibrosarcoma, lymphosarcoma, and mastocytoma (Bradley 1984; Vos and van der Gaag 1987). Malignant melanoma is rare (Bradley 1984). Most patients are middle-aged or older (Bradley 1984; Vos and van der Gaag 1987).

(a)

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). 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 flaps, and axial pattern flaps (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. Small and benign tumors can be removed with simple techniques. Wedge, rectangular, or pentagonal fullthickness skin incisions are made with a scalpel blade to remove the neoplasm, ensuring that adequate margins are obtained (Pavletic 1999) (Figure 5.17). 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

(b)

(c)

Figure 5.17.  (A) Mast cell tumor affecting the cheek of a 7-yearold 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 2 weeks following surgery.

Head and Neck Tumors  109

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 first 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 pull-down 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 full-thickness 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 5.18). A full-thickness advancement flap 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 5.19). 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 (Pavletic 1999; Swaim and Henderson 1997). 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 flap is elevated and advanced rostrally to close the defect. Areas in the flap 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 flap 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

(a)

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Figure 5.18.  (A) Local recurrence of a SCC on the dorsolateral lip of an 11-month-old male neutered Yorkshire terrier. A maxillectomy had been performed 7 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 3 years following surgery. (Images courtesy of Dr. Karen Tobias)

110  Veterinary Surgical Oncology

(a)

(b)

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Figure 5.19.  (A) A mast cell tumor 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 flap. Note the gingival mucosa left to facilitate closure. An incision was made at the dorsal extent of the resection and extended caudally. The flap was then advanced rostrally to close the defect. Sutures are placed first 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 2–3 weeks.

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 first 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 flap may deviate the planum to the side of the surgery; however, this typically resolves within 2–3 weeks. A similar flap 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

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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 flap 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 first 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 flap may be created (Figure 5.20). The cheek margin is advanced rostrally to fill 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. There are several axial pattern flaps that can be used in lip reconstruction. The caudal auricular axial pattern flap 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 flap. The dorsal midline is the dorsal border of the flap, 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 flap is rotated rostrally below the ear to close the mandibular defect. It can be connected via a tubed flap or a bridging incision. If a tube is used, it is transected 3–4 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 2–3 days later. A tube flap 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 superficial temporal artery axial pattern flap can be used to reconstruct the upper lip and can be combined with a maxillectomy if necessary (Lester and Pratschke 2003; Fahie and Smith 1997). The flap is based on the dorsal aspect of the zygomatic arch. The rostral incision extends dorsally from the lateral orbital rim,

(a)

(b)

Figure 5.20.  (A) A buccal rotation flap was used to repair the lip of a 7-year-old male neutered schnauzer. The lip was traumatized in a dog fight. The rotation flap is outlined with surgical marker. (B) The flap has been rotated into the defect. (Images courtesy of Dr. Geraldine Hunt)

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 flap toward its base. Atraumatic tissue handling is important, and the flap must be kept moist. The flap can then be rotated into the defect. A closed active suction drain can be placed deep to the flap. In one case report, porcine

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intestinal submucosa was used to close the mucosal defect (Lester and Pratschke 2003). It was removed 6 days after surgery, but was felt to be a useful scaffold for tissue regeneration. The angularis oris axial pattern cutaneous flap is oriented caudally from the commissure of the mouth (Yates et al. 2007). 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. The flap is elevated from caudal to rostral, deep to the platysma muscle. Careful dissection is performed at the flap base to preserve cutaneous vasculature. The donor site is closed primarily without tension. The flap can be used to reconstruct both the buccal surface and haired lip when the width of the flap is at least one half the width of the defect. The flap is flipped 180 degrees into the defect with hair facing the oral cavity. The upper border of the flap is sutured to the mucosal margin with 3-0 absorbable suture in a simple interrupted suture pattern. The flap is folded onto itself and sutured to the skin with 3-0 non-absorbable suture in a simple interrupted suture pattern. In patients with larger defects, the flap is used to reconstruct the buccal mucosa, and adjacent skin is mobilized over the flap to close the cutaneous defect (Figure 5.21). Lip margin that can be apposed without tension is sutured. The base of the flap is inverted, and the flap is placed into the defect with the haired portion facing the oral cavity. The flap 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 flap and inverse tube segment. This leaves a narrow opening to an epithelium-lined skin tube. In 4–6 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 flap 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 flap has healed, redundant tissue can be resected. As an alternative, a tubed flap can be used to reach the lesion in lieu of a bridging incision. The tube can be resected in 3–4 weeks after the flap has healed. Postoperative care An Elizabethan collar should be placed for 1–2 weeks after surgery to prevent trauma to the surgery site. In

patients with a caudal auricular axial pattern flap, a light 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 4 weeks after surgery, and playing with hard toys must be prevented. Antibiotics may be given in the perioperative period. Complications Billowing of the flap is seen with expiration when the flap 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 flap 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 hair in the mouth. Clients should be warned that buccal advancement flaps and commissure rotation flaps 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 flaps also move hair with different lengths or thickness, which will change facial appearance. Ear carriage may also be altered. Prognosis Outcome for tumors of the lip are often combined with those reported for tumors of the oral cavity (Todoroff and Brodey 1979; Vos and van der Gaag 1987; RamosVara 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 2 years after diagnosis (Bostock 1979). In another study, one-third of the patients with histologically malignant tumors were alive and tumor free more than 1 year after surgery (Schultheiss 2006). Overall, soft tissue sarcomas have a low incidence of metastasis (Vos and van der Gaag 1987). In a report of one dog with a mast cell tumor, there was no evidence of recurrence 9 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

Head and Neck Tumors  113

(a)

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Figure 5.21.  (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 flap is elevated. Alternatively, the angularis oris axial pattern flap can be mobilized into the defect. The skin flap will be used to reconstruct the buccal surface of the lip. The base of the flap is folded to make an inverse tube (as indicated by the forceps). (D) The skin flap 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 flap 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 flap. The triangular-shaped dimple is the opening of the epitheliumlined skin tube. This will become less obvious with hair regrowth. Mild discharge can be treated with clipping and gentle flushing of the tube and possible antimicrobial therapy. This is usually sufficient. However, if the discharge is more frequent, the tube can be resected 4–6 weeks after surgery, once revascularization of the flap has occurred. (I) Intraoral view of the flap 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. (Images courtesy of Dr. Doug Huber)

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 1 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).

114  Veterinary Surgical Oncology

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 well-differentiated sebaceous adenocarcinoma of the chin reconstructed with a caudal auricular axial pattern flap (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 5 months after surgery with probable metastatic disease to the regional lymph nodes. There is a report of a cat with a large periodontal fibromatous epulis involving the upper lip reconstructed with a superficial temporal axial pattern flap (Lester and Pratschke 2003). Seven months after surgery there was no evidence of recurrence.

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Brunnert, S.R. and N.H. Altman. 1990. Canine lingual acinic cell carcinoma (clear cell variant) of minor salivary gland. Vet Pathol 27(3):203–205. Brunnert, S.R. and N.H. Altman. 1991. Identification of immunoglobulin light chains in canine extramedullary plasmacytomas by thioflavine T and immunohistochemistry. J Vet Diagn Invest 3(3):245–251. Buback, J.L., H.W. Boothe, G.L. Carroll, et al. 1996. Comparison of three methods for relief of pain after ear canal ablation in dogs. Vet Surg 25:380–385. Buchholz, J., M. Wergin, H. Walt, et al. 2007. Photodynamic therapy of feline cutaneous squamous cell carcinoma using a newly developed liposomal photosensitizer: Preliminary results concerning drug safety and efficacy. J Vet Intern Med 21(4):770–775. Burek, K.A., R.J. Munn, and B.R. Madewell. 1994. Metastatic adenocarcinoma of a minor salivary gland in a cat. J Vet Intern Med Series A 41(6):485–490. Carberry, C.A., J.A. Flanders, W.I. Anderson, et al. 1987. Mast cell tumor in the mandibular salivary gland in a dog. Cornell Vet 77(4):362–366. Carberry, C.A., J.A. Flanders, H.J. Harvey, et al. 1988. Salivary gland tumors in dogs and cats: A literature and case review. J Am Anim Hosp Assoc 24:561–567. Carlotti, D.N. 1991. Diagnosis and medical treatment of otitis externa in dogs and cats. J Small Anim Pract 32:394–400. Carpenter, J.L. and M. Bernstein. 1991. Malignant mixed (pleomorphic) mandibular salivary gland tumors in a cat. J Am Anim Hosp Assoc 27:581–583. Clarke, R.E. 1991. Cryosurgical treatment of cutaneous squamous cell carcinoma. Australian Vet Pract 21:148–153. De Lorenzi, D., U. Bonfanti, C. Masserdotti, et al. 2005. Fine-needle biopsy of external ear canal masses in the cat: Cytologic results and histologic correlations in 27 cases. Vet Clin Pathol 34(2):100–105. de Vos, J.P., A.G.O. Burm, and B.P. Focker. 2004. Results from the treatment of advanced stage squamous cell carcinoma of the nasal planum in cats, using a combination of intalesional carboplatin and superficial radiotherapy: A pilot study. Vet Comp Oncol 2:75–81. Devitt, C.M., H.B. Seim, III, R. Willer, et al. 1997. Passive drainage versus primary closure after total ear canal ablation-lateral bulla osteotomy in dogs: 59 dogs (1985–1995). Vet Surg 26(3):210– 216. Dorn, C.R., D.O. Taylor, and R. Schneider. 1971. Sunlight exposure and risk of developing cutaneous and oral squamous cell carcinomas in white cats. J Natl Cancer Inst 46(5):1073–1078. Dunning, D. 2003. Oral cavity. In Textbook of Small Animal Surgery, third edition. pp. 553–572. D. Slatter, editor. Saunders: Philadelphia, PA. Evans, A.G., B.R. Madewell, and A.A. Stannard. 1985. A trial of 13-cisretinoic acid for treatment of squamous cell carcinoma and preneoplastic lesions of the head in cats. Am J Vet Res 46(12): 2553–2557. Evans, S.M. and D.E. Thrall. 1983. Postoperative orthovoltage radiation therapy of parotid salivary gland adenocarcinoma in three dogs. J Am Vet Med Assoc 182(9):993–994. Fahie, M.A. and M.M. Smith. 1997. Axial pattern flap based on the superficial temporal artery in cats: An experimental study. Vet Surg 26(2):86–89. Faustino, A.M. and P. Dias Pereira. 2007. A salivary malignant myoepithelioma in a dog. Vet J 173(1):223–226. Fidel, J.L., E. Egger, H. Blattmann, et al. 2001. Proton irradiation of feline nasal planum squamous cell carcinomas using an accelerated protocol. Vet Radiol Ultrasound 42(6):569–575.

Head and Neck Tumors  115 Gilger, B.C., R.D. Whitley, and S.A. McLaughlin. 1994. Modified lateral orbitotomy for removal of orbital neoplasms in two dogs. Vet Surg 23(1):53–58. Goodfellow, M., A. Hayes, S. Murphy, et al. 2006. A retrospective study of strontium-90 plesiotherapy for feline squamous cell carcinoma of the nasal planum. J Feline Med Surg 8(3):169– 176. Habin, D.J. and R.W. Else. 1995. Parotid salivary gland adenocarcinoma with bilateral ocular and osseous metastases in a dog. J Small Anim Pract 36(10):445–449. Hammer, A., D. Getzy, G. Ogilvie, et al. 2001. Salivary gland neoplasia in the dog and cat: Survival times and prognostic factors. J Am Anim Hosp Assoc 37(5):478–482. Hardie, E.M., K.E. Linder, and A.P. Pease. 2008. Aural cholesteatoma in twenty dogs. Vet Surg 37(8):763–770. Hayden, D.W. 1976. Squamous cell carcinoma in a cat with intraocular and orbital metastases. Vet Pathol 13(5):332–336. Hedlund, C.S. 2002. Surgery of the digestive system: Salivary mucoceles. In Small Animal Surgery, second edition. pp. 302–307. T.W. Fossum, editor. Mosby: St. Louis. Igarashi, Y. and J. Suzuki. 1985. Cochlear ototoxicity of chlorhexi­ dine gluconate in cats. Arch Otorhinolaryngol 242(2):167– 176. Indrieri, R.J. and R.F. Taylor. 1984. Vestibular dysfunction caused by squamous cell carcinoma involving the middle ear and inner ear in two cats. J Am Vet Med Assoc 184(4):471–473. Jha, A.K., G. Prasiko, H. Mod, et al. 2006. Curative interstitial brachytherapy for early stage carcinoma lip. JNMA J Nepal Med Assoc 45(162):252–257. Kim, H., M. Nakaichi, K. Itamoto, et al. 2008. Malignant mixed tumor in the salivary gland of a cat. J Vet Sci 9(3):331–333. Kipar, A., W. Baumgärtner, and E. Burkhardt. 1995. Round cell sarcomas of possible myelomonocytic origin localized at the lip of aged dogs. J Vet Intern Med Series A 42(3):185–200. Kirpensteijn, J., S.J. Withrow, and R.C. Straw. 1994. Combined resection of the nasal planum and premaxilla in three dogs. Vet Surg 23(5):341–346. Kneissl, S. and A. Probst. 2006. Magnetic resonance imaging features of presumed normal head and neck lymph nodes in dogs. Vet Radiol Ultrasound 47(6):538–541. Lambrechts, N.E. and J. Pearson. 2001. Cervical teratoma in a dog. J S Afr Vet Assoc 72(1):49–51. Lana, S.E., G.K. Ogilvie, S.J. Withrow, et al. 1997. Feline cutaneous squamous cell carcinoma of the nasal planum and the pinnae: 61 cases. J Am Anim Hosp Assoc 33(4):329–332. Lane, I.F. and D.G. Hall. 1992. Adenocarcinoma of the middle ear with osteolysis of the tympanic bulla in a cat. J Am Vet Med Assoc 201(3):463–465. Lanz, O.I. and B.C. Wood. 2004. Surgery of the ear and pinna. Vet Clin North Am Small Anim Pract 34(2):567–599. Lascelles, B.D., R.A. Henderson, B. Seguin, 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(2):137–146. Lascelles, B.D., A.T. Parry, M.F. Stidworthy, et al. 2000. Squamous cell carcinoma of the nasal planum in 17 dogs. Vet Rec 147(17): 473–476. Lester, S. and K. Pratschke. 2003. Central hemimaxillectomy and reconstruction using a superficial temporal artery axial pattern flap in a domestic short hair cat. J Feline Med Surg 5(4):241– 244. Little, C.J.L., G.R. Pearson, and J.G. Lane. 1989. Neoplasia involving the middle ear cavity of dogs. Vet Rec 124(3):54–57.

London, C.A., R.R. Dubilzeig, D.M. Vail, et al. 1996. Evaluation of dogs and cats with tumors of the ear canal: 145 cases (1978–1992). J Am Vet Med Assoc 208(9):1413–1418. Louw, G.J. and S.J.E.M. Van Schouwenburg. 1984. A case of a highly invasive carcinoma of a salivary gland in a crossbred dog. J S Afr Vet Assoc 55: 131–132. Lucke, V.M. 1987. Primary cutaneous plasmacytomas in the dog and cat. J Small Anim Pract 28:49–55. Lucroy, M.D., K.M. Vernau, V.F. Samii, et al. 2004. Middle ear tumours with brainstem extension treated by ventral bulla osteotomy and craniectomy in two cats. Vet Comp Oncol 2:234–242. Lurie, D.M., B. Seguin, P.D. Schneider, et al. 2006. Contrast-assisted ultrasound for sentinel lymph node detection in spontaneously arising canine head and neck tumors. Invest Radiol 41(4): 415–421. Marino, D.J., J.M. MacDonald, D.T. Matthiesen, et al. 1994. Results of surgery in cats with ceruminous gland adenocarcinoma. J Am Anim Hosp Assoc 30:54–58. Marino, D.J., J.M. MacDonald, D.T. Matthiesen, et al. 1993. Results of surgery and long-term follow-up in dogs with ceruminous gland adenocarcinoma. J Am Anim Hosp Assoc 29:560–563. Matthiesen, D.T. and T. Scavelli. 1990. Total ear canal ablation and lateral bulla osteotomy in 38 dogs. J Am Anim Hosp Assoc 26:257–267. Mazzullo, G., A. Sfacteria, N. Iannelli, et al. 2005. Carcinoma of the submandibular salivary glands with multiple metastases in a cat. Vet Clin Pathol 34(1):61–64. McAnulty, J.F., A. Hattel, and C.E. Harvey. 1995. Wound healing and brain stem auditory evoked potentials after experimental total ear canal ablation with lateral tympanic bulla osteotomy in dogs. Vet Surg 24(1):1–8. Militerno, G., R. Bazzo, and P.S. Marcato. 2005. Cytological diagnosis of mandibular salivary gland adenocarcinoma in a dog. J Vet Intern Med. Series A 52(10):514–516. Moisan, P.G. and G.L. Watson. 1996. Ceruminous gland tumors in dogs and cats: A review of 124 cases. J Am Anim Hosp Assoc 32(5):448–452. Morrison, W.B. 2002. Paraneoplastic syndromes and the tumors that cause them. In Cancer in Dogs and Cats: Medical and Surgical Management, second edition. pp. 731–744. W.B. Morrison, editor. Teton NewMedia: Jackson, WY. Nieweg, O.E., P.J. Tanis, and B.B. Kroon. 2001. The definition of a sentinel node. Ann Surg Oncol 8(6):538–541. Nyman, H.T., A.T. Kristensen, I.M. Skovgaard, et al. 2005. Characterization of normal and abnormal canine superficial lymph nodes using gray-scale B-mode, color flow mapping, power, and spectral Doppler ultrasonography: A multivariate study. Vet Radiol Ultrasound 46(5):404–410. Oyamada, T., H. Okujima, R. Ando, et al. 2007. A case of malignant mixed salivary tumor composed of squamous cell carcinoma and osteosarcoma in a cat. J Japan Vet Med Assoc 60:724–728. Pavletic, M.M. 1999. Facial reconstruction. In Atlas of Small Animal Reconstructive Surgery, second edition. pp. 297–327. Saunders: Philadelphia, PA. Peaston, A.E., M.W. Leach, and R.J. Higgins. 1993. Photodynamic therapy for nasal and aural squamous cell carcinoma in cats. J Am Vet Med Assoc 202(8):1261–1265. Pentlarge, V.W. 1984. Peripheral vestibular disease in a cat with middle and inner ear squamous cell carcinoma. Compendium on Continuing Education for the Practicing Veterinarian 6:731– 734.

116  Veterinary Surgical Oncology Pérez-Martínez, C., R.A. García-Fernández, L.E. Reyes Avila et al. 2000. Malignant fibrous histiocytoma (giant cell type) associated with a malignant mixed tumor in the salivary gland of a dog. Vet Pathol 37(4):350–353. Psalla, D., C. Geigy, M. Konar, et al. 2008. Nasal acinic cell carcinoma in a cat. Vet Pathol 45(3):365–368. Ramos-Vara, J.A., M.E. Beissenherz, M.A. Miller, et al. 2000. Retrospective study of 338 canine oral melanomas with clinical, histologic, and immunohistochemical review of 129 cases. Vet Pathol 37(6):597–608. Roberts, W.G., M.K. Klein, M. Loomis, et al. 1991. Photodynamic therapy of spontaneous cancers in felines, canines, and snakes with chloro-aluminum sulfonated phthalocyanine. J Natl Cancer Inst 83(1):18–23. Rogers, K.S. 1988. Tumors of the ear canal. Vet Clin North Am Small Anim Prac. 18(4):859–868. Rohleder, J.J., J.C. Jones, R.B. Duncan, et al. 2006. Comparative performance of radiography and computed tomography in the diagnosis of middle ear disease in 31 dogs. Vet Radiol Ultrasound 47(1):45–52. Rowland, P.H., B.A. Valentine, K.E. Stebbins, et al. 1991. Cutaneous plasmacytomas with amyloid in six dogs. Vet Pathol 28(2): 125–130. Ruslander, D., B. Kaser-Hotz, and J.C. Sardinas. 1997. Cutaneous squamous cell carcinoma in cats. Compendium on Continuing Education for the Practicing Veterinarian 19:1119–1129. Salisbury, S.K., D.C. Richardson, and G.C. Lantz. 1986. Partial maxillectomy and premaxillectomy in the treatment of oral neoplasia in the dog and cat. Vet Surg 15:16–26. Salvadori, C., C. Cantile, and M. Arispici. 2004. Meningeal carcinomatosis in two cats. J Comp Pathol 131(2–3):246–251. Schultheiss, P.C. 2006. Histologic features and clinical outcomes of melanomas of lip, haired skin, and nail bed locations of dogs. J Vet Diagn Invest 18(4):422–425. Simpson, A.M., L.L. Ludwig, S.J. Newman, et al. 2004. Evaluation of surgical margins required for complete excision of cutaneous mast cell tumors in dogs. J Am Vet Med Assoc 224(2):236– 240. Smeak, D.D. and N. Inpanbutr 2005. Lateral approach to subtotal bulla osteotomy in dogs: Pertinent anatomy and procedural details. Compendium on Continuing Education for the Practicing Veterinarian 27:377–384. Smith, M.M. 1995. Surgical approach for lymph node staging of oral and maxillofacial neoplasms in dogs. J Am Anim Hosp Assoc 31(6):514–518. Smith, M.M. 2002. Surgical approach for lymph node staging of oral and maxillofacial neoplasms in dogs. J Vet Dent 19(3): 170–174. Smrkovski, O.A., A.K. LeBlanc, S.H. Smith, et al. 2006. Carcinoma ex pleomorphic adenoma with sebaceous differentiation in the mandibular salivary gland of a dog. Vet Pathol 43(3):374–377. Sozmen, M., P.J. Brown, and J.W. Eveson. 2002. Sebaceous carcinoma of the salivary gland in a cat. J Vet Intern Med Series A 49(8):425–427. Sozmen, M., P.J. Brown, and J.W. Eveson. 2003. Salivary gland basal cell adenocarcinoma: A report of cases in a cat and two dogs. J Vet Intern Med Series A 50(8):399–401. Spangler, W.L. and M.R. Culbertson. 1991. Salivary gland disease in dogs and cats: 245 cases (1985–1988). J Am Vet Med Assoc 198(3):465–469. Stell, A.J., J.M. Dobson, and K. Langmack. 2001. Photodynamic therapy of feline superficial squamous cell carcinoma using topical 5-aminolaevulinic acid. J Small Anim Pract 42(4):164–169.

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6 Oral tumors Julius M. Liptak, 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 cancer in cats and dogs with oral tumors. For instance, an incisional biopsy is often required for definitive 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. Also, clinical staging requires excision of the regional lymph nodes, which is important for determining postoperative treatment plans and prognosis. And the most common definitive 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 that is 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, 1991b; 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 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 definitive surgery. Diagnosis and clinical staging The diagnosis and clinical staging of animals with oropharyngeal masses is imperative before definitive surgical excision. A biopsy is required for definitive 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 and Withrow 2007). 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 definitive diagnosis. Cytologic touch or aspiration preparations are usually not rewarding and can result in an incorrect diagnosis because many oral tumors are associated with a high degree of necrosis and inflammation (Liptak and Withrow 2007). Dogs with exophytic or ulcerated masses

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will generally tolerate a deep wedge or core punch biopsy without general anesthesia. Biopsy is recommended in the diagnostic workup 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, inflamed, or necrotic, and it is important to obtain a large specimen. Cautery may distort the specimen and should be used only 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 field. 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., peripheral odontogenic fibromas, 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 there should be photographic evidence, to detail the size and anatomical 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.

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

Clinical staging—local tumor imaging 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 and Withrow 2007). 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 or MRI scans will provide more information on the local extent of the tumor than will regional radiographs. This information is important for planning the definitive surgical procedure (or radiation therapy if indicated).

Figure 6.2.  CT scan of a dog with a multilobular osteochondrosarcoma arising from the caudal mandible. CT scans provide superior detail on the extent of the tumor and tumor invasion and is the preferred imaging modality for planning of surgical resection of tumors involving the caudal mandible.

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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 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 difficult. Currently, lymph node aspirates are recommended for all animals with oral tumors, regardless of the size or degree of fixation of the lymph nodes (Herring et al. 2002; Williams and Packer 2003). It is hoped that 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 lymphoscintigraphy, intraoperative blue dyes, and intraoperative gamma probes (Balogh et al. 2002). Lymphoscintigraphy, intraoperative dyes, and contrastenhanced ultrasonography have been described in dogs with various tumors, including head and neck cancer (Balogh et al. 2002; Lurie et al. 2006). En bloc resection of the regional lymph nodes has been described and, although the therapeutic benefit of this approach is unknown, it may provide valuable staging information (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 five lymph nodes, is located between the bifurcation of the jugular vein and division of the lingofacial 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 manidbular salivary gland rostrally and the bra­ chiocephalicus and sternocephalicus muscles dorsally (Smith 1995). Clinical staging–distant metastasis The final 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 significantly 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).

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 fibroma, 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, 1991b; 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 fibrosarcoma in the dog. If possible, SCC in the cat should be treated with surgical margins greater than 2 cm because of high local recurrence rates. However, these margins may not be possible without significant 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

122  Veterinary Surgical Oncology Table 6.1.  Clinical staging (TNM) of oral tumors in dogs and cats. Primary Tumor (T)   Tis Tumor in situ   T1 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 IV

T1 T2 T3 Any T Any T Any T

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

M0 M0 M0 M0 M0 M1

margins may result in acceptable rates of local tumor control (Syrcle et al. 2008). Where 3 cm margins are not possible without significant 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.

Rostral and segmental bony resections may be sufficient for benign lesions and rostral SCC in dogs. Larger resections, such as hemimandibulectomy, hemimaxillectomy, orbitectomy, and radical maxillectomy, are necessary for more aggressive malignant tumors, especially fibrosarcoma, 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, 1991b; White 1991; Wallace et al. 1992; Kirpensteijn et al. 1994; Lascelles et al. 2003, 2004; Verstraete 2005). Reconstruction following mandibular resection has been described, 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). 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 short surgical times and excellent vascular supply to the oral cavity. However, some surgeons prefer the use of prophylactic antibiotics (such as a first-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 first 24 hours after surgery (Dernell et al. 1998a). Analgesia Regional nerve blocks and systemic nonsteroidal antiinflammatory drugs and narcotics are recommended for perioperative analgesia to minimize morbidity and improve postoperative comfort (Beckman and Legendre 2002). Recent research also suggests minimizing perioperative pain may help decrease the rate of metastasis following oncologic surgery (Exadaktylos et al. 2006). See Table 6.2 for an outline of suggested analgesic protocols for cats and dogs undergoing maxillofacial resection and reconstruction.

Oral Tumors  123 Table 6.2.  Suggested analgesic protocols for oral surgery in cats and dogs. Analgesic Protocols

Cats

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Preoperative

Fentanyl patch placed the day before surgery (3–4 mcg/kg/hr) Intravenous NSAID once at induction or following full recovery if hemorrhage expected (e.g., carprofen 1–2 mg/kg [healthy cats] or meloxicam 0.1 mg/kg) Bupivicaine regional nerve blocks at induction Continuous rate IV infusion of • hydromorphone (0.005–0.01 mg/kg/hr), fentanyl (2–4 mcg/kg/hr), or morphine (0.05 mg/kg/hr) • medetomidine (1–4 mcg/kg/hr) • ketamine (0.1–0.5 mg/kg/hr) • Oral NSAID for 5–14 days at approved dose. Suggest meloxicam 0.1 mg/kg once on day 1 (perioperative dose), 0.05 mg/kg q 24 hrs for 4 days, 0.025 mg/kg q 24 hrs for 4 days, then 0.025 mg/kg q 48 hrs. 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 mcg/kg q 8–12 hrs) for 7–10 days, or fentanyl patch replaced as required. • Oral opioid derivative (e.g., tramadol 4 mg/kg PO q 12 hrs) for 7–10 days, or fentanyl patch replaced as required.

Fentanyl patch placed the day before surgery (3–4 mcg/kg/hr) Intravenous NSAID once at induction or following full recovery if hemorrhage expected (e.g., Carprofen 4 mg/kg or meloxicam 0.1 mg/kg)

Perioperative

Discharge

Bupivicaine regional nerve blocks at induction Continuous rate IV infusion of • hydromorphone (0.005–0.02 mg/kg/hr), fentanyl (2–4 mcg/kg/hr), or morphine (0.1 mg/kg/hr) • medetomidine (1–2 mcg/kg/hr) • lidocaine (25–30 mcg/kg/min) • ketamine (2 mcg/kg/min) • Oral NSAID for 10–14 days at approved dose. Do not use if the dog is stressed or has any risk factors for gastrointestinal ulceration. • Oral opioid derivative (e.g., tramadol 4 mg/kg PO q 6–12 hrs) for 7–10 days, or fentanyl patch replaced as required.

Positioning and preparation

Surgical considerations

Animals are placed in the appropriate position and, if necessary, a mouth gag is placed on the lower or nonsurgical 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 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 field. The oral cavity is irrigated with 10% povidone-iodine solution, which is first diluted 1:10 with tap water (Dernell et al. 1998a). Towel clamps or staples are used to secure the drapes in such a manner as to allow for mobilization of the labial tissues.

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 findings, 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 fibroma (Dernell et al. 1998a; Liptak and Withrow 2007). 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 sufficient for bony margins. 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 nonsymphyseal 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

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Figure 6.3.  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.

osteotome and mallet. Monofilament 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 inflammation (Salisbury et al. 1986; Dernell et al. 1998a). A reverse-cutting swaged-on needle is preferred for suturing fibrous 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 closures 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 6.3).

Surgical Approach to Tumors of the Mandible Anatomy The lower jaw consists of two hemimandibles that form a fibrocartilaginous symphysis rostrally and articulate caudally with the skull at the temporomandibular joint (Evans and Christensen 1979). The hemimandible consists of the body and ramus (Figure 6.4). Teeth erupt along the alveolar margin of the mandibular body. The mandibular canal is an important oncological 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 Christensen 1979). Tumors involv-

Figure 6.4.  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. (Reproduced with permission from Evans, H.E. and A. deLahunta, editors. 2000. The head. In Guide to the Dissection of the Dog, pp. 259–321. Saunders: Philadelphia.)

ing 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. The ramus consists of three prominent processes: the coronoid process on the dorsal aspect of the ramus, the condylar process on the caudal aspect of the ramus, and the angular process on the caudoventral aspect of the ramus (Figure 6.4) (Evans and Christensen 1979). 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 6.5) (Evans and Christensen 1979). 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 hemimandibulectomy.

Oral Tumors  125

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Figure 6.5.  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) Cutout to show the deep portion of the masseter muscle. Reproduced with permission from Evans, H.E. and G.C. Christensen, editors. 1979. Muscles. In Miller’s Anatomy of the Dog, pp. 269–410. Philadelphia: Saunders.

Rostral mandibulectomy—unilateral Unilateral rostral mandibulectomy is recommended for dogs with benign acanthomatous ameloblastoma or SCC lesions that are rostral to the second premolar tooth and do not cross the mandibular symphysis. Bilateral rostral mandibulectomy should be considered for these tumor types that cross the mandibular symphysis, and hemimandibulectomy 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 6.6A) (Dernell et al. 1998a). This incision is continued rostrally to the mandibular symphysis and caudally to the planned osteotomy site. The labial mucosa is reflected off the mandible with periosteal elevators to preserve the soft tissue of the lip that will be used later for reconstruction of the defect (Figure 6.6B). 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 6.6C). This

126  Veterinary Surgical Oncology

(a)

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Figure 6.6.  Unilateral rostral mandibulectomy. (A) The labial and gingival mucosa are incised with a minimum of 1 cm margins from an acanthomatous ameloblastoma localized to the mandibular canine tooth. (B) The mucosa is then reflected 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, E) The caudal osteotomy is performed with an oscillating saw with minimum margins of 1–2 cm for benign tumors, such as this acanthomatous ameloblastoma, 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 monofilament absorbable suture material.

osteotomy can be performed with an oscillating saw, biradial saw, or osteotome and mallet (Dernell et al. 1998a). A bone cutter may be sufficient 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 sufficient. The caudal osteotomy should be performed with an oscillating saw and tapered at the occlusional

margin to minimize wound tension during closure (Figures 6.6D, 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 is used for this osteotomy; hence, this should be avoided. Following mandibulectomy, the sublingual mucosa is sutured to the labial mucosa in a single layer of a simple interrupted or simple continuous suture pattern using monofilament absorbable suture material (Figures 6.6F, G) (Dernell et al. 1998a).

Oral Tumors  127

Rostral mandibulectomy—bilateral

Segmental mandibulectomy

Bilateral rostral mandibulectomy is recommended for dogs with benign acanthomatous ameloblastoma or SCC lesions rostral to the first premolar tooth and across 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 difficulty 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’s 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 reflected 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 6.7A, 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 anatomical 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 sufficient. The caudal osteotomy should be performed with an oscillating saw and tapered at the occlusional margin to minimize wound tension during closure (Figure 6.7C) (Dernell et al. 1998a). Stabilization of the remaining portions of the hemimandible has been described (Boudrieau et al. 1994; Bracker and Trout 2000; Boudrieau et al. 2004; Spector et al. 2007), but is not necessary because 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 monofilament absorbable suture material (Figure 6.7D) (Dernell et al. 1998a).

Segmental mandibulectomy is recommended for dogs with benign acanthomatous ameloblastoma or lowgrade malignant tumors, such as SCC, located in the midmandibular body. Furthermore, these tumors should not penetrate cortical bone. Segmental mandibulectomy is contraindicated for malignant tumors other than SCC. 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 6.8A). 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 6.8B). Margins of 1–2 cm for acanthomatous ameloblastoma and 2–3 cm for SCC should be sufficient 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 monofilament absorbable suture material (Figure 6.8C). Subtotal and total hemimandibulectomy Hemimandibulectomy is recommended for malignant tumors, particularly those with extensive involvement of the mandibular body. The only difference between subtotal and total hemimandibulectomy is the caudal margins. For subtotal hemimandibulectomy, the mandible is osteotomized caudal to the mandibular canal, and this is primarily indicated when the tumor can be excised with 3 cm caudal margins without sacrificing the ramus or temporomandibular joint. It should be noted, however, that preservation of these structures does not improve postoperative function or cosmesis; hence, subtotal hemimandibulectomy should not be performed if caudal margins will be compromised. Total hemimandibulectomy includes the temporo­ mandibular joint and ramus. This procedure is more aggressive and is indicated for tumors in which 3 cm caudal margins cannot be attained with subtotal hemimandibulectomy. Dogs are positioned in lateral recumbency for hemimandibulectomy (Dernell et al. 1998a). To improve exposure for total hemimandibulectomy, 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 hemimandibulectomy.

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Figure 6.7.  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 reflected 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 monofilament absorbable suture material.

(a)

(b)

(c)

Figure 6.8.  Segmental mandibulectomy. (A) The labial and gingival mucosa are incised with minimum margins of 1 cm from an acanthomatous ameloblastoma arising from the lateral alveolar ridge of the third premolar tooth, and the mucosa is then reflected 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 1−2 cm. Note that this segmental mandibulectomy is not recommended for malignant tumors, and hence larger margins are not required. (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 monofilament absorbable suture material.

128

Oral Tumors  129

For both subtotal and total hemimandibulectomy, the labial and buccal mucosa are incised with a minimum of 1 cm margins around the mass (Figure 6.9A) (Dernell et al. 1998a). The mucosal incisions are continued rostrally to the level of the planned ostoeotomy and caudally to the ramus (Figure 6.9B). The lateral border of the tongue is freed as the medial incision is continued rostrally into the sublingual mucosa. During this dissection, the mandibular and sublingual salivary ducts may be encountered. Some surgeons recommend identification 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, whereas a bone cutter may be sufficient in cats and small dogs (Figure 6.9C). Separation of the mandibular symphysis permits lateral movement of the hemimandible and better exposure and visualization for caudal dissection. Importantly, the inferior alveolar artery and vein should be identified and ligated as they course over the lateral surface of the medial pterygoid muscle before entering the mandibular foramen (Figure 6.9D). For subtotal hemimandibulectomy, the caudal osteotomy is positioned at the rostral edge of the insertion of the masseter muscle (Figure 6.9E) (Dernell et al. 1998a). This osteotomy should be performed with an oscillating saw. For total hemimandibulectomy, 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 hemimandible in a caudodorsal direction (Figure 6.9F, G); the digastricus muscle is elevated from its insertion along the caudoventral border of the mandibular body (Figure 6.9H); and the pterygoid muscles are elevated from their insertion on the medial aspect of the caudoventral surface of angle of mandible (Figure 6.9I) (Dernell et al. 1998a). The temporomandibular joint capsule is incised laterally and medially and then luxated (Figure 6.9J) (Dernell et al. 1998a). Finally, the tem­ poralis 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 hemimandibulectomy and two layers following subtotal hemimandibulectomy (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 monofilament absorbable suture material. A simple interrupted pattern is recommended for wounds under tension, whereas a simple continuous pattern is sufficient for wounds with minimal or no tension (Figure 6.9K). The commissure of the lip can be advanced rostrally to the level of the first 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. Advancement of the commissure of the lip may improve postoperative cosmesis, but it may also increase the risk of wound complications. Caudal (vertical ramus) mandibulectomy Caudal mandibulectomy is indicated for benign or lowgrade malignant lesions confined to the mandibular ramus, such as osteoma or multilobular osteochondrosarcoma. More extensive hemimandibulectomy 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 6.10A). 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 6.10B) (Dernell et al. 1998a). During this dissection, the infraorbital artery, vein, and nerve coursing along the medial aspect of the zygomatic arch should be identified 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 6.10C). 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

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Oral Tumors  131 Figure 6.9.  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 1 cm in a cat with a mandibular squamous cell carcinoma, and the mucosa is reflected with periosteal elevators to protect soft tissues from trauma during osteotomy of the mandible. (C) The rostral mandibular symphyseal separation can be performed with an oscillating saw, osteotome and mallet, or bone cutters (pictured). (D) The hemimandible is reflected laterally, and the inferior alveolar artery and vein are identified and ligated (arrow) caudal to their entry into the mandibular foramen. (E) 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. (F, G) For total hemimandibulectomy, the dotted lines indicates where the masseter “F” and digastricus “G” muscles are incised from the caudal mandible. (H) The digastricus “D” muscle is reflected off the ventral aspects of the caudal mandible. (I) The pterygoid muscles “P” are reflected from the medial and ventral aspects of the caudal mandible. (J) The masseter muscle is reflected dorsally to expose and incise the temporomandibular joint (dotted line). (K) The resultant defect is closed in two to three layers. The first 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 monofilament absorbable suture material. (Line diagrams 6.9A, F, G, and J reproduced with permission from Withrow, S.J., and D.L. Holmberg. 1983. Mandibulectomy in the treatment of oral cancer. J Am Anim Hosp Assoc 19:277–278. Line diagram 6.9E reproduced with permission from Dernell, W.S., P.D. Schwartz and S.J. Withrow. 1998. Mandibulectomy. In Current Techniques in Small Animal Surgery, pp. 132–142. M.J. Bojrab, G.W. Ellison, and B. Slocum, editors. Baltimore: Williams & Wilkins.)

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 6.10D) (Dernell et al. 1998a). For caudal mandibulectomies, which preserve the temporomandibular joint, the inferior alveolar artery and vein should be identified 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 (Figures 6.10E, F). 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 first molar tooth for this more extensive caudal mandibulectomy (Figure 6.10E). This osteotomy should also be performed with an oscillating saw or pneumatic burr. 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 finally 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 that of

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 hemimandibulectomy are the most commonly indicated and performed procedures for the management of mandibular tumors in cats (Figure 6.9). The surgical technique is the same as for dogs; however, an esophageal or gastric feeding tube should be inserted as eating can be problematic following mandibulectomy in cats (Figure 6.11) (Northrup et al. 2006). Postoperative management Analgesia In the immediate postoperative period, intravenous fluids 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). Analgesia should include a nonsteroidal antiinflammatory drug and an opioid. Cyclooxygenase-2 (COX-2) selective or specific nonsteroidal antiinflammatory drugs are preferred because of their safety index, efficacy, and possible anticancer effects (Umar et al. 2003). Nonsteroidal anti-inflammatory drugs should either not be administered or their dose decreased in animals with conditions such as renal failure, hypotension, or hepatic disease (Mathews 2000; Lascelles et al. 2007). Opioids, such as fentanyl or morphine, are preferably administered as a continuous rate infusion

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Figure 6.10.  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, 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. (Line diagrams A and E are reproduced with permission from Withrow, S.J., and D.L. Holmberg. 1983. Mandibulectomy in the treatment of oral cancer. J Am Anim Hosp Assoc 19:277–278.)

rather than intermittent intramuscular injections. Continuous rate infusions of opioids can be combined with ketamine and/or lidocaine for an enhanced analgesic effect. Animals can usually be weaned off continuous rate infusions over a 24- to 48-hour period. Cats and

dogs should be discharged with a nonsteroidal antiinflammatory drug and an oral opioid, such as codeine or tramadol. Nonsteroidal anti-inflammatory drugs should be used with care, particularly in cats (Lascelles et al. 2007). See Table 6.2 for suggested perioperative

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Bradley et al. 1984; Withrow et al. 1985; Salisbury et al. 1986; Salisbury and Lantz 1988; Kosovsky et al. 1991; Schwarz et al. 1991a, 1991b; Hutson et al. 1992; Wallace et al. 1992; Lascelles et al. 2003). Enteral feeding tubes are not usually required following oral surgery in dogs, but they are recommended for cats treated with any type of mandibulectomy as eating can be difficult for 2–4 months following surgery (Hutson et al. 1992; Northrup et al. 2006). Cosmetic appearance

Figure 6.11.  It is important that a feeding tube be inserted following any mandibulectomy procedure in cats because voluntary intake is often poor for at least 2 weeks postoperatively.

analgesic protocols for cats and dogs undergoing mandibular resections. Nutrition Intravenous fluids should be continued until the dog eats voluntarily and is drinking sufficient 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 4 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 five 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 6.11). 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, epistaxis, increased salivation, mandibular drift and malocclusion, and difficulty prehending food (Withrow and Holmberg 1983;

The cosmetic appearance of cats and dogs following mandibulectomy is usually good to excellent. As recommended 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, before surgery. Owner satisfaction with the cosmetic appearance and functional outcome following mandibulectomy is high, with 83% and 85% of owners satisfied 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 6.12A–D). These procedures are rarely performed in cats, although cosmetic appearance is also unchanged following caudal mandibulectomy. Bilateral rostral mandibulectomy is the most cosmetically challenging of the mandibulectomy procedures in both cats and dogs because of mandibular shorten­ ing, excessive drooling and cheilitis, and the tongue hanging out, especially when panting or excited (Figure 6.13). Subtotal and total hemimandibulectomy 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 6.14) (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 difficulties are reported in 44% dogs and 73% 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 difficulty in prehending food. Prehension difficulties 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

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Figure 6.12.  (A, B) The typical postoperative appearance of a dog following unilateral rostral mandibulectomy. Note the saliva accumulation rostrally and minimal change in cosmesis. (C,D) The typical postoperative appearance of a dog following vertical ramus (or caudal) mandibulectomy. Note that the cosmetic appearance of the dog is unaltered.

difficulties adapt within 2 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 difficulties continue beyond 2 weeks, then other causes should be investigated. Injury to the hypoglossal nerve and mandibular drift can also occasionally result in difficulties 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). In cats, eating difficulties 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 hemimandibulectomy, 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 hemimandibulectomy, and 83% of cats with resection of greater than 50% of the mandible

experiencing eating difficulties (Northrup et al. 2006). 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. Incisional swelling Swelling of the surgical site is common following nonrostral mandibulectomies (i.e., segmental and caudal mandibulectomy, and subtotal and total hemimandibulectomy) (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 5–7 days. Ice packing every 4 hours and the administration of nonsteroidal anti-inflammatory drugs may assist in decreasing the severity of postoperative swelling.

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Figure 6.13.  The typical postoperative appearance of a dog following bilateral rostral mandibulectomy. Note the shortened mandible and the tongue hanging out.

Figure 6.15.  A ranula-like lesion (arrow) in a dog 1 day after subtotal hemimandibulectomy for an osteosarcoma. These may represent either a hematoma or accumulation of saliva. Treat­ ment is rarely required because these lesions often resolve spontaneously.

caused by trauma to the mandibular and sublingual salivary ducts, but hematoma or seroma formation are more likely. Ranula-like lesions will usually resolve spontaneously and treatment is rarely required. Wound dehiscence

Figure 6.14.  The typical postoperative appearance of a dog following subtotal (pictured) or total hemimandibulectomy. The mandible drifts toward the midline and the tongue hangs out on the resected side.

Ranula-like lesions Ranula-like lesions are uncommon and appear as soft, fluctuant, nonpainful swellings in the frenulum of the tongue ipsilateral to the mandibulectomy procedure (Figure 6.15) (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 hemimandibulectomy. Ranula-like lesions may be

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 3–7 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. 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 1–2 weeks.

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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 significantly 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 cheiloplasty. Mandibular drift and malocclusion Mandibular drift is common following mandibulectomy, especially the more aggressive mandibulectomy techniques, and is characterized by the mandible drifting toward the contralateral side (Figure 6.14) (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 toward 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, hemimandibulectomy, 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 is associated with increased expense and risk of complications. Miscellaneous complications Other complications reported following mandibulectomy include hemorrhage, infection, pain, difficulty

grooming, and osteoarthritis of the temporoman­ dibular 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 hemimandibulectomy. To avoid this complication, the inferior alveolar artery should be identified 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 or cautery of the inferior alveolar artery and vein. Alternatively, products that either chemically or physically promote hemostasis, such as Gelfoam or bone wax, can be used if the inferior alveolar 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 crossmatched 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 finding, particularly in any animal with mandibular drift, but it 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 difficulties, then nonsteroidal anti-inflammatory drugs and chondroprotective agents should be administered. Grooming difficulties are a specific complication in cats, especially following hemimandibulectomy where 26% of cats have been reported to have long-term grooming problems (Northrup et al. 2006). The cause of these grooming difficulties may be related to ptyalism, tongue protrusion, mandibular drift, and possibly pain. They are difficult to manage, and in these cases, owners must groom their cats. In one retrospective review of mandibulectomy in cats, grooming difficulties were infrequent (18%) but had a major impact on the perceived quality of life for affected cats (Northrup et al. 2006).

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Surgical Approach to Tumors of the Maxilla Anatomy For successful maxillofacial surgery, a detailed knowledge of the anatomy is required. This includes not only a fundamental knowledge of the bones comprising the maxilla and face (frontal, nasal, maxillary, incisive, and pterygoid) (Figures 6.16A, 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 skull) 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. This includes the major palatine and sphenopalatine arteries for rostral maxillectomies and the infraorbital artery and maxillary artery for caudal maxillectomies (Figures 6.16C, D) (Evans and Christensen 1979). Maxillectomy refers to the en bloc excision of a tumor on the upper jaw, which may involve parts the incisive, palatine, lacrimal, zygomatic, frontal, and vomer bones in addition to the maxilla (Evans and Christensen 1979). The resultant defects are closed using soft tissue flaps, particularly vestibular (e.g., alveolar and buccal) mucosal-submucosal flaps with or without palatal mucoperiosteal flaps. Various maxillectomy procedures have been described, including incisivectomy (previously known as premaxillectomy), unilateral and bilateral rostral maxillectomy, central maxillectomy, and 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 confined to the incisive bone (Withrow et al. 1985). Premaxilla is not accepted veterinary anatomical nomenclature, and incisivectomy is therefore more appropriate to describe resection of the area rostral to the canines. Incisivectomy is recommended for dogs with peripheral odontogenic fibroma or small SCC lesions confined

to the incisive bone and associated incisors (Figure 6.17A). More aggressive rostral maxillectomy procedures should be considered for malignant tumors other than SCC and larger acanthomatous ameloblastoma and SCC lesions extending further caudally. 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 reflected 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 flap. The flap 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 flap is sutured into position with a two-layer closure, with the first layer consisting of simple interrupted sutures preplaced through holes predrilled in the bone of the hard palate. The labial and oral mucosa are opposed using simple interrupted sutures (Figure 6.17B) (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 that 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

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Figure 6.16.  Anatomy of the maxilla and skull. (A, 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. (C, 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 identified for rostral maxillectomies and the infraorbital and maxillary arteries for caudal maxillectomies. (Diagrams A and B reproduced with permission from Evans, H.E. and A. deLahunta, editors. 2000. The head. In Guide to the Dissection of the Dog, pp. 259–321. Philadelphia: Saunders. Diagrams C and D reproduced with permission from Evans, H.E. and G.C. Christensen, editors. 1979. Systemic arteries. In Miller’s Anatomy of the Dog, pp. 652–756. Philadelphia: Saunders.)

labial and gingival mucosa and palatine mucoperiosteum are incised with a minimum of 1 cm margins around the mass (Figure 6.18A) (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 reflected off the underlying bone with periosteal elevators to preserve the soft tissues that will be used later for reconstruction of the

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Figure 6.17.  (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.

defect. Osteotomies are performed in the maxilla, incisive bone, and hard palate with either a pneumatic burr, small oscillating saw, biradial saw (Figure 6.18B), 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 6.18C). Bleeding can be significant 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 flap as described for incisivectomy. The flap is created by undermining the labial mucosa to include the mucosa, submucosa, and as much subcutaneous tissue as possible (Figure 6.18D) (Dernell et al. 1998b). It is important to undermine sufficient tissue to prevent the overlying skin from being drawn medially, resulting in a poor cosmetic result. The flap is sutured into position with a two-layer closure, with the first layer consisting of simple interrupted sutures preplaced through holes predrilled in the bone of the hard palate (Figure 6.18E, F). The labial and oral mucosa are opposed using simple interrupted sutures (Figure 6.18G) (Dernell et al. 1998b). 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 6.19A) (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 reflected off the underlying bone with periosteal elevators to preserve the soft tissues that will be used later for reconstruction of the defect (Figure 6.19B). 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 6.19C). Bleeding can be significant 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. To minimize drooping of

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Figure 6.18.  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 transected 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, or 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 flap 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 monofilament absorbable suture material. (Diagram A reproduced with permission from Dernell, W.S., P.D. Schwartz, and S.J. Withrow. 1998. Maxillectomy and premaxillectomy. In Current Techniques in Small Animal Surgery, pp. 124–132. M.J. Bojrab, G.W. Ellison, and B. Slocum, editors. Baltimore: Williams & Wilkins.)

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Figure 6.19.  Bilateral rostral maxillectomy. (A) Bilateral rostral maxillectomy is indicated for dogs with benign invasive tumors, such as this dog with an acanthomatous ameloblastoma, or small SCC 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 reflected 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 ameloblastoma, 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 monofilament absorbable suture material.

the nose, which is a common postoperative cosmetic defect following bilateral rostral maxillectomy because of loss of ventral support, 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 (Figure 6.20) (Pavletic 1999).

The defect is closed with bilateral labial mucosalsubmucosal flaps. The flaps 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 flaps are sutured in a T-shape with a two-layer closure, with the first layer consisting of simple interrupted sutures preplaced through holes predrilled in the bone of the hard palate. The labial and oral

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Figure 6.20.  (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) monofilament 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. (Illustrations courtesy of Dave Carlson)

mucosa are opposed using simple interrupted sutures (Figure 6.19D) (Dernell et al. 1998b). Rostral maxillectomy—bilateral combined with nasal planum resection Bilateral rostral maxillectomy combined with nasal planum resection is indicated for SCC of the nasal planum

that has invaded the incisive area or rostral maxilla (Figure 6.21A) (Kirpensteijn et al. 1994). Dogs are positioned in sternal recumbency with the mouth held open with a gag. The head should be elevated to facilitate access to the oral cavity for resection and reconstruction. The pharynx should be packed with gauze sponges to minimize the risk of aspirating blood and lavage fluid.

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Figure 6.21.  (A) Bilateral rostral maxillectomy combined with nasal planum resection is indicated in this dog with a nasal planum SCC 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 SCC. (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, 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 monofilament 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.

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144  Veterinary Surgical Oncology Figure 6.22.  Radical maxillectomy. (A, 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 fibrosarcoma (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 flap 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 monofilament suture material. (F) Figure-eight suture pattern. The lip margins from the left and right sides are aligned with a figure-eight suture pattern (F, part 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 (F, part B). (G) Rolling figure-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 orifice, the skin edges are sutured to bone tunnels in the maxillary bone using either a rolling figure-eight (see G) or simple interrupted pattern, and the lip is reconstructed along the rostral aspect of the maxilla (see D). (Some images (C–E) and line diagrams (F and G) are reproduced with permission from Lascelles, B.D.X., R.A. Henderson, B. 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.)

The nasal planum, labial and gingival mucosa, and palatine mucooperiosteum are incised a minimum of 1 cm caudal to the extent of the tumor (Kirpensteijn et al. 1994). The nasal planum excision usually involves full-thickness incisions through the rostral lips (Figure 6.21B). 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 6.21C). 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 6.21D). 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 orifice 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 subcuta­ neous tissue sutured to bone tunnels drilled in the maxillary bone and skin to the nasal mucosa using a

simple interrupted suture pattern (Figures 6.21E, F) (Kirpensteijn et al. 1994). Radical maxillectomy Radical bilateral maxillectomy is recommended for tumors of the rostral maxilla extending dorsally into the nasal cavity and malignant tumors caudal to the second premolar teeth and extending across the midline (Lascelles et al. 2004). The surgical approach is similar to nasal planum resection combined with bilateral maxillectomy. Dogs are positioned in sternal recumbency with the mouth held open with a gag. The head should be elevated to facilitate access to the oral cavity for resection and reconstruction. The pharynx should be packed with gauze sponges to minimize the risk of aspirating blood and lavage fluid. The first 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 6.22A, B) (Lascelles et al. 2004). As the skin incision is continued deeply

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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 fullthickness incisions in the left and right lips. The osteotomy is performed from a dorsal approach with an oscillating saw perpendicular to the maxilla. To facilitate reconstruction, the osteotomy should be performed slightly caudal to the level of the skin and mucosal incisions (Figure 6.22C). 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 orifice and also divides the nasal and oral cavities. Recreation of the rostral lip requires either a unilateral or bilateral labial flap (Lascelles et al. 2004). The labiogingival reflection on each side is incised as necessary to mobilize the labial flap. The mucosa of the labial flaps is removed except for a 0.5–1.0 cm width adjacent to the labial margin (Figure 6.22D). 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 6.22E) (Lascelles et al. 2004). Next, the labial skin margins are sutured together using a figure-eight suture pattern (Figure 6.22F). To reconstruct the nasal orifice, the skin edges are sutured to bone tunnels drilled in the maxillary bone using either a rolling figure-eight or simple interrupted suture pattern (Figure 6.22G). Suture tightening results in the skin covering the rostral edge of the maxilla (Figure 6.22H) (Lascelles et al. 2004). Caudal maxillectomy—intraoral approach Caudal maxillectomy using an intraoral approach is recommended for unilateral benign and malignant tumors located along the alveolar margins of the mid-to-caudal maxilla (Figure 6.23A) (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 inferior orbit, because of better exposure, 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 and 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. Dogs are positioned in lateral or dorsolateral recumbency with the mouth held open with a gag. The pharynx should be packed with gauze sponges to minimize the risk of aspirating blood and lavage fluid. 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 6.23B). Bleeding can be brisk following the palatine incision due to 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 reflected off the underlying maxillary and palatine bone with periosteal elevators to preserve the soft tissues that will be used later for reconstruction of the defect (Figure 6.23C). 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 difficult 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 inferior 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 difficult 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 6.23D). 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 flap as described for other maxillectomy procedures (Dernell et al. 1998b). The flap is created by undermining the labial mucosa to include the mucosa and submucosa (Figure 6.23E). It is important to undermine

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Figure 6.23.  (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 fibrosarcoma 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 fluid intraoperatively. (C) Following incisions using appropriate margins in the gingival and labial mucosa and palatine mucoperiosteum, the mucosa and mucoperiosteum are reflected off their underlying bone to protect the soft tissues from trauma during osteotomies and to 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 flap for reconstruction of the intraoral defect and also minimize the lip being drawn medially, resulting in a poor cosmetic result. (F, 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 monofilament absorbable suture material (G). (Line diagrams B and E reproduced with permission from Dernell, W.S., P.D. Schwartz, and S.J. Withrow. 1998. Maxillectomy and premaxillectomy. In Current Techniques in Small Animal Surgery, pp. 124–132. M.J. Bojrab, G.W. Ellison, and B. Slocum, editors. Baltimore: Williams & Wilkins.)

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148  Veterinary Surgical Oncology Figure 6.24.  (A) A caudal maxillectomy through a combined approach is recommended for tumors that arise or extend dorsolaterally from the caudal maxilla or inferior orbit, such as this squamous cell carcinoma (SCC) arising from the rostral inferior orbit and zygomatic arch. (B) A skin incision is performed along the dorsolateral aspect of the muzzle and extended 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) that 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 flap, 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, superficial levator nasolabialis muscle; DNV, dorsal nasal vein; and LNV, lateral nasal vein). (G) Following periosteal elevation of the muscles and appropriate hemostasis, the bipedicle flap can be retracted dorsally or ventrally to improve exposure for tumor excision (SCC, 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 (I) pneumatic burr in the dorsolateral (see number 3 in part H) and (J) rostral (see number 2 in part H) maxilla, with an oscillating saw or osteotome and mallet in the hard palate (K), and then through the inferior orbit (labeled “A” in part H) 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 monofilament suture material. (O) The dorsolateral skin incision is closed routinely. (Images F and H reproduced with permission from Lascelles, B.D.X., M.L. Thomson, W.S. Dernell, 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.)

sufficient tissue to prevent the overlying skin being drawn medially, resulting in a poor cosmetic result. The flap is sutured into position with a two-layer closure, with the first layer consisting of simple interrupted sutures preplaced through holes predrilled in the bone of the hard palate. The labial and oral mucosa are opposed using a simple interrupted or continuous suture pattern (Figures 6.23F, 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 that either arise or extend dorsolaterally and/or caudally to the alveolar margin (Figure 6.24A) (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). 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 (see 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 with a gag. The pharynx should be packed with gauze sponges to minimize the risk of aspirating blood and lavage fluid. The dorsolateral skin incision is created first with an incision lateral to the midline of the dorsal aspect of the nasal cavity and extending caudally and ventrally to the eye along the zygomatic bone (Figure 6.24B) (Lascelles et al. 2003). This incision is continued through the subcutaneous tissue, between the paired levator nasolabialis muscles, and down to bone (Figure 6.24C). 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, and the masseter muscle is elevated from the ventral aspect of the zygomatic arch using a combination of sharp and blunt dissection (Figure 6.24D) (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 difficult and

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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 reflecting the periosteum and associated soft tissues with a periosteal elevator. A second incision is made in the buccal musosa dorsal to the gingiva and with appropriate margins through an intraoral approach (Figure 6.24E). 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 flap (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 6.24F), 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). The bipedicle flap can be retracted dorsally and ventrally to allow visualization of the lateral aspect of the maxilla and improve exposure for tumor excision (Figure 6.24G) (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 (Figures 6.24H–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 6.24K). 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 inferior 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 inferior 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 6.24 L). 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 tur­ binates. Cautery is rarely successful for turbinate bleeding. The intraoral incision is closed first. This is best approached from a dorsal direction through the bipedicle flap (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 being drawn medially, resulting in a poor cosmetic result, particularly following extensive resection of the hard palate, a labial mucosal-submucosal flap may be required. The flap is sutured into position with a two-layer closure (Figure 6.24M,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 fibrovascular free edge of the lip is sutured to predrilled 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 first, followed by the mucosa-mucoperiosteum closure. Finally, the dorsolateral skin incision is closed routinely (Figure 6.24O). 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 orifice. 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 need 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. Hemimaxillectomy, either via an intraoral or combined approach (Figures 6.25A–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

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Figure 6.25.  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 flap. (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.

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, with eating and grooming rarely affected in comparison. Although rarely necessary, an esophageal or gastric feeding tube could be considered for nutritional supplementation postoperatively. Postoperative management Analgesia In the immediate postoperative period, intravenous fluids and analgesia are continued, and an Elizabethan

collar should be placed as soon as the animal is ster­ nally recumbent to prevent self-trauma (Dernell et al. 1998b). Analgesia should include a nonsteroidal antiinflammatory drug and an opioid. COX-2 selective or specific nonsteroidal anti-inflammatory drugs are preferred because of their safety index, efficacy, and possible anticancer effects (Umar et al. 2003). Nonsteroidal antiinflammatory drugs should either not be administered or their dose decreased in animals with conditions such as renal failure, hypotension, or hepatic disease (Mathews 2000; Lascelles et al. 2007). Opioids, such as fentanyl or morphine, are preferably administered as a continuous rate infusion rather than intermittent intramuscular

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Figure 6.26.  (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 toward the midline of the muzzle. Although some medialization of the lip is to be expected, this can be minimized by undermining the labial submucosal-mucosal flap.

injections. Continuous rate infusions of opioids can be combined with ketamine and/or lidocaine for an enhanced analgesic effect. Animals can usually be weaned off continuous rate infusions over a 24–48 hour period. Cats and dogs should be discharged with a nonsteroidal anti-inflammatory drug and an oral opioid, such as codeine or tramadol. Nonsteroidal antiinflammatory drugs should be used with care, particularly in cats (Lascelles et al. 2007). See Table 6.2 for suggested perioperative analgesic protocols for cats and dogs undergoing mandibular resections. Nutrition Intravenous fluids should be continued until the dog eats voluntarily and is drinking sufficient 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 difficulty 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 2–3 weeks (Lascelles et al. 2003). Supplemental nutrition is rarely required in either dogs or cats following most maxil-

lectomy 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 4 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 1–3 days postoperatively (Figure 6.26A). This rarely requires treatment, but the volume should be monitored. Following radical maxillectomy, the surgical site oozes serosanguineous fluid and becomes crusty and contaminated with food material and saliva. Topical petrolatum-based antibiotic ointment is initially placed around the nasal orifice wounds and a topical misting of physiological saline administered by 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 orifice

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Figure 6.27.  ( A) The postoperative appearance of a dog following unilateral rostral maxillectomy. The lesion was relatively small and the labial mucosal-submucosal flap has been sufficiently undermined to prevent excessive medialization of the lip. (B) For dogs with larger lesions, there may be tension on the labial mucosal-submucosal flap resulting in medialization of the lip such that the lip is positioned medial to the ipsilateral mandibular canine tooth. Medialization of the lip can be minimized by undermining the labial submucosal-mucosal flap, but it can be difficult to prevent this cosmetic result.

with saline-soaked cotton balls or cotton swabs for approximately 4 weeks. The surgical site does not tend to be contaminated with food material once healing is complete (by 8 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 orifice does not cause any problems, and we have not seen any cases of selftrauma of the new orifice 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 post­ operative appearance and function is improved with a thorough discussion, including the use of pre-and postoperative images of the appropriate procedure, before surgery. Owner satisfaction with the cosmetic appearance and functional outcome following maxillectomy is high, with 85% of dog owners satisfied following partial maxillectomy (Fox et al. 1997). Following unilateral rostral and caudal maxillectomies (Figures 6.26A–E), the skin and lip are often drawn medially toward the midline, and the extent of this will depend on the medial extent of the resection, resulting

Figure 6.28.  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.

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 6.27A,B). Postoperative swelling can also be significant, 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 6.28) (White et al. 1985;

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(a)

(b)

Figure 6.29.  (A, B) 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.

Withrow et al. 1985; Salisbury et al. 1986; Schwarz et al. 1991b; White 1991; Wallace et al. 1992; Lascelles et al. 2003). 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 (Figures 6.29A, B) (Lascelles et al. 2004). For owners that have elected to proceed with this procedure, children within the family and uninformed visitors have the greatest difficulty in accepting the altered cosmetic appearance. Owners should be thoroughly counseled prior to surgery regarding 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 the dog’s behavior is not altered and its function remains good to excellent. The most significant functional effects include difficulty or inability in retrieving or picking up items, difficulty in eating dry food, and messy eating and drinking. Eating difficulties Eating difficulties 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). Dogs treated with radical maxillectomy may have difficulty 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 2–3 weeks. Supplemental feeding may be required for up to a week in cats following bilateral rostral maxillectomy, with or without nasal planum resection, or radical maxillectomy. Wound dehiscence and oronasal fistula Wound dehiscence is the most common complication following maxillectomy and is reported in 5%–33% of dogs and can result in the development of an oronasal fistula (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). Wound dehiscence most commonly occurs within 3–7 days of surgery and usually caudal to the canine teeth (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; Withrow et al. 1985; Harvey 1986; Salisbury et al. 1986; Schwarz et al. 1991b; White 1991; Wallace et al. 1992;

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Figure 6.31.  The oronasal fistula has been debrided and repaired with an transposition flap of adjacent skin. Mucosal or mucoperiosteal flaps are preferred for repair of oronasal defects, but these tissues are often not available because of previous tumor resection.

Figure 6.30.  Dehiscence of the intraoral incision following caudal maxillectomy through an intraoral approach with the subsequent development of an oronasal fistula (arrow).

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 first layer, under minimal tension with long-lasting monofilament suture material. Tension can be decreased with careful planning and harvesting of the labial mucosal-submucosal flap. Cautery is frequently cited as the cause for dehiscence, however, it 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 flap can result in the development of an oronasal fistula (Figure 6.30). A number of techniques have been described for the management of oronasal fistulae (Kirby 1990; Griffiths 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 flaps (Bryant et al. 2003), advancement of skin flaps into the oral cavity (Figure 6.31) (Dundas et al. 2005), or free microvascular grafts of the rectus abdominis muscle may be useful (Lanz 2001). If the

dehiscence does not involve an oronasal fistula, 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. Incisional swelling Swelling of the surgical site is common following caudal maxillectomy, particularly with the combined intra­ oral-dorsolateral approach, and radical maxillectomy (Lascelles et al. 2003, 2004). Swelling usually resolves spontaneously within 3 weeks. Ice packing every 4 hours and the administration of nonsteroidal antiinflammatory 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 (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). The ulcerated region is usually caused by the ipsilateral mandibular canine tooth (Figure 6.32), 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

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Figure 6.32.  Ulceration of the upper lip in a cat following unilateral hemimaxillectomy. 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.

source of the ulceration has been identified, the tooth or teeth are removed or capped. Miscellaneous complications Other complications reported following maxillectomy include hemorrhage, pain, subcutaneous emphysema, infection, and nasal discharge secondary to rhinitis. Intraoperative hemorrhage can be profuse if the major palatine or maxillary artery are not ligated prior to caudal hemimaxillectomy (Dernell et al. 1998b). To avoid this complication, the maxillary artery should be identified as it courses along the ventral aspect of the inferior orbit and 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, 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). Subcutaneous emphysema, with skin over the surgical site moving with respiration, is occasionally noted in the early postoperative period after maxillectomy proce-

dures involving exposure of the nasal cavity, particularly caudal maxillectomies (Dernell et al. 1998b). This is usually mild, nonprogressive, and resolves spontaneously within 7 days. Infection is very rare following maxillectomy because of the rich vascular supply to the oral cavity (Dernell et al. 1998b). 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 fibrosarcoma (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, 1991b; White 1991; Wallace et al. 1992). Other malignant oral tumors include osteosarcoma, chondrosarcoma, anaplastic sarcoma, multilobular osteochondrosarcoma, intraosseous carcinoma, myxosarcoma, hemangiosarcoma, 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; Liptak and Withrow 2007). 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; Liptak and Withrow 2007). A summary of the common oral tumors is found in Table 6.3.

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

Feline

Malignant Melanoma

Squamous Cell Carcinoma

Fibrosarcoma

Acanthomatous Ameloblastoma

Squamous Cell Carcinoma

Fibrosarcoma

Frequency Age (years) Sex predisposition Animal size Site predilection

30%–40% 12 None-Male

17%–25% 8–10 None

8%–25% 7–9 Male

5% 8 None

70%–80% 10–12 None

13%–17% 10 None

Smaller Gingiva, buccal, and labial mucosa

Larger Rostral mandible

None Rostral mandible

— Tongue, pharynx, and tonsils

— Gingiva

Lymph node metastasis

Common (41%– 74%)

None

Rare

Rare

Distant metastasis Gross appearance

Common (14%– 92%) Pigmented (67%) or amelanotic (33%), ulcerated Common (57%)

Rare (21.9 seconds) were more likely to have complications than patients with normal values. It is therefore recommended that routine prebiopsy coagulation profiles (i.e., one-stage prothrombin time, activated partial thromboplastin time, and platelet count) be performed prior to ultrasound-guided biopsy

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procedures (Bigge et al. 2001; Rawlings and Howerth 2004). 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 fine-needle liver aspirates and surgical wedge biopsies were 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). A second study showed that the morphological diagnosis assigned to a needle biopsy specimen concurred with the definitive histological diagnosis in only 40% (36 of 91) of dogs and cats with hepatic disease (Cole et al. 2002). These discrepancies should serve as a caution to clinicians considering a fine-needle aspirate to be a definitive diagnostic tool when characterizing infiltrative 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 identified 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 quantification of alphafetoprotein (AFP) is another novel technique that has been investigated as a means to confirm 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). In China, AFP monitoring has become a routine screening tool for detection of hepatocellular carcinoma (Lowseth et al. 1991). A single canine study demonstrated significantly higher serum levels of AFP in dogs with hepatocellular carcinoma 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). Additionally, the 2D imaging achieved with laparoscopy is superior to that of traditional laparotomy, as images are magnified by the laparoscope (Rawlings and Howerth 2004). Laparoscopy is routinely used as an adjunct staging tool when preoperative imaging analysis has failed to instill confidence 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 sufficient to achieve a definitive 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 sufficient 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 sufficient for accurate histological assessment. When performing this technique, it is important to avoid penetration of more than

Alimentary Tract  199

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 fit) 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, monofilament absorbable suture such as 3-0 to 4-0 polydioxinone) 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 biopsyrelated 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 infiltrated 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 sufficiently 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 (finger fracture

Figure 7.10.  (A) Illustration demonstrating the guillotine technique for procuring an incisional biopsy of a liver nodule located on the periphery of a lobe. (B, C) Illustration demonstrating the mattress suture (wedge) technique for procuring an incisional biopsy of a liver nodule located on the periphery of a lobe. (Illustration courtesy of Dave Carlson.)

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 finger 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. Complete lobectomy A ventral midline celiotomy, extending from the xiphoid process to the caudal aspect of the abdomen, is the preferred surgical approach for most liver lobectomy procedures. A combination midline celiotomy and paracostal approach can be used if additional lateral exposure is necessary (Martin et al. 2003). A caudal sternotomy combined with incision into the diaphragm is routinely required to facilitate exposure of very large tumors, tumors originating from an entire liver division, tumors

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with extensive visceral or omental adhesions, and for dissection of tumors originating within the right division (right lateral or caudate lobes). Incision of the diaphragm toward the caval foramen is reported to normalize intrathoracic pressure, thus relaxing the diaphragm, allowing for more caudal mobilization of the liver (Bjorling et al. 1985). Diaphragmatic incision without caudal sternotomy is commonly employed by many oncological surgeons and this technique can also dramatically facilitate exteriorization and visualization of difficult to access liver masses. To ensure adequate visualization of the liver, the falciform ligament must be removed in its entirety. Since the liver serves as a receptacle for metastasis 2.5 times more frequently than a source of primary liver tumor development, a complete exploratory laparotomy should be performed prior to addressing the liver tumor (Strombech 1978; Cullen and Popp 2002). It is not uncommon for liver tumors to have extensive omental adhesions or be adhered to surrounding visceral structures such as the diaphragmatic border of the stomach, the peritoneal wall, the surrounding normal liver lobes, gall bladder, pancreas, or the diaphragm itself. Initial dissection should concentrate on relieving these adhesions so that adequate visualization of the extent of the tumor may be accomplished. Care must be taken to identify large and important vessels (i.e., pancreatic branch of the splenic artery) within the omentum as significant displacement and anatomical derangement of this tissue can occur. To minimize hemorrhage during dissection of the omentum, the author prefers to use the LigaSure Tissue Sealing Device (Covidien [Valleylab], Boulder, CO) or the LDS stapling device (LDS-2 Reusable Instrument with DS-15W Stainless Steel Disposable Loading Unit; Covidien [Autosuture], Norwalk, CT) to alleviate omental adhesions. If rupture of the tumor capsule is evident, a margin of normal omentum should be left behind on the tumor capsule so that additional contamination of the abdomen does not occur when the omentum is returned to its normal anatomical position. The three commonly used surgical techniques for total liver lobectomy include mass suture ligation, dissection and ligation of individual vessels and ducts, and use of linear surgical stapling equipment (Martin et al. 2003; Blass and Seim 1985). Prior to implementation of any technique, the associated triangular ligament of the affected lobe must be severed, as this will allow improved access to the hilum of the lobe (Martin et al. 2003). Mass suture ligation should be reserved for cats and small dogs with tumors located distal to the hilum. To facilitate knot security, a tissue “crush zone” may need to be created within the liver parenchyma near the

hilum. A single encircling ligature is reported to be sufficient for mass ligation; however, authors recommend double ligation based on the demonstrated safety of this approach in research animals undergoing lobectomy (Martin et al. 2003; Lewis et al. 1990). In general, most oncological surgeons prefer to use surgical stapling equipment when performing liver lobectomies. A study in healthy research dogs demonstrated that staple-assisted lobectomies could be performed significantly faster (mean time of 173 seconds vs. 759 seconds with individual ligation) than blunt dissection and individual vessel ligation (Lewis et al. 1990). Importantly, stapled lobectomies also resulted in a more complete excision when compared to the individual suture ligation technique. Suture techniques consistently resulted in 5–15 mm of liver parenchyma remaining along the excision line distal to the ligatures, which could make the difference in achieving an adequate tumor tissue margin during lobectomy (Lewis et al. 1990). It is also reported that less hepatic vein length is required when performing a stapled lobectomy, which may be an important consideration if the tumor is encroaching on the hilum (Martin et al. 2003). The thoracoabdominal (TA-30 Premium Reusable Stapler) stapling device with V3 stapling cartridge (white color) is preferred for occlusion of hilar vessels during complete lobectomy (Covidien [Autosuture], Norwalk, CT). Both TA-55 and TA-90 stapling devices can be used for lobectomies when the hilar tissue exceeds the V3 cartridge length of 30 mm (Figures 7.11A, B) (Martin et al. 2003). It has been recommended that individual vessel ligation be completed when liver parenchymal vessels are 2 mm or more in diameter (Martin et al. 2003). Since the green-colored (TA-55 and TA-90) stapling cartridge achieves a closed staple height of only 2 mm after discharge, use of this cartridge should be avoided if possible (Martin et al. 2003; Tobias 2007). After application of the linear stapling device, it is not uncommon to have focal regions of hemorrhage at the lobectomy site. Minor hemorrhage can be addressed through the application of hemoclips or hemostatic agents such as Gelfoam absorbable gelatin powder (Pfizer [Pharmacia & Upjohn Co.], New York, NY). If generalized oozing from the lobectomy stoma is present, authors prefer to cover the stoma with contoured strips of the hemostatic agent Surgicel (Ethicon 360 [Johnson & Johnson Inc.], New Brunswick, NJ). Excessive parenchymal hemorrhage can be controlled by compression of the hepatic artery and portal vein within the epiploic foramen (Pringle maneuver) (Blass and Seim 1985). Digital compression is preferred over vascular clamp application since the common bile duct is often incorporated into the compressed tissue and

Alimentary Tract  201

(a)

(b)

Figure 7.11.  (A, B) Intraoperative image of TA-90 linear stapling device used for partial lobectomy of a hepatocelluar carcinoma located on the periphery of the lobe. Mild to moderate hemorrhage from the staple should be expected once the cartridge is released. This hemorrhage is generally controlled with tamonade, hemoclips, or application of a hemostatic agent.

posttraumatic bile duct stricture may be less likely with digital occlusion. Application of the Pringle maneuver can be sustained for periods up to 15 minutes without resultant deleterious effects to hepatic structure and function (Blass and Seim 1985). If hemorrhage persists despite compression of the hepatic artery and portal vein, bleeding from the hepatic venous system should be investigated (Blass and Seim 1985). With severe hemorrhage and life-threatening hypotension, the descending aorta can also be temporarily occluded at the aortic hiatus to increase blood pressure and flow to critical organs (Martin et al. 2003). Hepatic lobectomies of central (quadrate and right medial lobes) and right division-based tumors often pose technical challenges that require special consideration prior to attempting excision. Tumors arising from the lobes within the central division often envelop or form robust adhesions to the gallbladder, making its dissection from the hepatic fossae more difficult. Additionally, dissection of the gallbladder away from the tumor often results in laceration of the tumor capsule causing contamination. Based on the intimate association of the quadrate and right medial liver lobes, tumors within the central division or gallbladder often involve both lobes, particularly if its location is near the hilum. It is for these reasons that lobectomy of tumors in the central division often requires a combined cholecystectomy and removal of both of the lobes that constitute the division (Figure 7.12). Dissection and individual ligation of the cystic duct is preferred if cholecystectomy is required; however, this is often not possible. En bloc

Figure 7.12.  Postoperative image of a central division liver lobectomy after a mass effect within the gallbladder caused rupture and secondary bile peritonitis. Adhesions were present in the region of the hilus; however, with careful dissection, the cystic duct could be isolated and individually ligated. After this, both the quadrate and right medial liver lobes could be excised en bloc using a TA-90 (blue cartridge) stapling device.

ligation of the cystic duct and the hilar vessels of both lobes are routinely accomplished using TA stapling equipment, without an increased incidence of postligation hemorrhage or bile leakage. Preligation retrograde catheterization of the common bile duct is generally not required unless obvious pathology within this organ is present.

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Tumor excision arising from lobes within the right division can be particularly challenging due to their intimate association with the caudal vena cava and because of difficulty visualizing and exteriorizing these lobes. A right paracostal incision should be considered to enhance visualization and to assist with precision placement of stapling equipment at the hilum (Lewis et al. 1987, 1990). Reflection of the hepatic parenchyma from the caudal vena cava is necessary and can be achieved using a combination of blunt and sharp dissection (Martin et al. 2003). If the hepatic tissue is friable, blunt dissection with the thin inner component of a Poole suction tip is also helpful (Martin et al. 2003). Authors have found the Poole dissection technique useful for creating a “safe zone” for staple application during liver lobectomies (in any division) where the tumor encroaches on the hilum and cannot be completely excised. This is especially useful during combined cholecystectomy and liver lobectomy of the entire central division, as the hilum is difficult to definitively isolate in this area. In people, use of the Cavitron Ultrasonic Surgical Aspirator, or CUSA (CUS Ultrasonic Surgical Aspiration System; Covidien [Valleylab], Boulder, CO), for hepatic dissection during lobectomies has consistently resulted in a reduction in perioperative blood loss, duration of operative procedures, and postoperative morbidity and mortality (Storck et al. 1991; Fasulo et al. 1992; Farid and O’Connell 1994). Recent reports in the human medical literature also support the use of an electrothermal bipolar vessel sealing system (LigaSure device) for hepatic lobectomy. Like the CUSA, the Ligasure device has been shown to reduce the amount of intraoperative hemorrhage and contributes to a significantly faster operative time when compared to traditional operative techniques (Campagnacci et al. 2007; Saiura et al. 2006; Romano et al. 2005). Application of the ligasure device in human patients with cirrhotic livers results in an increased incidence of hemorrhage and therefore use of the ligaSure in veterinary patients with extremely friable liver tissue should be avoided (Romano et al. 2005). Authors have used both the CUSA and the LigaSure with good success during dissection of hepatic parenchyma for total lobectomy in the dog. Regardless of the technique, during a right division-based liver lobectomy, it is recommended that precautionary measures be taken to control hemorrhage prior to parenchymal dissection around the vena cava. This is best accomplished through the placement of Rommel tourniquets around the caudal vena cava (cranial and caudal to the liver), the portal vein, and the celiac and cranial mesenteric arteries so that massive hemorrhage can be contained while adequate repair of the traumatized vessel can be accomplished (Blass and Seim 1985). In general, the

complication rate associated with complete liver lobectomy for the treatment of liver tumors is relatively low. In the most comprehensive study to date, intraoperative complications occurred in 28.6% of dogs (12 of 42) undergoing exploratory celiotomy and liver lobectomy for primary hepatocellular carcinoma (Liptak et al. 2004a). These complications consisted of traumatic laceration of the vena cava (3 of 42), mild to moderate hemorrhage after lobectomy (7 of 42), and vascular compromise to the left lateral liver lobe (necessitating removal) after excision of the left medial lobe (2 of 42). Two of the 3 dogs suffering from iatrogenic laceration of the vena cava died during the procedure, whereas, the remaining dogs with complications recovered uneventfully (Liptak et al. 2004a). The operative mortality rate in this study was 4.8% (2 of 42). When considering operative mortality rate based on tumor location, none of the dogs with left (28 of 42) or central division (8 of 42) tumors died intraoperatively. A total of 5 dogs were treated for right-sided liver lobe tumors and 2 of these dogs died during surgery, making the intraoperative mortality rate 40% for right division-based tumors (Liptak et al. 2004a). This distinction reiterates the importance of thorough client communication prior to attempting resection of tumors located within the right division of the liver. Recently, a novel surgical technique has been described for isolation and ligation of liver lobes at the level of the hilus (Covey et al. 2009). In this pilot anatomical study of seven cadaver dogs, a detailed description of the vascular and biliary supply to each hepatic lobe was provided. A predictable consistency of the hepatic vasculobiliary anatomy was identified within each lobe, and detailed descriptions for hilar lobectomy were provided. Although the clinical utility of this technique has not been evaluated, its proposed use is in cases where the tumor encroaches on the hilus, making lobectomy through traditional techniques unlikely to yield complete tumor excision (Covey et al. 2009). Aftercare The following variables dictate the intensity of care in the postoperative setting: the preoperative health status of the patient, the existence of underlying secondary or metastatic liver disease, and the type of liver resection that was performed (Blass and Seim 1985). Of primary concern is the potential for postoperative hemorrhage resulting from either technical errors in hemostasis or from the development of an acquired coagulopathy. Serial monitoring of the patient’s blood pressure, heart rate, packed cell volume (PCV), and total protein (TP) levels is essential for establishing trends related to bleeding complications. Commonly, a transient decline in the

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PCV and TS will be observed shortly after surgery, which is likely secondary to fluid dilution during surgery. Impaired synthesis of prothrombin and other coagulation factors may occur after extensive hepatic resection or if metastatic disease is present, resulting in postoperative coagulopathies (Blass and Seim 1985). Serial monitoring of blood coagulation parameters should be performed in at-risk patients and therapeutic intervention with parenteral vitamin K therapy, fresh whole blood, or fresh-frozen plasma should not be delayed if hemostatic derangement is identified. Functional outcome Dogs and cats tolerate hepatectomy well, presuming that the remaining volume of liver is healthy and that the patient’s general condition is not plagued by a multitude of nonhepatic diseases or systemic metastasis from their underlying hepatic neoplasia. Variables associated with a reduced tolerance to hepatectomy in dogs include serum albumin levels less than 2 g/100 mL, prolonged biliary obstruction, and liver cirrhosis (Martin et al. 2003). Creation of a side-to-side portocaval shunt for portal decompression has been shown to improve survival in research dogs after extensive hepatectomy (Mitsumoto et al. 1999; Martin et al. 2003). It is not uncommon for clients to question the regenerative capacity of the liver in their animals after hepatectomy. The liver has an immense capacity to regenerate, which begins within 24 hours after hepatectomy and peaks at the third postoperative day (Martin et al. 2003; Bjorling et al. 1985). It is reported that after 70% hepatectomy, the liver is capable of complete restoration of its mass by the sixth postoperative week. This is accomplished through both compensatory hypertrophy and hyperplasia of the remaining hepatocytes (MacKenzie et al. 1975; Martin et al. 2003; Bjorling et al. 1985). Up to 70% of the canine liver can be resected without resulting in gross metabolic abnormalities, whereas dogs receiving 84% partial hepatectomy resulted in uniform fatality (Ogata et al. 1997). Common tumors for which this procedure is performed Primary liver tumors are uncommonly reported in the dog and cat, comprising 0.6%–1.3% and 1.0%–2.9% of all canine and feline neoplasms, respectively (Liptak et al. 2004b, 2007). It should be reiterated that the liver serves as a receptacle for metastatic disease 2.5 times more frequently than it does for primary liver tumor development (Strombech 1978; Cullen and Popp 2002; Liptak et al. 2004b). Metastases to the liver commonly result from hematogenous spread; therefore, tumors arising from organs within the portal circulation would

be expected to show high rates of hepatic metastasis (Magne and Withrow 1985). Histologically, most hepatic metastases are carcinomas or variants thereof, with the most commonly reported sites of origin being from the mammary glands, spleen, adrenal glands, pancreas, bone, and lung (Magne and Withrow 1985). Primary liver tumors can be differentiated into four distinct categories based on the histological origin of the tumor: (1) Hepatocelluar, (2) bile duct, (3) carcinoid (neuroendocrine), and (4) mesenchymal (Patnaik et al. 1980; Liptak 2007). Benign liver tumors are more common than malignant tumors in cats, whereas dogs are more commonly diagnosed with malignant tumors (Patnaik et al. 1980; Liptak 2007; Liptak et al. 2004a; Post and Patnaik 1992; Lawrence et al. 1994). When determining candidacy for surgical intervention, the morphological distribution of the tumor (see above) is equally as important as the biology of the underlying disease. Since a preoperative tissue diagnosis is often not attained prior to surgical intervention, the morphologic distribution of the tumor trumps other variables as the single most important factor for determining whether or not a patient is treated surgically. Often in dogs this decision is based on the likelihood of the tumor being a massive hepatocellular carcinoma, and although this is a reasonable and appropriate assumption, it reinforces the necessity of comprehensive preoperative discussion with the animal’s owner and the necessity of a core understanding of the biology of all potential primary liver tumors. Hepatocellular Hepatocellular carcinoma (HCC) is the most common primary liver tumor in dogs and the second most common in cats (Patnaik et al. 1980; Liptak 2007; Liptak et al. 2004a; Post and Patnaik 1992; Lawrence et al. 1994). In dogs with HCC, the massive morphological subtype predominates, representing 61% (30 of 49) of all HCC cases (Figure 7.13). Nodular and diffuse subtypes tend to occur with relatively equal frequency, consisting of 29% (14 of 49) and 10% (5 of 49), respectively (Patnaik et al. 1981a). Additionally, these tumors have a predilection for developing within the left division of the liver, accounting for 67% (20 of 30) to 68.3% (28 of 42) of cases (Liptak et al. 2004b; Patnaik et al. 1981a). This is important because dogs with massive HCC treated for left-sided tumors tend to have less severe intraoperative complications, resulting in significantly longer survival times when compared to dogs with right-sided tumors (Liptak et al. 2004b). The metastatic rate for dogs with HCC is variable, with reported rates ranging from 4.8% (2 of 42) to 61% (35 of 57) (Liptak et al. 2004b; Patnaik et al. 1981a).

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(a)

(b)

Figure 7.13.  (A, B) Postoperative image of canine (A) and feline (B) HCC, both of which were of the massive morphological distribution and were easily excised using en bloc staple ligation of the hilar vessels.

Metastatic potential seems to correlate with tumor morphology. In one study, 35.6% (11 of 30) of dogs with massive HCC had evidence of distant metastasis, whereas 93% (13 of 14) and 100% (5 of 5) of nodular and diffuse HCCs had metastasis, respectively (Liptak et al 2004a; Patnaik et al. 1981a). The most common sites of metastasis include lymph nodes, lungs, other lobes of the liver, and the peritoneum (Liptak et al. 2004b; Patnaik et al. 1981a). Minimal, large-scale veterinary studies assessing the efficacy of surgical treatment for HCC have been published. In the study by Liptak et al. (2004a) surgical treatment (via lobectomy) of 42 dogs with massive HCC yielded a median survival time (MST) of more than 1,460 days. In contrast, dogs that were not treated surgically had a MST of 270 days (range, 0–415 days), which was significantly less than that of surgically treated dogs. The calculated tumor-related mortality rate was 15.4 times higher in dogs treated medically compared to dogs treated with surgery. Interestingly, completeness of excision did not significantly impact long-term survival, and local recurrence was not reported in the 4 dogs with incompletely excised tumors (Liptak et al. 2004a). In the study by Kosovsky et al. (1989), local recurrence was only detected in 1 of 18 dogs after partial liver lobectomy for HCC. These 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 indentified in only 4% (3 of 62) of the study population (Lawrence et al. 1994; Post and Patnaik 1992). Therefore, specific prognostic criteria and ex­­ pected 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 scientific studies. Bile duct Carcinoma of the bile duct is the most common primary liver tumor in the cat and the second most common in dogs (Patnaik et al. 1980, 1981b; Liptak 2007; Liptak et al. 2004a; Post and Patnaik 1992; Lawrence et al. 1994). Adenomas represent the second type of bile duct tumor identified 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

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(a)

(b)

Figure 7.14.  (A, B) Postmortem images of a cat with a massive cystadenoma originating from the left division of the liver. Note the characteristic fluid-filled cystic component of the mass.

(Figures 7.14A, B). Hepatobiliary cystadenomas are relatively uncommon in dogs (Liptak et al. 2004b; Post and Patnaik 1992; Lawrence et al. 1994; Adler and Wilson 1995; Trout et al. 1995). 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; Liptak et al. 2004b; Post and Patnaik 1992; Lawrence et al. 1994). 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 (Liptak et al. 2004b; Patnaik et al. 1981b). Diffuse intraperitoneal metastasis and carcinomatosis is frequently reported in cats with bile duct carcinoma, representing 67%–80% of cases (Figure 7.15) (Patnaik 1992; Liptak et al. 2004b; Post and Patnaik 1992; Lawrence et al. 1994).

Figure 7.15.  Intraoperative image of a cat with bile duct carcinoma and secondary carcinomatosis.

206  Veterinary Surgical Oncology Table 7.2.  Literature summary of the frequency of morphologic classifications of malignant primary liver tumors in dogs. Tumor Type

Massive

Nodular

Diffuse

Hepatocellular carcinoma Bile duct carcinoma Neuroendocrine tumor Sarcoma (mesenchymal)

53%–84%

16%–25%

0%–9%

37%–46% 0%

0%–46% 33%

17%–54% 67%

36%

64%

0%

Source:  Reproduced with permission from Liptak, J.M., W.S. Dernell, and S.J. Withrow. 2004. Liver tumors in cats and dogs. Compend Contin Educ Pract Vet 26:50–57.

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 7.2) (Liptak et al. 2004b; Patnaik et al. 1980, 1981b). Liver lobectomy for treatment of massive bile duct carcinoma has been recommended in dogs and cats. Unfortunately, largescale clinical studies are not available, and no prognostic factors have been identified. Clients should be cautioned, however, that most animals treated for bile duct carcinoma tend to succumb to the disease within 6 months of therapy secondary to local recurrence or distant metastasis (Liptak et al. 2004b). 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 nonspecific 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 (Liptak et al. 2004b; Adler and Wilson 1995; Trout et al. 1995). 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 five cats undergoing lobectomy for treatment of

hepatobiliary cystadenomas, surgical complications were not observed and tumor recurrence or tumorrelated mortality was not observed (Trout et al. 1995). 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 identified (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 8 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; Liptak et al. 2004b; Morrell et al. 2002; Willard et al. 1988). Unfortunately, due to the typical morphological distribution of these tumors within the liver, surgical therapy is not usually considered beneficial. 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 identified 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 fibrosarcoma, representing 9%, 3%, and 1% of all primary hepatic malignancies, respectively. Other types of primary hepatic sarcomas include liposarcoma, rhabdomyosarcoma, osteosarcoma, and malignant mesenchyma. In general, however, malignant primary and nonhematopoietic sarcomas are rare in dogs and cats (Patnaik et al. 1980, 1981b; Patnaik 1992; Liptak et al.

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2004b; Post and Patnaik 1992; Lawrence et al. 1994). 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 identified in 86%–100% of cases (Liptak et al. 2004b; Patnaik et al. 1980; Kapatkin et al. 1992). 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 (Liptak et al. 2004b; Patnaik et al. 1980). Surgical treatment for solitary massive hepatic sarcomas has been recommended; however, prognosis is usually poor unless metastatic disease is not a factor. Adjuvant therapies Controlled studies evaluating the efficacy of specific chemotherapeutic regimens for animals with malignant hepatic neoplasia have not been performed (Liptak 2007). Likewise, the therapeutic benefit of radiation therapy has not be investigated scientifically, however, it is unlikely to be efficacious based on the fact that the canine liver is unable to tolerate cumulative doses beyond 30 Gy (Liptak 2007). 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 benefit (Kokudo et al. 2010). Transarterial chemoembolization (TACE) is commonly employed in the treatment of people with advanced-stage or nonresectable liver tumors (primarily HCC) (Liapi et al. 2007). TACE involves selective, percutaneous catheterization (using fluoroscopy) of the desired hepatic artery branch based on tumor location. Angiography is used to define the affected region, and once identified, the vessel targeting the specific tumor bed is accessed. A combination of cisplatin, doxorubicin, and mitomycin C mixed with ethiodol is injected until stasis of blood flow 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 significant improvement in 2-year survival compared with control (either

conservative treatment or less favorable therapy, such as intravenous 5-fluorouracil). TACE-treated patients showed a median survival of more than 2 years compared to a median survival of 4 to 7 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 four dogs with HCC has been reported (Weisse et al. 2002).

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 and is positioned dorsally to the great vessels including the portal vein. The anatomy of the pancreatic duct system differs significantly 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 7.16). 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). It most often drains the left lobe of the pancreas (Figure 7.16). Sixty-eight percent 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 aboral to 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 7.16). Branches of the splenic artery enter the left limb. The

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Figure 7.16.  Anatomy of the canine pancreatic duct system and vascular system. (Illustration courtesy of Dave Carlson)

celiac artery branches into the hepatic artery to supply the body of the pancreas. The hepatic artery receives blood from the right gastroepiploic artery and continues as the gastroduodenal artery, also supplying the body and the cranial right limb. The gastroduodenal artery receives blood from duodenal arterial branches to become the cranial pancreaticoduodenal artery, supplying the cranial half of the right limb of the pancreas. The cranial mesenteric artery supplies only the caudal portion of the right limb, as the caudal pancreaticoduodenal artery. Damage to the the right cranial and caudal pancreaticoduodenal arteries may lead to duodenal devitalization, because these vessels also supply the duodenum. Surgical procedures and principles Pancreatic biopsy Biopsies may be used to differentiate pancreatitis, fibrosis, 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 ultrasound-guided needle-core biopsy (TruCut) and open surgical approaches such as wedge, suture fracture technique, or blunt dissection and ligation. These procedures are performed without significant 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 Fine-needle aspiration (FNA) can also be performed for sample collection of pancreatic abnormalities and is

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creas should be minimized to avoid postoperative pancreatitis and because identifying abnormal areas of the pancreas such as small tumors can be more difficult, once the pancreas has been inflamed. Indications

Figure 7.17.  Enucleation of a pancreatic mass (insulinoma) using blunt dissection. (Image courtesy of Dr. Simon Kudnig)

generally performed with the assistance of ultrasound guidance. This can be very successful for the diagnosis of exocrine neoplasia (see below), but may be best avoided for cystic pancreatic structures such as abscesses. 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 7.17). 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 identified and ligated. Seventy-five percent 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 significant regenerative capacity (Cornell and Fischer 2003). Monofilament, synthetic absorbable suture material is used; nonabsorbable, braided, or cat-gut sutures are avoided. Hemoclips or TA-30 or -55 staples can also be used to assist in removal (Bellah 1994). Handling of the pan-

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, with only five cases reported (Greene and Bright 2008; Kraje 2003; McMillan et al. 1985, O’Brien et al. 1990; Hawks et al. 1992). Total pancreatectomy Total pancreatectomy is generally avoided in dogs with clinical pancreatic disease due to the difficulty 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 insufficiency. The primary difficulty 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 fibrosis 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 long-term pancreatic supplementation of both endocrine and exocrine functions. Aftercare Prevention of pancreatitis is assisted by intravenous fluid therapy, nothing by mouth for the first 36–48 hours, and withholding oral food for 3–5 days after surgery. Small amounts of oral water are tried first, from 36 to 48 hours after surgery, and if no vomiting is seen, a few teaspoons of low-fat bland food are tried on postoperative day 3. A jejunostomy tube may be needed to bypass the pancreas, and this is often placed preemptively at the initial surgery. Partial or total parenteral nutrition may also be required postoperatively in

210  Veterinary Surgical Oncology

individual animals. Antiemetics are generally given preemptively as part of postoperative management. Imaging of pancreatic neoplasia Specific 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). 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 identified, it generally appears as a pancreatic or peripancreatic nodule or mass lesion of variable size and echogenicity (Hecht et al. 2007; Lamb et al. 1995; Seaman 2004; Bennett et al. 2001). However, ultrasonographic features in feline pancreatic nodular hyperplasia include pancreatic nodules of up to 1 cm diameter, and there is significant overlap between the ultrasonographic findings 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 finding 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 identified 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 (1) identify pancreatic mass(es) and (2) 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 five 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 specific form of somatostatin receptor scintigraphy) detected 6 of 14 (43%) primary insulinomas (Robben et al. 2005). Although conventional pre- and postcontrast CT was more sensitive than ultrasound or SPECT in this study, it significantly overestimated metastases (28 falsepositive 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 peptide-producing extrapancreatic tumors (Boari et al. 1995)(see Table 7.3). Dynamic CT (with contrast medium injection and images taken in arterial and pancreatic phases) clearly identified a pancreatic nodule in one dog with insulinoma, and tumor size and location on CT correlated with surgical findings. 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).

Alimentary Tract  211 Table 7.3.  Differential diagnosis for hypoglycemia in dogs. 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 deficiency, glucagon deficiency (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

Source:  Adapted from Feldman and Nelson 2004; Cornell and Fischer 2003.

Dual-phase CT angiography (CTA) has been reported in three dogs with histopathologically confirmed pancreatic insulinoma. In all three dogs, there was agreement between the dual-phase CTA findings and the surgical findings, and dual-phase CTA findings identified lesions not seen with abdominal ultrasonography. The arterial and portal phases of the dual-phase study were critical for complete identification of all lesions present (Mai and Caceres 2008). 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 five dogs, but only defined 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). Histopathology is the gold standard for the diagnosis of pancreatic disease (Webb et al. 2008). Laparoscopy is a method of obtaining pancreatic biopsies; however, its use for the diagnosis and staging of canine insulinoma remains to be fully evaluated. Exploratory surgery, pancreatic biopsy, and histopathology are ultimately required in most cases for a definitive diagnosis and accurate staging. Visible metastases are found in

40%–50% of insulinomas at surgery (Leifer et al. 1986; Caywood et al. 1988; Trifonidou et al. 1998). Infusion of methylene blue (3 mg/kg diluted in 250 mL 0.9% sodium chloride and administered over 30–40 minutes), can potentially facilitate identification of nodules. However, this can be harmful through the production of Heinz body hemolytic anemia and can also cause pseudocyanosis and acute renal failure (Siliart and Stambouli 1996). When appropriately diluted to levels that are almost clear to the human eye, methylene blue becomes a moderate-strength fluorophore. After intravenous injection into insulinoma- bearing transgenic mice, primary and metastatic tumors, even when less than 1 mm, were visible intraoperatively under nearinfrared fluorescent light (Joshua et al. 2010). 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 (Oberkirchner et al. 2009; Allenspach et al. 2000). Abdominal ultrasonography was conducted in eight cases of canine glucagonoma, but a pancreatic mass was visible in only one case (Gross et al. 1990; Allenspach et al. 2000; Torres, Caywood, et al. 1997; Torres, Johnson, et al. 1997; Bond et al. 1995; Miller et al. 1991) Contrast-enhanced CT diagnosed a primary pancreatic mass in one dog, where gas-filled 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 (Gibril et al. 1996; Schirmer et al. 1995; Altschul et al. 1997).

212  Veterinary Surgical Oncology

Imaging of exocrine neoplasia

Carcinoma

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).

As previously mentioned, many nonmalignant diseases such as pancreatic nodular hyperplasia, which is a common incidental finding in old dogs and cats, can mimic pancreatic carcinoma ultrasonographically (Jubb 1993). Therefore, imaging findings need to be related to clinical signs, laboratory data, and ultimately cytology or histopathology to obtain a definitive 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). In one 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 fluid in cases where there is a malignant effusion. Radiographically, a lack of serosal detail (4 of 6 cats) and abdominal mass effect (6 of 6 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). 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 (Feldman and Nelson 2004; Zerbe and Washabau 2000). Thoracic radiographs usually do not identify pulmonary metastatic disease; however, they may be used to reveal megaesophagus (secondary to severe esophagitis). Contrast fluoroscopy may show esophageal hypomotility (Kyles 2003).

Surgery for endocrine pancreatic neoplasia Insulinoma Medical management to stabilize blood glucose is required prior to and following surgery (see Chapter 13). For an in-depth discussion on medical management, see Feldman and Nelson 2004. 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 identified 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 7.18). 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 identified, it is removed, paying close attention to the pancreatic vasculature and ductal pattern (Figure 7.18). Diffusely infiltrative 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 unidentified tumors are most often located in the body and no single limb is more commonly affected than another (Siliart and Stambouli 1996). Feldman and Nelson (2004) recommended against removal of insulinomas from the body (central section) of the pancreas due to concerns for creating severe, life-threatening pancreatitis. Caywood et al. (1988), Tobin et al. (1999), and Trifonidou et al. (1998) did not find any correlation between tumor location and prognosis. 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 7.4 and Figure 7.18), 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 time of exploratory surgery (Tobin et al. 1999).

Alimentary Tract  213 Table 7.4.  Staging for insulinoma. Stage I II III

(a)

(b)

Confined to pancreas Pancreas and regional lymph nodes Distant metastasis (i.e. liver)

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. In one study, only three of even dogs with ultrasound evidence of hepatic metastasis had confirmed β-cell metastasis (Mehlhaff et al. 1985). 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 difficult. Studies have shown that survival can be prolonged in dogs that receive tumor debulking and medical management compared to dogs receiving medical treatment only (Polton and Brearley 2007; Tobin et al. 1999). 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 up to 1 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

(c)

Figure 7.18.  (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).

Intraoperative complications. The inability to find 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 specific mass, and no predisposition for tumor location within the pancreas (left limb, body, or right limb) has been identified (Caywood et al. 1988). Other intraoperative complications include the identification of

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previously unseen metastatic disease, the identification 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 head of the pancreas (Tobin et al. 1999; Feldman and Nelson 2004; Mehlhaff et al. 1985; Trifonidou et al. 1998). 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 occurs in 52%–100% dogs (Tobin et al. 1999; Kyles 2003) with the mean time 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% 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 (Leifer et al. 1986; Mehlhaff et al. 1985). 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 (Feldman and Nelson 2004; Mehlhaff et al. 1985), as well as a paraneoplastic peripheral neuropathy (see Chapter 13).

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 a MST of 1,316 days (Polton and Brearley 2007). Poor prognostic factors that are reported with insulinoma include the following.

• Conservative treatment. MST is 74 days with conser• • •

• •

• •

•

vative treatment versus 381 days for partial pancreatectomy (Tobin et al. 1999). Age. Survival time is significantly decreased in younger dogs (Caywood et al. 1988). Serum insulin levels. High preoperative serum insulin levels indicates poorer prognosis (Caywood et al. 1988). Higher stage of disease. Stage III insulinomas have MST less than 6 months versus 18 months for stage I and II disease. Eighty percent of dogs are alive at 14 months when the disease is confined 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 versus 680 days for normoglycemic dogs (Trifonidou et al. 1998). Clinical stage. Clinical stage influences the duration of normoglycemia following surgical resection. Dogs with stage I insulinomas maintain normoglycemia for a median of 14 months versus 1 month for dogs with stage II and III disease (Caywood et al. 1988). 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 versus 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).

Prognosis for insulinoma treated with surgery

Gastrinoma

Caywood et al. (1988) reported a median survival time (MST) of 18 months for stage I disease, and a MST of 6

Gastrointestinal ulceration (with or without perforation) is common and occurs in 80% of cats and dogs

Alimentary Tract  215 Table 7.5.  Reported survival times for dogs with insulinoma treated with surgery ± medical therapy Reference

Number of cases

Survival time (ST)

Surgical technique

Adjunctive medical managementa

Unspecified in 23 dogs, partial pancreatectomy specified in 2 dogs Local enucleation Partial pancreatectomy Unspecified

Yes

Partial pancreatectomy

Yes

Partial pancreatectomy

Yes

Partial pancreatectomy

Yes

Unspecified

No

Kruth et al. 1982

25

12.3 months (mean ST)

Mehlhaff et al. 1985 Mehlhaff et al. 1985 Leifer et al. 1986

10 15 18

Caywood et al. 1988

47

Tobin et al. 1999

26

Polton and Brearley 2007

28

Trifonidou et al. 1998

31

11.5 months (mean ST) 17.9 months (mean ST) 435 days (14.5 months) (median ST) 18 months (stage 1 data) (median ST) 381 days (12.7 months) (median ST) 547 days (18.2 months) (median ST) 258 days (8.6 months) (median ST)

Yes Yes No

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

with gastrinomas (Feldman and Nelson 2004; Zerbe and Washabau 2000; Altschul et al. 1997; Simpson and Dykes 1997; Green and Gartrell 1997; Brooks and Watson 1997). 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 confirm superficial necrolytic dermatitis (SND), although the diagnosis of SND does not confirm the presence of glucagonoma (Langer et al. 2003). Complete surgical resection of the glucagonsecreting 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 difficult 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 (metastatic spread to the mesentery) 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. 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 flow in the presence of pancreatic disease is much more difficult (Cornell and Fischer 2003). In humans, complete pancreatectomy and pancreati­ coduodenectomy (Whipple procedure) have a 5%–30% operative mortality rate (Withrow 2007a). Gastrojejunostomy 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

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prognosis (due to a metastatic rate and the anatomical location of the tumor) and associated high morbidity and mortality (Cornell and Fischer 2003). One-year survival has not been reported, and radiation or chemotherapy has been shown to be of limited benefit in people and animals (Withrow 2007a). Other exocrine tumor types include adenoma, lymphosarcoma, 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 oral to a soft-tissue density, supporting a diagnosis of an intestinal mass that is causing obstruction of the bowel. Additional radiographic findings can include the presence of free gas or fluid 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 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 an

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 inflammatory conditions within the bowel (Penninck et al. 2003). Another distinct benefit 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 efficacy of this modality 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% specificity 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 definitive 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 and has been used in clinical practice for the past 20 years (Willard et al. 2001). Despite this, limitations of this modality must be recognized as deficiencies 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 (Willard et al. 2001; Van der Gaag and Happe 1990). 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 inflammatory bowel disease 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 confirmed a diagnosis of LSA in only 33% (3 of 9) of

Alimentary Tract  217

cats that had biopsy-confirmed 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 (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 threeportal 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. 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 significant 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 significant amount of redundancy exists within the small intestine. The overall intestinal length is relative to animal size and is approximately five 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 significantly 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 braches in the most oral and aboral 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 inflammation 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 fixed location in the right paralumbar region. The area of the proximal duodenum must be respected at all times. This is an extremely difficult 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 long-term exocrine pancreatic enzyme supplementation

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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 significant 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 identified 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 identified, and transection is performed with 5 cm margins of normal intestine on either end of the mass (Crawshaw et al. 1998). The cut edges of the remaining intestine are then placed in close proximity to one another and the anastomosis 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 first, followed by a single suture placed at 180 degrees from the first 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. Once all sutures have been placed, the intestinal lumen can be occluded with the opposed fingers 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 finger occlusion can be carefully pressed between the index finger 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 intralumenal distension, beyond the bursting strength of the anastomosis, can result in leakage. Once the anastomosis is completed, the mesenteric defect is then closed using a monofilament 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 degrees 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 degrees 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 to this stapling technique is the rapidity with which the procedure can be performed. Stapled small intestinal anastomoses are performed in approximately oneseventh the 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).

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(a)

(b)

(c)

(d)

Figure 7.19.  (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 fired 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. (Images courtesy of Dr. Pam Schwartz)

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. The resection procedure is performed as 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 7.19A). The GIA stapler is advanced into the lumen of each small intestinal orifice (Figure 7.19B). The stapler is then fired, which creates a large stapled side-to-side anastomosis between the two lumens. At this point, a common lumen has been created between

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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 suffices) is used to close the free end of the common lumen (Figure 7.19C). An anchoring suture is always placed at the end of the anastomotic staple line because this region is under the greatest amount of tension (Figure 7.19D). The mesenteric defect is then closed. Leak testing can then be performed using sterile saline as previously described (Ullman et al. 1991). Occasionally, significant 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 for 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. 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 flow and lymphatic drainage (Hosgood 1990). Increase in blood flow to the surgical site helps to control infection if compromised blood flow 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 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 monofilament 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) findings 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 hours), 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 gastrojejunostomy (GJ) feeding tubes in cases of extensive bowel resection or in patients with peritonitis. The benefit 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 significant 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 fluid volume is quantified every 4–6 hours by aspirating the gastric component of the tube system) and managed (motility

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medication is titrated based on trends in calculated residual volumes). With the GJ-tube system, J-tube feedings are generally initiated within 12 hours of surgery using a continuous rate infusion of a commercially available liquefied 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 hours 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 fluid 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 fluid therapy and appropriate analgesia) for 24–48 hours 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 total protein 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). Severe protein deficiencies may require transfusions of human or canine albumin in order to control clinical signs and facilitate wound healing while protein deficiencies are replaced through enteral nutritional supplementation. Although controversial, clinical studies have found that systolic blood pressure, serum albumin, and total solid levels are significantly 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 (Francis et al. 2007; Cohn et al. 2007; Yamaya et al. 2004). As an alternate 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 (Trow et al. 2008; Mazzaferro et al. 2002). For most intestinal procedures, a first- or secondgeneration cephalosporin is prescribed perioperatively; however, antibiotics are not indicated in the postoperative period unless active infection is identified 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 finding. Trends in the patient’s body temperature, abdominal comfort, and intraabdominal fluid volume are also useful to assess healing because pyrexia, pain, and an increase in fluid volume could be indicative of intestinal-mediated surgical complication. Shifts in the immature white blood cell lines (development of a degenerative left shift) within the first 2–5 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 significant postoperative complication associated with small intestinal resection procedures. Dehiscence generally occurs within 3–5 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). 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

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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. Two other clinical studies have not substantiated hypoalbuminemia as a risk factor for wound healing after intestinal surgery (Harvey 1990; Shales et al. 2005). 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 resection-anastomosis 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 inflammatory (lag) phase and therefore should be avoided during the generation of an intestinal anastomosis (Ellison 1989). 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 (i.e., 5 cm) 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 gastrojejunostomy procedure [Billroth II] earlier in this chapter). 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 entero-

cyte 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 8 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 identified and 12 of 15 (80%) of the dogs and cats that underwent extensive small bowel resection were reported to have good longterm outcomes (Gorman et al. 2006). Postoperative ileus is common after intestinal surgery and generally occurs within the first 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 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 1 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 identified. 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 for which this procedure is performed Four general categories of tumors occur within the small intestine. These include epithelial, smooth muscle (mesenchymal), neuroendocrine, and round cell neoplasms

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(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 confirmed 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 is documented, then surgical excision is warranted. 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 3 months with metastatic disease (Paoloni et al. 2003; Crawshaw et al. 1998; Birchard et al. 1986). 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 1-year survival rate was reported to be 66.7% compared to 20% if documented lymph node metastasis had occurred. It is therefore recommended to sample regional lymph nodes (if they are accessible) prior to surgery with ultrasoundguided needle aspirates. Regional lymph nodes should also be biopsied at the time of definitive 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 2 weeks (Kosovsky et al. 1998; Birchard et al. 1986).

Mesenchymal neoplasms of the gastrointestinal tract have recently been divided into gastrointestinal stromal tumors (GISTs) and leiomyosarcomas (GILMs). GISTs are most commonly identified 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 oral 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 median survival time 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 significant difference in survival rates between GILMs or GISTs and with both tumor types; approximately 80% of dogs were tumor free at 1 year and 65% at 2 years (Maas et al. 2007). Adjuvant therapies There is no evidence of benefit associated with the administration of chemotherapy in animals suffering from epithelial- or mesenchymal-based neoplasms. Che­­­ motherapy is generally also not thought to be helpful in humans with small intestinal neoplasia (Stanclift and Gilson 2004). 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, allowing for the development of two commercially available therapeutics (Palladia [toceranid phosphate, SU11654] and Kinavet [mastinib]), which may be appropriate for use in dogs with documented advanced-stage GISTs (London 2009; Russel et al. 2007). At this time, however, only anecdotal reports of successful use of these agents has been reported and use of these agents for GIST is considered to be off-label.

Colorectal Tumors Clinical workup and biopsy principles During a complete physical examination, abdominal palpation may identify a palpable abdominal mass in some cases. In a digital rectal examination, the tumor is

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Figure 7.20.  Phases of fine-needle aspiration 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 finger is extracted from the anus, and the material is sprayed on a slide for cytological examination.

often palpable as, mainly in dogs, most rectal tumors are located 3–8 cm from the anus; stenosis may be felt if the tumor growth is circumferential. Anorectal stricture may be very rarely idiopathic as a result of anorectal spastic contraction. The latter condition is usually seen in German shepherd dogs and disappears under general or epidural anesthesia (Niebauer 1993). It is important during palpation to identify infiltrative tumors. As the normal rectum is freely movable, in case of full-thickness wall infiltration the rectal tube may be variably fixed to the surrounding tissues. Infiltration may be caused by the primary rectal tumor (more often an adenocarcinoma) that, after its growth into the full thickness of the intestinal wall, has invaded surrounding tissues; as an alternative, the rectum may be secondarily invaded by tumors arising from pelvic organs (mainly the prostate gland; see Chapter 10). During digital rectal examination, the so-called sublumbar lymph nodes are palpated. 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, hypogastric, and sacral lymph nodes) and the iliofemoral lymph nodes (Bezuidenhout 1993). The sublumbar lymph nodes draining the anus, rectum, and colon are the hypogastric (ventral to the sixth and seventh lumbar vertebrae and adherent to the external and internal iliac arteries) and

the medial iliac lymph nodes (ventral to the fifth and sixth lumbar vertebrae, between the deep circumflex and external iliac arteries). 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 finger and interposed between a surgical rubber glove and the finger part of another glove on the same index finger. The animal may need to be sedated for the procedure. After manual evacuation of any feces from the caudal rectum, the lubricated index finger 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 finger-glove first and the entire thickness of the intestinal wall second. The stylet is removed, a 2–5 mL syringe is connected, and aspiration is performed (Figure 7.20). 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 be not reached if they are even slightly enlarged. Alternatively, a transabdominal ultrasoundguided fine-needle aspiration 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

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Figure 7.21.  The rectal mass is exposed by traction on four stay sutures applied 1–2 cm cranially to the anorectal line. 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 Figures 7.28F, 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. (From Buracco P. 2007. Tumori colorettali. In Oncologia del cane e del gatto G. Romanelli, editor. London: Elsevier. Used by permission.)

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. Biopsies may be collected directly, without anesthesia, if the mass is prolapsed through the anus. This technique is not advised as only superficial samples are collected and bleeding may be a concern. 2. A needle core biopsy (Tru-Cut needle) may be done through the anus after rectal eversion by traction on four stay sutures applied 1–2 cm cranially to the anorectal line (Figure 7.21). 3. As an alternative, an incisional biopsy may be performed. This procedure requires anesthesia (including an epidural) and does not yield any information regarding the large intestine cranial to the lesion.

4. Endoscopic examination (proctocolonoscopy) may also be done. Preparation for endoscopy may be provided by fasting the animal 1.5–2 days before the procedure; drinking is allowed until 8 hours before the examination. The day before the examination, warm water enemas (10–20 mL/kg twice daily) are performed; finally, the evening before, an osmotic laxative is administered orally to the patient. Proctocolonoscopy is necessary to characterize the tumor (single or multiple lesions, position, size, length, and circumferential extension) (Figure 7.22A–C) and to obtain a biopsy. Due to the procurement of only superficial samples, endoscopic biopsies can sometimes be inadequate (Morello et al. 2008). The large intestine cranial to the lesion is also inspected for multiple tumors. The complication rate of flexible 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, the colotomy (occasionaly performed for tumor biopsy), will be not described here. Imaging techniques Radiography and contrast studies At present, radiography and contrast studies have been largely superseded by ultrasonography as the latter is much 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 7.23A) whereas contrast studies may outline the site of obstruction (Figure 7.23B) Ultrasound Ultrasound examination of the abdomen (Myers and Penninck 1994; Rivers et al. 1997; Slawienski et al. 1997; Paoloni et al. 2003; Llbrés-Diaz 2004) is considered to be the most appropriate for intestinal malignancies, even though the precise site (small or large intestine) may be not 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, fluid and/or fecal material accumulation (obstructive lesion),

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Figure 7.22.  Endoscopic view of (A) a rectal leiomyosarcoma (the same as in Figure 7.21); (B) a rectal adenocarcinoma; and (C) a 35 cm long 360-degree colorectal adenocarcinoma (C1: CT view; C2: endoscopic view). (Photos in (A) and (B) from Buracco P. 2007. Tumori colorettali. 2007. In Oncologia del cane e del gatto G. Romanelli, editor. London: Elsevier. Used by permission. Endoscopic pictures courtesy of Dr. Caccamo Roberta.)

(a)

(b)

Figure 7.23.  (A) megacolon caused a colorectal adenocarcinoma in a dog; (B) barium enema in a case of colonic lymphoma in a dog.

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and/or abdominal lymphadenomegaly (colic, sublumbar), as well as other abdominal abnormalities (mainly on the omentum, mesentery, and mesenteric lymph nodes). It has been reported that the different tumor histotypes should have distinct ultrasonographic appearance, and diffuse echogenicity is described in the case of adenocarcinoma in most dogs. Ultrasound-guided fine needle aspiration (with a 22- or 20-gauge spinal needle) or biopsy (with a 18-gauge Tru-Cut biopsy needle) of these lymph nodes, as well as of any intestinal lesion, may be attempted transcutaneously. Thorax radiography Radiographic evaluation of the thorax (three views: two lateral, one dorsoventral) is needed to evaluate the presence of lung metastases, although they are extremely rare in these diseases. Contrast-enhanced CT and MRI Contrast-enhanced CT and MRI are indicated to detect intrapelvic infiltration of the rectal tumor, determine the extent of the disease, and confirm intrabdominal/ sublumbar lymphadenomegaly (Figure 7.24; see also 7.22, 7.33, and the section on perianal tumors). 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 space, as well as to take biopsies. Surgical techniques Preparation for colorectal surgery A canine experimental study has confirmed the 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 low-residue diet started from 2–3 days (Hedlund and Fossum 2007b) to 1 week before surgery and no warm water enema or laxative within the preoperative hours, from 3–72 hours (Hedlund and Fossum 2007b; Holt and Brockman 2003), if a standard surgical excision is to be performed. The author of this section of the chapter prescribes 4–5 days of low-residue diet before surgery and avoids performing an enema during the preoperative 72 hours. 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 water access (Hedlund and Fossum 2007b). 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, cefazolin and metronidazole, and neomycin and erythromycin (Holt and Brockman 2003; Hedlund and Fossum 2007b). Cephalosporins are used at induction of anesthesia and then every 2 hours of operative time. Positioning of the patient varies depending on the surgical procedure: dorsal recumbency 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 onethird 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 packed 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 identified 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 neutral-buffered 10% formalin. Surgical instruments and gloves are changed at this stage. Surgical procedures Typhlectomy This procedure is indicated for tumors confined to the cecum. The cecum can be removed from the colon only or in conjunction with the distal ileum and proximal colon, depending on the extent of resection required to achieve excisional 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

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(b) (a)

(d)

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Figure 7.24.  (A) intraoperative view of an infiltrative 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 infiltration and obstruction caused by the tumor (B) and an enlarged sublumbar lymph node (arrow) (C). (D) The tumor is resected through a combined approach, abdominal first and then transanal (see also Fig. 7.33 and 7.35). The two enlarged colic lymph nodes are visible and resected with the tract of the intestine that is removed. (A and B reprinted with permission from Buracco P., Tumori colorettali. In Oncologia del cane e del gatto, edited by Romanelli G, 2007, Elsevier)

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 7.25A). 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 distal ileum and proximal colon (Figure 7.25B). 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 degrees, with the antimesenteric border shorter than the mesenteric one; or partially oversewing the colon to reduce its diameter. An ileocolonic 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 monofilament material (polydioxanone, polyglyconate, or poliglecaprone 25) with the knots in

Alimentary Tract  229

(a)

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Figure 7.25.  (A) A typhletomy for a small cecal leiomyosarcoma has been performed, including a Parker-Kerr suture for closure. (B) A typhectomy has been performed in another dog for a larger leiomyosarcoma, and the cecum has been removed together with a portion of both small and large intestine. (Photographs courtesy of Dr. Romanelli Giorgio)

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; Hedlund and Fossum 2007b; Tobias 2007; Banz et al. 2008). 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 as 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 causes obstruction), recurrence, and metastasis. The removal of the ileocolic junction in cats (Sweet et al. 1994) and dogs may result in clinical signs, such as increase in the 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. For the extent of resection, see above. Colectomy Indications for colectomy are tumors confined to the colon only. Although this situation is rare, particularly in dogs where large intestinal tumors are more frequently colorectal (Selting 2007), 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). 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 excisional 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 final tensionfree end-to-end anastomosis. The colon is exteriorized, and the area to be removed is identified. 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 cranial and caudal to the two Carmalt clamps on the section of intestine to be preserved; as an alternative, the assistant may use his or her fingers (index and middle fingers) 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 distal 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; Hedlund and Fossum 2007b). 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 save major colic vessels when the extent of the disease allows this to occur. Despite this recommendation, no

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(a)

(c)

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 7.26B, C). Stapling may be a problem in cats and small dogs because of size limitations (Holt and Brockman 2003; Hedlund and Fossum 2007b) but 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). Recently, a successful endto-end colocolic anastomosis technique with biofragmentable rings after subtotal colectomy in cats has been reported (Ryan et al. 2006) (Figure 7.26D). 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 as either side of the anastomosis is digitally occluded), an abdominal lavage with warm sterile saline and aspiration precede both wrapping the anastomotic site with omentum and standard closure of the abdomen. Postoperative care Important postoperative considerations for postoperative care include the provision of analgesia for 24–48 hours, fluid and electrolyte therapy, antibiotics in the case of established postoperative infection and peritonitis, and Elizabethan collars. 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 3 days (Holt and Brockman 2003). Functional outcome is usually good.

(b)

Figure 7.26.  (A) Colocolonic end-to-end anastomosis obtained in a cat using a manual suture technique. (B) Colocolonic end-toend 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). (Photographs B and C courtesy of Dr. Eric Monnet)

postoperative complications were seen in a recent paper 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 confirm that sufficient macroscopic margins have been achieved. Further resection, using a new set of surgical instruments and gloves, can be considered in the event that excisional margins are questionable. End-to-end anastomosis (ileocolonic or colocolonic) may be manual (see typhlectomy and Figure 7.26A) or by stapling depending on the surgeon’s

Potential complications Complications may include short-term rectal bleeding, loose feces, tenesmus, stricture (that can require a second surgery if it causes obstruction), dehiscence and peritonitis (that require patient stabilization and surgical exploration), and potential loss of reservoir continence if most of the colon is removed (see also later). Loss of reservoir continence results in more frequent conscious defecation (Guilford 1990; Dean and Bojrab 1993). Cats tolerate more removal than dogs (90%–95% of the colon) (Bertoy et al. 1989); however, no long-term adverse effects is seen in dogs after removal of up to 70% of the entire colon (Bertoy et al. 1989; Jimba et al. 2002; Hedlund and Fossum 2007b). In a recent paper, subtotal colectomy with preservation of the ileocolic junction in dogs resulted 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) was achieved within 5–10 weeks (median 7 weeks) (Nemeth et al. 2008). For the extent of resection, see above.

(a)

(d)

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Figure 7.27.  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 locally (C, D). In this case the rectal incision was closed with a one-layer continuous suture (4-0 poliglecaprone 25) (E). (F, G) the lesion (see Figures. 7.21 and 7.22A) is exposed. Excisional biopsy is performed by incising the rectal mucosa at the periphery of the lesion (F), and the mass is excised by blunt dissection and traction. Finally, the rectal wall is sutured with a simple interrupted suture pattern using absorbable monofilament material (G). (Photographs F and G are from Buracco P. 2007. Tumori colorettali. 2007. In Oncologia del cane e del gatto G. Romanelli, editor. London: Elsevier. Used by permission.)

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Figure 7.28.  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. (Photograph courtesy of Prof. Gualtieri Massimo)

Simple excision This procedure should be reserved for small, single and superficial benign tumors (e.g., polyps) located in the caudal-midrectum (Figure 7.27B–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). Excision may be performed using sharp instruments (Figure 7.27C) or with an electrosurgical snare or cautery tip used in conjunction with proctocolonoscopy (Palminteri 1966; Holt and Durdey 1999) (Figure 7.28). As an alternative, cryosurgical, laser, or TA stapler devices may be used (Valerius et al. 1997; Shelley 2002; Tobias 2007; Swiderski and Withrow 2009). Standard surgical excision relies on prolapse of the rectum (pull out procedure) through a transanal approach (Figure 7.27A, B, F). After standard 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 rectocutaneous line. The lesion is exposed externally, which may require the sequential placement of further stay sutures as necessary (see Figure 7.21), and excision of the mass can begin. 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 or deeper (Figure 7.27C). 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 monofilament material (3-0 or 4-0 polydioxanone, polyglyconate, or poliglecaprone 25) (Figure 7.27E–G). As an alternative, a linear stapling device may be used.

In a recent paper, the use of a 30 mm, vascular thoracoabdominal (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 (Swiderski and Withrow 2009). The procedure is indicated for superficial tumors located in the distal third of the rectum, with a base of attachment of less than 3 cm; the reported complication rate was low, operative time was short (around 15 minutes), deep resection was beyond the mucosal layer but full-thickness resection was avoided (to prevent infection), and the final closure line was inverted into the rectal lumen. Regardless of the procedure performed, the stay sutures are then removed. Postoperative care is described below. Functional outcome is usually good. Potential complications Possible complications are rectal bleeding and tenesmus for 1–4 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. Colorectal resection (variable portions of both descending colon and rectum) This technique 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 reflection; the latter is at the level of the second caudal vertebra. The rectococcygeus muscles (that attach the rectum to the ventral fifth caudal vertebra) are caudal to this reflection. Each side of the rectum is supported laterally by the levator ani and coccygeus muscles. On each side, at the level of the peritoneal reflection, 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 infiltration of the extrarectal tissues is evident (see Figures 7.22 and 7.24A, B).

Alimentary Tract  233

(a)

(d)

(b)

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(f)

Figure 7.29.  (See also Figures 7.24D and 7.32.) 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 close to completion, and the stay sutures have been released.

Dorsal inverted (dorsal perineal) approach The technique described here reflects that originally reported in two reports (Mckeown et al. 1984; Anderson et al. 1987). Indications for this procedure include rectal resections for small malignant tumors located in the caudal-midrectum. 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 U-shaped incision is made over the dorsal aspect of the anus, terminating on both sites 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 identified. The

rectococcygeus muscle is severed between the coccygeal vertebrae and rectum or more proximally to free the rectum (Figure 7.29B). 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 reflection is identified. 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 proximal 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

234  Veterinary Surgical Oncology

part of the rectum bearing the tumor is removed and opened to confirm 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 field. End-to-end approximating anastomosis is performed using a simple interrupted suture pattern with absorbable monofilament 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 degrees. 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 (Hedlund and Fossum 2007b; Tobias 2007; Banz et al. 2008). Both levator ani muscles are reattached with mattress sutures if previously severed; the rectococcygeous 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 claimed that healing at the anastomotic site could be disturbed if the drain is against the site (Hedlund and Fossum 2007b). 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. 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. Rectal pull-through procedure This procedure is indicated for confirmed malignant tumors and for recurrences of previously excised benign tumors located in the midcaudal rectum. Incision is started circumferentially over the anal skin (Figure 7.30A); bilateral anal sac removal is often concomitantly performed if the procedure involves their openings (Aronson 2003). The rectum is progressively dissected and pulled caudally out of the body with the help of stay sutures or grasping forceps; the rectococcygeus muscle is

also transected (Figure 7.30B). Care is taken, if feasible, to save the external sphincter muscle, undermining inside the circumference of this muscle. Cranial rectal transection is performed according to the extent of resection required to achieve excisional 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 started (Figure 7.30C). The removed tract 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 7.29D). 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 7.29E and 7.30E). 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 doublelayer suture pattern, the deeper one approximates the intestinal serosa (or adventitia)/muscularis to the perianal subcutaneous tissues, and the superficial layer approximates the submucosa/mucosa to the skin (Aronson 2003). This author usually performs a singlelayer 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-to-end anastomosis. Resection with this approach usually involves only the rectum; however, it can be extended beyond the caudal peritoneal reflection for a small portion of the distal descending colon. Transanal pull-through procedure This procedure is indicated for confirmed malignant tumors and for recurrences of previously excised benign tumors located in the midcranial rectum (Aronson 2003; Hedlund and Fossum 2007b; Morello et al. 2008). The rectal wall is prolapsed through the anus with four stay sutures (see Figures 7.21, 7.27A, and 7.29A). A fullthickness circumferential incision is made through the rectal wall. When feasible, a minimum of 1–1.5 cm of

Alimentary Tract  235

(a)

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(b)

(c)

(e)

Figure 7.30.  Rectal pull-through procedure. (A) Circumferential skin incision. (B) The rectum is exteriorised 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 final image of the area are shown. (Photographs from Buracco P. 2007. Tumori colorettali. 2007. In Oncologia del cane e del gatto G. Romanelli, editor. London: Elsevier. Used by permission.).

distal rectum is spared in order to preserve fecal continence (Morello et al. 2008). The rectum is mobilized following transection of the rectococcygeal muscles (Figures 7.29B and 7.30B.), and blunt dissection is performed along the external surface of the bowel (Figures 7.29C and 7.30B). 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 longitudinally opened, the latter is avoided in the case of a 360-degree circumferential tumor. If a longitudinal opening is used, progressive resection and suturing are accomplished sequentially without touching the tumor (Figures 7.29D). If not opened previously, this is done after resection to confirm 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 distal rectal stump with

one (preferably full-thickness sutures) or two layers (sero-muscular and mucosal-submucosal layers) in the situation where there is tension at the anastomotic site, with simple appositional interrupted sutures (3-0 or 4-0 polydioxanone, polyglyconate, poliglecaprone 25) (Figure 7.29E). The release of the stay sutures allows the rectal anastomotic site to return into the pelvic canal (Figure 7.29F). As an alternative, an end-to-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. Caudal abdominal approach with either sagittal pubic symphyseal separation or osteotomy This approach is indicated for tumors located in the cranial rectum and for those tumors with further extension into the distal colon (Davies and Read 1990; Allen and Crowell 1991; Aronson 2003; Hedlund and Fossum

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(b)

Figure 7.31.  (A) Both the pubis and ischium are spread apart with a Finocchietto retractor. (Photo courtesy of Dr. Julius Liptak) (B) After bilateral ischial and pubic osteotomy, both a colorectal resection and an end-to-end anastomosis have been completed.

2007b). 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 (Figure 7.31A). To increase exposure, osteotomy of both the pubis and ischium has been recently described (Yoon and Mann 2008). In detail, the various steps are as follows. 1. Subperiosteal elevation of adductor muscles up to two-thirds of the obturator foramina. 2. Incision of the prepubic tendon along the pubis rim as needed.

3. Predrilling of a hole using a pin and Jacob’s chuck on each side of the four planned longitudinal osteotomies (two pubic and two ischial) to facilitate subsequent closure. 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 both obturator foramina, bilaterally). 5. Subperiosteal elevation of only one of the two internal obturator muscles from the pubis/ischium to enable reflection of the osteotomized bone plate on the other side. 6. Excision of the affected segment of bowel (this is isolated by careful undermining and 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). The specimen is then opened to confirm that enough macroscopically healthy tissue has been maintained at resection margins; manual or stapling end-to-end anastomosis are then performed as previously described (Figure 7.31B). 7. Preplacement of sutures (orthopedic wire or 0 polydioxanone, the latter in small dogs and cats only) in the predrilled holes and reduction of the segment of bone plate by tightening the sutures. 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 apposition of the prepubic tendon with 3-0 polydioxanone interrupted sutures through the bone tunnels. 10. Thorough lavage of the area prior to routine skin closure. 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 pass along the borders of the symphysis rather than through predrilled holes given that the bone at this level 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. The exposure provided by sagittal pubic symphyseal separation to perform both resection and anastomosis can be limited (Williams and Niles 2005). The osteotomy procedure reported by Yoon and Mann (2008)

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appears to offer several advantages, including good operative space as well as the option to bluntly dissect both the cranial peritoneal reflection and pelvic nerves (on both sides of the rectum) and to ligate only specific 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) is required for at least 2–3 days, as 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. Functional outcome Limping may be evident for some days after surgery (mainly after symphyseal distraction), but prolonged analgesia with nonsteroidal anti-inflammatories may improve the clinical signs. For complications related to colorectal resection, see below. Specific complications Possible complications of this surgical approach may be a sinus tract related to the wire cerclage suture (Davies and Read 1990), nonunion at the site of the pubic symphyseal separation. with the need to restrict activity for a minimum of 4 months (Allen and Crowell 1991), and risk of sacroiliac subluxation. 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). All animals had exercise restricted for 4 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 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 distal 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. A caudal celiotomy is performed first. The 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 (Figure 7.32A), 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 findings. 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. 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 7.32B). At this point two different techniques may be used 1. The first technique is the so called Swenson’s pull through (Swenson and Bill 1948; White and Gorman 1987; Holt and Brockman 2003; Hedlund and Fossum 2007b). The dog is positioned in dorsal recumbency. A second surgeon introduces an Allis tissue forceps into the rectum and both grasps and everts the distal rectum through the anus. This everted portion is resected circumferentially over 360 degrees (or the Parker-Kerr suture is removed) until the suture material connected to the proximal segment is exposed. This suture material is grasped and used as a stay suture; further stay sutures may be applied in the proximal colorectal portion as needed. Finally, the distal segment (bearing the tumor) is resected, and after removal of the Parker-Kerr suture from the proximal segment, an end-to-end anastomosis (in one or two layers, see above) is performed manually or with an EEA stapling device. 2. In a recently reported modified technique (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 and connected with sutures, and 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 7.24D, 7.29C, and 7.32C). After excision of the distal colorectal stump bearing the tumor, the suture used to oversew the cranial stump is removed and the surgical procedure is concluded 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-to-end anastomosis (as discussed below).

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(a)

(b)

(c)

Figure 7.32.  (See also Figures 7.24D and 7.29.) (A) Two Doyen clamps are applied on the colon cranially and caudally to the proposed point of division. (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 2 cm between the two intestinal stumps. (C) A transanal pull-through procedure is performed until the proximal stump emerges. At this point the procedure is terminated as in the transanal pull-through procedure. (Photograph C is from Buracco P. 2007. Tumori colorettali. 2007. In Oncologia del cane e del gatto G. Romanelli, editor. London: Elsevier. Used by permission.).

Postoperative care, potential complications, and extent of resection are described later Functional outcome is usually good, but complications may develop. Complicatons are described below. Metastasis resection Metastatic lesions 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 7.24 and 7.53; hypogastric, Figures 7.33A and B, and see also Figure 7.54); colic (see Figures 7.24A, D); and mesenteric lymph nodes, liver, spleen, and omentum. If feasible, metastatic lesions are excised and submitted for histological examination, or alternatively, biopsy samples are taken when the lesions are infiltrative and/ or multiple. Intraoperative radiation, if available, may 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; Hedlund and Fossum 2007b). In this author’s experience, such procedures are rarely accepted by owners due to the difficultly in managing the animal. The permanent end-on-colostomy (Hedlund and Fossum 2007b) is performed after resection of the distal colon by creating a stoma at the level of the left abdominal wall and suturing the serosa of the proximal colon to the abdominal musculature with a 3-0 monofilament absorbable suture and a full-thickness suture between the colon and skin. A colopexy is then performed adjacent to the stoma to avoid herniation, and 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 colonostomy” at the level of the left flank (Hedlund and Fossum 2007b). In this case, the descending colon is not resected but used for the colonostomy. 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

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(a)

(b)

Figure 7.33.  (See also Figure 7.24.) (A) Enlarged metastatic sublumbar lymph nodes (hypogastric lymph nodes), one of which is pointed out with the tip of a cotton swab. (B) Excision of one of these lymph nodes.

colon is then incised longitudinally and the stoma is completed by suturing the colonic seromuscular layer to the skin. A fecal storage device is then attached to the stoma and the stoma closed when it is no longer required. To achieve palliation for extensive benign colorectal tumors and as an alternative to radical and full-thickness excision, a transanal endoscopic treatment has been recently proposed based on 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 5 dogs, palliation in 3, and were poor in 5 dogs. Complications of the technique (arising usually 4–5 days after the treatment) included rectal perforation with peritonitis and death. Nonsurgical treatments Local radiotherapy has been used for small nonmetastatic rectal adenocarcinomas less than 3 cm in size and localized to the distal 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). Perforation with subsequent peritonitis was reported in a second paper (Church et al. 1987). According to the first report, tumor control and survival rates at 1 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 1–2 days of the procedure that usually resolved within 2 weeks (Turrel and Theon 1986). Perforation with subsequent peritonitis was reported in the second paper (Church et al. 1987), and no further use of this procedure has been reported. Radiation should only be recommended if the tumor can be exposed out of the body, is small-sized, and is able to be completely irradiated. However, it is this author’s opinion that surgical excision may be a faster option in many of these cases. Finally, in an experimental model using normal dogs undergoing proctectomy and stapling anastomosis, the possibility of treating colorectal recurrence with photodynamic therapy with motexafin lutetium was evaluated. The procedure is still under investigation; however, the preliminary results of this study show that the technique could be proposed as an adjuvant treatment together with chemotherapy and radiotherapy (Ross et al. 2006). Additional technical details for colorectal anastomosis The discussion below addresses all colorectal resections. For more information, see also specific sections. For manual end-to-end anastomosis trim the exuberant mucosa with Metzenbaum scissors, being sure to include all the intestinal layers in the sutures. More importantly, ensure that all the layers at least as deep as the submucosa, which is the holding layer of the suture,

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are included. Engage slightly more serosa than mucosa (Hedlund and Fossum 2007b). Surgical stapling The stapling equipment used in the large intestine surgery include thoracoabdominal (TA), gastrointestinal (GIA), and circular staplers (EEA, CEEA) (Holt and Brockman 2003; Hedlund and Fossum 2007b; Tobias 2007, Banz et al. 2008). 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 suture. A TA linear stapler may also be used for typhlectomy and, transanally, for removal of polyps of the distal rectum with a base of attachment of less than 3 cm (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 final result is an everting suture. 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 purse-string sutures secure the two intestinal ends to be anastomosed to the anvil of the EEA device. After firing, 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; Hedlund and Fossum 2007b; Tobias 2007; Banz et al. 2008) use a double approach (abdominal–transcecal, transcolonic, etc., and abdominal or transanal) (see Figure 7.26B,C). A recent paper using a porcine model 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 sygmoid, and a stapled colocolonic anastomosis (Leroy et al. 2009). Advantages of intestinal stapling procedures include decreased surgical time, good approximation of the two intestinal stumps, good hemostasis without compromising vascularization, higher bursting pressure during the early stage of healing and higher tensile strength at 7 days postsurgery compared to hand-

sutured anastomosis, minimal inflammation and necrosis, and good hemostasis. Potential complications include stricture, adhesion, dehiscence and peritonitis (caused by excessive tension, poor blood supply, or inappropriate staple size), mucosal ulcerations (more frequent than after manual anastomosis), hemorrhage, transient anal dysfunction (mainly in cats), and rectovaginal fistula (Klein et al. 2006; Tobias 2007; Banz et al. 2008). Postoperative care Care requires analgesia (opioids and nonsteroidal antiinflammatory drugs), fluid, and electrolyte therapy, according to acid-base status of the animal, until the animal eats spontaneously (usually after 2–3 days). Antibiotics are administered only when there is established infection. The animal should be monitored for disseminated intravascular coagulation (DIC) 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 3–4 times a day, with return to normal feeding after 2–3 days. Stool softeners (e.g., lactulose) should 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 may include postoperative hematochezia and dyschezia (from 1–2 days up to 1–2 weeks after surgery), and tenesmus (up to 1–2 months; see next below). The duration may depend on the amount of the colorectal resection performed. These complications are usually self-limiting. Stricture formation and tenesmus may be present. Postoperative stricture may usually be felt by digital rectal exploration. It may be caused by excessive colorectal resection, excessive inflammation 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 sphincteric continence has been preserved; see below). Sometimes the use of excessively stiff monofilament material for suturing may be the cause of a persistent colorectal inflammation and pain. If the problem persists, a colonoscopy is warranted in order to evaluate the severity of the lesion, to take a

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biopsy, and to decide if balloon dilation (bougienage) with or without a second surgery is required Infection may be present due to manipulation of the rectum with intraoperative spillage of fecal material. This should be avoided with appropriate surgical technique, the intraoperative use of antibiotics, abundant lavage and fluid aspiration, a change in surgical gloves and instruments if they become contaminated, and the use of surgical drains. Surgical drainage devices have been advocated when fecal contamination has occurred during surgery, despite the adverse effect they can have on anastomotic healing (Hedlund and Fossum 2007b); 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 of the colon and rectum and prefers to pay particular attention to minimizing intraoperative contamination combined with adequate preoperative patient preparation. 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. In selected cases, such as when there is a substantial amount of fecal material demonstrated 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. Postoperative dehiscence and infection may occur. The most common time for postoperative dehiscence is 3–5 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, 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). Fecal incontinence may also occur. The pathogenesis of fecal incontinence after 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 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 distal rectum preserved after

rectal resection and sparing of the rectal cranial peritoneal reflection (Anderson et al. 1987; Anson et al. 1988; Swenson and Bill 1948; Gaston 1948a, 1948b, Gaston 1961; Karlan et al. 1959). A minimum of 1–1.5 cm of distal 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 excisional margins is guaranteed. In one recent study using a transanal approach in dogs, the distal 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 5 months postoperatively for no identifiable reason (Morello et al. 2008). With the rectal pull-through procedure or when the distal rectal resection is at the level of the rectocutaneous junction, fecal incontinence remains a risk due to a combination of the distal 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 (Figure 7.34; see also 7.30 ). Fecal incontinence has also been associated with amputations involving more than 6 cm of rectum in combination with transection of the caudal peritoneal reflection (Anderson et al. 1987). In a recent paper, colorectal amputation of greater than 6 cm in length always included the peritoneal reflection; however, permanent fecal incontinence was not observed (Morello et al. 2008). Similar results also have been reported after anastomosis of the colon to the distal 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 distal part should have little influence on the fecal reservoir continence that may be lost after more extensive colonic resections make it impossible to store feces (Dean and Bojrab 1993; Gaston 1948a, 1948b, 1951, 1961; Karlan et al. 1959; Peck and Hallenbeck 1964). Clinical signs of fecal reservoir incontinence include more frequent conscious defecation (Guilford 1990). In general, this author believes that, provided the distal rectum has been spared, transient loss of fecal continence is generally associated with complications of wound healing, including inflammation/ colitis with diarrhea and stricture with tenesmus, particularly in small dogs that seem more prone to develop such problems. In small dogs, therefore, the aggressive colorectal surgical procedures should either be avoided or clearly discussed with owners when a “salvage” procedure is warranted. A short- to long-term follow-up is needed to thoroughly assess changes in continence (Sapin et al. 2006; Morello et al. 2008). In this author’s opinion, the key factors to increasing the probability of

242  Veterinary Surgical Oncology

(a)

(b)

Figure 7.34.  In this case the pull-through procedure was performed for an inflammatory disease. The last 1 cm of rectum was not spared (A). (B) The final result. This dog was permanently incontinent. Another dog with a similar surgery regained clinical fecal continence after 5 months for unknown reasons.

maintaining fecal continence include sparing the distal rectum, appropriate proper surgical technique and choice of suture material, absence of infection, avoidance of tension at the anastomotic site, and careful preservation of blood supply. The veterinary literature has not fully addressed the effect on fecal continence of anastomosis between the distal ileum and the distal 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). 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. Extent of resection There is apparently no limit to resectioning the large intestine beyond the caudal peritoneal reflection. Care is taken to ligate only those vessels that are definitively required to be ligated to maximize the preservation of blood supply to the remaining segment of bowel. The final goal should always be to achieve a tension-free endto-end anastomosis to avoid complications, including dehiscence, sepsis, and stricture formation. The combined procedures (the so-called Swenson’s pull-through and modifications 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 adequate excisional margins (Morello et al. 2008). In these cases, pubic/ ischial osteotomy may be an excellent 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, given that even a transient vascular insufficiency may result in healing and clinical complications of varying severity. Posttreatment prognosis Dogs Intestinal tumors account for less than 10% of all tumors (Selting 2007). The large intestine is more frequently affected and represents 36%–60% of all canine intestinal neoplasia. Colorectal tumors are more prevalent in male dogs (Holt and Lucke 1985; Birchard et al. 1986; Church et al. 1987; Patnaik et al. 1976). The reported mean age is around 7–8 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; Church et al. 1987; Patnaik et al. 1978). 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); plas-

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macytomas (Kupanoff et al. 2006; Rannou et al. 2009); and carcinoids (Patnaik et al. 1980; Sykes and Cooper 1982; Selting 2007). 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 and progress to malignancy (Morello et al. 2008). In most clinical situations, these lesions are often first marginally resected (with excisonal biopsy; see the discussion on simple excision above), and if the histopathology identifies an adenomatous polyp, periodical monitoring is warranted. If there is recurrence of the mass, a more radical surgery is indicated when a biopsy confirms malignant progression (Morello et al. 2008). It should be remembered, however, that endoscopic biopsies may be too superficial and fail to demonstrate malignant progression such as a carcinoma in situ. For this reason a resection margin of a minimum of 2 cm (see also discussion on adenocarcinoma) is recommended for excision of both polyps and carcinoma in situ previously excised marginally if recurrence occurs (Morello et al. 2008). Canine adenocarcinoma is described as nodular (single or multiple), pedunculated, or annularconstrictive (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 reported metastatic rate for rectal adenocarcinoma ranges from 0% to 80% (Patnaik et al. 1980; Church et al. 1987). The reported mean survival time for malignant colorectal carcinomas varies from 6 to 14 months (White and Gorman 1987; Williams and Niles 2005), to 22 months after surgical resection, and 24 months after cryosurgery (Church et al. 1987). 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; Aronson 2003; Williams

and Niles 2005; Danova et al. 2006). A modified TNM system for canine colorectal adenocarcinoma has been reported (Turrel and Theon 1986), and a further modification of this TNM system, with respect to the T grading, has been recently proposed by Morello et al. (2008). The newer scheme include 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 modification has been tentatively correlated to margins of resection and survival: 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. Median disease-free interval and survival times were not reached. Mean disease-free and overall survival times were 44.3 and 44.6 months (range, 0–75 months), respectively. Applying the modified 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 degree of excision is not always feasible. A recent paper 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 recent 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. 2010). 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 2 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 7.35A,B). Rarely, leiomyosarcoma may be associated with paraneoplastic hypoglycemia (Bagley et al. 1996). Leiomyosarcomas (see Figures 7.21 and 7.22A) are invasive but slow to metastasize. They may occur both in the small

244  Veterinary Surgical Oncology

(a)

(b)

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.

and large intestine (most commonly in the cecum). Gastrointestinal stromal tumors (GISTs) have been reported in dogs and are differentiated from leiomyoma and leiomyosarcoma only after immunohistochemistry (LaRock and Ginn 1997; Frost et al. 2003; Selting 2007; Maas et al. 2007). Histological malignancy in dogs is more often observed in cecal GISTs; in these cases, perforation and peritonitis are also more frequent (Maas et al. 2007). In humans, GISTs are the most common mesenchymal tumor of the gastrointestinal tract, and their origin from the interstitial cell of Cajal and distinctiveness from smooth muscle tumors have been recently documented. At present, their treatment is based on surgery (when feasible) and specific inhibitors of KIT tyrosine kinase function (e.g., imatinib mesylate) due to a positive immunohistochemical staining for KIT protooncogene mutations. These inhibitors may be used either as adjuvant treatment or palliation for unresectable and metastatic tumors (Gold and Dematteo 2006). The same positive immunohistochemical staining for KIT proto-oncogene mutations in dogs (Frost et al. 2003; Maas et al. 2007) should justify, in selected cases, the use of such KIT tyrosine kinase inhibitors in this species. Surgical margins for leiomyosarcoma and GIST carry the same rules as those applied to adenocarcinoma; however, leiomyoma may be resected marginally. 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 1- and 2-year 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 a recent publication, the 1and 2-year recurrence-free periods 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 a monoclonal gammopathy (Trevor et al. 1993). They are characterized by slow growth and lack of recurrence after complete excision (Kupanoff et al. 2006). Whereas the definitive margin of resection is not known, a 1–2 cm margin of macroscopically healthy tissue is generally recommended to surround the tumor. Carcinoids are rarely reported and may metastasize (Sykes and Cooper 1982; Patnaik et al. 1980; Selting 2007). 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). 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 2007). The reported mean age is 12.5 years, and a predisposition has been reported in Siamese cats. The most prevalent neoplasms include adenocarcinoma, lymphoma (many of

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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). Hemangiosarcomas have 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 of any metastatic lesion. Prognosis is poor, as all the four cats presented in one paper died or were euthanased within 1 week (Sharpe et al. 2000). 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 may increase survival times (Slawienski et al. 1997). Large intestinal mast cell tumors are rare in cats. 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). Feline large intestinal lymphoma may be metastatic 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 be indicated when the lesion is isolated. 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) in­­ hibitors (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). Adjuvant doxorubicin for feline colonic adenocarcinoma may lead to a median survival time that is longer (280 days; range, 210–354) in comparison with cats that did not receive doxorubicin (56 days; range, 2–259) (Slawienski et al. 1997). Chemotherapy (doxorubicin or mitoxantrone) and radiotherapy have been suggested for both canine leiomyosarcoma and adenocarcinoma, but their efficacy 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. The use of specific inhibitors of KIT tyrosine kinase function can be considered in cases of inoperable and/or metastatic GISTs, which are positive to KIT proto-oncogene mutations.

Perianal Tumors Surgical procedures Surgical procedures for perianal tumors include castration only, cytoreduction or marginal excision of perianal hepatoid adenoma 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 modified sebaceous glands that are called hepatoid due to their resemblance to liver cells on cytology and histology. They are usually visible and palpable (Figures 7.36 and 7.37), and in the case of malignancy, circumferential growth can result in palpable stenosis (Figure 7.38). Stricture in this area, however, is not pathognomonic for neoplasia as it may occur secondary to trauma and inflammatory diseases such as perianal fistulas (particularly in German shepherd dogs) and infection. Anal stricture can also be idiopathic as a result of anorectal spastic contraction. The latter 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 visible and can be palpated during rectal examination at the 4 o’clock and 8 o’clock positions (Figure 7.39), commonly as an incidental finding (Williams et al. 2003). This maneuver may facilitate performing a fine-needle aspiration biopsy (FNAB). During digital rectal examination, it is also important to gain information on the degree of fixation of the tumor to the surrounding tissues. Finally, it may be useful to detect any so-called sublumbar lymphadenomegaly (see also the discussion on “colorectal tumors”).

246  Veterinary Surgical Oncology

(a)

(b)

(c)

Figure 7.36.  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.

(a)

(b)

Figure 7.37.  (A, B) Two different presentations of canine perianal adenocarcinoma. (B) Adenocarcinoma metastatic to the sublumbar lymph nodes.

This includes the sacral (these do not actually drain the perianal region and are present in only 50% of dogs), hypogastric, and medial iliac lymph nodes (Bezuidenhout 1993). Complete laboratory workup (blood, urine). Possible changes observed include hypercalcemia, in 25%–50% and up to 90% of cases with anal sac adenocarcinoma and 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). Secondary hypophosphatemia and increases in renal parameters can be seen after prolonged hypercalcemia. In anal sac adenocarcinoma, hypercalcemia is caused by a parathyroid hormone-related protein (PTHrp) produced by the tumor (Rosol et al. 1990; Gröne et al. 1994); in perianal adenocarcinoma, the cause of hypercalcemia is uncertain and the author has not observed this finding in any clinical cases.

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Figure 7.38.  Hepatoid perianal adenocarcinoma in an 11-yearold male German shepherd causing anal stenosis.

Figure 7.40.  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 7th lumbar vertebra show some productive changes. (Thanks to Dr. Sheldon Padgett for this picture).

adenocarcinoma). The clinical differentiation between hepatoid adenoma and adenocarcinoma (as well as perianal fistulas) may also be difficult. For this reason, biopsy is mandatory. Indeed, diagnostic information is often provided by cytology for other tumor types found in this region.

• FNAB from enlarged sublumbar lymph nodes can be

aspirated during a digital rectal exploration (see also section on colorectal tumors; see also Figure 7.20) or via transabdominal ultrasonographic-guided aspiration (Llabrés-Diaz 2004) Biopsy samples from perianal tumors can be obtained • by using a Tru-cut 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. Imaging techniques Figure 7.39.  Right anal sac adenocarcinoma in a dog.

Cardiologic examination. This examination is particularly important in hypercalcemic dogs Tumor biopsy. FNAB and cytological examination can confirm the hepatoid nature of the tumor without, in many cases, giving an exact diagnosis (adenoma vs.

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 7.40). In selected cases, urethrocystography may be useful to outline urethral compression by an exceedingly large metastatic sublumbar lymph node (Hoelzler et al. 2001).

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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. During the procedure, transabdominal ultrasound guided FNAB (using a 22- or 20-gauge spinal needle) or biopsy (using a 18-gauge Tru-Cut biopsy needle) may be performed. Interestingly, even though not demonstrated histologically, all sublumbar lymph nodes greater that 1 cm have shown neoplastic progression in one report (Polton and Brearley 2007). The finding of large vessel infiltration 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 are more commonly seen with anal sac adenocarcinoma and malignancies other than those of hepatoid origin (Figure 7.41). A case of lung metastases caused by an anal sac adenocarcinoma associated with paraneoplastic hypertrophic osteopathy in a dog has been recently reported (Hammond et al. 2009). 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. CT can be used to assess the lungs, presence of lymphadenomegaly, and abdominal organs. In the case of sublumbar lymph node involvement, CT provides valuable information regarding tumoral involvement of great vessels and surgical resectability of nodes (Figures 7.42 and 7.43). Bone scintigraphy may be used in selected cases of anal sac adenocarcinoma to assess for bone metastases. Surgical techniques and procedures

Figure 7.41.  Multiple lung metastases from an anal sac adenocarcinoma in a dog. Metastasis is also present in a humerus.

(a)

Surgery of the perianal region may be performed traditionally, with a CO2 laser, or only for small lesions using cryosurgery (Dow et al. 1988; Liska and Withrow 1978; 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 2007); testicles and lymph nodes that are excised are also submitted for histology. Gloves

(b)

Figure 7.42.  (A) CT scan of a large sublumbar lymph node that caused a significant 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).

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(a)

(b)

(c)

Figure 7.43.  (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.

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.

and Hayes 1979). It should also be noted that a testicular interstitial cell tumor may be present in combination with a perineal hernia.

Castration

En bloc excision with or without anoplasty

Castration may be the sole procedure required in intact males for small, nonulcerated, and histologically confirmed 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 2 months, marginal or en bloc excision with or without castration, depending on the histological result).

A minimum of 1–3 cm of macroscopically normal tissue should be included around the tumor, depending on the tumor type; reconstruction often requires suturing the rectum to the skin (Figure 7.46). 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 (Figure 7.47), part or all of the anal canal up to the distal rectum (pull-through), and in some instances amputation of the tail (Figure 7.48). The reconstruction may warrant the use of local skin advancement or transposition flaps (Figure 7.49). 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 approximates the submucosa/ mucosa to the skin (using 3-0 or 4-0 absorbable braided, e.g., polyglactin 910, or monofilament material); in the two-layer suture pattern, absorbable monofilament material (3-0 or 4-0 polydioxanone, polyglyconate, poliglecaprone 25) is used for the first layer (adventitiamuscularis of the rectum/subcutaneous tissue), and in the second layer the epithelial lining (skin/rectal submucosa-mucosa or skin/skin depending on the

Cytoreduction or marginal excision This technique is used for histologically confirmed hepatoid adenoma (perianal and/or tail gland) together with castration in intact males (Figures 7.44 and 7.45). In females, marginal excision of perianal adenoma, usually of small size, may be sufficient. In this author’s opinion, the use of either a braided or monofilament 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

250  Veterinary Surgical Oncology

(a)

(c)

(b)

(d)

Figure 7.44.  (A–D) Marginal excision of a large perianal adenoma. (Photos from Buracco P. 2007. Tumori perianali. 2007. In Oncologia del cane e del gatto G. Romanelli, editor. London: Elsevier. Used by permission.).

excision performed) can be approximated with both 3-0 or 4-0 absorbable braided (e.g., polyglactin 910) or monofilament material. The sutures must be applied with as minimal tension as possible (Aronson 2003). This author generally uses a single-layer closure and reserves the two-layer closure for cases with excessive tension. Anal sac removal If hypercalcemia is present, this should be treated before surgery using parenteral fluid therapy, 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 rare cases (Ross et al. 1991; Emms

2005; Turek and Withrow 2007). As fecal continence is a concern, marginal excision may be the preferred choice in the case of bilateral anal sac tumors (Emms 2005). Prolonged survival can be achieved even when concurrent excision of metastatic regional lymph nodes is performed (Hobson et al. 2006; Polton et al. 2007). Anal sac adenocarcinoma occurs rarely in cats (Chun et al. 1997; Mellanby et al. 2002; Parry 2006) and excision is performed in a similar manner to anal sac tumors in dogs (Figures 7.50 and 7.51). Anal sac adenocarcinoma may also develop at the level of the controlateral anal sac some time subsequent to the removal of an anal sac tumor on one side (Turek and Withrow 2007; Emms 2005). Excision is often performed marginally, but en bloc excision (see previous section) is attempted in all the cases where this is

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(a)

(b)

Figure 7.45.  (A) Multiple perianal adenomas. (B) postoperative view after marginal excision.

(a)

(b)

Figure 7.46.  Phases of anoplasty. (A) The anal region has 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.

possible and is usually dependent on the size of the primary tumor. Resection of metastases Resection of metastases refers mainly to the sublumbar lymphadenectomy through a midline celiotomy and is performed principally in cases of anal sac adenocarci-

noma (Hobson et al. 2006; Polton and Brearley 2007), but 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) (Figure 7.52).

252  Veterinary Surgical Oncology

(a)

(b)

(c)

Figure 7.47.  Phases of the excision of a 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 flaps was not required in this case). The dog experienced transitory fecal incontinence.

(a)

(b)

Figure 7.48.  (A) The clinical presentation of a recurrent perianal adenocarcinoma. (B) To achieve sufficient margins of macroscopically normal tissue, the tail was amputated. For reconstruction, the dorsal skin of the tail was spared and used as a skin flap.

Identification 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 identified between the deep circumflex and external iliac arteries at the level of the fifth and sixth lumbar vertebrae (Figure 7.53), and

the hypogastric lymph nodes are identified between and in close association with the external and internal iliac arteries ventral to the sixth and seventh lumbar vertebrae (Bezuidenhout 1993) (see also Figures 7.33 and 7.54). Lymph node removal is performed with careful undermining and dissection and in some cases firm

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Postoperative care

adhesion of the nodes to either the sublumbar musculature or a vessel wall makes excision very risky due to hemorrhage (Ross et al. 1991) or even be impossible (see Figure 7.42). 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, spleen, and lung is occasionally performed for these tumors.

Systemic analgesics are recommended for 12–72 hours and food and water given within 8–12 hours, depending on the surgical procedure performed. An Elizabethan collar is recommended to prevent self-trauma, and ionized calcium levels should be monitored once a day during the first 48 hours when preoperative hypercalcemia has been documented. Normalization of ionized calcium levels usually occurs within 24 hours when adequate resection has been performed. In the case of anoplasty, the perianal region should be lubricated with petrolatum until the sutures are removed. 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 Hypocalcemia, while rare (Williams et al. 2003), is treated with 10% calcium gluconate intravenously with monitoring of cardiac rhythm during administration (Hedlund and Fossum 2007a). Hematochezia can be seen for 8–48 hours or longer, depending on the surgical procedure performed. This complication is usually self-limiting. Transient tenesmus is usually self-limiting within 1–5 days, depending on the surgical procedure performed. It may be associated with poor pain control. Dehiscence may occur when an anoplasty is performed with excessive tension or infection is present secondary to the manipulation of the rectum and anus.

Figure 7.49.  Advancement flap in a rectocutaneous plasty. These flaps 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.

(a)

(b)

Figure 7.50.  (A) marginal excision of an anal sac adenocarcinoma in a dog. (B) Macroscopic appearance of the tumor.

254  Veterinary Surgical Oncology

(a)

(d)

(b)

(c)

(e)

(f)

Figure 7.51.  Clinical (A) and CT view (B) of a large anal sac adenocarcinoma in an 11-year-old spayed bitch that was hypercalcemic at presentation. (C,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.

If possible, the wound should be resutured to avoid stricture, otherwise second-intention healing can be used, which necessitates frequent wound management, including warm hydrotherapy two to four times per day (Figures 7.55 and 7.56). Skin flap dehiscence is more likely if one border of the flap is adjacent to the to the base of the tail, as tail movement retards flap healing (see Figure 7.49). 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). Stenosis and strictures occur mainly after anorectal surgery, including in many cases also anal sac removal.

Figure 7.52.  Macroscopic view of several sublumbar lymph nodes after excision. One of these was removed piecemeal. Removal of all nodes (together with the primary tumor) is essential if the dog is hypercalcemic in order to normalize calcemia.

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Figure 7.53.  Intraoperative appearance of the excision of an enlarged medial iliac node in a dog with anal sac adenocarcinoma. (Photos from Buracco P. 2007. Tumori colorettali. 2007. In Oncologia del cane e del gatto G. Romanelli, editor. London: Elsevier. Used by permission.).

(a)

Figure 7.54:  Region of the hypogastric lymph nodes after excision.

(b)

Figure 7.55.  (A) This male German shepherd dog experienced dehiscence of the closure. (B) The wound was not sutured and was managed conservatively for 2 weeks.

Anal stricture may be the result of a poor epithelial apposition during surgery or excessive tension and infection with further dehiscence followed by a secondintention healing. It results in protracted tenesmus. Treatment options include bougienage, a simple incision, or a wedge resection. If the problem persists, en bloc excision should be performed Fecal incontinence can occur following anoplasty (Ross et al. 1991). If only half of the circumference of the sphincter is removed, incontinence may be transient

(see Figure 7.47B) (Turek and Withrow 2007). If resection involves a complete 360-degree circumference (Figure 7.57; see also Figures 7.46, 7.49, 7.55, 7.56), fecal incontinence is likely and should be discussed with the owner before surgery. Provided that tissue undermining is performed as close as possible to the anorectal wall, continence may be partially preserved (Figure 7.58), especially if a solid stool consistency is maintained with a low-residue diet.

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(a)

(b)

Figure 7.56.  (A) Anoplasty, (B) following dehiscence healing, has occurred via second-intention healing.

Figure 7.57.  Incontinent dog 2 years after surgery (compare to Figure 7.46).

This may be acceptable for many owners but this clinical result is difficult 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

Figure 7.58.  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.

of these structures are anatomically connected to some extent with the external sphincter muscle. 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

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(a)

(b)

Figure 7.59.  (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.

male dog suggests possible malignancy, and further diagnostic investigation is warranted (Turek and Withrow 2007). Recurrences are likely in cases of incompletely excised perianal and anal sac adenocarcinoma. As noted previously, a second anal sac adenocarcinoma may rarely develop at the level of the contralateral sac subsequent to the removal of an anal sac adenocarcinoma on one side (Emms 2005; Turek and Withrow 2007). Additional metastases are more likely in anal sac adenocarcinoma and occur less frequently with perianal adenocarcinoma. With malignant perianal tumors, clinical, laboratory, and diagnostic imaging evaluations are recommended every 3 months during the first year following surgery and every year thereafter. In cases of anal sac adenocarcinoma, disease progression may be in form of local recurrence and/or further metastasis and hypercalcemia. Common perianal tumors and prognosis This discussion refers only to dogs, as cats have only anal sacs and not perianal hepatoid glands. Most tumors originate from the modified sebaceous hepatoid glands located in the perianal or circumanal region (see Figures 7.36, 7.37, 7.38), tail (Figure 7.59), prepuce, 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 odor-producing glands via proteins that may act as an olfactory marker (Shabadash and Zelikina 1995; Martins et al. 2008). Immunohistochemistry for growth hormone was found to be positive in 23 of 24 canine perianal adenomas and in 5 of 5 perianal adenocarcinomas (Petterino et al. 2004). 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 2007). 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 7.60). Hyperadrenocorticism can be a concurrent finding in female dogs, and the adrenal gland is the source of androgenic stimulation (Dow et al. 1988; Hill et al. 2005). The vast majority of perianal adenomas are welldifferentiated tumors, with only about one quarter being moderately or poorly differentiated neoplasms (Berrocal et al. 1989; Vail et al. 1990; Turek and Withrow 2007). More recently, in a review of 240 perianal tumors (Martins et al. 2008), the Goldschmidt et al. (1998) histological classification was applied and compared to the older classification produced by Berrocal et al (1989):

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Perianal adenocarcinoma

Figure 7.60.  Perianal adenoma in a spayed bitch. This followed a similar excision 9 months previously for the same lesion.

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 classification adopted, gland differentiation (that also implies the presence of androgenic receptors on the surface of cells) is associated with both hormone-dependence and favorable prognosis after surgery. Martins et al (2008) suggest that immunohistochemistry for PCNA (proliferating cell nuclear antigen) 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. Another recent paper has proposed a differentiation between hepatoid adenoma versus carcinoma based on the use of mouse monoclonal antibodies (Ganguly and Wolfe 2006). Marginal excision and castration is the treatment of choice for perianal adenomas (Turek and Withrow 2007), and recurrence is rare, particularly in male dogs (Wilson and Hayes 1979).

These tumors are relatively slow growing, locally invasive, and often have a protracted clinical history that may include multiple previous excisions. The tumor metastasizes to the sublumbar lymph nodes in 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 occasionally seen, and the etiology is unknown at present. 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 first option for this tumor. The only prognostic factor identified 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, superficial or proliferative) and T2N0M0 (T2 = tumor of 2–5 cm or, with minimal invasion independent of size) had a 2-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 median survival of 6–12.5 months (Vail et al. 1990). The reported median survival time in dogs with confirmed metastasis (15% of cases at pre­ sentation) was 7 months (Vail et al. 1990). Recently, the evaluation of computer-assisted nuclear cytological morphometric parameters has been proposed and 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. Significant 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). Anal sac adenocarcinoma These neoplasms are less common than perianal hepatoid tumors and generally affect elderly dogs; dogs as young as 5 years, however, have also been reported (White and Gorman 1987; Ross et al. 1991; Williams et al. 2003; Turek and Withrow 2007). At present, no

Alimentary Tract  259

Figure 7.61.  Ventral vertebral changes caused by an adjacent metastatic sublumbar lymphadenomegaly originating from an anal sac adenocarcinoma in a dog. (Image courtesy of Dr. Sarah Boston)

Figure 7.62.  Humeral metastasis secondary to an anal sac adenocarcinoma in a 9-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.

gender predisposition has been documented (Ross et al. 1991; Straw et al. 1994; Bennett et al. 2002; Williams et al. 2003; Polten et al. 2006; Polton and Brearley 2007). The mean relative risk estimate associated with being neutered was 1.4 in one study, and the effect of neutering appeared to be more significant in male dogs compared to female dogs (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). Specific 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 46%–96% of dogs, with the main sites including regional lymph nodes (sublumbar and only rarely inguinal), lungs, liver, spleen, other abdominal organs, and the skeleton, including lumbar vertebrae (Goldschmidt and Zoltowski 1981; Ross et al. 1991; Bennett et al. 2002; Turek et al. 2003; Williams et al. 2003; Brisson et al. 2004; Turek and Withrow 2007; Hammond et al. 2009) (Figure 7.61; see also Figures 7.40 and 7.41).

In rare cases, lung or bone metastasis may develop without evidence of regional lymphadenopathy (Turek and Withrow 2007) (Figure 7.62). Hypercalcemia is present in 25%–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). When present, hypercalcemia caused by the PTH-like compound produced by the tumor (Rosol et al. 1990; Gröne et al. 1994) can be used as a marker for both metastasis and recurrent lesions. The primary tumor rarely involves both anal sacs 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). This tumor is not commonly reported in cats (Chun et al. 1997; Mellanby et al. 2002; Parry 2006). Surgery plays a fundamental role in the treatment of these tumors, independent of any adjuvant therapeutic modality (Williams et al. 2003). When feasible, an aggressive resection should be performed; however, only marginal excision is achieved in most cases (see Figures 7.50 and 7.51). After surgical excision, survival has been reported to be about 1 year, 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

260  Veterinary Surgical Oncology

et al. 2006). Concurrent excision of regional metastatic lymph nodes usually results in increased survival times (Hobson et al. 2006; Polton and Brearley 2007). 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) is unclear (Ross et al. 1991; Bennett et al. 2002; Turek et al. 2003; Williams et al. 2003), unless secondary renal failure has already occurred. Additionally, the prognostic significance of regional metastatic lymphadenopathy is unclear since it will likely develop, 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). Lung metastasis and primary tumors greater than 10 cm in size are associated with a decreased survival (Williams et al. 2003). Death is usually the consequence of recurrence and metastasis; the latter develops in almost all the patients after a variable amount of time. TNM clinical staging is the same as that used for skin tumors. One prognostic parameter for survival is the diameter of the primary tumor (improved survival with tumor size 10 cm or smaller) (Williams et al. 2003). A modified and more simplified clinical staging system that correlates with survival time has been proposed recently (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 sizes of the primary tumor are 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 significant 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 3 months) was documented in dogs with stage 4 disease. Despite the fact that chemotherapy did not influence outcome, the authors of this report still recommended its use in stage 3b lesions. Other perianal tumors Squamous cell carcinoma is a rare tumor that may develop from the anal sac (Esplin et al. 2003), anal canal, and perianal skin (Figure 7.63). These tumors demonstrate malignant behavior, both in terms of local infiltration and regional and systemic spread.

Figure 7.63.  Squamous cell carcinoma of the anal region in an 11-year old male German shepherd.

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; Young et al. 2005). Its behavior is unknown, but it is likely to be highly malignant, as are its more typical oral counterparts (Kim et al. 2005). One report has dealt with a transient local palliation by electrochemotherapy with cisplatin in a dog (Spugnini, Filipponi, et al. 2007). Lymphoma (Figure 7.64), mast cell tumors, benign tumors (lipoma, leiomyoma, hemangioma; Figure 7.65), and soft tissue sarcomas (see Figure 7.47) are also seen in the perianal region (Ueno et al. 2002; Brønden 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), radiation, and hyperthermia (Grier et al. 1980; Gillette 1970). The excellent results achieved with surgical treatment render these procedures unattractive (Turek and Withrow 2007). A potential treatment is the use of drugs for chemical castration (Turek and Withrow 2007). For perianal adenocarcinoma, radiation may be an option. 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).

Alimentary Tract  261

Figure 7.64.  Lymphoma of the anal region in a 7-year-old female mongrel dog.

Figure 7.65.  Large hemangioma located between the anus and the tail base in a 5-year-old male Leonberger.

There is, however, only scant information regarding outcome 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). Finally, perianal adenoma and adenocarcinoma have also been treated with chemotherapy using bleomycin or cisplatin combined with electroporation (Tozon et al. 2005; Spugnini, Dotsinsky, et al. 2007). For anal sac adenocarcinoma, reported chemotherapeutic agents include cisplatin, carboplatin, doxorubicin with or without cyclophosphamide, mitoxantrone, epirubicin, melphalan, actinomycin D, mithramycin, chlorambucil, vincristine, L-asparaginase, gemcitabine, and piroxicam (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). 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). Mitoxantrone administration associated with radiotherapy has a reported overall median survival time 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 as the clinical behavior of this tumor is expected to be similar to that of dogs. With regard to radiotherapy, given that the surgical removal of anal sac adenocarcinoma is often marginal, 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 2007) may be justified. 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 1 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), as both a neoadjuvant and adjuvant treatment, or as a salvage procedure in inoperable cases, has been also used (Polton and Brearley 2007). Finally, electrochemotherapy with cisplatin has been proposed in a dog as an adjuvant treatment for an

262  Veterinary Surgical Oncology

incompletely excised anal sac adenocarcinoma (Spugnini et al. 2008).

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8 Respiratory tract and thorax Marina Martano, Sarah Boston, Emanuela Morello, Stephen J. Withrow

Rhinotomy 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 findings with imaging and biopsy results. The most frequent clinical sign is unilateral epistaxis; 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. Symptoms may be present for approximately 1–6 months prior to diagnosis. Clinical suspicion is confirmed by biopsy, which can also rule out other nasal diseases, such as fungal or bacterial infections, nasal foreign bodies, parasites, or systemic diseases (ehrlichiosis, leishmaniasis, coagulopathies, etc.). In cats, nasopharyngeal polyps should also be considered. Blood testing, while usually unremarkable, is necessary to evaluate the overall condition of the patient, and a coagulation profile is always recommended to evaluate the risk of hemorrhage from biopsy procedures or rhinotomy. Biopsy specimens can be obtained either blindly or with endoscopic guidance. With the latter, a rigid endoscope is introduced through the nares and, after the procedure has been completed, a small biopsy sample is withdrawn with forceps. With this procedure, a falsenegative result (i.e., inflammatory rhinitis) may be

obtained because of inadequate and/or superficial 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 occluded with gauze sponges to avoid inhalation 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 identified 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 selflimiting. In cases of copious bleeding, the nasal cavity can be filled with a gauze sponge soaked in diluted epinephrine (1:100,000); alternatively, oxymetazoline 0.05% can be used. The withdrawn material is evacuated from the tube by using the syringe filled 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.

Veterinary Surgical Oncology, First Edition. Edited by Simon T. Kudnig, Bernard Séguin. © 2012 by John Wiley & Sons, Ltd. Published 2012 by John Wiley & Sons, Ltd.

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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 profile is disfigured to this degree only late in the course of the disease.

(a)

(b)

(c)

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.

The same procedure can be performed with a small curette introduced via the nostril, especially in small dogs and cats; the material is scooped out and the nasal cavity flushed 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). Brush cytology is diagnostic only in 50% of cases and is not usually recommended. Imaging techniques Each imaging technique should be performed before the biopsy is taken, as the blood and exudates can create artifacts that are difficult to interpret.

Survey radiographs of the skull can aid in the diagnosis, since 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 inflammatory diseases can have a

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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).

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(b)

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Figure 8.4.  Contrast-enhanced CT imaging of the nasal cavity. (A) Some hyperdense material referable to neoplastic infiltrate (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.

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 outflow of mucous secretion (“frontal mucocele”) and not to the tumor itself. Three-view thoracic radiographs complete tumor staging. Survey or contrast-enhanced computed tomography (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) (Thrall et al. 1989). They are also necessary for precise 3D planning of radiation therapy. Rhinoscopy is performed after the radiographs are taken. This technique allows direct visualization of the nasal cavities and is usually performed both with a rostral and caudal approach. The caudal approach is generally performed first, with a flexible 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. Rostral rhinoscopy is performed using a rigid scope introduced from the nostril, and it provides a view of

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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. (Image courtesy of Dr. Roberta Caccamo)

the nasal meatus, ventral concha, alar cartilage, and the ventral and common nasal passages (Figure 8.5A, 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. 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 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 both procedures, after the animal is anesthetized and intubated, the pharynx is packed with sponge gauzes to avoid inhalation of blood or secretions during surgery. At the time of extubation, the tracheal tube is extracted with the cuff slightly inflated to facilitate the removal of accumulated blood or secretions. Dorsal rhinotomy The dorasal 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 nasal 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 (Figure 8.6A). This latter is then elevated and reflected laterally on both sides of the

incision to expose the underlying bone. A unilateral or bilateral bone flap is then created using an osteotome or an oscillating saw (Figure 8.6B) and reflected rostrally (Figure 8.6C), 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. Once the nasal cavity is exposed, it is flushed 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, this is performed with scissors or a curette. If the surgery has curative intent, the turbinates of one or both sides, depending on tumor extension and as previously evaluated by the imaging studies, are removed (Figure 8.6D). The frontal sinuses are inspected, mucous secretions are eliminated, and tumor debulking is also completed in this area if necessary. Bleeding can be copious, but can be controlled by flushing with ice-cold saline, applying digital pressure with gauzes soaked in diluted epinephrine (1:100,000), 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, should be avoided in cats. The nasal cavity is flushed and suctioned before closure to eliminate the majority of blood clots and reduce obstruction during the postoperative period. The bone flap can be repositioned, if not invaded by the tumor, or discarded (particularly if adjuvant orthovoltage radiation will follow). If preserved, the flap is sutured in place with nonabsorbable monofilament sutures prepositioned in three to four holes drilled on the sides of the bone and tied after the flap is in place. Metal wires should not be used if follow-up radiotherapy is planned. If the bone is discarded, the soft tissues are

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Figure 8.6.  Dorsal rhinotomy. (A) After a midline incision, the skin and subcutaneous tissues are reflected laterally and the nasal bone exposed. (B) A bone flap is created using a high speed burr or an oscillating saw. (C) The bone flap is elevated with an osteotome and discarded (or kept moist in sterile gauze sponges). (D) The nasal cavity is inspected and the turbinates removed. The cavity is then washed with cold sterile saline solution. (E) The subcutaneous tissues and skin are closed using the standard technique.

closed with absorbable monofilament sutures in a simple continuous pattern (Figure 8.6E). The skin is sutured routinely. To avoid subcutaneous emphysema, which always occurs if the bone flap 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. The gap will naturally close within a few days. Packing the nasal cavities with sponges can help to control severe hemorrhage, but it obstructs nasal air-flow, 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 has 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

fistula 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. A midline mucoperiosteal incision is made from the canine tooth to the level of the fourth premolar. The palate periosteum is undermined and elevated laterally (Figures 8.7A, 8.8A). Alternatively, the incision can be U-shaped, parallel to the dental arcade, with the U open caudally; the mucoperiosteal flap is then reflected 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

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Figure 8.7.  Ventral rhinotomy in a dog. (A) A midline incision is made through the mucoperiosteal tissues of the hard palate with two shorter perpendicular incisions made at the extremities of the first incision. (B) The tissues are elevated and kept retracted with four stay sutures. A flap 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. (C) After lavage of the nasal cavity with cold sterile saline, the soft tissues are closed in one or two layers with simple interrupted absorbable sutures. This is the same dog as in Figure 8.5B.

rostrally, midway between the midline and the dental arcade. A rectangular bone flap is created with a bone saw, air drill, or osteotome (Figure 8.8B) and discarded. Hemorrhage is controlled as previously described, but electrocautery is avoided if possible. Once the nasal cavities are entered, the gross tumor is removed with a curette (Figures 8.7B, 8.8C), or a biopsy is taken as described for the dorsal approach. The nasal cavity is then flushed with cool sterile saline solution. The mucoperiosteal tissue is closed in a one- or twolayer pattern with simple interrupted sutures using 3-0 to 5-0 monofilament absorbable material (Figures 8.7C, 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 incisional margins are kept open with stay sutures, and the exploration performed. The soft palate defect is closed in two or three layers with simple interrupted or continuous absorbable monofilament sutures. The hard palate is closed as previously described. The end of the soft palate is then reflected rostrally and the nasopharynx flushed with saline and aspirated to remove clots. Temporary carotid artery occlusion Temporary carotid artery occusion 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 as 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 continued. 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 field 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.

Figure 8.8.  Ventral rhinotomy in a cat. The procedure is similar to that described in the dog. The bone flap can be created either with an osteotome or an oscillating saw.

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 con the Rumel tourniquet placed around the carotid artery after the isolation 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.

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Aftercare The oro- and nasopharynx are cleaned of fluids and blood clots before extubation. The animal’s head is kept slightly down to avoid aspiration. 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 3–5 days. 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 flap is repositioned or if the tumor was associated with infection. 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 both procedures, and a feeding tube is rarely required. In cats, appetite stimulants such as diazepam, oxazepram, and mirtazapine may be indicated in some cases. If the ventral approach is performed, the animal is offered only soft food for the first 10 days, and gradually switched to canned food that will be offered for the next 4–6 months. 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 flap 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. 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. Packing the nasal cavity with sponges for several days is another option to avoid hemorrhage, however it is not well tolerated. 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 flap is removed, unless a small rhinostomy is left or a rhinostomy tube is placed. This is, however, usually self-limiting and resolves in 1–2 weeks. Airway obstruction by blood clots is another potential complication that can be limited by abundant flushing

of the nasal cavity before wound closure and by keeping the nares clean afterward. If the cribriform plate is eroded by the tumor or if the biopsy or the curettage procedure breaches the cribiform plate, a brain lesion may occur. With the ventral approach, an oronasal fistula can develop if hard food is offered prematurely or can be secondary to self-trauma. 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%–2% of all tumors (Rassinick et al. 2006; Turek and Lana 2007). Eighty percent are malignant, and 60%–75% are of epithelial origin in dogs (Rassinick 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). Animals affected with nasal tumors 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). 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 3 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). Medical treatment with steroids or COX-2 inhibitors did not improve prognosis, even when, at least in epithelial tumors, COX-2 expression has been detected (Kleiter et al. 2004). The standard of care for nasal tumors is megavoltage radiation therapy. Surgical debulking is indicated preoperatively if an orthovoltage machine is used, since its penetration ability is inferior to that of megavoltage radiation. Median survival of dogs with nasal adenocarcinoma treated with megavoltage radiation is about 14–21 months (Adams et al. 2005; Henry et al. 1998), which is significantly longer than that of animals treated

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with surgery alone (median 126 days). The response to radiotherapy of mesenchymal tumors, such as chondrosarcoma, is not as good as for epithelial tumors, as reported by Popovitch et al. (1994); however, surgery can achieve good palliation of symptoms (median 270 days). Even though surgery alone is not considered curative in nasal tumors, its adjuvant use combined with megavoltage radiotherapy has been shown to improve the quality of life in dogs affected with nasal neoplasia (Adams et al. 2005). In cats with nasal lymphoma, radiation therapy alone (Straw et al. 1986) or combined with chemotherapy (Haney et al. 2009; Sfiligoi et al. 2009) can achieve longterm survival and is better tolerated than surgery. Adjuvant treatments Surgery itself can be used in an adjuvant setting for nasal tumors, especially in dogs. 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 long survival time in one report (Langova et al. 2004). Mitoxantrone and carboplatin have also been used in dogs, but without promising results. Chemotherapy as a radiosensitizer has been recently proposed (Nadeau et al. 2004). 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. Surgery is not indicated with nasal lymphoma.

Laryngeal Tumors

Figure 8.11.  Endoscopic image of an arytenoid chondrosarcoma in a 9-year-old Doberman that was treated with arytenoidectomy. (Image courtesy of Dr. Richard White)

Figure 8.12.  Oral examination of a dog with a laryngeal rhabdomyosarcoma. (Image courtesy of Dr. Richard White)

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 8.11, 8.12). 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 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. An incisional biopsy of the mass should be performed for histopathology. This 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 assisted with pressure on the biopsy site. Cytology alone has been shown to be inaccurate in the diagnosis of rhabdomyosarcoma in dogs and 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 more definitive diagnosis should be achieved prior to initiating therapy. Incisional biopsy was found to be a reliable method for the definitive 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

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Figure 8.13.  Lateral radiograph of a dog with a laryngeal rhabdomyosarcoma. (Image courtesy of Dr. Paolo Buracco)

not correlate with the rest of the clinical picture (Jakubiak et al. 2005). If a tracheostomy is performed, it should be done with instruments different from those used for an incisional biopsy to prevent seeding of tumor cells at the tracheostomy site. Cytology or biopsy of the submandibular lymph nodes should be performed to evaluate for metastatic disease. It is currently unknown whether surgical removal and evaluation of the lymph nodes in deeper locations (i.e., retropharyngeal and parotid lymph nodes) is clinically important. One noninvasive method of evaluating the deeper lymph nodes of the head and neck is by advanced imaging. Imaging tests Radiographs of the larynx are helpful to localize disease. Common findings with laryngeal tumors include soft tissue opacity in the lumen and decreased margination of laryngeal structures (Figure 8.13) (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. Ultrasoundguided fine-needle aspiration (FNA) has also been reported with this technique in cats. 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 8.14, 8.15). A mass that is amenable to a partial or complete laryngectomy is one relatively confined within the larynx and that has not invaded the pharynx

Figure 8.14.  CT examination of a dog with a laryngeal rhabdomyosarcoma. (Image courtesy of Dr. Paolo Buracco)

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, inflammation, 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, monofilament, 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

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Figure 8.15.  CT reconstruction of a dog with laryngeal chondrosarcoma. Same dog as in Figures 8.1, 8.10. (Image courtesy of Dr. Charles Kuntz)

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Figure 8.16.  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. (Images courtesy of Dr. Bart Van Goethem)

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 8.16). 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. If it is not possible to close the site primarily, there are several techniques to close the defect. A myocutaneous flap can be elevated based on the sternohyoid muscle (Nelson 2003a). Preplanning is necessary if this flap is going to be used because the muscle and skin are not separated from one another during the approach. An island flap of the appropriate size is planned. The medial edge of the flap is the ventral midline incision. The rest of the island flap is harvested. The vessels supplying the flap are branches of the cranial thyroid

artery. The flap is depilated by shaving the epidermis down to dermis to prevent hair growth. The flap 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 are not routinely used (Nelson 2003a). Temporary tracheostomy should be placed in these patients to prevent obstruction due to postoperative laryngeal edema and inflammation. 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. There are currently no peer-reviewed case reports or papers that evaluate this technique and outcome in dogs. Epiglottectomy can be performed via a transoral approach (Figure 8.17). The patient is placed in sternal recumbency and the head is suspended with the mouth open. The epiglottis is grasped and resected. If possible the, mucosa at the base of the epiglottis is closed using a simple interrupted pattern of monofilament,

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(b)

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Figure 8.17.  Images from a dog with fibrosarcoma of the epiglottis. (A) Oral approach for epiglottectomy/partial laryngectomy. (B) Closure of the epiglottectomy site. (C) Specimen photo. (Images courtesy of Dr. Laurent Findji)

absorbable suture material. Alternately, a laser can be used for resection of the epiglottis. Total laryngectomy The patient is positioned in dorsal recumbency with the head extended. 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. 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 first tracheal ring. The orally placed endotracheal tube is retracted. The trachea is transected at the level of the first tracheal ring. 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 8.18). The hyoid apparatus is disarticulated bilaterally at the level of the thyrohyoid bone and the basihyoid and ceratohyoid bones. The thyropharyngeus, cricopharyngeus, sternothyroideus, and thyrohyoideus muscles are transected at their attachments to the larynx. Care must be taken to avoid damage to the nerves in this area, which provide

Figure 8.18.  Total laryngectomy specimen from a Sheltie with a laryngeal squamous cell carcinoma. (Image courtesy of Dr. Ralph Henderson)

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. The pharyngeal mucosa is then transected cranial to the larynx and the larynx is removed en bloc (Figures 8.19, 8.20). The area is lavaged with sterile saline. The pharyngeal mucosa is closed with a simple continuous inverting suture pattern. The paired thyropharyngeal and cricopharyngeal muscles are closed ventral to the pharyngeal mucosa. 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

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Figure 8.19.  Laryngeal chondrosarcoma in a 10-year-old dog. The trachea distal to the mass is being palpated with fingers. (Image courtesy of Dr. Charles Kuntz)

Figure 8.20.  Same dog as in Figure 8.19. En bloc resection of the larynx including the hyoid apparatus.

brane. 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 is closed routinely. 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 orifice is trimmed to fit 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. Aftercare

Figure 8.21.  Photograph of a Sheltie 7 days after surgery with a laryngeal squamous cell carcinoma treated with total laryngectomy and permanent tracheostomy (as depicted in Figure 8.18).

8.21). To convert a temporary tracheostomy to a permanent one, the severed proximal end of the trachea is flattened and closed using simple interrupted sutures. Alternately, the first two remaining tracheal rings are excised without removing the dorsal tracheal mem-

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-inflammatory dose. After hemilaryngectomy patients will need to monitored in an intensive care unit for care of their temporary tracheostomy tubes and for pain management. The tracheostomy tubes can be removed 3–4 days after surgery. This can be done by either covering the end of the tube, if there is room for the air to flow 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 and hemilaryngectomy include scar formation and stenosis of the upper airway, incomplete margins of tumor excision, and aspiration of either blood in the

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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 first oral feeding should be done under supervision to ensure normal swallowing function. Pain control should be provided for 5–7 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 confined to a small area of the larynx. An article that discusses two cases of laryngeal mast cell tumors in dogs reports that in two cases a partial laryngectomy was attempted that resulted in recurrence in both dogs (Crowe et al.1986). This is because it is difficult 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 carcinoma, squamous cell carcinoma, mast cell tumor, osteosarcoma, melanoma, lipoma, adenocarcinoma, chondrosarcoma, leiomyoma, fibropapilloma, fibrosarcoma, 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). 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 definitive diagnosis. Adjunctive therapy Laryngeal lymphoma in cats is a nonsurgical 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 finding. However, the dog went into a complete and long-standing remission when treated with melphalan and prednisone. 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 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

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Figure 8.22.  Chest radiographs. (A) Ventrodorsal view of the same mass, which appears to be pulmonary (arrow). (B) Laterolateral view of the thorax of a dog with an intrathoracic mass. 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.

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, a thoracoscopy is usually preferred because it is less invasive (Kovak et al. 2002). For the lungs, pericardium, pleura, and for mediastinal masses, ectopic thyroid tumors, and other spaceoccupying masses, biopsies can be performed by tho­ racoscopy. 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 with this technique (Lansdowne et al. 2005). Imaging To choose the best approach to access the thorax (intercostal thoracotomy versus median sternotomy) and to decide which side and intercostal space to use, left and right lateral and dorsoventral or ventrodorsal radio-

graphs of the thorax must be performed (Figure 8.22). The use of contrast-enhanced CT allows better visualization of small intrathoracic masses that may not be visible with radiography (Figure 8.23A); however, MRI is not usually employed because it requires more complicated respiratory-gated techniques to image the chest. Surgical techniques Intercostal thoracotomy Generally, a limited area of one side of the thorax is explored if a solitary lesion has been previously identified. Usually one-third of one thoracic cavity and the corresponding mediastinal area are fully visualized with this approach. The intercostal space (3rd to 10th) is chosen according to radiographs or CT scans taken before surgery (see Table 8.1). If a lung tumor is to be resected, the 4th or 5th intercostal space should always be chosen, regardless of the lobe affected, because the

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Figure 8.23.  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.

Table 8.1.  Access to the main thoracic structures for tumor excision. Organ Cardiac structures Lung lobes Cranial esophagus Caudal esophagus

Intercostal Space 4–5 4–5 3–4 7–8

Side Both Right or left Left Both

Note:  Thymomas are usually excised by median sternotomy.

lung lobe hilus is accessible only by this approach (Kuntz 1998). The animal is positioned in lateral recumbency and 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 in small dogs and cats. At this point it is easy to count the ribs by passing a finger cranially underneath the latissimus dorsi muscle to identify the first rib. The fifth rib is easily identified 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; the intercostal muscles are then incised in the middle, avoiding the nerves and

vessels that run parallel to the caudal aspect of each rib, and the parietal pleura is exposed (Figure 8.24A). The thorax is entered by bluntly incising the pleura with scissors and continuing dorsally and ventrally, paying attention to the internal thoracic arteries and veins that run lateral to the inner side of the sternum (Figure 8.24B). A Finochietto retractor is applied to spread the ribs, with moistened sponges placed between the retractor and the ribs (Figure 8.24C). The rib cranial to the incision is usually easier to retract than the caudal one. 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 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 8.25A). The thoracostomy tube is left open until airtight closure is accomplished, to avoid a tension pneumothorax. 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 nonabsorbable heavy-gauge monofilament (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 8.24D). To avoid damaging the underlying lungs and to decrease the risk of causing

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Figure 8.24.  Intercostal thoracotomy. (A) After the thorax is entered, blunt incision is made with scissors in the pleura and continued dorsally and ventrally. (B) 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. (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. (Image 8.24D courtesy Dr. R. Bussadori)

trauma to the intercostal vessels and nerves, the needle is inserted through the tissues with its blunt end first. The suture can be passed through small holes drilled in the rib itself, instead of surrounding it, to reduce postoperative pain and to avoid damaging the nerve and vessels on the caudal aspect of the rib caudal the incision (Rooney et al. 2004). 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, or directly injecting the local anesthetic in the thoracostomy tube (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

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Figure 8.25.  (A) The thoracic drain is applied 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 Chinese finger 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.

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 et al. (1988). In this technique, a rib cranial to the incision is rotated (pivoted) out of the surgical field. 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 smallgauge 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. 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

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incision and provides better exposure of the thorax. A secure closure is more difficult 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

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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. It should not, therefore, be considered an inferior approach. The animal is placed in dorsal recumbency, with the front legs extended and secured cranially (Orton 1995b). A skin incision is performed over the midline of the sternum, from the level of the manubrium to the xyphoid 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 8.26), paying careful attention to avoid

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Figure 8.26.  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 performed. (Image 8.26B courtesy of Dr. R. Bussadori)

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Figure 8.27.  (A) The closure of the sternum is achieved by preplacing some figure-eight wire sutures and tying them (B). Soft tissues are then sutured routinely. (Image 8.27A courtesy of Dr. R. Bussadori)

damaging the underlying structures, such as the internal thoracic vessels. 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 xyphoid process intact to achieve stable closure of the sternum and avoid dehiscence. A Finochietto retractor is applied to gently spread the incision (Figure 8.26D), 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 figure eight orthopedic wires around each sternebra, incorporating the costosternal junction (Figure 8.27) (Davis et al. 2006). In small dogs and cats, heavy-gauge monofilament 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). 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. 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.

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 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. 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 acidbase 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 flushing with sterile warm saline solution. The thoracostomy tube is aspirated at least every hour for the first 4 hours after surgery, then every 2 to 4 hours until removal. The presence of air, fluid, or blood is

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evaluated and recorded, and the tube can be removed as early as 2 hours after surgery if it is nonproductive or when the fluid 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). If the tube is nonproductive after 2 hours, however, the position and patency of the tube should be checked by thoracic radiographs and flushing, respectively. 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 to 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). Even if severe, they are rarely fatal if the animal is closely monitored in the immediate postoperative period and during follow-up. Suture dehiscence due to unstable closure, neurological deficits on the front leg, and sternal osteomyelitis can develop after median sternotomy. Subcutaneous emphysema due to a nonairtight closure, wound edema, and discharge are sometimes seen after intercostal thoracotomy. Hemorrhage, pain, and swelling may occur after either procedure. Because of the position of the animal during surgery, respiratory deficits are more likely following the intercostal procedure, whereas circulatory and cardiac problems are more likely during median sternotomy. To avoid inadvertent thoracostomy tube removal and consequent pneumothorax, the animal should not be left unattended. Depending on the type of intrathoracic surgery performed, pneumothorax, hemothorax, pulmonary edema, circulatory shock, or other specific complications may occur. The functional outcome of the surgical procedure itself is usually excellent. Oncologic outcome depends on the tumor removed. Thymomas in both dogs and cats have good prognosis if complete removal can be achieved; the prognosis for lung tumors is related to the extension of the disease, histologic grade, and the presence of metastatic lymph nodes at presentation (Zitz et al. 2008; McNiel et al. 1997). Heart base, esophageal, and metastatic tumors usually have a guarded prognosis.

Tracheal Tumors Biopsy principles If the patient is stable and time allows, tracheoscopy is an important step in the diagnosis and treatment of tracheal. Tracheoscopy allows visualization of the mass and the ability to evaluate the trachea for the presence of more than one mass. Often when clinical signs are apparent, the mass is too large for an endotracheal tube or the bronchoscope to pass caudal to the mass. Tracheoscopy is also an important step because it allows for biopsy of the mass to determine tissue type before definitive surgery. This can be achieved by both brush cytology and bronchoscopic biopsy of the mass for histopathology. Imaging Tracheal masses can often be diagnosed by plain radiographs (Figure 8.28). A mass within the tracheal lumen is well-visualized due to the contrast with the surrounding air. The lateral projection is usually the best view to evaluate for a tracheal mass because there are fewer overlying structures. The most common findings with tracheal masses are either soft tissue opacity within the trachea or stenosis of the trachea (Jakubiak et al. 2005; Carlisle et al. 1991). Masses are usually not mineralized except for osteochondromas (Carlisle et al. 1991). Three-view thoracic radiography would usually be performed as part of the workup for a dyspneic patient. They become an important tool for staging the patient once a tracheal mass has been identified to assess for pulmonary metastasis. CT is also a useful tool to more accurately evaluate the size, location, and extent of a

Figure 8.28.  Lateral radiograph of a dog with a tracheal chondrosarcoma. (Image courtesy of Dr. J. Liptak)

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Figure 8.29.  (A, B) CT scan of a dog with a tracheal chondrosarcoma. (C) Reconstruction of CT images to allow sagittal view. (Images courtesy of J. Liptak)

tracheal mass for surgical planning (Figure 8.29). The CT is also a useful tool to evaluate for metastasis to lymph nodes and lungs. Surgical techniques Resection and anastomosis Resection and anastomosis is the treatment of choice for most tracheal tumors. One notable exception is lymphoma. The surgical approach depends on the location of the tracheal tumor. For the entire length of the trachea, there are several important principles to keep in mind. The trachea is surrounded by adventitia. Within this connective tissue are the lateral pedicles. These lateral pedicles contain the segmental blood supply to the trachea. The blood supply to the trachea is made up of branches of the cranial and caudal thyroid arteries and veins, bronchoesophageal arteries and veins, and the internal jugular veins (Hedlund 1987, 1991). The recurrent laryngeal nerves are also contained within the lateral pedicles and must be protected during resection. The adventitia must be bluntly dissected from the trachea to prepare for resection and anastomosis. This is performed by starting this dissection plane directly against the tracheal wall. Dissection must be kept to the area to be resected to preserve the blood supply unless there is excessive tension on the trachea and a need for mobilization. It is recommended to start with a conservative dissection of the surrounding fascia and increase it if needed to decrease tension on the anastomosis site. Tracheal resection requires thoughtful preservation of the airway at all times during the surgery and good communication with the anesthetist. There are two options for maintaining the airway during tracheal resection. One method is to retract the endotracheal tube cranially

so that it is not in the resection site. Stay sutures are placed in the proximal and distal segments of the trachea proximal and distal to the proposed resection site. The resection is carried out quickly, and the stay sutures are then used to pull the remaining segments of trachea together. The endotracheal tube is then advanced into the distal segment (Figure 8.30). The other technique involves transection at the distal site first and the placement of a sterile endotracheal tube, elbow, and extension into the distal trachea to maintain anesthesia. The orally placed endotracheal tube is retracted but not removed. The segment of trachea to be removed is excised. Stay sutures are used to approximate the two segments, the sterile endotracheal tube is removed, and the orally placed endotracheal tube is advanced across the anastomosis site. The technique used depends on the surgeon and anesthetist’s preference and also on the length of time the resection may take. In larger resections, the sterile placement of an endotracheal tube is recommended as this will allow for more time to approximate the two segments of the trachea and perform tension-relieving techniques if necessary. A sterile endotracheal tube should always be available at the time of resection to allow quick intubation of the distal segment, if needed. The inner surface of the trachea is a clean-contaminated environment. There is also potential for contamination of the surgical site with manipulation and/or exposure of an orally placed endotracheal tube. Prophylactic antibiotics should be used intraoperatively. After resection, the surgical site should be cultured and lavaged. The goal of the anastomosis is perfect apposition of the mucosa with minimal tension. The tracheal epithelium will heal quickly by epithelialization if the mucosal edges are in apposition. However, if there are gaps at the anastomosis site, it will heal with the development of

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Figure 8.30.  (A) Intraoperative photograph of a cat with a tracheal squamous cell carcinoma that has undergone resection. The orally placed endotracheal tube is retracted slightly during resection. A sterile endotracheal tube is placed in the caudal segment of the trachea while the sutures are preplaced. (B) The endotracheal tube that was in the caudal segment is removed, and the endotracheal tube that was place orally is advanced into the caudal segment. The anastomosis is completed with the preplaced sutures. (Images courtesy of Dr. J. Liptak)

granulation tissue and stenosis (Hedlund 1991). The two methods that are commonly reported are the splitcartilage technique (Hedlund 1987, 1991; Fingland et al. 1995; Urschel 1996) and the annular ligament-cartilage technique (Hedlund 1987, 1991; Vasseur 1979; Demetriou et al. 2006). The split-cartilage technique involves planning the proximal and distal incisions in the trachea so that they bisect a tracheal ring proximally and distally. When the two segments are apposed, the two portions of the transected rings are aligned. The annular ligamentcartilage technique involves placing the incisions in the annular ligament between each ring. The two segments are apposed, and suture is placed around the adjacent cartilage rings. The split-cartilage technique is preferred because it leads to more accurate apposition with a higher chance of first-intention healing and a decreased risk of postoperative stenosis (Hedlund 1984; Fossum et al. 2007a). It is recommended that the stay sutures be placed in the proximal and distal tracheal segments prior to resection to prevent retraction of the segments (Figure 8.30). This is particularly important when working in the caudal cervical trachea or thoracic inlet. The stay sutures are also used to manipulate the proximal and distal segments. The optimal type of suture pattern for tracheal anastomosis is controversial. There are two recent reports in dogs that evaluate suture patterns in vivo and in vitro. Fingland et al. (1995) evaluated large-segment tracheal resection in vivo and compared simple continuous versus a simple interrupted suture patterns. Lateral tension sutures were placed in both groups. The authors

concluded that there was significantly less luminal stenosis and more precise histologic apposition using simple interrupted sutures (Fingland et al. 1995). An in vitro study by Demetriou et al. (2006) evaluated pullout strength in vitro in the canine trachea. For this technique, the annular ligament-cartilage resection technique was employed. Pullout strength was compared for a simple interrupted, simple continuous, and simple interrupted pattern with tension-relieving horizontal mattress suture. The authors concluded that the simple continuous and simple interrupted reinforced with horizontal mattress patterns were significantly stronger than the simple-interrupted suture pattern. In this study, the constructs failed at the annular ligament, so it is possible that resection technique played a role in mode of failure (Demetriou et al. 2006). Urschell et al. (1996) compared the pullout strength of a simple-interrupted versus a horizontal mattress pattern in vivo in rat tracheas. The resection technique was a split-cartilage technique. This author found no difference in the strength of these two suture patterns. Based on these studies, a simple interrupted suture pattern is recommended. This may need to be reinforced with tension-relieving sutures placed laterally and ventrally if there is tension on the anastomosis site (Figure 8.31). The sutures in the dorsal tracheal membrane are placed first. The ventral sutures are placed next, and the rest of the sutures are filled in to ensure that the trachea is precisely approximated. The sutures should encircle the remaining portion of the proximal and distal cartilages. The sutures should be placed so that the knots are extraluminal (Hedlund 1991).

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Figure 8.31.  (A) Intraoperative photograph of a dog with a tracheal chondrosarcoma undergoing resection. (B) Specimen photograph of a tracheal chondrosarcoma removed from a dog. (C) Resection and anastomosis of the tracheal chondrosarcoma using simple interrupted sutures and reinforcement with mattress sutures. (Images courtesy of Dr. J. Liptak)

A monofilament, nonreactive, absorbable or nonabsorbable suture material should be used (Hedlund 1991). A recent study evaluating polyglactin, polydiaoxanone, and polypropylene in an experimental model for tracheal resection and anastomosis in sheep found no difference in suture type on the outcome of anastomosis (Behrend and Klempnauer 2001a). After resection of the tracheal segment with the tumor, the edges of resection should be inked to evaluate the margins of resection. Surgical approaches A ventral midline approach is used for the cervical trachea. The patient is placed in dorsal recumbency with the forelimbs affixed caudally. The head is affixed in an extended position. However, for extensive resections, the head may have to be released to decrease tension on the

anastomosis site. The sternohyoideus muscles are dissected along the midline. The peritracheal fascia is bluntly dissected from the trachea, taking care to prevent damage to the lateral pedicles and recurrent laryngeal nerves. The tracheal mass is located by visualization and/or palpation. A mass in the cranial thoracic trachea or within the thoracic inlet can also be resected using this approach. The sternum should be included in the surgical preparation because a cranial sternotomy may be necessary (Hedlund 1987, 1991). The thoracic trachea is approached by a right-sided third to fifth intercostal space thoracotomy. The third or fourth intercostal space will allow access to the caudal trachea. The fifth intercostal space will allow access to the carina. At the third intercostal space, a standard right lateral thoracotomy is performed, and the right cranial lung lobe is packed off cranially to allow visualization.

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Figure 8.33.  Bronchial mass has been resected, and an anastomosis of the bronchus has been performed. (Image courtesy of Dr. G. Romanelli)

Figure 8.32.  Surgical approach to the bronchus by lateral thoracotomy. (Image courtesy of Dr. G. Romanelli)

The mediastinal pleura overlying the trachea is incised dorsal to the vagus nerve. The vagus nerve lies between the trachea and cranial vena cava. A second incision is made in the pleura just ventral to the vagus nerve to allow ventral retraction of the nerve (Smith and Waldron 1993). The soft tissue is dissected circumferentially around the trachea, taking care to stay directly against the tracheal wall. The tracheal resection and anastomosis at this site is performed similarly to the cervical tracheal resection. At the fifth intercostal space, a standard lateral thoracotomy is performed, and the right middle and cranial lung lobes are packed off (Figure 8.32). The azygous vein will be visualized as it crosses the trachea and enters the cranial vena cava. The azygous vein is ligated and transected. The pleura is incised, and the vagus nerve is protected and retracted as above (Smith and Waldron 1993). For tumors of the caudalmost extent of the trachea, the mainstem bronchi are transected at the level of the carina. Sterile endotracheal tubes are placed in each bronchus to allow for continued ventilation. The blunt dissection is performed to free the carina/caudal trachea from the surrounding soft tissues. The caudal segment is transected. The right bronchus is anastomosed to the caudal trachea as an end-to-end anastomosis (Figure 8.33). The left bronchus is anastomosed to the caudal trachea as an end-to-side anastomosis (Nelson 2003b). Incomplete cartilage rings and the size discrepancy in

this area make the anastomoses more challenging at this site (Nelson 2003b; Hedlund 1991). Knots are positioned away from blood vessels to prevent erosion of the blood vessels with movement of the intrathoracic structures (Hedlund 1991). A pleural or pericardial patch can be sutured over the anastomosis site to reinforce the anastomosis (Nelson 2003b; Hedlund 1987, 1991). Within the thoracic cavity, the anastomosis site can be assessed for leakage intraoperatively by filling the thoracic cavity with warm saline and monitoring leakage. A chest tube is placed prior to closure of the thorax to allow monitoring for a pneumothorax. Tension-relieving techniques There are several techniques that have been reported to decrease the tension on the anastomosis site for large segment resections. The decision to use these techniques is based on the surgeon’s judgment intraoperatively. Intraoperatively, simple techniques involve the use of tension-relieving sutures and an increase in the amount of dissection of the adventitia and fascia surrounding the trachea. The tension-relieving sutures are placed one to two cartilage rings from the anastomosis site. The sutures should encircle a tracheal ring. The sutures can be either a horizontal or vertical mattress sutures. Three tension-relieving sutures should be placed, one ventral and two lateral (Hedlund 1984, 1991; Vasseur 1979; Nelson 2003b). Care must be taken not to buckle or deform the trachea with these sutures (Dallman and Bojrab 1982). If the amount of dissection around the trachea is extended cranially and caudally, care must be taken not to disrupt the blood supply to the trachea or the recurrent laryngeal nerves. More complex methods to relieve tension intraoperatively include tracheal

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stretch by incisions in the annular ligaments and laryngeal release. Tracheal stretch is achieved by incision of the annular ligaments cranial and caudal to the anastomosis site to relieve tension. Care must be taken not to penetrate the mucosa with these incisions. This will result in a weakening of the trachea, which could lead to complications such as tracheal disruption (Hedlund 1991; Nelson 2003b). Laryngeal release is reported in human patients when there is excessive tension on the anastomosis site (Wright et al. 2004). It has been suggested that this technique be used in humans when more than 4 cm of trachea are resected (Wright et al. 2004). With this technique, the attachments of the hyoid apparatus are dissected free from the thyroid cartilage (Hedlund et al. 1991). This technique is not used commonly in canine patients. In experimental large segment resections in dogs where laryngeal release was not performed, the larynx was found to be caudally displaced

Figure 8.34.  A postoperative neck flexion harness is being used to prevent neck extension and stress after tracheal resection and anastomosis. (Image courtesy of Dr. J. Liptak)

(a)

when pre- and postoperative radiographs were compared (Fingland et al. 1995; Dallman and Bojrab 1982). This indicates that there is significant tension on the larynx with large segment resections, and laryngeal release may be helpful in some cases to decrease tension on the anastomosis site. Postoperatively, immobilizing the head in a flexed position can also be used to relieve tension. This can be done by suturing the skin on the chin to the manubrium or by attaching a muzzle to a body harness to hold the neck flexed (Nelson 2003b; Hedlund 1984, 1991) (Figure 8.34). Tracheal stenting For tumors that are not suitable for surgical resection, either due to the length of resection that is required, diffuse disease of the trachea, or evidence of metastasis, palliation with tracheal stenting should be considered. The self-expanding, metallic stents are placed under fluoroscopic guidance in the same manner as for tracheal collapse in dogs (Figure 8.35). The maximal trachea diameter is measured radiographically, and a stent that is 10%–15% larger than this in diameter is selected to ensure that the stent is held in position under tension. The stent selected is 2 cm or longer than the tracheal segment that requires stenting to ensure that the stent will span 1 cm of normal-diameter trachea cranial and caudal to the stenosed area (Culp et al. 2007). This technique has been reported to successfully palliate a cat with a tracheal carcinoma. The cat succumbed to metastatic disease 6 weeks after stent placement, but no stent associated complications were noted (Culp et al. 2007). This technique has been reported for use in humans with malignant tracheobronchial stenosis (Miyazawa et al. 2000). Aftercare After tracheal resection, patients should be monitored in an intensive care unit for dyspnea and pain

(b)

Figure 8.35.  (A) Preoperative radiograph of a tracheal carcinoma causing tracheal obstruction caudal to the thoracic inlet. (B) Postoperative radiograph after intraluminal stent placement. (Images courtesy of Dr. W. Culp)

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management. Patients with a cervical tracheal resection and anastomosis should be monitored for subcutaneous emphysema. Patients with a thoracic tracheal resection and anastomosis should have a thoracic tube placed intraoperatively so that they can be monitored for pneumothorax. Both would indicate separation of the anastomosis site and air leakage. Dogs should be walked with a body harness postoperatively to minimize tension and pressure on the trachea. Patients need to be kept confined postoperatively. Ideally, they should have strict cage rest for a week to prevent disruption of the tracheal anastomosis site. Cough suppressants should be considered if the patient is coughing after surgery to prevent excessive pressure on the anastomotic site. Tracheoscopy can be performed as necessary to monitor patients postoperatively for stenosis, airway leakage, or to evaluate healing. Lateral radiographs of the trachea can also be used to evaluate for stenosis. However, this technique has been shown to be relatively insensitive as a tool for this purpose (Fingland et al. 1995). Complications The most common complication of tracheal resection and anastomosis is stenosis. There are two causes of postoperative stenosis: excessive tension, leading to separation of the anastomosic site and healing by second intention, and poor mucosal apposition, with a similar consequence. The amount of stenosis has been shown to correlate to the amount of tension on the anastomotic site (Behrend and Klempnauer 2001a). A second common complication is breakdown of the anastomotic site and air leakage. This will generally require a second surgery unless the leakage is very mild. Quantity of trachea that can be safely removed The amount of trachea that can be safely removed is controversial. Many recommendations are based on reports in human thoracic surgery. These, in turn, are often based on dog and sheep models. There is a difference in the amount of tension that the trachea can withstand in puppies compared with adult dogs (Hedlund 1991; Fossum et al. 2007a). The most commonly cited references for the amount of trachea that can be resected is 25% in puppies and 20%–60% in adult dogs (Hedlund 1991; Fossum et al. 2007a). In sheep, which are used for a model of tracheal resection for humans, up to 9 cm have been resected with good results in vivo (Behrend and Klempnauer 2001b). There are no case reports of successful massive resections of the trachea in dogs. The resections that are reported are generally small and

successfully managed with primary anastomosis and minimal tension-relieving techniques. Two experimental reports of canine tracheal resection and anastomosis exist. The aim of both studies was to create a hightension anastomosis. This was performed by removing 8 (Fingland et al. 1995) and 15–17 (Dallman and Bojrab 1982) rings of the trachea. Minimal tension-relieving techniques were used, and most of these experimental resections were successful. Given that there are 35–45 rings in the canine trachea (Hedlund 1991), this would correspond to 20%–40% of the trachea resected successfully in experimental dogs. In humans, there are similar discrepancies in the amount of trachea that can be safely removed. A limit of 4.5 cm has been cited as a limit for tracheal resection in humans to prevent excessive tension and failure of the anastomotic site (Grillo et al. 1964; Mulliken and Grillo 1968). A recent retrospective study that evaluated complications associated with tracheal resection and anastomoses in humans found that there was an increase in the complication rate when 4 cm or more of trachea was resected (Wright et al. 2004). Although 4 cm was not considered an absolute cut off in this article, it was suggested that if more than 4 cm was to be resected, a laryngeal release procedure should be performed. Other citations are more liberal with the amount of trachea that can be resected, with 50% being cited as a limit for the amount of trachea that can be safely resected (D’Cunha and Maddau 2003). Another source suggests that 30% of the trachea can be resected without any tension-relieving techniques, with up to 70% resection possible with major tension-relieving techniques and organ displacement (Halsband 1987). As with puppies, the trachea in pediatric humans is not as amenable to resection. Thirty percent is the recommended limit in human pediatric tracheal resection (Wright et al. 2002). Patients that were 17 years old or younger were found to be more likely to have anastomotic complications in a retrospective study of human patients with tracheal anastomosis (Wright et al. 2004). The margins that are required depend on the tumor type. Even with a carcinoma or sarcoma of the trachea, 3 cm margins are unlikely to be achievable. Margins of 1 cm in each direction are recommended (Fossum et al. 2007a). Common tumor types In dogs, the reported tracheal tumor types include osteochondroma, chondroma, osteosarcoma, chondrosarcoma, adenocarcinoma, carcinoma, lieomyoma, mast cell tumor, plasmacytoma, fibrosarcoma, and rhabdomyosarcoma (Morrison 1980; Beck et al. 1999; Carlisle

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et al. 1991; Brodey et al. 1969; Black et al. 1981; Hill et al. 1987; Chaffin et al. 1988; Mahler et al. 2006; Yanoff et al. 1996). Tracheal tumors are rare. There are several reports in the literature of tracheal osteochondromas (Morrison 1980; Beck et al. 1999; Dubielzig and Dickey 1978; Gourley et al. 1970; Hough et al. 1977). These are benign tumors of dogs less than 1 year of age that can be successfully treated with surgical resection (Morrison 1980; Beck et al.1999; Dubielzig and Dickey 1978; Gourley et al. 1970; Hough et al.1977; Carlisle et al. 1991). Reported tracheal tumor types in cats include lymphoma (Brown et al. 2003; Kim et al. 1996; Schneider et al. 1979), adenocarcinoma (Culp et al. 2007; Cain and Manley 1983; Evers et al. 1994; Veith 1974), disseminated histiocytic sarcoma (Bell et al. 2006), inflammatory polyp (Sheaffer and Dillon 1996), and carcinoma (Brown et al. 2003). The distinction between lymphoma and the other tumor types is very important because the treatment of lymphoma is nonsurgical, with chemotherapy and/or radiation being the treatment of choice. Generally, the treatment of excision will be the same for the other tumor types. However, the margins of resection for an inflammatory polyp will be much less than for a malignant tumor.

Figure 8.36.  Anatomy of the canine lungs. (Illustration courtesy of Dave Carlson)

Adjunctive therapy Adjunctive therapy will depend on the tumor type. For benign tumors or low-grade tumors with clean margins of resection, no adjunctive therapy is necessary. For tumors with a more aggressive course, adjunctive chemotherapy may be recommended. Radiation therapy has been reported for the treatment of tracheal lymphoma in cats (Brown et al. 2003).

Lung Surgical procedures Oncologic surgical procedures performed on the lungs of cats and dogs include the collection of biopsies to diagnose local or diffuse disease and partial or complete lobectomy or complete pneumonectomy for primary or metastatic primary or metastatic lung tumors (Mehlhaff and Monney et al. 1985; Miles et al. 1988; Ogilvie et al. 1989; O’Brien et al. 1993; McNiel et al. 1997; Hahn and McEntee 1998; Kuntz 1998; Liptak et al. 2004a, 2004b). Surgical anatomy The trachea of cats and dogs bifurcates into two mainstem bronchi, which in turn divide into lobar bronchi, one for each lung lobe. The two lungs are separated by the mediastinum (Dunning and Orton et al. 1998).

Deep fissures divide the lungs of dog and cat in lobes allowing for the change in shape when the diaphragm moves or the spine bends (Figure 8.36). The left lung consists of the cranial lobe, which is further divided by an incomplete fissure into a cranial (formerly called the apical lobe) and a caudal part (formerly called the cardiac lobe) (Figure 8.36). The caudal lobe of the left lung (formerly called the diaphragmatic lobe) is completely separated from the adjacent caudal part of the cranial lobe by a fissure (Evans 1993). The right lung is larger than the left, and it is divided into cranial (formerly called the apical lobe), middle, accessory (also called the intermediate lobe), and caudal lobes (Figure 8.36). Ventrally, the caudal portion of the cranial right lobe and the cranial part of the middle lobe fail to cover the heart surface. This area corresponds to the cardiac notch of the right lung, and it is usually located at the ventral aspect of the fourth intercostal space. At this site, about 5 cm2 of sternocostal surface of the heart is exposed to the thoracic wall, thereby creating a window for cardiac puncture and ultrasonographic cardiac imaging (Evans 1993). The notch for the caudal vena cava is located between the dorsal and the right lateral processes of the accessory lobe. At this point, in close

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association with the vena cava, the right phrenic nerve is located. The pulmonary trunk from the right ventricle bifurcates into the left and right pulmonary arteries, which ramify into branches that enter the lung lobes. The pulmonary veins from the left lung lobes usually maintain their separate identity and enter the left atrium. The veins from right cranial and middle lobes join to form a single vein that returns to the left atrium; the veins from the caudal and accessory lobes join before entering the heart. Variations in vascular anatomy, however, are common (Evans 1993). The pulmonary vessels closely follow the lobar distribution of the bronchi. Pulmonary arteries are located on the craniodorsal aspect of each bronchi, whereas pulmonary veins are situated caudoventrally (Dunning and Orton et al. 1998). The lobar bronchi are positioned between the arteries (lateral) and the veins (medial) (Grandage 2003). For the most part, the pulmonary lymphatics drain into the three groups of the tracheobronchial lymph nodes around the tracheal bifurcation. In a few dogs, pulmonary lymph nodes are also found on the dorsal surfaces of the lobar bronchi at the edge of the lung parenchyma (Evans 1993). Biopsy procedures Definitive diagnosis of lung lesions requires evaluation of tissue samples or cytologic specimens. The nature of a pulmonary nodule can be investigated by performing a transthoracic fine-needle aspiration (FNA) by a blind collection technique or under the guide of ultrasound, CT, or fluoroscopy. The technique used depends on the accessibility of the lesion. Diagnoses obtained by FNA cytopathology accurately reflected the diagnosis obtained on histopathological examination in 82% of cases. The agreement between cytopathological and histopathological interpretation was higher in samples collected with ultrasound guidance than in those collected in a blind fashion (DeBerry et al. 2002). Pulmonary lesions located in the periphery of the lobe can be more easily aspirated. The role of FNA and the requirement for preoperative diagnosis in the management of focal lung lesions is controversial. Most authors agree that FNA of pulmonary parenchymal lesions represents a useful, accurate, and safe tool for diagnosis of lung neoplasia and should always be performed. The reported accuracy of this technique for diagnosis in dogs and cats with pulmonary lesions varies between 82% and 91% (Teske et al. 1991; Wood et al. 1998; Reichle and Wisner et al. 2000; DeBerry et al. 2002; Zekas et al. 2005). The incidence of complications (i.e., pneumothorax, hemorrhage) ranges from 0% to 31% (Teske et al. 1991; Wood

Figure 8.37.  Postoperative view of lung cancer. Note the presence of necrotic and purulent material in the tumor that may confuse cytological interpretation of transthoracic FNA.

et al. 1998; Reichle and Wisner et al. 2000; DeBerry et al. 2002). In contrast, other authors cite that FNA of pulmonary lesions is diagnostic for neoplasia in only 37%– 50% of cases (Mehlhaff and Monney et al. 1985; McNiel et al. 1997). Focal lung tumors often have a necrotic and purulent center that may confuse interpretation (Figure 8.37) (Withrow 2007). For this reason, and due to the fact that FNA or other biopsy-obtained diagnoses rarely change the course of the treatment, it is appropriate to recommend surgical excision of a lung mass without attempting a preoperative FNA or other biopsy procedure. This decision is also influenced by the size and location of the nodule, the results of a CT examination that exclude other pulmonary lesions or lymph node involvement, the general health status of a patient, and the owner’s decision making. Tracheal wash, bronchoalveolar lavage, or brush cytopathology have poor sensitivity for diagnosis of lung neoplasia unless the cancer invades the tracheobronchial tree (Ogilvie et al. 1989; Hahn and McEntee et al. 1997; McNiel et al. 1997). These techniques provide the most information when there is interstitial or alveolar disease rather than a focal pulmonary lesion (Ogilvie et al. 1989). The utility of cytological analysis of pleural effusions in animals with lung tumors is controversial. In one study the diagnosis was confirmed based on the cytology of pleural effusion in 12 of 13 cats that had thoracocentesis performed (Hahn and McEntee 1997). In another report, however, a diagnosis was obtained in only 1 of 8 cats (Barr 1987). Samples for histopathological analysis can be obtained by percutaneous lung biopsy with a cutting needle

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Figure 8.38.  Thoracic radiographs taken in (A) right lateral, (B), left lateral, (C) and dorsoventral projections of a 11-year-old dog with a well-circumscribed mass in the left cranial lung lobe. After surgical excision, the lung mass was diagnosed as an adenocarcinoma.

(Reichle and Wisner et al. 2000), or via transbronchial biopsy via a fiber-optic bronchoscope (Kuehn and Hess et al. 2004). Neither of these techniques is routinely used in cats and dogs. Biopsy samples of the pleural surface, lymph nodes, pericardium, and lung can be obtained via thoracoscopy using a transdiaphragmatic or intercostal approach (Griffin 2004) or via a lateral thoracotomy or median sternotomy. Imaging tests Conscious chest radiographs are a key step in the diagnosis of lung tumors (Mehlhaff and Monney et al. 1985; Kuntz 1998). Left and right lateral and ventrodorsal views of the thorax are always recommended (Figure 8.38). Radiographic appearance of primary lung tumors varies from a single, discrete mass in one lobe to multiple lesions and/or the diffuse involvement of entire

lung lobes (Mehlhaff and Monney et al. 1985; Miles 1988). Occasionally, pneumothorax or pleural effusion may complicate the radiographic diagnosis. Chest radiographs, however, can have limited diagnostic accuracy in detecting pulmonary metastases, pulmonary carcinosis, and tracheobronchial lymphadenopathy (Johnson et al. 2004; Paoloni et al. 2006). CT has been shown to be more efficacious than conventional radiography for detection of lung metastases (Nemanic et al. 2006) and for evaluation of tracheobronchial lymphadenopathy in the staging process (Paoloni et al. 2006) (Figure 8.39). MRI can also be used for the evaluation of lymph nodes. CT also allowed a clear identification of pleural nodules in case of malignant pleural mesothelioma (Echandi et al. 2007). In one study, thoracic radiography failed to reveal approximately 90% of pulmonary nodules that were subsequently detected on CT examination. The size of nodule detection is approximately 1 mm in diameter for CT, and that for thoracic radiography approaches

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(a)

(c)

(b)

Figure 8.39.  (A) Right lateral and (B) left lateral (projections of the thorax of an 11-year-old German shepherd with mammary tumors and mandibular fibrosarcoma). Metastatic lesions were not detected on radiographs. CT scan of the thorax of the same dog (C) obtained at the level of the cranial lobes: a single subpleural nodule (arrow) was clearly identified in the left cranial lobe. (Image courtesy of Dr. Mauro Di Giancamillo)

7–9 mm for reliable detection (Nemanic et al. 2006). The high sensitivity but the lower specificity of CT screening can result in the diagnosis of a large number of falsepositive nodules (Li et al. 2004). In human medicine, therefore, the false-positive rate has highlighted the need to differentiate benign from malignant nodules. Higher accuracy in the radiologist’s evaluation of lung nodule morphology (size, lobulation, presence of coarse speculation, heterogeneous central attenuation) facilitated by, if needed, the use of automated computerized schemes can mitigate the problem of false-positive nodules (Li et al. 2004; Markowitz et al. 2007). If pulmonary metastases are suspected on throacic radiographs, it is the author’s recommendation that if the owner declines CT or MR, or if they are not available, thoracic radiographs should be repeated after 4–6 weeks to assess for the development of pulmonary nodules. Ultrasonography is not superior to radiography for the detection of pulmonary lesions. It is, however, indicated to guide diagnostic transthoracic aspiration or biopsy, thereby improving the accuracy of this procedure, particularly when pleural fluid is present. Pleural fluid may obscure details of thoracic structures on radiographs; however, it can enhance the diagnostic potential of thoracic ultrasound (Moore and Ogilvie et al. 2006). Isolated, discrete pulmonary lesions are unlikely to benefit from bronchoscopy. This procedure is, however, useful to visualize and biopsy intrabronchial lesions (Ogilvie et al. 1989; Kuehn and Hess 2004). Surgical procedures The thorax can be approached by a lateral intercostal thoracotomy or by a median sternotomy (for more details refer to section on thoracotomy).

Figure 8.40.  Intraoperative view of an enlarged tracheobronchial lymph node. (Image courtesy of Dr. Giorgio Romanelli)

Lung lobectomy Partial or complete lung lobectomy can be performed. Because the cranial and caudal parts of the cranial left lobe share common bronchi and vessels, it is difficult to excise one without removing the other. They are, therefore, usually removed together. On the right side, the accessory lobe divides incompletely from the caudal lobe, and it is generally resected with the caudal lobe. The caudal left and right lobes, the middle right lobe, and the cranial right lobe can, however, be separately removed (Orton 1995a). When lung tumor excision is performed, tracheobronchial lymph nodes (Figure 8.40) should always be palpated and biopsied if enlarged. If the pleural wall or mediastinum adheres to the tumor, these structures should be biopsied to evaluate

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the completeness of surgical excision. Surgical margins should be inked and submitted for histologic evaluation in addition to the primary tumor mass (Kuntz 1998). Partial lobectomy The peripheral two-thirds or less of the lung lobe can be removed to obtain a biopsy sample or to treat peripheral focal lesions such as small tumors (Orton 1995a; Dunning and Orton et al. 1998; Nelson and Monnet 2003; Fossum et al. 2007b). Partial lobectomy can be performed through a left or right fourth-fifth intercostal thoracotomy or via median sternotomy. The affected lobe is identified, carefully exteriorized from the thoracic cavity, and gently palpated to assess the extent of lung excision. A moist laparotomy sponge can be placed under the lobe. To avoid spillage of neoplastic or infected cells, a pair of crushing forceps is placed across the lobe proximal to the lesion, at the resection site. Continuous overlapping sutures (2-0 to 4-0 absorbable suture) are placed 3–4 mm proximal to the forceps (Figure 8.41). If the partial lobectomy is performed at the proximal third of the lobe, larger bronchi and blood vessels may be encountered. To decrease the risk of hemorrhage or air leaks after resection, these structures can be individually occluded before performing the previously described suture pattern or a second row of continuous overlapping suture can be placed (Figure 8.41). At this point, the lung is transected with a scissor or a surgical blade proximal to the forceps, leaving a small portion of lung

Figure 8.41.  Partial lung lobectomy with two continuous overlapping sutures oversewn with a simple continuous suture. (Illustration courtesy of Dave Carlson)

distal to the suture line. The incision is oversewn with a simple continuous pattern of absorbable suture (3-0 to 5-0) (Figure 8.42). The remaining portion of the lobe is replaced in the thoracic cavity. Surgical gloves and instruments should be changed before closing the thorax. At this point, the chest cavity is filled with warm sterile saline solution to cover the excision site and positive pressure ventilation is maintained for a few seconds to evaluate for air leaks at the suture line. Simple interrupted sutures or hemoclips are placed to close air leaks. The fluid is removed, and a thoracostomy tube placed prior to closing the thorax. Thoracic radiographs (laterolateral and dorsoventral views) can be taken after surgery to evaluate pneumothorax and to check the position of the thoracostomy tube (Figure 8.43). Partial lobectomy can also be performed using surgical staples (LaRue et al. 1987; Walshaw 1994; Liptack et al. 2004a; Tobias 2007). A thoracoabdominal (TA) surgical stapler is adequate for this purpose. This instrument places two or three staggered rows of stainless steel staples into the tissue, which assume a B shape when compressed. TA devices are available as a reusable reloadable stainless steel stapler or as a disposable stapler that can be reloaded up to seven times. The reusable staplers are available in 30, 55, and 90 mm widths (TA 30, TA 55, TA 90), with cartridges having staples of 2.0, 3.5, or 4.8 mm. The disposable reloadable staplers are available in 30, 45, 60, 90 mm widths, with cartridges having a staple size of 2.5, 3.5, or 4.8 mm. Staple cartridges are available in different colors depending on staple size. The blue cartridges contain two rows of staples 4.0 mm wide, with a leg length of 3.5 mm and a closed height of 1.5 mm. The green cartridges have two rows of staples with a crown width of 4.0 mm, leg length of 4.8 mm, and closed height of 2.0 mm. The white ones, known as V3, contain three rows of staples 3.0 mm wide, with legs of 2.0 or 2.5 mm and a closed height of 1.0 mm. They come in 30 mm widths only. The V3 cartridges are preferred due to the added security provided by the additional row of staples and the smaller closed height. The selection of staple length and the height depends on the compressed width of the lung or bronchus at the resection site and on the compressed thickness of the tissue at the same point, respectively. It is important that all tissues to be ligated are comfortably placed within the staple line. For most partial lobectomies in dogs and cats, either the TA 55 or TA 90 stapler is used, with 3.5 mm staples. The stapler is placed across the lobe proximal to the lesion and fired (Figure 8.44). The lobe is transected, using the TA edge as a cutting guide. Before cutting the tissue from the stapler, the lung

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(a)

(b)

(c)

(d)

Figure 8.42.  Operative view of partial lung lobectomy. The affected lobe is grasped with a dry laparotomy sponge (A). A crushing forceps is placed across the lobe proximal to the lesion, and a continuous overlapping suture is placed 4 mm proximal to the forceps (B). The lung is transected proximal to the forceps, leaving a small portion of lung distal to the suture line (C). The incision is oversewn with a simple continuous pattern of absorbable suture (D).

is clamped with a hemostat to avoid the spread of infected and/or tumor cells into the pleural space. The staple line is inspected for hemorrhage and air leakage. When performing a stapled partial lobectomy, there is no indication to routinely oversew staple lines. If persistent points of blood or air leakage are noted, they can be independently occluded either with individual sutures or vascular clips. It can be more expedient, with less risk of hemorrhage and pneumothorax to perform a complete rather than a partial lobectomy, particularly when dealing with a neoplastic process for which it is important to achieve adequate margins. Complete lobectomy The preferred surgical approach for complete lung lobectomy is via a left or right intercostal thoracotomy

over the affected lobe and its hilum (Dunning and Orton et al. 1998; Nelson and Monnet 2003; Fossum et al. 2007b). Median sternotomy does not allow easy visualization of pulmonary vessels and bronchi. When there are large amounts of infected material in the lobe to be removed, the bronchus should be clamped to prevent the passage of this material into the proximal bronchi and trachea (Fossum et al. 2007a). To isolate the lobe, moist laparotomy sponges are used. To isolate the hilus of the lobe, the pulmonary ligaments that attach the lobe to the mediastinum are transected while the visceral pleura is incised to visualize the pulmonary vessels. Careful attention is paid to correctly identify the vasculature and bronchus associated with the lobe to be resected. Using blunt dissection for the nonvisible deep side of the vessel, the pulmonary artery is exposed on its

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entire circumference. To facilitate vessel ligation and to have a temporary emergency suture available for hemostasis in the event of vessel rupture, a small moistened umbilical tape can be passed around the artery for traction. The artery is ligated with nonabsorbable or absorb-

Figure 8.43.  Postoperative thoracic radiograph to evaluate pneumothorax and to check the position of the thoracostomy tube.

able suture material (2-0 to 3-0) (Figure 8.45A). A simple encircling ligature is first placed at the proximal end of the vessel near its bifurcation. Care is taken not to compromise the lumen of the parent vessel from which this artery arises. A second ligature is applied distal to the point where the artery is to be transected (Figure 8.45A). For safety, a transfixing suture should be placed proximal to the transection site. The artery is severed between the two distal sutures. The veins are approached on the ventral side of the bronchus, after retraction of the lobe dorsally. The pulmonary veins are ligated in a manner similar as for the arteries, with the exception that the distal suture should be placed first (Figure 8.45A). Care is taken not to lacerate the thin-walled veins during dissection and to avoid incorporating an adjacent vein in the suture. The main bronchus of the lobe is first dissected and then clamped with a pair of crushing forceps or Satinsky forceps, placed proximal and distal to the point where the transection is to be performed, close to the lobe (Figure 8.45B). The bronchus is transected between the two clamps and sutured proximal to the remaining clamp with a continuous or interrupted horizontal mattress suture (2-0 to 3-0 nonabsorbable monofilament suture) (Figure 8.45c). In small dogs and cats, a transfixing

Figure 8.44.  Operative view of a partial lung lobectomy performed with surgical staples. The lung lobe is lifted up (A), and the stapler is placed across the lobe proximal to the lesion and fired (B). (C) The lobe is transected, using the TA edge as a cutting guide.

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surgical gloves and instruments should be changed. The thoracic cavity is filled with warmed sterile saline, and positive pressure ventilation is applied to check for air leaks. Before closure, fluid and sponges are removed and the packed off lungs are assessed for appropriate reinflation. A thoracostomy tube is routinely placed. Complete lobectomy can be performed with absorbable or nonabsorbable suture material. In the presence of an infectious process, braided, multifilament, and/or nonabsorbable material should be avoided (Fossum et al. 2007b). Complete lobectomy can be accomplished using an en bloc hilar stapling procedure (Walshaw 1994; LaRue et al. 1987). The hilus of the lobe to be excised is isolated sufficiently from the surrounding structures so that it fits easily into the cartridge of the TA stapler. With this technique, it is not necessary to individually isolate, ligate, and transect the pulmonary vessels. Only the surrounding adventitia needs to be dissected from the point of resection. Care is taken not to include the phrenic or vagus nerve in the staple line. A TA 30 stapler with 2.5 mm (white, V or V3) staple cartridges is preferred for complete lung lobectomy (Walshaw 1994). Before cutting distal to the staple line, large hemostats are placed to clamp the tissue distal to the staples to avoid spillage of material (infected or neoplastic) into the pleural cavity. There is no indication to routinely oversew staple lines after either partial or complete lobectomy (Walshaw 1994) (Figure 8.46). Pneumonectomy

Figure 8.45.  Hand suture technique for lung lobectomy. (A) Ligation of the veins and arteries, (B) division of the mainstem bronchus between the clamps, (c) mattress sutures, (D) simple continuous oversew of the bronchus. (Illustration courtesy of Dave Carlson)

suture can be used. A simple continuous suture pattern (3-0 to 4-0 absorbable suture) is placed on the distal end of the severed bronchus to oversew it (Figure 8.45D). To decrease the risk of adhesions and air leaks, some sutures can be placed in the surrounding pleura to cover the stumps of the vessels and bronchus. At this point,

A pneumonectomy refers to the resection of all lung lobes on either the right or left side (Figure 8.47), and it can be performed in both dogs and cats (Nelson and Monnet 2003; Liptak et al. 2004a). Removal of more than 75% of the lung is fatal (Dunning and Orton et al. 1998). The left and right lungs account for 42% and 58% of lung volume, respectively. Dogs tolerate a left pneumonectomy or resection of less than 50% of the lung volume, provided that the right lung is healthy. Compensation occurs by existing mechanisms only, such as the distention of the remaining lung and increased pulmonary blood flow, resulting in the recruitment of existing physiological reserves of diffusion capacity and the remodeling of the existing alveolar–capillary network. After right pneumonectomy (55%–58% of lung tissue is excised), compensation is due to the same mechanisms as left pneumonectomy as well as new or regenerative alveolar-capillary growth (Hsia et al. 1993, 1994; Nelson and Monnet 2003; Liptak et al. 2004a). Neoplasia involving all lobes of one lung is an indication for pneumonectomy (Nelson and Monnet 2003).

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Figure 8.47.  Postoperative view of the left lung after pneumonectomy. (Image courtesy of Dr. Giorgio Romanelli)

Figure 8.46.  Intraoperative view of complete lung lobectomy performed with staples. (A) The hilus of the lobe to be excised is isolated sufficiently from the surrounding structures to fit easily into the staple cartridge. (B) There is no indication to routinely oversew staple lines after complete lobectomy. (Image courtesy of Dr. Giorgio Romanelli)

To improve visibility and operative space in the thorax, the affected lobes can be double-clamped at their pedicle and resected before performing vessel ligation. Pneumonectomy can be accomplished by en bloc resection by ligating the pulmonary artery, vein, and mainstem bronchus (Nelson and Monnet 2003; Clements et al. 2004; Liptak et al. 2004a) or by individual lobectomies for each lobe of one lung (Liptak et al. 2004a). It is wise to have a temporary salvage suture placed around the pulmonary artery of the lung to be resected, close to the bifurcation of the pulmonary trunk, in the event of hemorrhage and to provide traction. The pulmonary artery to be transected can be ligated by the placement of two simple encircling sutures (for vessels smaller than 5 mm) with or without a transfixation suture or oversewn (vessels greater than 5 mm) with a double layer of

4-0 or 5-0 simple continuous monofilament nonabsorbable suture. Before being transected and oversewn, two noncrushing vascular clamps are placed: the proximal clamp on the pulmonary artery adjacent to the main pulmonary trunk and the second clamp 1 cm further distally. The artery is then divided, leaving no more than 5 mm of artery distal to the proximal clump to decrease the length of the “blind end” where thrombi can potentially form. The artery is then oversewn. The veins are always double-ligated with a transfixing suture, depending on their size. Before approaching the bronchus, it is important to withdraw the endotracheal tube proximal to the carina or advance it in the contralateral bronchus. The mainstem bronchus is then clamped distal to the transection site. A monofilament nonabsorbable suture can be placed through the tracheal wall just adjacent to the bronchus for traction. A simple interrupted or continuous horizontal mattress suture (3-0 or 4-0 monofilament nonabsorbable suture material) is placed on the bronchus, 5–10 mm distal to the carina. The transection is made 3 mm distal to the suture, and the proximal cut edge of the bronchus is oversewn with a simple continuous suture. Since the mainstem bronchus has tracheatype cartilage rings, air leaks can occur as it does not easily collapse after suturing and the sutures can cut through the cartilage. The closure, therefore, can be reinforced by suturing a piece of pleura, pericardium, or fascia over the stump (Nelson and Monnet 2003). As an alternative to en bloc removal, individual complete lobectomies can be performed whereby pulmonary vessels are sutured and transected as previously described for a complete lung lobectomy. The mainstem bronchus is closed with interrupted or continuous mattress sutures and oversewn with a simple continuous suture pattern,

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as for complete lobe resection. An en bloc hilar stapling technique can also be performed for each lobe (Walshaw 1994). The excision site is checked for bleeding, and the thorax is filled with saline, as previously described, to evaluate for air leaks. A thoracostomy tube should be always placed. As an alternative to pneumonectomy, an experimental study on extracorporeal lung resection in dogs has been described (Matsumoto et al. 2004) whereby the unilateral lung is extirpated, the pulmonary lobe with cancer is removed, and the residual pulmonary lobe is reimplanted. The technique is proposed for cases in which tumor removal is difficult, even by complete lobectomy or pneumonectomy. The extensive lymph node dissection required in some cases, however, has severe adverse effects on bronchial anastomotic healing (Matsumoto et al. 2004). Thoracoscopy Complete or partial lobectomy can be performed via thoracoscopy using an endoscopic stapling device, thereby using a minimally invasive approach (Brissot et al. 2003; Lansdowne et al. 2005) (Figure 8.48). This procedure is particularly useful for small neoplastic lung masses, located away from the hilus. Among all lobes, the caudal left lung lobe appears to be the easiest to remove successfully without intraoperative complications (Lansdowne et al. 2005). Biopsies from the tips or margins of lung lobes can also be performed. Biopsy samples are obtained via thoracoscopy by inserting a commercially available or selftied loop ligature (Roeder knot), through an instrument portal (Fossum et al. 2007b). A minimally invasive technique can also use a keyhole thoracotomy technique under thoracoscopic guidance (thoracoscopic-assisted keyhole thoracotomy) (Figure 8.49). A small intercostal incision is made, and Babcock forceps are used to grasp and exteriorize the lung tip to be biopsied. A ligature is placed around the margin or a thoracoabdominal stapler is used to resect the lung (Fossum et al. 2007b). Biopsy samples from peribronchial lymph nodes can also be obtained via thoracoscopy to stage the neoplastic disease for prognostic purposes. The advantages of thoracoscopy include decreased morbidity, decreased postoperative pain, and a more rapid recovery. Disadvantages include the cost of specialized equipment, the expertise required to perform the procedure, decreased gas exchange, and the possibility of cardiovascular compromise, both of which also occur with thoracotomy. A limitation of thoracoscopy is the ability to removal large tumors or tumors of any size located close to the hilus. Thoracoscopic lobectomy is best performed when the lungs are completely deflated, using a one-lung

Figure 8.48.  Thoracoscopic view of (A) a total lung lobectomy in a cat before placement of staples and of (B) a partial lung lobectomy in a dog after placement of staples. (Image courtesy of Dr. Jilles Duprè)

Figure 8.49.  Biopsy samples are obtained through a keyhole procedure via thoracoscopy. The lesion is localized via thoracoscopy, and a small intercostal incision is made to exteriorize the lung tip to be biopsied. A thoracoabdominal stapler is used to resect the lung. (Image courtesy of Dr. Giorgio Romanelli)

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ventilation technique. Partial lung collapse due to the pneumothorax created by the introduction of trocar cannulas into the thoracic cavity is usually sufficient for exploratory thoracoscopy for biopsy of pleura or lung. Complications associated with thoracoscopy requiring conversion to a thoracotomy include hemorrhage from a lacerated intercostal vessel causing blood loss and poor intraoperative visibility, failure to maintain the lung deflation, and poor surgical access. The latter usually occurs with right middle lung lobe resection due to the fact that, after the placement of the cannulae, there is insufficient working space for safe application of staples at the hilus (Lansdowne et al. 2005). Thoracoscopy in humans is contraindicated in the case of endobronchial tumors, evidence of thoracic wall or mediastinal involvement, presence of concurrent lung disease making one-lung ventilation poorly tolerated, or enlarged mediastinal lymph nodes (Lansdowne et al. 2005). Similar contraindications are likely to exist in small animals. To decrease the risk of tumour seeding when removing lung tumors via thoracoscopy, the use of an endoscopic retrieval bag is preferred (Lansdowne et al. 2005). Readers are referred to endoscopic texts for more detailed information regarding thoracoscopic techniques. Metastasectomy Metastatic lesions in the lung parenchyma can be excised either by partial or complete lobectomy through lateral thoracotomy or via sternotomy when there is bilateral lung lobe involvement. When nodules up to 5 mm are located in the visceral subpleural tissues, they can be elevated with hemostats and excised, following the placement of a purse-string suture (3-0 or 4-0 monofilament absorbable suture material), to close the surrounding lung parenchyma. The placement of a low-pressure chest tube should prevent pneumothorax if the suture falls off. For subpleural lesions over 5 mm, a stapled wedge excision should be used (O’Brien et al. 1993). The number of metastatic lesions is one of the key factors that influences the success of lung metastasectomy; a more sensitive imaging technique than radiography, therefore, should be used to screen dogs for multifocal disease prior to metastasectomy (Liptak et al. 2004b). Postoperative care Animals should be hospitalized and closely monitored during the postoperative period for approximately 2–3 days. Respiratory function should be evaluated by blood gas analysis. Pain management should be addressed: provision of analgesia after thoracotomy is extremely important to facilitate recovery and to improve ventilation (Kuntz 1998).

Complications of thoracic surgery Perioperative mortality is rare after partial or complete lung lobectomy. Complications are related to the surgical technique but are uncommon (LaRue et al. 1987). The use of staples of inadequate length or height increases the chance of air leakage or hemorrhage due to insufficient tissue compression (Walshaw 1994). The major complications after partial and complete lobectomy or pneumonectomy include pneumothorax and/ or hemorrhage. Minor air leaks usually seal spontaneously and are self-limiting. Massive leaks (i.e., copious hemorrhage, sustained pneumothorax) require reexploration of the chest. Animals should be closely monitored in the postoperative period. Lung lobectomy should not be attempted where necrotic or tumor tissue is included in the staple or suture line, as it can result in suture dehiscence or in staple line disruption with subsequent hemothorax or pneumothorax (LaRue et al. 1987). High rates of morbidity and mortality are reported after pneumonectomy in human medicine. Acute and chronic respiratory, cardiac, and gastrointestinal complications are relatively common in both humans and animals (Liptak et al. 2004a). They include respiratory insufficiency or failure, pneumonia, pulmonary edema, thromboembolism and hypertension, chylo- and hemothorax, pleural effusion, congestive heart failure, supraventricular arrhythmia, myocardial ischemia, esophageal dysmotility and dilation, esophagopleural fistula, and delayed gastric emptying. The entrapment of the endobronchial blocker tip used for selective lung ventilation by a surgical staple has been reported in a dog (Levionnois et al. 2006). Types of lung tumors Primary lung tumors in the dog (Mehlhaff and Monney et al. 1985) and cat (Hahn and McEntee 1997) are rare; however, their prevalence appears to be increasing (Moulton et al. 1981). This trend may be due to a number of reasons, including longer companion animal life expectancy, the development of more accurate diagnostic techniques, an increased number of necropsies and biopsies being performed, and the constant improvement in standards of pet care (Moore and Ogilvie et al. 2006). Although most affected dogs come from urban areas, there is no apparent association between the environment and development of lung tumors (Ogilvie et al. 1989; Reif et al. 1992). Recently, however, an increased risk of lung cancer was observed in dogs with higher amounts of anthracosis (Bettini et al. 2010). Primary lung tumors are described by their site of origin (i.e., bronchial, bronchoalveolar, alveolar) or by their

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(a)

(b)

(c)

Figure 8.50.  Eleven-year-old domestic shorthair cat affected by digit lung syndrome. Lung masses are evident on a lateral thoracic radiograph (A). It is characterized by metastatic spread of lung tumors to digits with evidence of digit ulceration (B) and phalangeal bone lysis on radiographs (C).

histopathological appearance (i.e., adenocarcinoma, squamous cell carcinoma) (Moulton et al. 1981). However, it is commonly difficult to classify lung tumors based on location due to their advanced status at the time of diagnosis (Moulton et al. 1981). Adenocarcinomas are the most common primary lung tumor reported in both species (Ogilvie et al. 1989, Hahn and McEntee 1997). Squamous cell carcinomas, anaplastic carcinoma, and other type of carcinomas are less frequently seen (Mehlhaff and Monney et al. 1985). Benign lung adenomas and primary mesenchymal lung neoplasms (osteosarcoma, hemangiosarcoma, and fibrosarcoma) are infrequently reported in the dog and cat. Lymphomatoid granulomatosis is a rare neoplasm of the lung in young to middle-aged dogs. Lobar consolidation or a large granuloma is evident on radiographs, and hilar

lymphadenopathy, circulating basophilia, and leukocytosis are common findings (Berry et al. 1990; Fitzgerald et al. 1991). Malignant histocytosis is a lung tumor that is highly metastatic. It is most commonly described in Bernese mountain dogs, but has also been described in rottweilers and golden retrievers (Rosin et al. 1986; Hayden et al. 1993; Ramsey et al. 1996). Metastatic pulmonary tumors are more common than primary lung tumors in dogs and cats (Moulton et al. 1981). Primary tumors that are most frequently associated with metastatic lung lesions on thoracic radiographs include transitional cell carcinoma, thyroid carcinoma, hemangiosarcoma, melanoma, and osteosarcoma (Miles et al. 1988). Distinguishing primary lung carcinomas from metastases is often a challenging task. The thyroid transcription factor-1 (TTF-1), a nuclear protein expressed in follicular cells of the thyroid gland and pneumocytes, was found to be 100% specific and 85% sensitive for primary lung carcinomas. Antibodies to TTF-1 have been found to be a useful marker for distinguishing between primary and metastatic canine epithelial tumors (Bettini et al. 2009). Primary lung neoplasms are highly aggressive and tend to metastatize to the lung, regional lymph nodes, pleural space (Hahn and McEntee 1997), skeletal musculature (Hahn and McEntee 1997; Langlais et al. 2006), bone (Hahn and McEntee 1997; Dhaliwal, KufuorMensah et al. 2007), heart, liver, kidney, etc (Dhaliwal, Kufuor-Mensah et al. 2007). The median age in dogs at diagnosis varies from 10 to 11 years (Miles et al. 1988; Ogilvie et al. 1989). For cats, the median age at diagnosis is approximately 12 years (Mehlhaff, Monney et al. 1985; Hahn, McEntee et al. 1997). Sex and breed predisposition have not been reported (Mehlhaff et al. 1984), although in an earlier study, a higher incidence of lung carcinomas was found in the boxer (Brodey and Craig 1965). Primary pulmonary masses are single in 54% and multiple in 37% of dogs (Ogilvie et al. 1989). Clinical signs may be absent in both dogs and cats in the early phases of the disease (Ogilvie et al. 1989); therefore, animals with pulmonary neoplasia can appear normal on physical examination. The finding of primary pulmonary neoplasia may be incidental when thoracic radiographs are taken for other reasons. Symptoms appear late in the course of the disease and may depend on the amount of lung involved, the invasiveness of the tumor, and the presence of metastatic disease (Mehlhaff et al. 1984). Clinical signs can be directly or indirectly associated with pulmonary tumors. With effusion secondary to the tumor, commonly encountered clinical signs include a nonproductive cough of a few weeks’ to several months’ duration (Mehlhaff et al. 1984) and/or

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Figure 8.51.  (A) Lateral thoracic projection of an 11-year-old mixed dog with a pulmonary mass in the caudal lung lobe. The same dog showed lameness due to hypertrophic osteopathy. (B) Diffuse periosteal reaction is evident on the radiograph of the affected limb.

dyspnea. Decreased bronchovesicular sounds occasionally may be seen with large tumors, secondary spontaneous pneumothorax, or with pleural effusion (Mehlhaff et al. 1984; Hahn, McEntee et al. 1997). Coughing and other signs referable to the respiratory tract are a less consistent finding in the cat, noted only in about onethird of cases (Mehlhaff, Monney et al. 1985). Other nonspecific and frequently detected signs in animals with lung tumors include lethargy, malaise, inappetence, weight loss, exercise intolerance, and pyrexia. Such nonspecific signs are most commonly seen in the cat (Mehlhaff, Monney et al. 1985). Occasionally, dogs and cats are presented for lameness (Mehlhaff, Monney et al. 1985; Hann, McEntee et al. 1997). This can be secondary to hypertrophic osteopathy (Mehlhaff, Monney et al. 1985; McNiel et al. 1997) whereby the distal limbs appear diffusely swollen and painful. Lameness can also result from distant metastatic spread of the primary lung neoplasm to bone or skeletal muscle (Hahn, McEntee 1997; Langlais et al. 2006), with a focal soft tissue swelling and pain on palpation of the affected bone (Mehlhaff, Monney et al. 1985). Neurologic signs secondary to tumor involvement of neurologic tissue has also been reported (Ferreira et al. 2005). In cats, the “digit lung syndrome” is characterized by metastatic spread of lung tumors to digits, with lameness, evidence of digit ulceration, and phalangeal bone lysis described (Figure 8.50) (Jacobs and Tomlinson 1997; Gottfried et al. 2000).

Paraneoplastic syndromes are not commonly associated with lung tumors in either dogs or cats, but can include hypertrophic osteopathy (Figure 8.51), hypercalcemia, fever, and primary lung tumor-induced secretion of adrenocorticotropic hormone (Ogilvie et al. 1989; Hahn, McEntee et al. 1997). Surgery is the most effective and commonly recommended treatment for lung tumors in cats and dogs (Melhlaff et al. 1984; Mehlhaff, Monney et al. 1985; Miles et al. 1988; Ogilvie et al. 1989; O’Brien et al. 1993; McNiel et al. 1997; Hahn and McEntee 1998; Kuntz 1998; Liptak et al. 2004a). Adjuvant therapy Limited data are available on the efficacy of chemotherapy in the treatment of lung tumors. Patients that may benefit from chemotherapy include those with unresectable lesions that require palliation, those with recurrent disease, or cases with negative prognostic factors such as high-grade, poor differentiation, and regional lymph node involvement. Vindesine (with or without cisplatin) has been shown to be of some benefit in dogs (Mehlhaff et al. 1984). Vinorelbine has been used in a few dogs with lung tumors, with a partial response (Poirier et al. 2004). Vincristine, cyclophosphamide, and methotrexate have been used in combination in dogs (Mehlhaff et al. 1984). The administration of mitoxantrone has been described in a cat with well-differentiated

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adenocarcinoma (Clements et al. 2004) and in dogs combined with doxorubicin (McNiel et al. 1997). Because of the small number of animals treated with adjuvant chemotherapy, it is not possible to assess the impact of chemotherapy on prognosis. Intrapleural administration of cisplatin has been shown to be of some benefit in animals with malignant pleural effusion (Moore et al. 1991). The delivery of cytotoxic chemotherapy and cytokines by aerosol for the treatment of primary or metastatic lung cancers has also been described with encouraging results (Hershey et al. 1999; Khanna, Vail et al. 2003). The only lung mass that shows a good and rapid response to chemotherapy is lymphomatoid granulomatosis (Berry et al. 1990). Radiation therapy for lung tumors is largely untried in veterinary oncology because of the potential for serious and life-threatening effects on lungs, such as pneumonitis and subsequent fibrosis (LaRue et al. 1995; McNiel et al. 1997). It is likely that adjuvant radiation therapy would increase survival when combined with surgery in incompletely excised lung tumors (Moore, Ogilvie et al. 2006). More sophisticated methods of irradiation for lung tumors, such as intensity-modulated radiation therapy, have been recently introduced in veterinary oncology with some promising results (Ballegeer et al. 2006). Photodynamic therapy may have some efficacy as an adjuvant treatment for pulmonary metastases from sarcoma (Anderson et al. 2003). Prognosis The most significant prognostic factor in dogs with isolated lung lesions is lymph node involvement (Ogilvie et al. 1989; McNiel et al. 1997; Polton et al. 2008). Dogs with metastatic spread to regional nodes have diseasefree intervals and median survival times shorter than those of dogs without lymph node involvement (6 days versus 351 days and 26 days versus 452 days, respectively) (McNiel et al. 1997). Histologic grade also has prognostic value. Dogs with well-differentiated tumors have significantly 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). Other factors of prognostic value include the presence of clinical symptoms. Survival time is longer (median survival time 545 days) in dogs with lung tumors that are an incidental finding than in dogs that are symptomatic (median survival time 240 days) (McNiel et al. 1997). Primary tumor size has shown some influence on prognosis, with larger tumors having a poorer prognosis

(Ogilvie et al. 1989; McNiel et al. 1997). The tumor stage (T) is also prognostic for median survival time (T1 tumors, 790 days; T2 tumors, 196 days; T3 tumor, 81 days) (McNiel et al. 1997). Primary tumor stage T1 and histologic type (papillary tumor type) were found to be statistically significant favorable prognostic indicators (Polton et al. 2008). Dogs with adenocarcinoma (mean survival time [MST] 19 months) have a much better prognosis than dogs with squamous cell carcinoma (MST 8 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 (Withrow 2007). Dogs with small (diameter less than 5 cm), isolated, well-differentiated adenocarcinomas, without evidence of spread to regional lymph node and without pleural effusion, have the best prognosis; 1 year survival can be expected in more than 50% of these animals (Mehlhaff et al. 1984; Ogilvie et al. 1989). 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. 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

Table 8.2.  Clinical stages of primary lung tumors. T: Primary lung tumor (based on clinical and surgical evaluation)

T0: No evidence of tumor T1: Solitary tumor surrounded by lung or visceral pleura T2: Multiple tumors of any size T3: Tumor invading neighboring tissues

N: Regional lymph nodes (based on surgical and histologic evaluation)

N0: No evidence of lymph node involvement N1: Bronchial lymph node involved N2: Distant lymph node involved

M: Distant metastasis (based on surgical and histologic evaluation)

M0: No evidence of distant metastasis M1: Distant metastasis detected

Clinical stages (TNM) of primary lung tumors. (Modified from Owen LN. 1980. Geneva: WHO; adapted from McNiel et al 1997.)

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1998). Grade of differentiation and lymph node involvement are of prognostic value in cats. Cats with moderately differentiated tumors (median survival time 698 days) and those without enlarged nodes (median survival time 421 days) have significantly 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).

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 an ultimate metastatic rate over 90% versus 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 synovial cell 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 3 months for the first year, with decreasing intervals for year 2 and beyond. Once metastasis is identified, full staging may be in order (involving CT of the chest, an abdominal ultrasound, and a nuclear bone scan), 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). General considerations for metastasectomy include the following: 1. Time to detection.  The longer the interval from primary tumor control to detection of metastasis,

the better, with 300 days suggested as the break point from early versus 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. 2. Number of lesions.  One or two metastases are biologically much less than three or more. The typical scenario is the asymptomatic detection of lung nodule(s) on plain radiographs. Three-view films in a conscious (fully aerated) patient are recommended (Prather et al. 2005). CT scans may help define lesions not clearly seen on plain films but can also reveal small nonneoplastic 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 nontumor tissue (Ballegeer et al. 2006). 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. 3. 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. 4. Technique.  Open intercostal thoracotomy is the usual surgical technique, although a sternal split 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 deflation may aid in digital palpation of nodules. Thoracoscopy, or video-assisted thoracic surgery (VATS), is becoming increasingly popular in the hands of experienced surgeons when lesions are definable 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).

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(a)

(b)

Figure 8.52.  (A) A ventrodorsal projection radiograph of a dog with a rib chondrosarcoma. (B) A lateral projection radiograph of a dog with a rib chondrosarcoma. (Image courtesy of Dr. Julius Liptak)

5. 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 1–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). The role of postmetastasectomy chemotherapy is undefined, 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). Postmetastasectomy surveillance begins again at 3-month intervals and repeat metastasectomy can be considered (Bielack et al. 2009). Metastasis of cancer is generally a poor prognostic sign, especially with carcinomas. Carefully selected patients may benefit 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. 2004). Nonpulmonary 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 An incisional biopsy is 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 definitive 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 8.52). The point of

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Figure 8.53.  Postcontrast transverse CT of an osteosarcoma involving the fifth rib. (Image courtesy of Dr. Simon Kudnig)

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, Kamstock et al. 2008). CT is the imaging modality of choice to evaluate chest wall tumors (Figure 8.53). It 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 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. If nuclear scintigraphy is not available, long-bone survey radiography is an alternative method to evaluate for other bone lesions. Liptak, Kamstock and colleagues (2008) found a 16% rate of metastasis to bone with primary rib osteosarcoma in a recent study. Abdominal ultrasound is recommended for staging in certain tumor types. This test should be performed in cases of known hemangiosarcoma or when a pleural effusion accompanies the thoracic wall mass. Description of surgical procedures Rib tumors Preoperative surgical planning is very important for the surgical treatment of rib tumors. Rib tumors are usually sarcomas, and aggressive resection is critical to success-

Figure 8.54.  Resection of a subcutaneous hemangiosarcoma. In this case, skin was included in the chest wall resection.

ful treatment. Completeness of surgical excision has been shown to have a significant effect on survival and disease-free interval in dogs with chest wall tumors (Pirkey-Ehrhart et al. 1995; Liptak, Kamstock et al. 2008). The planned margins of resection should include one rib cranial and one rib caudal to the lesion (Liptak, Kamstock et al. 2008; Baines et al. 2002). Dorsal and ventral margins should be 3 cm along the ribs (Liptak, Kamstock 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, Dernell et al. 2008; Pirkey-Ehrhart 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 or eight ribs increases the risk of causing severe respiratory compromise and dysfunction. The location of the tumor may determine the ability of the surgeon to remove more than six ribs. This is better tolerated in the caudal thorax, where diaphragmatic advancement is possible. In the cranial thorax, the creation of a flail chest with the removal of more than six ribs may cause ventilatory failure (NJ Ehrhart, personal communication). In general, skin is not resected en bloc with tumors arising from the rib. This is contrary to a recent paper that used en bloc resection and a myocutaneous flap for reconstruction of primary rib chondrosarcoma in five 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 8.54). The common rib tumors such as osteosarcoma and chondrosarcoma tend to remain somewhat encapsulated within the periosteum. This concept is similar to

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Figure 8.55.  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 8.53. (Image courtesy of Dr. Simon Kudnig)

the resection of distal radial osteosarcomas that spare surrounding soft tissues in a limb-sparing procedure. The overlying muscle also serves as another plane that is a barrier to extension of the tumor into the subcutaneous tissue and skin. 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 8.55). 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. 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 8.55). 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 8.56). The length of the intercostal approach is dictated

Figure 8.56.  Intraoperative photograph of a dog with a rib chondrosarcoma. The lateral thorax has been entered at the proposed intercostal space of excision. (Image courtesy of Dr. Julius Liptak)

Figure 8.57.  Intraoperative photograph of a dog with a rib chondrosarcoma after thoracic wall resection. (Image courtesy of Dr. Julius Liptak)

by the size of the tumor. Rib cutters are used to cut the ribs at the dorsal and ventral margins. The intervening intercostal tissue is cut with Mayo scissors or electroscalpel. The intercostal vessels caudal to the ribs should be located and ligated 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, Dernell et al. 2008). The final cranial or caudal intercostal incision is made to remove the chest wall en bloc (Figure 8.57). Generally, rib tumors are located in the area of the costochondral junction (Montgomery et al. 1993). The thoracic mass

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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 field with tumor cells. The involved tissues should be removed with the chest wall. This may involve a pericardiectomy or a partial lung lobectomy using a TA stapler (Mattieson et al. 1992; Liptak, Dernell 2008; Pirkey-Ehrhart et al. 1995). 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 first rib. Resection including the first rib has been reported to be successful with no impairment of limb function (Liptak, Kamstock et al. 2008). Invasive soft tissue masses of tissues lateral to the ribs In general, invasive soft tissue masses lateral to the ribs are 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 8.54). 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 et al. 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 once the skin incision has been made 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 con-

tinue 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, Gor-Tex, and Vicryl. Marlex is the most commonly reported implant used in veterinary and human thoracic wall reconstruction techniques. Local tissue flaps have also been reported either alone or in combination with prosthetic mesh. The most commonly used local tissue is a latissimus dorsi flap, either alone or as a myocutaneous flap (Liptak, Dernell et al. 2008; Halfacree et al. 2007; Raffoul et al. 2001; Mansour et al. 2002). Marlex mesh was first 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 fibrous 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 8.58). The mesh is sutured in place by laying the

Figure 8.58.  Intraoperative photograph of mesh that is used to reconstruct a defect after chest wall resection.

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Figure 8.59.  Intraoperative photograph of a dog with a rib chondrosarcoma. The defect in the chest wall has been repaired using mesh. (Image courtesy of Dr. Julius Liptak)

mesh along the pleural surface of the defect and suturing it in place with circumcostal and mattress sutures through the chest wall (Figure 8.59) (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. When a large number of ribs are removed, chest wall stability has also been restored by using spinal plates at the sites of rib resection. The plates are affixed 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. The latissimus dorsi flap was first 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 flap and a musculocutaneous flap when skin is resected (Liptak, Dernell et al. 2008; Halfacree et al. 2007). The latissimus dorsi muscle originates from the superficial 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 classified 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 flap, 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 fibers, allowing the muscle to be rotated into the defect. The dominant vascular pedicle containing the thoracodorsal artery is preserved (Pavletic 2003). Alternately, the muscle flap can be harvested from its insertion at the level of the humerus and used to repair defects more caudally (Seguin, personal communication). For the latissimus dorsi myocutaneous flap, the flap 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 flap 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. The ventral border is incised first, and the ventral border of the latissimus dorsi muscle is located. The flap is developed by continuing the incisions from the skin to the ventral aspect of the latissimus dorsi. The myocutaneous flap can be rotated into the defect, and the donor site skin can be closed primarily (Figure 8.60) (Pavletic 2003; Halfacree et al. 2007). 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 flank incision and tunneling the omentum in the subcutaneous tissue and into the defect. Skin is then closed over the omentum (Figure 8.61) (Orton 2003). 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 fixation (Figure 8.62). 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.

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Figure 8.60.  (A) Intraoperative photograph showing elevation of the latissimus dorsi muscle flap. (B) Intraoperative photograph showing rotation of the latissimus dorsi flap cranially. The flap will be brought ventrally to fill the defect in the chest wall. (Image courtesy of Dr. Julius Liptak)

Liptak, Dernell, and colleagues (2008) recently 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 flap 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 meshmethyl 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 flap or mesh so that it is taut. However, absolute rigid reconstruction of the thoracic

Figure 8.61.  The omentum has been placed over the thoracic defect to provide an additional autogenous tissue to close the defect. (Image courtesy of Dr. Simon Kudnig)

wall has not been shown to be necessary in dogs (Liptak, Dernell et al. 2008). Sternectomy Masses of the sternum can be approached in much the same way as masses in other areas of the thoracic wall.

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Figure 8.62.  (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. (Images courtesy of Dr. Julius Liptak)

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Figure 8.63.  CT scan of a cat with a sternal chondrosarcoma. (Image courtesy of Dr. G. Romenelli)

Incisional biopsy for tissue diagnosis and 3D imaging will guide preoperative planning (Figure 8.63). The decision to include skin in the resection will be based on the same logic as for rib tumors. The overlying pectoral muscle may be resected with the tumor. The amount of sternum resected will depend on the amount of bone involved on CT imaging. Threecentimeter margins should be taken cranial and caudal to the tumor. The ribs are cut 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 8.64). The defect is reconstructed using Marlex mesh (Figure 8.64), a Marlex mesh–poly(methyl methacrylate) sandwich, heterogenous bone and mesh, spinal plates (Figure 8.65), or an autogenous muscle flap. 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 recently been reported as a method to repair the chest wall after sternectomy in dogs (Liptak, Dernell et al. 2008). This can be used alone or in combination with a latissimus dorsi flap and/or Marlex mesh. 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 fibrous raphe along midline. The insertion is to the greater tubercle of the humerus and the medial brachial fascia (Evans et al. 2000). The flap 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 flap is rotated across ventral midline into the contralateral defect. Alternately, the flap can be rotated cranially and dorsally on the lateral thoracic pedicle (Liptak, Dernell 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–poly(methyl methacrylate) sandwich and autogenous tissue. There was an increased incidence of early complications seen in sternal resections and reconstruction in dogs in a recent retrospective study (Liptak, Dernell et al. 2008). This may indicate that this location is 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 infusionss can also be considered. A chest tube should be placed intraoperatively to monitor for and manage pleural effusion, should it occur. Nasal oxygen will be helpful in some cases 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 fluids until they are eating and drinking. In a large thoracic resection, fluid loss from hemorrhage and evaporative losses intraoperatively can be substantial. Careful monitoring of the patient’s hydration 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

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Figure 8.64.  (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. (Images courtesy of Dr. G. Romanelli)

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Figure 8.65.  (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.

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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, Dernell et al. 2008; Pirkey-Ehrhart et al. 1995). Lameness, infection, and dehiscence are also possible complications. 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 inflammatory 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 common reported primary tumors of the chest wall are osteosarcoma and chondrosarcoma. Other reported tumor types include fibrosarcoma, hemangiosarcoma, soft tissue sarcoma, and leiomyosarcoma (Baines et al. 2002; Montgomery et al. 1993; Liptak, Dernell et al. 2008; Mattieson et al. 1992; Pirkey-Ehrhart et al. 1995). Adjunctive therapy Rib osteosarcoma has been shown to have a similar biological behavior to appendicular osteosarcoma. PirkeyEhrhart 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, Kamstock 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 1,080 days (Pirkey-Ehrhart et al. 1995) and greater than 3,820 days. Pulmonary metastasis has been reported in cases of chondrosarcoma (Liptak, Kamstock 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 dorsal extension into the vertebra.

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328  Veterinary Surgical Oncology Polton, G.A., M.J. Brearley, S.M. Powell, et al. 2008. Impact of primary tumour stage on survival in dogs with solitary lung tumours. J Small Anim Prac 49:66–71. Popovitch, C.A., Weinstein, M.J., Goldschmidt, M.H., et al. 1994. Chondrosarcoma: A retrospective study of 97 dogs (1987–1990). J Am Anim Hosp Assoc 30:81–85. Prather, A.B., C.R. Berry, and D.E. Thrall. 2005. Use of radiography in combination with computed tomography for the assessment of noncardiac thoracic disease in the dog and cat. Vet Radiol Ultrasound 46(2):114–121. Purinton, P.T., J.N. Chambers, and J.L Moore. 1992. Identification and categorization of the vascular patterns to muscles of the thoracic limb, thorax, and neck of dogs. Am J Vet Res 53(8):1435–1445. Quiros, R.M. and W.J. Scott. 2008. Surgical treatment of metastatic disease to the lung. Semin Oncol 35(2):134–146. Raffoul, W., M. Dusmet, M. Landry, et al. 2001. A novel technique for the reconstruction of infected full-thickness chest wall defects. Ann Thor Surg 72(5):1720–1724. Ramsey, I.K., J.S. McKay, H. Rudolf, et al. 1996. Malignant histiocytosis in three Bernese mountain dogs. Vet Rec 138(18):440–444. Rassnick, K.M., C.E. Goldkamp, H.N. Erb, et al. 2006. Evaluation of factors associated with survival in dogs with untreated nasal carcinomas: 139 cases (1993–2003). J Am Vet Med Assoc 229(3):401– 406. Reichle, J.K. and E.R. Wisner. 2000. Non-cardiac thoracic ultrasound in 75 feline and canine patients. Vet Radiol Ultrasound 41(2): 154–162. Reif, J.S., K. Dunn, and G.K. Ogilvie. 1992. Passive smoking and canine lung cancer risk. Am J Epidemiol 135(3):234–239. Ringwald, R.J. and S.J. Birchard. 1989. Complications of median sternotomy in the dog and literature review. J Am Anim Hosp Assoc 25:430–434. Rooney, M.B., M. Mehl, and E. Monnet. 2004. Intercostal thoracotomy closure: Transcostal sutures as a less painful alternative to circumcostal suture placement. Vet Surg 33(3):209–213. Rosin, A., P. Moore, and R. Dubielzig. 1986. Malignant histiocytosis in Bernese mountain dog. J Am Vet Med Assoc 188(9):1041–1045. Ross, J.T., D.T. Matthiesen, K.E. Noone, et al. 1991. Complications and long-term results after partial laryngectomy for the treatment of idiopathic laryngeal paralysis in 45 Dogs. Vet Surg 20(3):169– 173. Rossi, G., C. Tarantino, and E. Taccini. 2007. Granular cell tumour affecting the left vocal cord in a dog. J Comp Path 136:74–78. Rudorf, H. and P. Brown. 1998. Ultrasonography of laryngeal masses in six cats and one dog. Vet Radiol Ultrasound 39(5):430–434. Saik, J.E., S.L. Toll, and R.W. Diters. 1986. Canine and feline laryngeal neoplasia: A 10-Year survey. J Am Anim Hosp Assoc 22:359–365. Schneider, P.R., C.W. Smith, and D.L. Feller. 1979. Histiocytic lymphosarcoma of the trachea of a cat. J Am Anim Hosp Assoc 15(4):548–549. Schulman, A.J. and C.L. Lippincott. 1988. Rib pivot thoracotomy. Compend Contin Educ Pract Vet 10(8):927–930. Sfiligoi, G., A.P. Théon, and M.S. Kent. 2009. Response of nineteen cats with nasal lymphoma to radiation therapy and chemotherapy. Vet Radiol Ultrasound 48(4):388–393. Sheaffer, K.A. and A.R. Dillon. 1996. Obstructive tracheal mass due to an inflammatory polyp in a cat. J Am Anim Hosp Assoc 32(5):431–434. Smith, M.M. and D.R. Waldron, editors. 1993. Approaches for General Surgery of the Dog and Cat. Philadelphia: Saunders.

Straw, R.C., S.J. Withrow, E.L. Gillette, et al. 1986. Use of radiotherapy for the treatment of intranasal tumors in cats: Six cases (1980– 1985). J Am Vet Med Assoc 189(8):927–929. Tattersall, J.A. and E. Welsh. 2006. Factors influencing the short-term outcome following thoracic surgery in 98 dogs. J Small Anim Pract 47(12):715–720. Teske, E., A.A. Stokholf, T.S.G.A.M. Van den Ingh, et al. 1991. Transthoracic needle aspiration biopsy of the lung in dogs with pulmonic diseases. J Am Anim Hosp Assoc 27(3):289–294. Thrall, D.E., I.D. Robertson, D.A. McLeod, et al. 1989. A comparison of radiographic and computed tomographic findings in 31 dogs with malignant nasal cavity tumors. Vet Radiol Ultrasound 30(2):59–66. Tobias, K.M. 2007. Surgical stapling devices in veterinary medicine. Vet Surg 36(4):341–349. Turek, M.M and S.E. Lana. 2007. Canine nasosinal tumors. In Small Animal Clinical Oncology, 4th edition. S.J. Withrow and D.M. Vail, editors. St Louis: Saunders. Urshcel, J.D. 1996. Comparison of anastomotic suturing techniques in the rat trachea. J of Surg Oncol 63(4):249–250. Vasseur, P. 1979. Surgery of the trachea. Vet Clin N Am 9(2): 231–243. Veith, L.A. 1974. Squamous cell carcinoma of the trachea of a cat. Feline Pract 4(1):30–32. Walshaw, R. 1994. Stapling techniques in pulmonary surgery. Vet Clin N Am (Small Anim Pract) 24(2):335–366. Weyant, M.J., S.B. Manjit, E. Venkatraman, et al. 2006. Results of chest wall resection and reconstruction with and without rigid prosthesis. Ann Thorac Surg 81(1):279–285. Wheeldon, E.B. and T.C. Amis. 1985. Laryngeal carcinoma in a cat. J Am Vet Med Assoc 186(1):80–81. Wheeldon, E.B., P.F. Suter, and T. Jenkins. 1982. Neoplasia of the larynx in the dog. J Am Vet Med Assoc 180(6):642–647. Williams, J.M. and R.A.S. White. 1993. Median sternotomy in the dog: An evaluation of the technique in 18 cases. Vet Surg 22(3):246. Winek, T.G., T.M. Sasaki, D. Luallin, et al. 1988. Hemilaryngeal reconstruction using an axial island cheek flap supported by marlex and stainless steel wire mesh. Am J Surg 156(4):235–237. Withrow, S.J. 2007. Lung cancer. In Withrow and MacEwen’s Small Animal Clinical Oncology, 4th edition, pp. 517–525. S.J. Withrow and D.M. Vail, editors. St Louis: Saunders. Wood, E.F., R.T. O’Brien, and K.M. Young. 1998. Ultrasound-guided fine-needle aspiration for focal parenchymal lesions of the lung in dogs and cats. J Vet Intern Med 12(5):338–342. Wright, C.D., B.B. Graham, H.C. Grillo, et al. 2002. Pediatric tracheal surgery. Ann Thorac Surg 74(2):1033–1037. Wright, C.D., H.C. Grillo, J.C. Wain, et al. 2004. Anastomotic complications after tracheal resection: Prognostic factors and management. J Thoracic Cardiovas Surg 128(5):731–739. Yanoff, S.R., C. Fuentealba, H.W. Boothe, et al. 1996. Tracheal defect and embryonal rhabdomyosarcoma in a young dog. Can Vet J 37(3):172–173. Zekas, L.J., J.T. Crawford, and R.T. O’ Brien. 2005. Computer tomography-guided fine needle aspirate and tissue core biopsy of intrathoracic lesions in thirty dogs and cats. Vet Radiol Ultrasound 46(3):200–204. Zitz, J.C, S.J. Birchard, G.C. Couto, et al. 2008. Results of excision of thymoma in cats and dogs: 20 cases (1984–2005). J Am Vet Med Assoc 232(8):1186–1192.

9 Cardiovascular system Simon T. Kudnig, Eric Monnet

Heart and Heart-Base Tumors Common surgical procedures The most common surgical procedures undertaken for heart and heart-base 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 definitive diagnosis (Dunning et al. 1998). Removal of the pericardium without cardiac tumor excision, however, does remove the potentially beneficial 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 significantly 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 fifth intercostal thoracotomy is used depending on echocardiographic findings, and the cranial lung lobe is packed caudally with a moistened laparotomy sponge. The mass is identified and the mediastinal pleura dissected over the mass via sharp dissection, being careful to avoid adjacent structures including the vagus nerve, 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 fifth 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 (Kudnig et al. 2003) to improve visualization, thoracoscopic biopsy and pericardiectomy techniques are generally achieved without pulmonary exclusion (Dupre

Veterinary Surgical Oncology, First Edition. Edited by Simon T. Kudnig, Bernard Séguin. © 2012 by John Wiley & Sons, Ltd. Published 2012 by John Wiley & Sons, Ltd.

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Figure 9.1.  Echocardiogram identifying pericardial effusion (PE). RV, right ventricle; LV, left ventricle; LA, left atrium; RA, right atrium.

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. 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 is the most sensitive test for identifying pericardial effusion; however, it can be difficult to differentiate cardiac tumors from idiopathic pericardial effusion (Boon 1998). 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 fluid 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 identified (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, at which point there is an absence of pericardial effusion and a 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 infiltration 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 flow. The presence of pericardial effusion facilitates the identification 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 “floating” in the pericardial sac (Boon 1998) (Figure 9.2). Therapeutic and diagnostic pericardiocentesis is recommended at the time of echocardiography to treat pericardial tamponade. The results of pericardiocentesis rarely provide a definitive diagnosis as there is significant overlap in pericardial pH between neoplastic and nonneoplastic effusions (Fine et al. 2003), and there is significant 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 identified a significantly higher concentration in confirmed cases of hemangiosarcoma compared to cases with idiopathic pericardial effusion (Shaw et al. 2004). Abdominal ultrasonography is recommended when a cardiac tumor is identified to

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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.

evaluate for primary or metastatic lesions in the abdomen. Electrocardiographic changes are generally related to the effect of pericardial effusion which can result in dampening of the QRS, P-mitrale, 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 specific 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). Surgical techniques Preoperative treatment of pericardial effusion is imperative prior to any surgical intervention. Cardiac tamponade is a potentially life-threatening consequence of cardiac tumors and occurs when the intrapericardial pressure equals or exceeds right ventricular diastolic filling 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 fibrosis. Pericardiocentesis is the recommended means to restore

intrapericardial pressures and ventricular filling. The site of pericardiocentesis is between the costochondral junction and the sternum of intercostal spaces four, five, 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 artery. A rightsided 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 fluid that rarely clots. If the fluid clots, it is likely to have been inadvertently collected from the ventricle or coronary artery. As the pericardial fluid is removed, the resolution of the cardiac tamponade is manifested as a decreased heart rate, increased arterial pressure, and decreased central venous pressure. A minimum database and coagulation profile is 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). 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 appears to provide information superior to echocardiography regarding tumor resectability. Resectability is based on the size of the tumor and its location. Hemangiosarcomas are locally invasive tumors; clean margins are therefore difficult 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 significantly improve survival time (Ogilvie et al. 1996), subtotal pericardiectomy alone has not been found to prolong

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Figure 9.3.  A TA 30 stapler is placed across the base of the right auricle and fired.

survival times in dogs with cardiac hemangiosarcoma (Dunning et al. 1998). A right fourth or fifth 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 identified 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 fluid 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 fired, 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

Figure 9.4.  Placement of tangential forceps on the right auricle to remove a right auriclar hemangiosarcoma.

Figure 9.5.  Right auricle specimen after excision.

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, 9.5), and the auricle is incised distal to the clamp leaving a “cuff ” of tissue for suturing. 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. Thoracoscopic right auriculectomy can be

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performed using an Endo-GIA stapling device. A right intercostal approach is required to perform an auriculectomy under thoracoscopy. After performing a large pericardial window, the right atrial appendage is gently grabbed 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 has 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). Tumors involving the right atrium are more problematic to remove. Inflow occlusion is required in these cases, with Rumel tourniquets placed around the caudal and cranial vena cava and the azygous vein. The use of a pericardial patch graft to reconstruct the right atrium after resection of atrial tumors has been described (Brisson and Holmberg 2001). Alternatively, preplaced sutures are placed around the tumor, and these are tied after resection. 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 difficult 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. Postoperative care Postoperative management of surgical patients with cardiac or heart-base 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 fluid 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 (Kudnig et al. 2004; de Gray et al. 1997). 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 incisional related problems. Long-term complications include local disease recurrence, metastatic disease, and portal site metastasis (Brisson et al. 2006). Common tumor types and prognosis Cardiac tumor types include both benign and malignant tumors, with malignant tumor types being more common (Ware and Hopper 1999). 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 most common cardiac tumor types in cats are lymphoma and metastatic tumors (Tilley et al. 1981). Benign cardiac tumor types include fibroma, myxoma, and rhabdomyoma. Malignant cardiac tumor types include hemangiosarcoma, fibrosarcoma, rhabdomyosarcoma, and chondrosarcoma. The most common metastatic cardiac tumors in dogs include hemangiosarcoma, adenocarcinoma, osteosarcoma, and mast cell tumors (Aupperle et al. 2007; Ware and Hopper 1999). Primary cardiac tumors are more common than metastatic tumors (Ware and Hopper 1999). Heart-base tumors include chemodectomas, ectopic thyroid or parathyroid carcinomas, and aortic body tumors. Given the high metastatic rate of hemangiosarcoma in dogs, adjuvant chemotherapy is recommended to improve survival times in dogs (Weisse

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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 7 months of initial diagnosis (Dunning et al. 1998). Mean survival time in 38 dogs with cardiac hemangiosarcoma was 4 months in one study after surgery when adjuvant therapy was not used (Aronsohn 1985). Survival time in another study was significantly 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). 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 significantly longer survival time (730 days) compared to dogs that did not (42 days) (Ehrhart et al. 2002). A survival benefit 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 to 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 depends on the volume of the effusion, the rate of fluid accumulation, and the physical characteristics of the pericardium. A reduction in pericardial compliance can be seen with either pericardial neoplasia or chronic pericardial inflammation. 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 filling in mid to late diastole. This results in the atrial and ventricular tracings showing a rapid descent followed by an abrupt

Figure 9.6.  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 on the picture), a regular thoracic clamp can be placed ventral in order to apply traction to the pericardium. (Image courtesy of Dr. Gilles Dupré)

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 central venous pressure (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 fluid analysis is rarely diagnostic due to a difficulty in distinguishing between reactive mesothelial cells and tumor cells. Surgical techniques A pericardial window can be performed via thoracoscopy using a right lateral (Figure 9.6) or subxiphoid approach (Figure 9.7) (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 cm by 3 cm window is created with Metzenbaum scissors, and the pericardial biopsy is submitted for histopathology (Figure 9.9). 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

Cardiovascular System  335

Figure 9.7.  The patient is in dorsal recumbency, and the thoracoscope can be applied either subxiphoid (as on the picture) or paraxiphoid. One instrument is entered on each side of the chest. The ventral mediastinum is dissected, and the pericardium will be grasped from one side and cut from the other (Figure 9.8). (Image courtesy of Dr. Gilles Dupré)

Figure 9.9.  Thoracoscopic pericardial biopsy.

Moore et al. 1991). 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 definitive diagnosis (Dunning et al. 1998). Median survival time of 13.6 months has been reported for dogs with mesothelioma (Dunning et al. 1998). 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.

Carotid Body Tumors

Figure 9.8.  The pericardium is grasped under thoracoscopic visualization.

heart-base tumors. 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. Common tumor types and prognosis The most common pericardial tumor type is pericardial mesothelioma. Subtotal pericardiectomy is considered to be palliative, and intracavitary cisplatin is recommended to improve survival times (Closa et al. 1999;

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 flow Doppler sonography, which is useful to evaluate blood flow. Magnetic resonance imaging (MRI) is a useful imaging modality for carotid body tumors as it defines the soft tissue extent of the mass (Figure 9.10). Thoracic radiographs are recommended to evaluate for metastatic disease. Fine-needle aspirate of these masses is usually nondiagnostic (Obradovich et al. 1992). As with thyroid tumors, a preoperative incisional biopsy is not generally performed due to the risk of hemorrhage.

336  Veterinary Surgical Oncology

(a)

(b)

Figure 9.10.  Contrast-enhanced sagittal (A) and transverse (B) T1 MRI of a carotid body tumor at the carotid bifurcation (see arrows). (Image courtesy of Dr. Ralph Henderson)

Surgical techniques and prognosis Surgical resection of carotid body tumors is the treatment of choice (Figures 9.11, 9.12); however, local invasion can make removal difficult, 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. Preoperative transcatheter embolization techniques have been used in humans to decrease the morbidity associated with the surgery (Kafie 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, and lungs (Obradovich et al. 1992).

Vascular Oncologic Surgery—Tumor Emboli Excision Tumor emboli 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 posthepatic caudal vena cava can result in ascites, whereas involvement of the prehepatic caudal vena cava can result in rear limb edema. Only 8% of adrenal tumor thrombi, however,

Figure 9.11.  Surgical resection of a carotid body tumor at the carotid bifurcation. (Image courtesy of Dr. Ralph Henderson)

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). Diagnostic tests and imaging modalities Diagnostic evaluation of animals with suspected tumor emboli include ultrasonography, vascular contrast studies, MRI, CT, and coagulation profiles. Sensitivity and specificity of abdominal ultrasound to detect caval

Cardiovascular System  337

Figure 9.12. Carotid body tumor after resection. (Image courtesy of Dr. Ralph Henderson)

thrombi secondary to adrenal tumor emboli has been reported as 80% and 90%, respectively (Kyles et al. 2003). A minimum database and coagulation profile is recommended to evaluate for hypercoagulability. Thoracic radiographs are performed to evaluate for the primary tumor mass and metastatic disease. Thoracic ultrasonography with color flow 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 for venous occlusion secondary to tumor embolism (Figure 9.13). 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 fluoroscopy, 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 contrastenhanced helical CT (Holsworth et al. 2004; Louvet et al. 2005). Surgical techniques Surgical options for tumor emboli 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 (Las-

Figure 9.13.  Angiogram demonstrating invasion of a cranial mediastinal thymoma into the cranial vena cava. (Image courtesy of Dr. Julius Liptak and Dr. Geraldine Hunt)

celles et al. 2003; Esato et al. 1981) and jugular venografts (Holsworth et al. 2004) have been described for vascular reconstruction. Ligation of the cranial vena cava will 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 et al. 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” caudally to facilitate placement of a Rumel tourniquet cranial to it. 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.” 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 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

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vena cava results in decreases in systemic arterial pressure, decreased central venous pressure, 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 inflow 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 (Raffuci et al. 1953). Recent work has demonstrated that portal triad clamping results in significant 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 flow, altered vascular integrity, and abnormalities of the coagulation/fibrinolytic 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 embolectomy include 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-molecularweight 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 heparin-induced thrombocytopenia (Duplaga et al. 2001; Mischke et al. 2001; Hull and Pineo 1993). 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 1 week after surgery (Holsworth et al. 2004). Tumor embolectomy does not appear 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.

References Aupperle, H., I. Marz, C. Ellenberger, et al. 2007. Primary and secondary heart tumours in dogs and cats. J Comp Pathol 136(1):18–26. Aronsohn, M. 1985.Cardiac hemangiosarcoma in the dog: A review of 38 cases. J Am Vet Med Assoc 187(9):922–926. Bernard, F., S.T. Kudnig, and E. Monnet. 2006. Hemodynamic effects of interpleural lidocaine and bupivacaine combination in anesthetized dogs with and without an open pericardium. Vet Surg 35(3):252–258. Besso, J.G., D.G. Penninck, and J.M. Gliatto. 1997. Retrospective ultrasonographic evaluation of adrenal lesions in 26 dogs. Vet Radiol Ultrasound 38(6):448–455. Boon, J. 1998. Manual of Veterinary Echocardiography. Baltimore: Williams and Wilkins. Brisson, B.A. and D.L. Holmberg. 2001. Use of pericardial patch graft reconstruction of the right atrium for treatment of hemangiosarcoma in a dog. J Am Vet Med Assoc 218(5):723–725. Brisson, B.A., F. Reggeti, and D. Bienzle. 2006. Portal site metastasis of invasive mesothelioma after diagnostic thoracoscopy in a dog. J Am Vet Med Assoc 229(6):980–983. Brownlie, S.E. and D.G.C. Jones. 1985. Successful removal of a heartbase tumor in a dog with pericardial haemorrhagic effusion. J Small Anim Pract 26:191–197. Closa, J.M., A. Font, and J. Mascort. 1999. Pericardial mesothelioma in a dog: Long-term survival after pericardiectomy in combination with chemotherapy. J Small Anim Pract 40(8):383–386. de Gray, L., E.M. Rush, and J.G. Jones. 1997. A noninvasive method for evaluating the effect of thoracotomy on shunt and ventilation perfusion inequality. Anaesthesia 52:630–635. de Laforcade, A.M., L.M. Freeman, E.A. Rozanski, et al. 2005. Biochemical analysis of pericardial fluid and whole blood in dogs with pericardial effusion. J Vet Intern Med 19(6):833–836. Dunning, D., E. Monnet, E.C. Orton, et al. 1998. Analysis of prognostic indicators for dogs with pericardial effusion: 46 cases (1985– 1996). J Am Vet Med Assoc 212(8):1276–1280. Duplaga, B.A., C.W. Rivers, and E. Nutescu. 2001. Dosing and monitoring of low-molecular-weight heparins in special procedures. Pharmacotherapy 21(2):218–234. Dupre, G.P., J.P. Corlouer, and B. Bouvy. 2001. Thoracoscopic pericardectomy performed without pulmonary exclusion in 9 dogs. Vet Surg 30(1):21–27.

Cardiovascular System  339 Ehrhart, N., E.J. Ehrhart, J. Willis, et al. 2002. Analysis of factors affecting survival in dogs with aortic body tumors. Vet Surg 31(1):44–48. Esato, K., K. Shintani, S. Yasutake, et al. 1981. Experimental replacement of vena cava with expanded polytetrafluroethylene graft. Int Surg 66(3):227–232. Fine, D.M., A.H. Tobias, and K.A. Jacob. 2003. Use of pericardial fluid pH to distinguish between idiopathic and neoplastic effusions. J Vet Intern Med 17:525–529. Fossum, T.W. and S.J. Birchard. 1986. Lymphangiographic evaluation of experimentally induced chylothorax after ligation of the cranial vena cava in dogs. Am J Vet Res 47:967–971. Holsworth, I.G., A.E. Kyles, N.L. Bailiff, et al. 2004. Use of a jugular vein autograft for reconstruction of the cranial vena cava in a dog with invasive thymoma and cranial vena cava syndrome. J Am Vet Med Assoc 8(225):1205–1210. Holt, D., H.M. Saunders, L. Aronson, et al. 1999. Caudal vena cava obstruction and ascites in a cat treated by balloon dilation and endovascular stent placement. Vet Surg 28(6):489–495. Hull, R.D. and G.E. Pineo. 1993. Therapeutic use of low-molecularweight heparins. Haemostasis 23(Suppl 1):2–9. Hunt, G.B., C.R. Bellenger, and M.R. Pearson. 1996. Transportal approach for attenuating intrahepatic portosystemic shunts in dogs. Vet Surg 25(4):300–308. Hunt, G.B., R.K. Churcher, D.B. Church, et al. 1997. Excision of a locally invasive thymoma causing cranial vena caval syndrome in a dog. J Am Vet Med Assoc 210(11):1628–1630. Hunt, G.B., R. Malik, C.R. Bellenger, et al. 1992a. Total venous inflow occlusion in the normothermic dog: A study of haemodynamic, metabolic and neurological consequences. Res Vet Sci 52(3):371– 377. Hunt, G.B., R. Malik, C.R. Bellenger, et al. 1992b. A new technique for surgery of the caudal vena cava in dogs using partial venous inflow occlusion. Res Vet Sci 52(3):378–381. Jackson, J., K.P. Richter, and D.P. Launer. 1999. Thoracoscopic partial pericardiectomy in 13 dogs. J Vet Intern Med 13(6):529– 533. Kafie, F.E. and J.A. Freischlag. 2001. Carotid body tumors: The role of preoperative embolization. Ann Vasc Surg 15(2):237–242. Kudnig, S.T., E. Monnet, M. Riquelme, et al. 2003. Effect of one-lung ventilation on oxygen delivery in anesthetized dogs with an open thoracic cavity. Am J Vet Res 64(4):443–448. Kudnig, S.T., E. Monnet, M. Riquelme, et al. 2004 Cardiopulmonary effects of thoracoscopy in anesthetized normal dogs. Vet Anaesth Analg 31(2):121–128. Kyles, A.E., E.C. Feldman, H.E. De Cock, et al. 2003. Surgical management of adrenal gland tumors with and without associated tumor thrombi in dogs: 40 cases (1994–2001). J Am Vet Med Assoc 223(5):654–662. Lascelles, B.D., E. Monnet, J.M. Liptak, et al. 2003. Surgical treatment of right-sided renal lymphoma with invasion of the caudal vena cava. J Small Anim Pract 44(3):135–138. Lespinasse, W. 1947. Ligation of the vena cava above the renal veins with or without nephrectomy. Q Bull Northwest Univ Med Sch 21:312–316.

Louvet, A., P. Lazard, and B. Denis. 2005. Phaeochromocytoma treated by en bloc resection including the suprarenal caudal vena cava in a dog. J Small Anim Pract 46(12):591–596. Mischke, R., S. Grebe, C. Jacobs, et al. 2001. Amidolytic heparin activity and values for several hemostatic variables after repeated subcutaneous administration of high doses of a low molecular weight heparin in healthy dogs. Am J Vet Res 62(4):595–598. Moore, A.S., C. Kirk, and A. Cardona. 1991. Intracavitary cisplatin chemotherapy experience with six dogs. J Vet Intern Med 5(4):227–231. Nemec, A., J. Pecar, A. Seliskar, et al. 2003. Assessment of acid-base status and plasma lactate concentrations in arterial, mixed venous, and portal blood from dogs during experimental hepatic blood inflow occlusion. Am J Vet Res 64(5):599–608. Obradovich, J.E., S.J. Withrow, B.E. Power, et al. 1992. Carotid body tumors in the dog. Eleven cases (1978–1988). J Vet Intern Med 6(2):96–101. Ogilvie, G.K., B.E. Powers, C.H. Mallinckrodt, et al. 1996. Surgery and doxorubicin in dogs with hemangiosarcoma. J Vet Intern Med 10(6):379–384. Peacock, J.T., T.W. Fossum, A.M. Bahr, et al. 2003. Evaluation of gradual occlusion of the caudal vena cava in clinically normal dogs. Am J Vet Res 64(11):1347–1353. Raffucci, F.L. 1953. The effects of temporary occlusion of the afferent hepatic circulation in dogs. Surgery 33:342–351. Sabanathan, S., J. Eng, and A.J. Mearns. 1990. Alterations in respiratory mechanics following thoracotomy. J R Coll Surg Edinb 35(3):144–150. Shaw, S.P., E.A. Rozanski, and J.E. Rush. 2004. Cardiac troponins I and T in dogs with pericardial effusion. J Vet Intern Med 18(3):322–324. Stepien, R.L., N.T. Whitley, and R.R. Dubielzig. 2000. Idiopathic or mesothelioma-related pericardial effusion: Clinical findings and survival in 17 dogs studied retrospectively. J Small Anim Pract 41(8):342–347. Tilley, L.P., B. Bond, A.K. Patnaik, et al. 1981. Cardiovascular tumors in the cat. J Am Anim Hosp Assoc 17:1009–1021. Vicari, E.D., D.C. Brown, D.E. Holt, et al. 2001. Survival times of and prognostic indicators for dogs with heart-base masses: 25 cases (1986–1999). J Am Vet Med Assoc 219(4):485–487. Walsh, P.J., A.M. Remedios, J.F. Ferguson, et al. 1999. Thoracoscopic versus open partial pericardectomy in dogs: Comparison of postoperative pain and morbidity. Vet Surg 28(6):472–479. Ware, W.A. and D.L. Hopper. 1999. Cardiac tumors in dogs: 1982– 1995. J Vet Intern Med 13(2):95–103. Weisse, C., N. Soares, M.W. Beal, et al. 2005. Survival times in dogs with right atrial hemangiosarcoma treated by means of surgical resection with or without adjuvant chemotherapy: 23 cases (1986– 2000). J Am Vet Med Assoc 226(4):575–579. Wray, J.D., M. Bestbier, J. Miller, et al. 2006. Aortic and iliac thrombosis associated with angiosarcoma of skeletal muscle in a dog. J Small Anim Pract 47(5):272–277. Yoon, J., D.A. Feeney, D.E. Cronk, et al. 2004. Computed tomographic evaluation of canine and feline mediastinal masses in 14 patients. Vet Radiol Ultrasound 45(6):542–546.

10 Reproductive system Maurine J. Thomson, Tara A. Britt

Female Reproductive System Biopsy techniques Presurgical biopsy of ovarian or uterine masses is rarely indicated, as surgical resection remains the definitive treatment option and is unlikely to be influenced 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 confirm a malignant effusion (Klein 2007). 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 definitive 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 versus 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 definitive 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 definitive 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 are used to determine any evidence of 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 is recommended but oophorectomy can be performed. A standard ovariohysterectomy 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 16cm, 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.

Veterinary Surgical Oncology, First Edition. Edited by Simon T. Kudnig, Bernard Séguin. © 2012 by John Wiley & Sons, Ltd. Published 2012 by John Wiley & Sons, Ltd.

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oid 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. 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. 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. (Image courtesy of Dr. Phil Thomas)

Histologic tumor types Ovarian tumors are uncommon in dogs and cats due to early neutering in these species. They are generally classified as epithelial, germ-cell, sex-chord stromal, and mesenchymal in origin, according to the World Health Organization (WHO) classification. Two recent 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 (Infante et al. 1998; Patnaik and Greenlee 1987). 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 chord 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 polyp-

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 ovariohysterectomy and removal of metastatic foci if possible. Standard celiotomy and ovariohysterectomy is 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, fibroleiomyomas, leiomyosarcomas, adenomas, adenocarcinomas, and fibromas. 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 dermatofibrosis 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 findings at surgery or necropsy, though

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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 ovariohysterectomy 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 transfixation 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 in the rectum, and the vulvar area 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 identification 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 infiltrative and extensive lesions, such as malignancies (Figure 10.4). Dogs are placed in sternal recumbency and a purse-string suture 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 floor 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. 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 1990b (see Chapter 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 vagino-urethroplasty technique (see Chapter 11). Histologic tumor types Vaginal tumors are the second most frequently reported tumors of the female reproductive system, following

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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. (Photograph courtesy of Dr. Phil Thomas)

mammary tumors (Brodey and Roszel 1967; Lana et al. 2007; Murphy et al. 1994). 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 (TVT) most commonly occur on the external genitalia in endemic regions, appearing as a cauliflower-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 (Davies and Read 1990b; Magne et al. 1985; Norris et al. 1992) (see Chapter 11). Mast cell tumors

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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. (Photograph courtesy of Dr. Phil Thomas)

occur on the vulva and require resection with 2–3 cm margins and a tissue plane deep.

surgery depends on the size of the tumor, number of masses, and invasiveness into underlying tissues.

Prognosis

Lumpectomy

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 (Bilbrey et al. 1989; Davies and Read 1990b; Magne et al. 1985; 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.

In dogs, lumpectomy or nodulectomy is performed for small masses that are superficial and entails removing a margin of about 1 cm of skin and surrounding mammary tissue.

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 methotrexate, as in the treatment of bladder TCC, though insufficient data are available for dogs with urethral/vaginal tumors treated with chemotherapy to allow any assessment of an improved survival time. Canine mammary tumors Surgery Surgery is the treatment of choice for all mammary tumors, except patients with inflammatory carcinoma or distant metastatic disease. The type and extent of

Mammectomy Mammectomy or single mastectomy is the removal of a gland and is indicated for centrally located tumors 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 fifth mammary gland and is usually removed with it. The axillary nodes are difficult to access, rarely

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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. (Reproduced with permission from Bilbrey SA, 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).

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involved, and only removed if enlarged or cytologically positive (Lana et al. 2007). Radical mastectomy Radical 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 superficial epigastric artery and veins are identified 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. Bilateral removal of mammary glands 4 and 5 Bilateral removal of mammary glands 4 and 5 can be reconstructed with the use of flank fold flaps, as described by Hunt 1995 (Figure 10.5). Dogs are placed in dorsal recumbency and the skin 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 superficial epigastric arteries and veins usually need to be ligated. The flank folds are pulled away from the thigh and incised from the stifle toward the flank, leaving the base attached over the flank region. The medial and lateral aspects of the elevated flank 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 flaps 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 2 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 flank 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. 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. Ovariohysterectomy and mammary tumors The role of ovariohysterectomy (OHE) in the prevention of mammary tumors is widely accepted (Overley et al. 2005; Withrow and Susaneck 1986), but its role in the treatment of mammary tumors is controversial. The advantage of ovariohysterectomy at the time of resection of mammary tumors is unclear. Sorenmo et al. 2000 showed a survival benefit for those dogs treated with OHE at the time of mammary tumor removal or 2 years prior to presentation, compared to those intact or spayed longer than 2 years prior to presentation. However, three other recent papers did not show any survival advantage with OHE at the time of presentation (Morris et al. 1998; Yamagami et al. 1996; Philibert et al. 2003). Chang et al. 2005 did show a survival benefit with OHE at the time of mammary tumor removal, and this was more significant for dogs with complex carcinoma. Inflammatory mammary carcinoma Surgery is contraindicated for inflammatory carcinoma. These tumors are poorly differentiated carcinomas with extensive lymphatic involvement, edema, and marked inflammatory 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 half of mammary tumors in dogs are benign and the other half are malignant. Benign mammary tumors are cured with surgical resection. Factors that confer

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Figure 10.5.  Bilateral caudal regional mastectomy in the dog reconstructed with flank fold flaps 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 flank folds are pulled away from the thigh and incised from the stifle toward the flank, leaving the base attached over the flank region. The flank fold on the right side has been pivoted over the caudal abdominal defect. The point of the flap that was close to the stifle 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 flaps have been elevated bilaterally and sutured together on midline over the ventral abdominal defect. (Images courtesy of Dr. Julius Liptak)

a worse prognosis for canine malignant mammary tumors are masses greater than 3 cm, invasive masses, ulcerated masses, tumors present longer than 6 months, positive lymph nodes for neoplastic cells, poorly differentiated or anaplastic carcinoma, inflammatory carcinoma, lack of estrogen receptors, and invasion into the vascular or lymphatic system (Chang et al. 2005; Hellman et al. 1993; Lana et al. 2007; Philibert et al. 2003). 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 versus 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 a 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 6 months, had a much higher incidence of spread to regional lymph nodes.

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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 recent 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 chemotherapytreated 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). Feline Mammary Tumors Surgery Radical unilateral or bilateral mastectomy is the recommended surgical method for the treatment of feline

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malignant mammary tumors as it significantly reduces the chance of local recurrence (MacEwen et al. 1984). This technique is the method of choice regardless of the size of the tumor. Currently available data support performing a radical bilateral mastectomy in all cats (Novosad et al. 2006). 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 10-6). 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. A fentanyl patch can be placed 24 hours prior to surgery,

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Figure 10.6.  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, has 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. (Images courtesy of Dr. Julius Liptak)

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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 flaps as described above for the dog can also be used for cats. Many cats can have a radical bilateral mastectomy performed as a single procedure, but in some cats it needs to be staged 3–6 weeks apart where a radical unilateral mastectomy is performed twice. 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 can be done or not, 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. Histologic tumor types and prognosis Feline mammary tumors are malignant in over 85% of cases, with the majority being adenocarcinoma. Tumor size and lymphatic invasion are prognostic factors that consistently affect survival time for feline mammary tumors (Hahn and Adams 1997; Ito et al. 1996; MacEwen et al. 1984; Skorupski et al. 2005; Viste et al. 2002). In one study, median survival time without lymphatic invasion was 863 days versus 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 a median survival time greater than 3 years (Ito et al. 1996; Viste et al. 2002). A recent study demonstrated significantly improved survival times with the use of bilateral mastectomy with median survival time of 917 days versus 428 days for those with a regional mastectomy and 348 days for unilateral mastectomy (Novosad et al. 2006). Adjuvant therapy In one multicenter study, all cats underwent surgical resection followed by doxorubicin chemotherapy (Novosad et al. 2006). Cats with lymph node involvement had long survival times with a median greater than 1,500 days while those with pulmonary metastases had a median survival time of 331 days. Finishing all five doses of doxorubicin also positively affected prognosis with a median survival time of 442 days versus 117 days or less for those not completing the full course. Overall, 52% of cats developed metastatic disease. Ulcerated mammary tumors were associated with more advanced

disease, and anaplastic or high-grade tumors were also associated with shorter survival times. In this study, cats with tumors larger than 3 cm treated with surgery and chemotherapy had an overall median survival time of 416 days compared to historical controls of 4–6 months. Based on these results, surgery and chemotherapy can offer a better prognosis for cats with more advanced disease compared to surgery alone (Novosad et al. 2006).

Male Reproductive System Biopsy techniques Presurgical biopsy of testicular tumors is often not necessary, since castration will often provide a diagnosis and definitive treatment. However, FNA has been reported as a diagnostic test for testicular tumors (Spugnini et al. 2000). Penile masses can be diagnosed by FNA (Struble et al. 1997) or ultrasound-guided needle core biopsy. If the mass is ill defined on palpation, the aid of ultrasound guidance is advised. Cytology or biopsy of a penile mass should be performed to rule out nonsurgical tumors such as lymphoma (Struble et al. 1997) or transmissible venereal tumors that can occur in this region. Prostatic masses can be diagnosed by an ultrasoundguided needle core biopsy, ultrasound-guided aspiration, traumatic catheterization, endoscopic biopsy, and biopsy performed via a celiotomy. Traumatic catheterization is recommended over FNA and needle core biopsies because FNAs and needle core biopsies performed on carcinomas, especially transitional cell carcinoma, can seed the needle tract with neoplastic epithelial cells (Nyland et al. 2002). Lymphoma has been reported in the prostate and can be diagnosed by FNA (Winter et al. 2006). Diagnostic imaging Testicular tumors undetected on physical examination are sometimes detected as incidental findings with ultrasound or other advanced imaging modalities such as MRI or CT. In one study, 28% of dogs that were castrated and with undetectable testicular tumors on physical examination had evidence of tumor on histopathology (Peters et al. 2000). Testicular tumors are the most common tumor of the male genitalia and the second most common tumor found in sexually intact male dogs (Fan and De Lorimier 2007). Testicular tumors detected on physical examination in most cases will be amenable to surgical resection. Retained testicles are best evaluated for tumors with ultrasound or surgical exploration with removal and biopsy. Less than 15% of patients with testicular tumors will develop distant metastasis (Fan and De Lorimier 2007). Chest radiographs and

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abdominal ultrasound are advised as part of the staging process since metastasis to the liver, lungs, kidneys, spleen, adrenals, pancreas have been detected (Fan and De Lorimier 2007). Ultrasound is the most accessible diagnostic tool for evaluating prostatic and penile neoplasms, as well as for detection of metastasis to abdominal organs, including sublumbar lymph nodes. Thoracic radiographs are important to rule out evidence of pulmonary metastasis in patients with prostatic or penile neoplasms. Concurrent lameness should be evaluated with radiography since carcinomas can metastasize to bone. Advanced imaging such as CT or MRI can be used to evaluate the extent of the local tumor as well as to screen for distant metastasis. These advanced tools may be helpful for larger tumors to aid in planning the surgical resection, but in many cases are not necessary. Testicular tumors Orchiectomy Preoperative considerations Serum hormone concentrations may be abnormal in patients with Sertoli cell tumors and seminomas. Hyperestrogenism can lead to hematologic abnormalities. Complete blood counts can show pancytopenia, including nonregenerative anemias, leukopenias, and thrombocytopenias. Bone marrow evaluation in these patients is recommended. Bone marrow regeneration can occur after tumor removal but may take several weeks or even months. A more guarded prognosis should be given to patients with bone marrow abnormalities since coagulation abnormalities and infection are more likely in affected patients. Surgical decision making Surgery is the best treatment option for testicular tumors. A scrotal ablation with en bloc bilateral orchiectomy should be performed in patients with a testicular tumor within a testis that has descended into the scrotum, especially if there are scrotal adhesions. If a testicular tumor is an incidental finding after a routine closed prescrotal castration, and the tumor has not grossly broken through the parietal vaginal tunic, the testes can be submitted for histologic evaluation prior to performing additional surgery. In the author’s opinion, most cases will not require additional surgery since the majority of these tumors are within the testicular parenchyma and do not invade into the parietal vaginal tunic. A celiotomy for an orchiectomy should be performed if a testicular tumor has developed in a retained

Figure 10.7.  Sertoli cell tumor of a cryptorchid testicle with torsion. (Photograph courtesy of Dr. Julius Liptak)

cryptorchid testis (Figure 10.7). Abdominal testicular tumors can become very large, up to 15 cm in one review (Post and Kilborn 1987) (Figure 10.8). The testicular artery, vein, and ductus deferens should be individually double-ligated and the tumor removed. The abdominal organs should be evaluated for evidence of metastasis and a biopsy performed if suspicious areas are found. Gloves and instruments should be changed and the abdomen thoroughly lavaged after tumor removal. Sublumbar lymph nodes extirpation is warranted if lymphadenopathy is present to differentiate between reactive nodes and metastatic disease. Histologic types As previously stated, testicular tumors are the most common tumor of the male genitalia and the second most common tumor found in intact male dogs (Fan and De Lorimier 2007). The most common tumors of the testicles include Sertoli cell tumors (Figure 10.8), Leydig cell tumors (interstitial), and seminomas, each of which has been shown to occur with equal frequency (Cotchin 1960). However, in a study from the Netherlands, Leydig cell tumors and seminomas were found to occur in equal numbers, but Sertoli cell tumors were much less common (Peters et al. 2000). This study evaluated clinically detected testicular tumors (n = 28), as well as the incidence of nonclinically detected tumors from dogs castrated for reasons other than testicular disease (n = 74). The dogs with clinically detectable testicular tumors ranged in age from 6 to 16 years. Bilateral tumors were found in 61% of the dogs with clinically detected testicular tumors, and multiple tumors within one testis were found in 46% of the dogs (Peters et al. 2000). The majority (86%) of the clinically detected tumors were found in the geriatric dogs (Peters et al. 2000). Twenty-eight percent of clinically normal dogs (21 of

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Figure 10.9.  Gynecomastica in a male dog with a Sertoli cell tumor. (Photograph courtesy of Dr. Julius Liptak)

Figure 10.8.  Sertoli cell tumor (left) after castration. Note the size difference between the normal testicle (right) and testicle with the tumor (left). (Photograph courtesy of Dr. Julius Liptak)

74) had evidence of tumor on histopathology. Many of these dogs had bilateral tumors or multiple tumors in a single testicle. Forty nonclinically detected tumors were found in 21 dogs. There does not seem to be a breed disposition. Extraskeletal osteosarcoma (Patnaik 1990), rete testis mucinous adenocarcinoma (Radi et al. 2004), and testicular efferent ductile cysts (Wakui et al. 1997) have also been reported in the testis. Feminization syndrome may be seen secondary to Sertoli cell tumors and seminomas and is caused by hyperestrogenemia or an increased estrogen-to-testosterone ratio. Clinical signs of feminization include gynecomastia (Figure 10.9), alopecia, decreased libido, pendulous swelling of the prepuce and atrophy of the penis (Post and Kilborn 1987), redistribution of fat, and onset of hypothyroidism (Brodey and Martin 1958). These clinical signs usually resolve 2–6 weeks after tumor removal, but recovery is variable (Post and Kilborn 1987). Some reports show that hyperestrogenism is present in one-third of Sertoli cell tumor patients (Brodey and Martin 1958). Atrophy of the contralateral testis is often seen due to the lack of secretion of gonadotrophic hormones from the anterior pituitary caused by excessive circulating estrogen or estrogen-like substances (Post and Kilborn 1987; Brodey and Martin 1958). Extratesticular interstitial and Sertoli cell tumors in previously castrated dogs and cats is rare but has been reported in 17 cases, 12 dogs and 5 cats (Doxsee et al.

2006). The mean age of castration of the dogs was 8.5 months, and the mean age of identification of the tumor was 9.2 years. The mean age of castration of the cats was 10 months, and the mean age of identification of the tumor was 9.6 years. The size of the tumors varied with a range of 1.5–5.5 cm3 in the dogs and 1–1.5 cm3 in the cats. The location of the extratesticular tumors in the dogs varied and were found in the spermatic cord (n = 6), scrotal skin (n = 4), and the prescrotal incision site (n = 2). The extratesticular tumors were found in the scrotal skin (n = 2) and the spermatic cord (n = 3) in the cats. One of the 11 dogs with Sertoli cell tumor displayed feminization, and all five cats exhibited tom cat behavior. None of these cases had metastases or recurrence after surgical excision. The authors of this study proposed that transplantation of testicular cells may have occurred during the castration either by excessive pressure on the testis resulting in embolization of testicular cells into the pampiniform plexus or by inadvertent incision through the tunica albuginea (Doxsee et al. 2006). Therefore, placing pressure on the testis and incising the tunica albuginea should be avoided during routine castration (Doxsee et al. 2006). Prognosis Most testicular tumors are localized, and surgical removal will result in a cure. Less than 15% of testicular tumors will metastasize (Fan and De Lorimier 2007). It is possible that tumors resulting in feminization syndrome are more likely to be infiltrative and have a higher metastatic and mortality rate (Doxsee et al. 2006). Metastasis occurs primarily through the lymphatics (Post and Kilborn 1987; Weaver 1983). Surgical removal of metastatic sublumbar nodes should be considered and may improve the long-term prognosis in the absence of visceral metastasis. There has been one documented case of canine hypertrophic osteoarthropathy

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associated with pulmonary metastasis from a malignant Sertoli cell tumor (Barrand and Scudamore 2001). Metastasis has been reported to the liver, lungs, kidneys, spleen, adrenals, pancreas, skin (Doxsee et al. 2006), eyes, and central nervous system (Fan and De Lorimier 2007). Prostatic tumors Surgical considerations Radical surgical resection of prostatic tumors via total prostatectomy has the potential for many complications, including urinary incontinence, necrosis of the bladder neck, and urethral stricture. In general, there is a high risk of complications associated with total prostatectomy that are not compatible with a good quality of life or acceptable to owners. Since total prostatectomies have not been shown to increase survival time in patients with prostatic carcinoma, this technique is not commonly used (White 2000). If attempted, careful case selection and thorough client education are extremely important. Many clinicians recommend other forms of treatment for prostatic neoplasms, including subtotal prostatectomy, and palliative procedures, such as urethral stenting, transurethral resection, cystotomy tube placement, radiation therapy, NSAID therapy, and chemotherapy (Freitag et al. 2007; Goldsmid and Bellenger 1991; Weisse et al. 2006). Other techniques that have been described but abandoned due to complications include ureterocolonic anastomosis (Stone, Walter et al. 1988; Stone, Withrow et al. 1988), gastric conduit urinary diversion (McLoughlin et al. 1992a, 1992b), and enterocystoplasty with cystectomy (Fries et al. 1991). Overall, the prognosis for prostatic tumors is poor to grave, and without treatment affected patients are generally euthanized within a month of diagnosis (Freitag et al. 2007). Currently, there is no standard of care agreed upon. Surgical techniques and outcomes Total prostatectomy Briefly, a total prostatectomy is performed through a caudal ventral midline celiotomy (Goldsmid and Bellenger 1991). A pubic osteotomy or symphysiotomy may be necessary to improve exposure (Freitag et al. 2007). A urinary catheter is aseptically placed (Goldsmid and Bellenger 1991). The bladder is retracted cranially, and the deferent ducts are ligated and transected. The peritoneal and retroperitoneal fat is dissected from the prostate as close to the prostate as possible and reflected laterally (Figure 10.10A). The neurovascular supply to

the bladder is preserved. The prostatic branches of the urogenital vessels are cauterized or ligated as close to the prostate as possible. The urinary catheter is withdrawn so that the urethra cranial to the prostate can be transected as close to the prostate as possible. The urethra caudal to the prostate is also transected as close to the prostate as possible (Figure 10.10B). Stay sutures are placed to prevent rotation of the remain­ ing urethra, and the urinary catheter is advanced across the defect into the bladder. The urethra is anastomosed with simple interrupted sutures using a 4-0 monofilament absorbable suture material (Goldsmid and Bellenger 1991) (Figure 10.10C). A cystostomy tube and/or urinary catheter can be maintained postoperatively. Goldsmid and Bellenger reported a 33% incontinence rate after total prostatectomies in 11 dogs with prostatic disease, suggesting that this lower rate of incontinence compared to other studies may have been from careful dissection close to the prostatic wall, avoidance of important neurovascular structures, and the preservation of more prostatic urethra by undermining both the cranial and caudal extents of the prostate. These authors also suggested that there may be an association between preoperative incontinence and prostatic neoplasia and postoperative incontinence. Of the three dogs in this study that had postoperative urinary incontinence, one had urinary incontinence as a presenting complaint, one had a prostatic neoplasia, and one had both a prostatic neoplasia and preoperative urinary incontinence. Most of the dogs in this study underwent a total prostatectomy for prostatitis. Interestingly, in a study evaluating total prostatectomy in dogs without prostatic disease, all 10 dogs were continent postoperatively, suggesting that incontinence may be associated with the underlying prostatic disease combined with the surgery (Basinger et al. 1987). Urinary incontinence is the most common complication after total prostatectomy as reported in 33%–100% of all cases (Freitag et al. 2007; Goldsmid and Bellenger 1991). Due to this high complication rate, total prostatectomy is generally not recommended. However, the total prostatectomy may become a more viable option for dogs with prostatic neoplasia as the technique becomes more refined and as early detection leads to smaller lesions more amenable to surgery. Subcapsular partial prostatectomy Variation on subcapsular partial prostatectomies have been described, including enterocystoplasty with cystectomy and subtotal intracapsular prostatectomy, subtotal prostatectomy using an ultrasonic surgical aspirator, and subtotal prostatectomy using Nd:YAG laser. In 1991,

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(a)

(b)

(c)

Figure 10.10. (A) Approach to the prostate (arrow), which involved a pubic symphysiotomy. The Finochietto retractors are retracting the symphysiotomy site. (B) A urethrotomy has been performed cranial (small arrow) and caudal (large arrow) to the prostate. A urinary catheter is present in the urethra. (C) A vesicourethral anastomosis has been performed (arrow). (Photograph courtesy of Dr. Julius Liptak)

the results of enterocystoplasty with cystectomy and subtotal intracapsular prostatectomy in eight healthy dogs were published (Fries et al. 1991). The parenchyma and prostatic urethra were removed via a ventral midline incision in the prostate. The prostatic capsule was closed along the ventral incision. The bladder was excised, and both ureters were transplanted via submucosal tunnels into the wall of a resected portion of jejunum that still contained an intact blood supply. This portion of jejunum was closed on one end and sutured to the hollow prostatic capsule, mimicking the urinary bladder. Complete obstruction of the ureterointestinal anastomosis occurred in four dogs, and all dogs were incontinent postoperatively with gradual improvement between 2 and 6 weeks after surgery. Urination occurred at hourly intervals since the portion of intestines was unable to

store concentrated urine because it was permeable to water and urinary solutes. Complications included cortical scarring in the kidneys, capsular adhesions, increased BUN from reabsorption of urea via the intestines. The technique was deemed feasible; however, the frequency of urination was too high for most client-owned pets, and the procedure cannot be recommended. Performing an intracapsular subtotal prostatectomy using an ultrasonic surgical aspirator has also been described (Rawlings 1994). This study was performed with seven healthy dogs, and the authors do not recommend this technique for dogs with neoplasia since most neoplasia also involves the urethra. An Ultrasonic Surgical Aspirator (CUSA) System 200 Macro-Dissector can be used to alter tissues high in water content such that their cells are fragmented, irrigated, emulsified, and

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aspirated (Rawlings 1994). The vibrator should be able to discriminate nerves, vessels, and collagenous connective tissue from glandular tissue, which has a higher water content. Partial prostatectomy for prostatic carcinomas has been described in eight dogs using Nd:YAG laser dissection (L’Eplattenier et al. 2006). The goal is careful dissection of the prostatic parenchyma for maximal tumor excision while controlling hemorrhage and avoiding neurovascular structures on the dorsolateral surface. In these eight patients with prostatic carcinoma, a urinary catheter was placed and a ventral caudal celiotomy performed to expose the prostate. The prostate was visualized by retracting the bladder and dissecting the periprostatic fat from the ventral surface while preserving the blood supply and innervation from the pelvic and hypogastric nerves on the dorsal surface (White 2000; L’Eplattenier et al. 2006). The Nd:YAG laser with a 600 µm optical fiber was used at 10 W (continuous wave) to incise the ventral midline of the prostate. Blunt dissection was used to separate the prostatic tissue from the capsule, and the laser was used to remove prostatic parenchyma while maintaining an intact urethra and dorsal capsule. The capsule was trimmed to remove dead space while closing the prostatic capsule over the urethra in a continuous pattern (L’Eplattenier et al. 2006). These patients also received intraprostatic injections of IL-2 and oral meloxicam (COX-2 inhibitor). Median survival times for these patients was 103 days, and none were incontinent; however, three patients died within 16 days of the procedure (L’Eplattenier et al. 2006). These three patients died or were euthanized because severe dysuria did not resolve in one postoperatively, bilateral ureteral obstruction occurred in another from tumor in the trigone region, and the last patient that died shortly after surgery had coagulation abnormalities and decreased albumin. Five dogs recovered well, and their clinical signs improved or resolved. None of these dogs developed urinary incontinence. The median survival time of these five dogs was 183 days (91–239 days). All dogs were eventually euthanized because of tumor progression into the lumen of the urethra or wall of the rectum. Retained urethral catheter after total prostatectomy and subtotal prostatectomy Placing a retained urethral catheter after either a total prostatectomy (n = 1) or concurrent with a subtotal prostatectomy (n = 2) was reported in three dogs (Mann et al. 1992). One dog had developed a urethral stricture after a total prostatectomy for prostatic adenocarcinoma. Bougienage was attempted to dilate the urethra

but failed. Nine weeks after a total prostatectomy a retained urinary catheter was placed. The dog was positioned in sternal recumbency with a polypropylene urinary catheter in place from the penile urethra into the bladder. A perineal urethrotomy was performed, the polypropylene catheter was removed, and a percutaneous nephrostomy catheter, modified by cutting off the tubing connector, was placed into the urethra at the urethrotomy site across the area of stricture. The skin was closed over the urethrotomy site. Radiation therapy was administered postoperatively. The other two dogs had the catheters placed concurrently with a subtotal prostatectomy. One dog was diagnosed with transitional cell carcinoma, and the other dog had prostatic adenocarcinoma. Modified nephrostomy catheters were placed from the urinary bladder via a cystotomy to the urethra in each dog. Complications postoperatively included hematuria, secondary to cystitis or urinary tract infections, and incontinence. The incontinence was expected postoperatively due to the conduit placed from the bladder to the penile urethra. Incontinence was present in the prostatectomized patient; however, incontinence was initially mild in the dogs that underwent a subtotal prostatectomy and actually resolved in one of these dogs. The authors concluded that the ideal location for the distal aspect of the catheter was caudal to the os penis for improved continence postoperatively. The nephrostomy tube used contained a coil that prevents dislodgement as it can only be straightened with a guide wire. Also, the nephostomy tubes are less likely to become obstructed by nearby tissue compared to other catheters since the fenestrations are on the inner curve of the coil. Tube cystostomy Placement of cystostomy tubes have been described in dogs and cats for palliative treatment of lower urinary tract obstruction (Beck et al. 2007; Smith et al. 1995). Generally, a ventral midline celiotomy is performed and the bladder is isolated. A purse-string suture is placed in the ventral wall of the bladder slightly off midline, and a stab incision is performed in the center of the purse string. A corresponding paramedian incision in the body wall is performed approximately 2 cm from midline. A mushroom-tip urinary catheter, Foley catheter, or a low-profile tube can be placed through the body wall and into the bladder. The purse string is secured once the catheter is placed into the bladder, and a cystopexy is performed. A cystopexy can be performed with four to five interrupted mattress sutures or two continuous suture patterns using absorbable

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monofilament suture material, allowing a seal between the bladder and body wall. A purse-string suture is placed in the skin around the tube site and can be combined with a Chinese finger-trap suture to secure the tube to the body wall. The median time tubes were in place for obstructive urinary tract neoplasia in one study was 83 days; however the duration ranged from 1 to 363 days (Beck et al. 2007). In general, the bladder is drained via the tube four times daily. There is a high complication rate associated with cystostomy tubes according to Beck et al. (2007), with almost 50% of patients having either a major or minor complication. Inadvertent tube removal was the most common complication occurring in 15% (12 of 76) of patients in this study. Uroperitoneum occurred in 5 of these 12 patients. Other complications resulting in a second surgery or euthanasia included the patient chewing on the tube (n = 2), breakage of the mushroom tip on removal (n = 2), fistula formation around the tube (n=1), persistent urinary leakage (n = 1), mushroom tip erosion (n = 1), and nonreducible rectal prolapse that possibly occurred secondary to the tube (n = 1). Minor complications or complication that did not require a second surgery included irritation or inflammation around the tube (n = 7), urine leakage around the tube (n = 7), hematuria (n = 3), bandage sores (n = 2), breakage of the suture securing the tube to the skin (n = 2), discomfort when emptying the bladder (n = 5), and urinary tract infections (21 of 24). Low-profile cystostomy tubes can be converted from long silicone gastrostomy tubes or be purchased as lowprofile tubes (Passport Low Profile Gastrotomy Device, Cook Veterinary Products, Spencer, IN) (Stiffler et al. 2003; Salinardi et al. 2003). These tubes are placed in a similar manner (Salinardi et al. 2003). They can also be used to replace a mushroom-tipped or Foley cystostomy 3 weeks after original placement when a mature cystocutaneous fistula has formed. General anesthesia is required to place a low-profile tube through a mature fistula. Generous amounts of lubrication and stretching of the distal end of the tube is advised; however, if the fistula is too small, a caudal celiotomy may be necessary to hold the bladder and body wall steady during insertion. If the latter is not possible, a cystotomy can be performed for normograde placement of a tube through the mature cystocutaneous fistula. Stiffler et al. recommend that the length of the low-profile tube from the skin to the valve is 1–3 cm to maximize the ease of grasping the valve without compromising the low profile feature. The antireflux valve that comes with the low-profile system is designed for use with an extension set. One common complication associated

with the antireflux valve is urine leakage (Stiffler et al. 2003). Urethral stenting For further information on urethral stenting, see Chapter 11. Urethral stenting is a palliative procedure that can generally be performed when the tumor is causing complete or partial obstruction of the urethra. Urethroscopy is performed to evaluate the extent of disease, and ideally, fluoroscopy is used to guide the placement of either a balloon-expandable metallic stent or a selfexpandable metallic stent (Weisse et al. 2006). Weisse et al. described urethral stenting in 12 dogs, and 8 of these were male dogs. Seven of the 8 male dogs were treated for prostatic carcinoma or adenocarcinoma, and 1 had osteosarcoma of the prostate (Weisse et al. 2006). In male dogs, the penis is manually extruded from the prepuce and an angled floppy-tip hydrophilic guidewire (0.035 inch diameter) is inserted into the urethra and advanced into the bladder using fluoroscopic guidance. A vascular sheath (7 French) and dilator are placed over the guidewire and advanced into the penile portion of the urethra. The penis is released, and the vascular sheath is sutured to the prepuce. The dilator is removed and an angiocatheter (4 French angled) is advanced into the bladder, allowing the guidewire to be removed. A cystourethrogram is used for evaluation of the urethra by distending the bladder with a 50:50 mixture of iohexol and sterile saline (Figure 10.11A). The catheter should be withdrawn to the distal part of the urethra, and the iohexol solution is injected under pressure to maximally distend the urethra. It is important to fill the bladder completely so that the caudal portion of the bladder is not mistaken for the proximal urethra (Weisse et al. 2006). The urethral diameter was measured, and regardless of the type of stent chosen, the stent size was chosen so that it would be 10% greater than the maximum luminal diameter determined by the contrast study. The goal of the stent is to have adequate mucosal apposition and minimize the chance of migration while reducing the risk of trauma to the urethral wall (Weisse et al. 2006). The ideal length of the stent is such that it does not extend further than 1 cm cranial and 1 cm caudal to the lesion (Weisse et al. 2006). In order to place the balloon-expandable metallic stents (BEMSs), balloon dilation was performed at the narrowed portion of the urethra to prevent displacement of the stent during advancement over the guidewire (Weisse et al. 2006). Following balloon dilation, the balloon-expandable stent was placed over the wire into position, and the balloon was expanded to a pressure of

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(a)

(b)

(c)

Figure 10.11.  (A) Cystourethrogram demonstrating a markedly narrowed prostatic urethra (arrow). Note the marker catheter in the colon used for determination of the size of the stent. (B) The self-expandable metallic stent (SEMS) in its sheath has been advanced over the guidewire and has been positioned across the prostatic urethra. (C) Cystourethrogram after deployment of SEMS verifying patency of urethra. (Images courtesy of Dr. Chick Weisse)

8 atm to position the stent against the urethral wall. Then the balloon is deflated and removed over the wire. One advantage to BEMSs is that they do not foreshorten, thus a more precise delivery is possible compared to some self-expandable stents that do foreshorten during placement (Weisse et al. 2006). Disadvantages of BEMSs include their relatively short length, sometimes necessitating placement of more than one stent, decreased flexibility, and decreased elasticity (Weisse et al. 2006). Self-expandable metallic stents (SEMSs) have become more commonly used compared to the BEMS. They are protected by a sheath system and do not need a balloon for deployment (Weisse et al. 2006). For delivery, the stent in its sheath is advanced over the guidewire and positioned across the obstruction (Figure 10.11B). The sheath is then removed. The SEMS used by Weisse et al. were nitonol (laser-cut nickel-titanium alloy), which do not undergo foreshortening. They are also flexible and have moderate expansile strength. After placement of either type of stent, a positivecontrast cystourethrogram was performed to verify

patency of the urethra (Figure 10.11C). Patients are generally maintained on intravenous fluids for 12 hours to maintain urine flow and minimize the potential for blood clot formation in the lower urinary tract (Weisse et al. 2006). Complications associated with urethral stent placement include dislodgement, stranguria, incontinence, and tumor progression. In the male dogs that had stents placed by Weisse et al., all but one could voluntarily urinate. Four of these maintained continence, 2 had mild incontinence, and 1 had severe incontinence. The median survival time in the study reported by Weisse et al. was 20 days for all 12 dogs (males and females) (range 6–105 days), and in 10 dogs the cause of death was not associated with urinary tract obstruction. Transurethral resection For further information on transurethral resection (TUR), see Chapter 11. TUR is a palliative technique that allows debulking of the tumor within the urethra. It requires special equipment and technical skill. This

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Figure 10.12.  Cystoscopic image of the prostatic urethra infiltrated with TCC. The cauterized cutting loop (arrow) is used to remove obstructive tissue. (Image courtesy of Dr. Julius Liptak)

technique was reported in three male patients as treatment for prostatic and urethral malignancies (Liptak et al. 2004). In the male dogs, a ventral cystotomy was performed using a rigid 2.9 mm, 12-degree oblique cystoscope. The bladder and urethra are dilated with sterile water or 1.5% glycine, and the transurethral resection is performed with a specialized cystoscopic cauterized cutting loop under direct cystoscopic observation. A piece of proliferative neoplastic tissue is isolated with the loop and the loop is retracted as it is activated (hot cutting) or inactivated (cold cutting) (Liptak et al. 2004) (Figure 10.12). This technique is repeated until a urethral diameter of approximately 12 mm is achieved. Hemorrhage is controlled with a cystoscopic coagulation rollerball. Two of the male dogs in this study had prostatic transitional cell carcinoma (TCC), and the other had undifferentiated prostatic carcinoma (Liptak et al. 2004). One of the male dogs was treated for prostatic TCC with a combination of transurethral resection, intraoperative radiation therapy, and piroxicam and mitoxantrone every 3 weeks for five treatments. This dog was able to urinate unassisted postoperatively, with dysuria and stranguria present for only 5 days. At 6 months after surgery, this dog developed sublumbar lymphadenopathy and implantation of TCC into the site of the cystostomy incision. Transurethral resection was repeated, and

the iliac lymph nodes were extirpated. Within 24 hours, this dog developed hypoproteinemia and dependent edema. A urethral rupture was diagnosed by a positivecontrast urethrogram, and the patient was euthanized 264 days after the initial transurethral resection procedure (Liptak et al. 2004). Another male dog was treated for prostatic TCC with transurethral resection. The cystoscope identified proliferative tissue from the trigone of the urinary bladder to the prostatic urethra. Transurethral resection was performed, and the patient was able to urinate normally at 24 hours after surgery. This dog was euthanized 74 days after TUR for distant TCC metastasis. The third male dog was diagnosed with undifferentiated prostatic carcinoma. Cystourethroscopy with transurethral resection followed by intraoperative radiation therapy was performed. Urination was normal within 24 hours after surgery, and defecation was normal within 72 hours. However, the dog was euthanized at 32 days due to caudal abdominal pain and dyschezia. It is suspected that colonic perforation occurred secondary to the radiation therapy or that there was colonic obstruction secondary to local recurrence (Liptak et al. 2004). The most common complication reported in this study by Liptak et al. is perforation of the urethral wall, which occurred in one of three male dogs and two of three female dogs. The authors feel that caution should be used if attempting cystoscopy in a patient less than 15 kg due to the small urethral size. Urethral perforations were managed by urine diversion using a combination of a cystostomy tube and indwelling urinary catheters. Full-thickness defects generally heal within 7 days by second intention (Liptak et al. 2004). Another possible complication is called TUR syndrome. This syndrome is a result of excessive absorption of lavage fluids during the procedure. It is dependent on the hydrostatic pressure of the fluid, vascularity of the prostate and urethra, type of lavage fluid, and duration of exposure to the fluid (Liptak et al. 2004). Excessive fluid absorption can cause circulatory overload, hyponatremia, glycine and ammonia toxicity, hypothermia, and neurologic signs secondary to cerebral edema (Liptak et al. 2004). TUR syndrome is more likely to occur after a perforation since the peritoneum has a large surface area capable of absorption. Histologic tumor types and prognosis Prostatic tumors are rare in dogs and even more rare in cats. There is an increased risk in neutered male dogs (Teske et al. 2002; Bryan et al. 2007; Sorenmo et al. 2003). In fact, castration has no effect on disease pro-

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gression nor does it prevent occurrence of prostatic carcinoma (Teske et al. 2002). All reported prostatic tumors are malignant, with adenocarcinoma and undifferentiated carcinomas being the most common (Mann et al. 1992; Krawiec and Heflin 1992; Krawiec 1994). Other histologic types of prostatic carcinoma include prostatic TCC, squamous cell carcinoma, as well as extension of carcinomas from the urinary bladder (Mann et al. 1992). Leiomyosarcoma and lymphoma have also been reported in the prostate (Mann et al. 1992; Struble et al. 1997; Winter et al. 2006). Clinical signs of patients with prostatic neoplasia include tenesmus, weight loss, stranguria, dysuria, and lower urinary tract infection (Krawiec and Heflin 1992; Krawiec 1994). Other signs include systemic illness, hind limb weakness and/or lameness, and pain (Krawiec and Heflin 1992; Krawiec 1994). Prostatic carcinomas are locally invasive and can grow into the urethra causing urinary obstruction (Krawiec and Heflin 1992; Krawiec 1994). They may also extend dorsally into the colon, cranially into the bladder, and into the pelvic musculature. However, not all patients with prostatic carcinoma have an enlarged prostate (Krawiec and Heflin 1992; Krawiec 1994). Metastasis is common, occurring most frequently to the iliac lymph nodes and also to the lumbar spine and lungs (Krawiec and Heflin 1992; Krawiec 1994).

Figure 10.13.  Elliptical incision around the prepuce and penis prior to a penile amputation. (Photograph courtesy of Dr. Julius Liptak)

Penile tumors Surgery Penile amputation Surgical treatment of penile tumors, such as squamous cell carcinoma and sarcomas, will likely require a penile amputation and prescrotal urethrostomy. In general, an elliptical incision is performed around the prepuce, penis, and scrotum (if scrotal ablation is to be performed), maintaining wide surgical margins from the tumor but saving adequate skin for closure (Figure 10.13). The penis is dissected cranial to caudal from the body wall (Figure 10.14). If necessary, a scrotal ablation is also performed. A urinary catheter is placed into the penile urethra and advanced across the scrotal urethra. The retractor penile muscle is excised over the urethra at the proposed prescrotal or scrotal urethrostomy site, and an incision in the urethra is performed over the urinary catheter. The length of the incision should be six to eight times the luminal diameter of the urethra (Fossum 2007). The urinary catheter can then be removed, and sutures 3-0 to 5-0, either absorbable or nonabsorbable, are placed from the urethral mucosa to the skin from caudal to cranial (Fossum 2007). Simple

Figure 10.14.  Dissection of the penis from the body wall during a penile amputation. (Photograph courtesy of Dr. Julius Liptak)

interrupted sutures have historically been used; however, a simple continuous closure may decrease postoperative hemorrhage (Newton and Smeak 1996). After the urethrostomy is performed, an encircling ligature using an absorbable suture is placed at the base of the penis just caudal to the proposed amputation site, and the penis is amputated. The site cranial to the urethrostomy site is closed in two layers. If the location of the penile tumor extends near the scrotal urethra, a perineal urethrostomy should be considered. Dehiscence and urine scalding are more common at the perineal site (Fossum 2007). A partial penile amputation is an option for small tumors at the tip of the penis or prepuce. To maintain

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visibility of the urethra during a partial penile amputation, a urethral catheter through the penile urethra and a tourniquet caudal to the proposed amputation site is recommended (Fossum 2007). A V-shaped incision is made through the tunica albuginea and cavernous tissue to the os penis. The os penis can be transected using bone cutters as far caudally as possible. The dorsal penile artery is ligated and the urethra cut 1–2 cm cranial to the penile transection and spatulated for closure to the tunica albuginea using a simple interrupted or simple continuous pattern. The prepuce should be shortened as well to approximately 1 cm cranial to the tip of the penis (Fossum 2007). A full-thickness elliptical piece of the ventral wall of the midprepuce is excised perpendicular to the long axis of the prepuce. The skin edges are apposed using a three-layer closure: mucosa, subcutaneous tissue, and skin. This allows the distal aspect of the prepuce to be retracted caudally resulting in a shortened prepuce (Boothe 2003). Alternatively, instead of shortening the prepuce in cases of partial penile amputation performed immediately caudal to the preputial fornix, the terminal portion of the urethra can be anastomosed with the caudal aspect of the preputial mucosa (Pavletic and O’Bell 2007). Histologic tumor types, prognosis, and other treatments Penile tumors are rare in dogs. The most common penile tumors are transmissible venereal tumors and squamous cell carcinoma. Other penile tumors include fibromas, papillomas, sarcomas, mast cell tumors, lymphoma, and multilobular osteochondrosarcomas (Figure 10.15). Biopsy and staging are important for penile tumors since various treatment options are available depending on the tumor type and the biological behavior is quite different depending on the tumor type. Transmissible venereal tumors are generally treated with vincristine,

then radiation, and surgery is used as a last resort. In most cases, lymphoma would be treated by chemotherapy rather than surgery. Mammary gland tumors in male dogs Mammary gland tumors in male dogs are very rare compared to female dogs. One study reports the incidence in male dogs as 4 in 100,000 compared to 207 in 100,000 female dogs (Saba et al. 2007). Mammary tumors in male dogs seem to affect the older population and cocker spaniels are overrepresented. Of eight male dogs diagnosed with mammary gland tumors, seven were benign, and none of these dogs died as a result of their tumors (Saba et al. 2007). Principles of surgical resection of male mammary tumors are similar to principles for female mammary tumors (see the section on female mammary glands). Mammary gland carcinomas in male cats Mammary gland carcinomas appear to be uncommon in male cats but seem to have many similarities to the disease in female cats. In one study with 39 male cats (Skorupski et al. 2005), a history of progestin therapy was present in 36% of cats for which this information was known. Local recurrence occurred in 45% of cats, and the median time to local recurrence was 310 days. Tumor size and lymphatic invasion were identified as negative prognostic factors. The median survival time was 344 days. Local recurrence trended toward correlation with less aggressive surgical procedures (P = 0.06). Although not statistically significant, aggressiveness of surgery was not prognostic for survival either (P = 0.9); however there were very few cats available for this analysis. Given the similarities between the disease between male and female cats and that 45% of male cats had local recurrence, it appears prudent to recommend a radical mastectomy in male cats as well, or at least a unilateral mastectomy.

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Figure 10.15.  Multilobular osteochondrosarcoma of the penis. (Photograph courtesy of Dr. Julius Liptak)

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Reproductive System  361 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. Boothe, H.W. Penis, prepuce, and scrotum. 2003. In Textbook of Small Animal Surgery, 3rd edition, pp. 1537–1539. D.H. Slatter, editor. Philadelphia: Saunders. Borzacchiello, G., V. Russo, and M. Russo. 2007. Immunohistochemical expression of cyclooxygenase-2 in canine ovarian carcinomas. J Vet Med 54(5):247–249. Brodey, R.S. and J.E. Martin. 1958. Sertoli cell neoplasms in the dog: The clinicopathological and endocrinological findings in thirty seven dogs. J Am Vet Med Assoc 133:249–257. Brodey, R.S. and J.F. Roszel. 1967. Neoplasms of the canine uterus, vagina, and vulva: A clinicopathologic survey of 90 cases. J Am Vet Med Assoc 151:1294–1307. Bryan, J.N., M.R. Keeler, C.J. Henry, et al. 2007. A population study of neutering status as a risk factor for canine prostate cancer. Pros­ tate 67:1174–1181. Cassali, G.D., H. Gobbi, C. Malm, et al. 2007. Evaluation of accuracy of fine needle aspiration cytology for the diagnosis of canine mammary tumours: Comparative features with human tumours. Cytopathology 18:191–196. Chang, S-C., C-C. Chang, T-J. Chang, et al. 2005. Prognostic factors associated with survival two years after surgery in dogs with malignant mammary tumors: 79 cases. J Am Vet Med Assoc 227(10): 1625–1629. Cotchin, E. 1960. Testicular neoplasms in dogs. J Comp Pathol 70:232–248. Davies, J.V. and H.M. Read. 1990a. Sagittal pubic osteotomy in the investigation and treatment of intrapelvic neoplasia in the dog. J Small Anim Pract 31:123–130. Davies, J.V. and H.M. Read. 1990b. Urethral tumors in dogs. J Sm Anim Pract 31:131–136. Diezbru, N., I. Garciareal, and E.M. Martinez. 1998. Ultrasonographic appearance of ovarian tumors in 10 dogs. Vet Radiol Ultrasound 39:226–233. Doxsee, A.L., J.A. Yager, S.J. Best, et al. 2006. Extratesticular interstitial and Sertoli cell tumors in previously neutered dogs and cats: A report of 17 cases. Can Vet J 47:763–766. Fan, T.M. and L.P. De Lorimier. 2007. Tumors of the male reproductive system. Withrow and MacEwen’s Small Animal Clinical Oncol­ ogy, 4th edition, pp. 637–648. S.J. Withrow and D.M. Vail, editors. St. Louis: Saunders. Fossum, T.W. 2007. Small Animal Surgery, 3rd edition. St. Louis: Elsevier. Freitag, T., R.M. Jerram, A.M. Walker, et al. 2007. Surgical management of common canine prostatic conditions. Compend Contin Educ Vet 29:656–658, 660, 662–653. Fries, C.L., A.G. Binnington, V.E. Valli, et al. 1991. Enterocystoplasty with cystectomy and subtotal intracapsular prostatectomy in the male dog. Vet Surg 20:104–112. Goldsmid, S.E. and C.R. Bellenger. 1991. Urinary incontinence after prostatectomy in dogs. Vet Surg 20:253–256. Hahn, K.A. and W.H. Adams. 1997. Feline mammary neoplasia: Biological behaviour, diagnosis and treatment alternatives. Feline Pract 25(2):5–11. Hellman, E., R. Bergstrom, L. Holmberg, et al. 1993. Prognostic factors in canine mammary tumors: A multivariate study of 202 consecutive cases. Vet Pathol 30:20–27. Hermo, G.A., P. Torres, G.V. Ripoll, et al. 2008. Perioperative desmopressin prolongs survival in surgically treated bitches with mammary gland tumours: A pilot study. Vet J 178:103– 108.

Hunt, G.B. 1995. Skin fold advancement flaps for closing large sternal and inguinal wounds in cats and dogs. Vet Surg 24: 172–175. Infante, B., E. Sorbe, G. Rodríguez, et al. 1998. Primary epithelial tumors in canine ovaries. Vet Trop 23(1)25–42. Ito, T., T. Kadosawa, M. Mochizuki, et al. 1996. Prognosis of malig­ nant mammary tumor in 53 cats. J Vet Med Sci 58(8):723– 726. Johnson, M.V., K. Root, and P.N.S Olson. 2001. Disorders of the canine ovary. In Canine and Feline Endocrinology and Reproduc­ tion, pp. 193–205. S.D. Johnson et al. editors. Philadelphia: Saunders. Klein, M.K. 2007. Tumors of the female reproductive system. In Withrow & MacEwen’s Small Animal Clinical Oncology, 4th edition, pp. 610–618. S. Withrow and D. Vail, editors. Philadelphia: Saunders. Krawiec, D.R. 1994. Canine prostate disease. J Am Vet Med Assoc 204:1561–1564. Krawiec, D.R. and D. Heflin. 1992. Study of prostatic disease in dogs: 177 cases (1981–1986). J Am Vet Med Assoc 200:1119– 1122. Kusy, R., A. Smiech, W. Opuszynski, et al. 2005. Clinical and histological characterization of ovary tumors in bitches. Medycyna Wetery­ naryjna 61(7)775–780. Kydd, D.M. and A.G. Burnie. 1986. Vaginal neoplasia in the bitch: A review of 40 clinical cases. J Sm Anim Pract 27:255– 263. Lana, S.E., G.R. Rutterman, and S.J. Withrow. 2006 Tumors of the mammary gland. In Small Animal Clinical Oncology, 4th edition, pp. 619–636. S. Withrow and E.G. McEwen, editors. Philadelphia: Saunders. L’Eplattenier, H.F., S.A. van Nimwegen, F.J. van Sluijs, et al. 2006. Partial prostatectomy using Nd:YAG laser for management of canine prostate carcinoma. Vet Surg 35:406–411. Liptak, J.M., S.P. Brutscher, E. Monnet, et al. 2004. Transurethral resection in the management of urethral and prostatic neoplasia in 6 dogs. Vet Surg 33:505–516. MacEwen G.E., A.A. Hayes, H.J. Harvey , et al. 1984. Prognostic factors for feline mammary tumors. J Am Vet Med Assoc 185(2):201– 204. MacEwen, E.G., H.J. Harvey, A.K. Patnaik, et al. 1985. Evaluation of effects of levamisole and surgery on canine mammary cancer. J Biol Response Mod 4:414–426. Magne, M.L., P.J. Hoopes, R.A. Kainer, et al. 1985. Urinary tract carcinomas involving the canine vagina and vestibule. J Am Anim Hosp Assoc 21(6):767–772. Mann, F.A., R.J. Barrett, and R.A. Henderson. 1992. Use of a retained urethral catheter in three dogs with prostatic neoplasia. Vet Surg 21:342–347. Marconato, L., G. Romanelli, D. Stefanello, et al. 2009. Prognostic factors for dogs with mammary inflammatory carcinoma: 43 cases (2003–2008). J Am Vet Med Assoc 235:967–972. Mathews, K.G. 2001. Surgery of the canine vagina and vulva. Vet Clin North Am Small Anim Pract 31(2):271–290. McLoughlin, M.A., R. Walshaw, M.W. Thomas, et al. 1992a. Gastric conduit urinary diversion in normal dogs. Part I: Upper urinary tract structure, function, and sepsis. Vet Surg 21:25–32. McLoughlin, M.A., R. Walshaw, M.W. Thomas, et al. 1992b. Gastric conduit urinary diversion in normal dogs. Part II: Hypochloremic metabolic alkalosis. Vet Surg 21:33–39. Moe, L. and B. Lium. 1997. Hereditary multifocal renal cystadenocarcinomas and nodular dermatofibrosis in 51 German shepherd dogs. J Sm Anim Pract 38:498–505.

362  Veterinary Surgical Oncology Moore, A.S., C. Kirk, and A. Cardona. 1991. Intracavitary cisplatin chemotherapy: Experience with six dogs. J Vet Intern Med 5:227–231. Morris, J.S., J.M. Dobson, D.E. Bostock, et al. 1998. Effect of ovariohysterectomy in bitches with mammary neoplasms. Vet Rec 142:656–658. Murphy, S.T., J.M Kruger, and G.L. Watson. 1994. Uterine adenocarcinoma in the dog: A case report and review. J Am Anim Hosp Assoc 30:440–444. Newton, J.D. and D.D. Smeak. 1996. Simple continuous closure of canine scrotal urethrostomy: Results in 20 cases. J Am Anim Hosp Assoc 32:531–534. Norris, A.M., E.J. Laing, V.E. Valli, et al. 1992. Canine bladder and urethral tumors: A retrospective study of 115 cases (1980–1985). J Vet Intern Med 6:145–153. Novosad, C.A., B.P. Andrew, P.J. Bergman, et al. 2006. Retrospective evaluation of adjunctive doxorubicin for the treatment of feline mammary gland adenocarcinoma: 67 cases. J Am Anim Hosp Assoc 42:110–120. Nyland, T.G., S.T. Wallack, and E.R. Wisner. 2002. Needle-tract implantation following us-guided fine-needle aspiration biopsy of transitional cell carcinoma of the bladder, urethra, and prostate. Vet Radiol Ultrasound 43:50–53. Olsen, J., J. Komtebedds, and A. Lackner. 1994. Cytoreductive treatment of ovarian carcinoma in a dog. J Vet Intern Med 8:133– 134. Overley, B., F.S. Shofer, M.H. Goldschmidt, et al. 2005. Association between ovariohysterectomy and feline mammary carcinoma. J Vet Intern Med 19:560–563. Patnaik, A.K. 1990. Canine extraskeletal osteosarcoma and chondrosarcoma: A clinicopathologic study of 14 cases. Vet Pathol 27:46– 55. Patnaik, A.K. and P.G. Greenlee. 1987. Canine ovarian neoplasms: A clinicopathologic study of 71 cases, including histology of 12 granulosa cell tumors. Vet Pathol 24(6):509–514. Pavletic, M.M. and S.A. O’Bell. 2007. Subtotal penile amputation and preputial urethrostomy in a dog. J Am Vet Med Assoc 230: 375–377. Peters, M.A., D.G. de Rooij, K.J. Teerds, et al. 2000. Spermatogenesis and testicular tumours in ageing dogs. J Reprod Fertil 120: 443–452. Philibert, J.C., P.W. Snyder, N. Glickman, et al. 2003. Influence of host factors on survival in dogs with malignant mammary gland tumors. J Vet Intern Med 17:102–106. Pluhar, G.E., M.A. Memon, and L.G. Wheaton. 1995. Granulosa cell tumor in an ovariohysterectomized dog. J Am Vet Med Assoc 207(8):1063–1065. Post, K. and S.H. Kilborn. 1987. Canine Sertoli cell tumor: A medical records search and literature review. Can Vet J 28:427–431. Radi, Z.A., D.L. Miller, and M.E. Hines. 2004. Rete testis mucinous adenocarcinoma in a dog. Vet Pathol 41:75–78. Rawlings, C.A., W.A. Crowell, J.A. Barsanti, et al. 1994. Intracapsular subtotal prostatectomy in normal dogs: Use of an ultrasonic surgical aspirator. Vet Surg 23:182–189. Riccardi, E., V. Greco, S. Verganti, et al. 2007. Immunohistochemical diagnosis of canine ovarian epithelial and granulosa cell tumors. J Vet Diagn Invest 19(4):431–435. Rogers, K.S., M.A. Walker, and H.B. Dillon. 1998. Transmissible venereal tumor: A retrospective study of 29 cases. J Am Anim Hosp Assoc 34:463–470. Saba, C.F., K.S. Rogers, S.J. Newman, et al. 2007. Mammary gland tumors in male dogs. J Vet Intern Med 21:1056–1059.

Salinardi, B.J., S.L. Marks, J.R. Davidson, et al. 2003. The use of a low-profile cystostomy tube to relieve urethral obstruction in a dog. J Am Anim Hosp Assoc 39:403–405. Simon, D., D. Schoenrock, W. Baumgartner, et al. 2006. Postoperative adjuvant treatment of invasive malignant mammary gland tumors in dogs with doxorubicin and docetaxel. J Vet Intern Med 20:1184–1190. Simon, D., D. Schoenrock, I. Nolte, et al. 2009. Cytologic examination of fine-needle aspirates from mammary gland tumors in the dog: Diagnostic accuracy with comparison to histopathology and association with postoperative outcome. Vet Clin Pathol 38:521–528. Skorupski, K.A., B. Overley, F.S. Shofer, et al. 2005. Clinical characteristics of mammary carcinoma in male cats. J Vet Intern Med 19:52–55. Smith, J.D., E.A. Stone, and S.D. Gilson. 1995. Placement of a permanent cystostomy catheter to relieve urine outflow obstruction in dogs with transitional cell carcinoma. J Am Vet Med Assoc 206:496–499. Sorenmo, K.U., M.H. Goldschmidt, F.S. Shofer, et al. 2003. Immunohistochemical characterization of canine prostatic carcinoma and correlation with castration status and castration time. Vet Comp Oncol 1:48–56. Sorenmo, K.U., F.S. Shofer, and M.H. Goldchmidt. 2000. Effect of spaying and timing of spaying on survival of dogs with mammary carcinoma. J Vet Intern Med 14:266–270. Spugnini, E.P., A. Bartolazzi, and D. Ruslander. 2000. Seminoma with cutaneous metastases in a dog. J Am Anim Hosp Assoc 36: 253–256. Stiffler, K.S., M.A. McCrackin Stevenson, K.K. Cornell, et al. 2003. Clinical use of low-profile cystostomy tubes in four dogs and a cat. J Am Vet Med Assoc 223: 309–310, 325–329. Stone, E.A., M.C. Walter, M.H. Goldschmidt, et al. 1988. Ureterocolonic anastomosis in clinically normal dogs. Am J Vet Res 49:1147–1153. Stone, E.A., S.J. Withrow, R.L. Page, et al. 1988. Ureterocolonic anastomosis in ten dogs with transitional cell carcinoma. Vet Surg 17:147–153. Stratmann, N., K. Failing, A. Richter, et al.2008. Mammary tumor recurrence in bitches after regional mastectomy. Vet Surg 37(1):82–86. Struble, A.L., G.W. Lawson, and G.V. Ling. 1997. Urethral obstruction in a dog: An unusual presentation of T-cell lymphoma. J Am Anim Hosp Assoc 33:423–426. Teske, E., E.C. Naan, E.M. van Dijk, et al. 2002. Canine prostate carcinoma: Epidemiological evidence of an increased risk in castrated dogs. Mol Cell Endocrinol 197:251–255. Viste, J.R., S.L. Myers, B. Singh, et al. 2002. Feline mammary adenocarcinoma: Tumor size as a prognostic indicator. Can Vet J 43(1):33–37. Wakui, S., M. Furusato, K. Yokoo, et al. 1997. Testicular efferent ductule cyst of a dog. Vet Pathol 34:230–232. Weaver, A.D. 1983. Survey with follow-up of 67 dogs with testicular sertoli cell tumours. Vet Rec 113:105–107. Weisse, C., A. Berent, K. Todd, et al. 2006. Evaluation of palliative stenting for management of malignant urethral obstructions in dogs. J Am Vet Med Assoc 229:226–234. White, R.A. 2000. Prostatic surgery in the dog. Clin Tech Small Anim Pract 15:46–51. Winter, M.D., J.E. Locke, and D.G. Penninck. 2006. Imaging diagnosis—urinary obstruction secondary to prostatic lymphoma in a young dog. Vet Radiol Ultrasound 47:597–601.

Reproductive System  363 Withrow, S.J. and S.J. Susaneck. 1986. Tumors of the canine female reproductive tract. In Current Therapy in Theriogenology, 2nd edition. D.A. Morrow, editor. Philadelphia: Saunders. Yamagami, T., T. Kobayashi, K. Takahashi, et al. 1996. Influence of ovariectomy at the time of mastectomy on the prognosis for

canine malignant mammary tumors. J Sm Anim Pract 37:462– 464. Zanghi A., G. Catone, G. Marino, et al. 2007. Endometrial polypoid adenmyomatosis in a bitch with ovarian granulosa cell tumor and pyometra. J Comp Pathol 136:83–86.

11 Urinary tract Nicholas J. Bacon, James P. Farese

Biopsy Procedures for Urinary Tumors General principles All animals scheduled for urinary tract biopsy should undergo a complete historical and physical evaluation. Complete blood count, biochemistry, and urinalysis are indicated prior to performing a urinary tract biopsy. Coagulation studies would be prudent. Tissue biopsies of the urinary tract can be obtained either through an open approach (laparotomy) or a closed-abdomen approach (percutaneous fine-needle aspirate [FNA] or needle core biopsy/Trucut, laparoscopy). Some benefits of an open approach include more accurate biopsy positioning, especially of the kidney; larger and more accurate tissue samples; and the ability to combine biopsy and surgical treatment (e.g., bladder mass). Closed abdominal biopsies are typically faster and cheaper but often result in smaller tissue samples and the inability to manage hemorrhage should it occur. Tumor cells may potentially be implanted along needle tracks during needle aspirates or core biopsies, and the only reported cases of seeding in veterinary species concern urogenital carcinomas, specifically the bladder, urethra, and prostate in dogs (Nyland et al. 2002). Needle-track implantation of carcinoma in the kidney has not been reported in dogs, but has been described in people (Kiser et al. 1986; Slywotzky and Maya 1994). Whereas in humans tumor-track implantation occurs with an estimated frequency of only 0.009% (Smith 1991), the incidence in dogs is unknown at this time and is likely underestimated. If a needle biopsy of a suspected urinary carcinoma is deemed critical to decision making in a case, particular care should be paid to biopsy position to

allow the needle track to be resected at surgery to reduce the potential risk of tumor implantation. Kidney Renal masses are typically unilateral, although 4% of primary tumors are reportedly bilateral (Bryan et al. 2006). If staging confirms a solitary renal lesion, then biopsy and surgery can be combined in a unilateral nephrectomy to reduce patient morbidity, and this approach was taken in 78% of renal tumors in one study (Bryan et al. 2006). If either open or closed biopsies are deemed necessary, however, appropriate attention should be paid to the following: 1. The kidneys are mobile, the left more than the right, and this may present a problem in closed biopsies as the kidneys often move away during biopsy procedures. 2. Any biopsy attempt should be made at the interface of normal and abnormal tissue. 3. Draining lymph nodes should be assessed. 4. Percutaneous FNAs can be taken under sedation, but needle core biopsies should be performed under general anesthesia. 5. An automated biopsy device (e.g., Bard® Magnum® biopsy instrument with Biopty-Cut® biopsy needles, Bard, Covington, GA) is preferred over a manual device because of speed and reliability of sample acquisition. 6. Color-flow Doppler should be used to avoid the larger interlobar vessels. 7. Biopsy passes in the kidney should be limited to two (Hager et al. 1985).

Veterinary Surgical Oncology, First Edition. Edited by Simon T. Kudnig, Bernard Séguin. © 2012 by John Wiley & Sons, Ltd. Published 2012 by John Wiley & Sons, Ltd.

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8. The kidney should be monitored by ultrasound for 10 minutes after biopsy for active bleeding or hematoma formation. Laparoscopy Laparoscopic-assisted percutaneous needle core biopsies may obtain more representative tissue than ultrasound-guided biopsies, and the biopsy site can be watched for evidence of hemorrhage. Nephroureterectomy in humans is commonly performed by laparoscopic or hand-assisted laparoscopic techniques via a transperitoneal or retroperitoneal approach (Raman and Scherr 2007). These techniques have yet to be widely performed in veterinary species. FNA and needle core biopsy FNA and needle core biopsy (e.g., Trucut) are infrequently used to diagnose renal tumors, possibly due to the concerns of abdominal tumor seeding associated with biopsy bleeding or biopsy-track implantation. This technique was reportedly only used to diagnose 1% of renal tumors in one study (Bryan et al. 2006). For large or generalized lesions, the needle should be orientated parallel to the long axis at the periphery of the kidney and not directed toward the hilus in order to avoid the medullary arcade of vessels. Incisional biopsy Incisional or wedge biopsies will yield large tissue samples for histopathology and are typically taken from the junction of normal and what appears to be abnormal kidney. An incisional biopsy might be indicated if a renal mass is discovered incidentally during surgery and obtaining a diagnosis is warranted before performing a nephrectomy. Before biopsy, the kidney should be freed from its retroperitoneal attachments, starting at the lateral surface and moving dorsally to rotate the lateral edge of the kidney ventrally toward the midline of the laparotomy. Gentle dissection around the hilus should allow the renal arteries and veins to be identified, but freeing these entirely of surrounding tissue is not necessary to place a Rumel tourniquet around them. The tourniquet (consisting of a short piece of rubber tubing, umbilical tape, or polypropylene suture and a mosquito clamp) should minimize bleeding while you are incising the kidney. After the tissue biopsy is taken, the tumor or renal capsule can be closed with either interrupted mattress sutures or a simple continuous pattern of monofilament absorbable material. Placing absorbable hemostatic collagen sponges (Gelfoam, Pharmacia & Upjohn, Kalamazoo, MI) over the biopsy site will reduce the risk of postbiopsy bleeding. The incisional biopsy site should be digitally compressed for 5 minutes after

the Rumel tourniquet is released and the kidney replaced back into the retroperitoneal fat. If concerns exist over the kidney being too mobile following this dissection, one or two nephropexy sutures of fine monofilament suture between the capsule and the fascia of the hypaxial muscles can be placed. Ureter Ureteric tumors are rare, and the diagnosis is likely to come from exploratory laparotomy and excisional biopsy. A percutaneous needle biopsy is also a possibility. Bladder Excisional Laparotomy and partial cystectomy is often used to definitively diagnose and treat discrete or multiple bladder masses, especially if the ultrasonographic appearance is suggestive of transitional cell carcinoma (TCC). The procedure is described in more detail later. Urine sedimentation Neoplastic cells can be identified in urine sediment in 30%–70% of cases of bladder neoplasia, although difficulty may arise in distinguishing reactive from neoplastic transitional epithelial cells (Burnie and Weaver 1983; Norris et al. 1992). Ideally, a catheterized sample is used rather than cystocentesis due to concerns over tumor seeding. A voided sample is likely to be less accurate. Ultrasound-guided traumatic catheterization A suction biopsy technique under ultrasound guidance with an open-ended urinary catheter is typically very successful in retrieving diagnostic cell harvests from bladder masses (Lamb et al. 1996). The urinary catheter is advanced into the bulk of the mass and repeated vigorous aspirations made with a 20 mL syringe. The suction is released prior to removing the catheter, and the catheter lumen typically contains small fragments of soft tissue. Carcinomas are generally friable and exfoliate well. Touch preparations of the retrieved tissue can often provide a cytologic diagnosis of neoplasia ahead of the histopathology report. Cystoscopic biopsy Cystoscopy is a valuable tool for diagnosing urinary tumors in the dog, but it is usually reserved for females, as the shorter, wider straighter urethra lends itself to rigid endoscopy access to the bladder. One disadvantage is that only small, superficial tissue fragments can be retrieved down the biopsy channel, occasionally providing misleading or inaccurate information. The real

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advantage of cystoscopy is that the tumor can be accurately imaged, mapped, and photographed. This allows for decisions to be made on the likelihood of resectability and comparison to future images to assess progression and response to treatment. Urethra Traumatic biopsies Urethral tumors, because of their relatively superficial location in the female, lend themselves to impression smear techniques from the urethral wall while the patient is under anesthesia. A sterile Volkmann spoon/ curette can easily be inserted into the urethral papilla either under digital guidance or by direct visualization using a speculum. Gently advancing the curette along the urethral wall as far as possible and then withdrawing with the spoon gently angled against the wall allows soft tissue fragments to accumulate in the spoon. Nasal brush biopsy techniques (de Lorenzi et al. 2006) can also be modified for the urethra to collect sufficient mucosal cellular material for cytologic evaluation. Open-ended catheters can be used for both male and female urethral suction biopsies. Simultaneous rectal manipulation is required to help position the tip of the catheter into the wall of the most affected segment of the urethra, and then intermittent vigorous suction is applied in a similar manner to ultrasound-guided bladder catheterization biopsies. Urethroscopic Endoscopic diagnosis and biopsy is fairly straightforward in the female urethra, and multiple small, superficial tissue biopsies can normally be obtained.

Imaging Techniques General principles of diagnosis/staging The majority of urinary neoplasia is epithelial in origin, and urothelial carcinomas display aggressive malignant behavior. Reportedly 16%–48% have evidence of pulmonary metastatic disease at time of presentation (Klein et al. 1987; Bryan et al. 2006). Regional metastasis is also common, and tumors of the renal pelvis and upper ureter spread to the paraaortic and para-caval lymph nodes, while distal ureteral, bladder, and urethral tumors metastasize to the pelvic nodes (typically sacral, hypogastric, or medial iliac lymph nodes). Computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound (US) can all detect lymph node enlargement, but US and MRI are more sensitive at detecting internal node architecture. Doppler ultrasound can also be used to evaluate nodal blood flow, which can differ from normal flow when the

node is infiltrated with tumor cells. US is also less cumbersome, less expensive, more available, and often faster than other cross-sectional modalities. Ultrasound also has the advantage that FNAs of lymph nodes can be performed at the same time. It is worth noting that in cases of urogenital cancer, which undergo a laparotomy, the authors routinely attempt to remove the medial iliac and hypogastric lymph nodes, regardless of their US, CT, or MRI appearance. On histologic examination, lymph nodes that appeared normal on imaging can occasionally have clusters of tumor cells in the nodal parenchyma or within the subcapsular sinuses. Radiography (with or without contrast) Thoracic radiography is undoubtedly a valuable screening tool to identify gross metastatic disease, but plain abdominal radiography for urinary tract neoplasia is less sensitive and specific. Abdominal radiographs in a dog with a renal tumor may often only demonstrate a midabdominal mass, and plain radiographs in dogs with bladder or urethral neoplasia may well be unremarkable. Radiography was not useful detecting intra-abdominal metastasis in one report of renal tumors (Bryan et al. 2006), although it can detect large pelvic lymphadenopathy from lower urinary tract tumors. Plain radiographs of the abdomen can also be used to screen the lumbar vertebrae for bony metastasis when a productive bony reaction is evident on the ventral borders of the caudal lumbar vertebral bodies. Contrast radiography provides much more valuable information: Intravenous excretory urograms; negative-, positive-, and doublecontrast cystograms; and retrograde urethrograms can all help delineate abnormalities in the urinary tract. These studies may help determine whether a retroperitoneal mass is of renal origin or another soft tissue, give a crude estimation of the likely resectability of bladder masses (e.g., trigone versus apex), and can outline urethral filling defects and give an indication of the length and extent of diseased urethra. Ultrasonography US can accurately and specifically characterize lesions that may simply appear as a midabdominal mass on conventional radiographs (Wisner and Pollard 2004), and abdominal ultrasound successfully diagnosed midabdominal masses as being renal in origin in 93% cases in one study (Bryan et al. 2006). Ultrasonography is especially valuable in investigating bladder disease because of the superficial location of the bladder and the excellent acoustic properties of urine (Bree and Silver 1981). US examination is reported to be able to detect 100% of bladder masses in dogs with TCC and is far superior to either double-contrast

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(a)

(b)

Figure 11.1.  (A, B) Ultrasonographic images (cranial is left, caudal right) of two different canine TCCs (arrows) involving the trigonal area of the urinary bladder and proximal urethra.

cystography or intravenous excretory urography (Léveillé et al. 1992). Findings such as multiple irregular nodules, bladder wall thickening or invasion, and pedunculated masses are common (Figure 11.1). Primary renal TCC in the cat is rare and usually originates from the renal pelvis as mass lesions, often invading renal and perirenal tissue. They may contain a central cyst or cause hydronephrosis. A single case of TCC forming a fluid-filled structure around the kidney has been reported (Raffan et al. 2007). Computed tomography Intravenous excretory urography has historically been used to evaluate the upper urinary tract, but more recently CT with a delayed “urographic” phase can be performed, allowing for characterization of the lesion and evaluation of the contralateral kidney, as well as providing staging information. Contrast-enhanced CT may also detect very small intraparenchymal lesions and filling defects that are undetectable using ultrasonography. This is especially true if image acquisition is timed to peak enhancement of the contrast agent (Wisner and Pollard 2004). CT-guided percutaneous biopsy is well described for renal biopsies in humans, and CT is becoming increasingly available for veterinary patients. Radio-opaque markers are typically placed on the skin to act as a surface reference point so that the appropriate needle entry site, angle, and depth can be selected. After needle insertion, a scan is made to check accurate placement, with one or two slices being made on either side.

CT is also gathering support to become the preferred screening tool for pulmonary metastasis in patients with neoplasia with high metastatic potential, including urinary carcinoma, due to the reliable detection of nodules significantly smaller in size that can be detected on conventional three-view radiographs. Magnetic resonance imaging Patient respiratory movement tends to degrade MR images of the abdomen, thus MRI is not commonly used for imaging the urinary system. Respiratory gating will improve image quality, but these techniques have yet to widely infiltrate veterinary imaging, and their impact has yet to be described. Fluoroscopy Intravenous excretory urograms can be followed in real time to image the renal silhouettes, path of the ureters, and location of the bladder. This may be useful to help identify the origin and anatomical relationships of a midabdominal mass, but US and CT have largely superseded fluoroscopy in this capacity. Positive-contrast retrograde urethrography can be used to diagnose abnormal urethral filling and mucosal contouring, especially in the male dog not amenable to urethroscopy. Nuclear scintigraphy Planar nuclear medicine using 99m technetium methylene diphosphonate (99mTc-MDP) to perform a bone scan is occasionally employed in the management of

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Figure 11.2.  Intraoperative view of a renal hemangiosarcoma affecting the cranial pole of a canine kidney.

urinary tumors as urothelial carcinomas have a propensity to metastasize to bone. This is an exquisitely sensitive technique and is typically employed as a screening test when dogs with previously diagnosed carcinomas exhibit bone pain, weakness, reluctance to exercise, or collapse.

Kidney Surgical techniques Nephroureterectomy The oncologic indications for complete (i.e., radical) or partial nephrectomy include primary benign tumors (hemangioma, leiomyoma) and primary malignancies such as carcinoma (e.g., tubular, transitional, and squamous cell), sarcoma (e.g., hemangiosarcoma leiomyosarcoma, osteosarcoma, fibrosarcoma) (Figure 11.2), and nephroblastoma (Figure 11.3). Nephroureterectomy is typically performed via a ventral midline approach. After mobilization of the kidney, the renal pedicle is dissected to visualize the renal artery and vein. The renal vessels are typically double-ligated with silk suture. Alternatively, the renal artery and vein can be stapled with a TA-30 using a three-row vascular cartridge (Figure 11.4). Stapling of the renal artery and vein has also been performed laparoscopically in humans using a GIA stapling device. Following division of the renal vessels, the ureter is dissected free to the point of its entry into the urinary bladder and ligated with monofilament suture. In human urologic surgery, radical nephroureterectomy with en bloc excision of the ipsilateral bladder cuff is the gold standard for patients with a normal contralateral kidney. This involves extirpating the entire

Figure 11.3.  Intraoperative nephroblastoma.

view

of

a

large

canine

distal ureter, including the intramural portion and ipsilateral ureteral orifice. This aggressive approach to removing all upper urinary urothelium is in part because upper urinary tract TCC has a worse prognosis than TCC of the bladder in humans (Stewart et al. 2005), a situation typically opposite that of the dog. Partial nephrectomy There are multiple surgical techniques for nephronsparing surgery reported in humans, including enucleation, segmental polar nephrectomy, wedge resection, major transverse resection, and extracorporeal partial nephrectomy with autotransplantation (Griffin 1996). In dogs, a simple suture guillotine method of transverse resection is possible: two straight eyed needles are threaded on a single strand of absorbable monofilament suture and passed through the kidney (Figure 11.5A.). After the eyes of the needles have been pulled through completely, the suture is then cut near the needle eyes. This creates three separate loops of suture material that are then tied individually in guillotine fashion to cut through the renal parenchyma and gather/ligate sizeable vessels (Figure 11.5B.). For closure, if possible, the capsule is sutured over the exposed parenchyma, and if the renal pelvis is opened during the excision, it is closed. The remaining portion of the kidney may be supported by creating a “duodenal hammock” (fixation of duodenal serosa to nearby transversus abdominus muscle). Partial nephrectomy is most commonly performed for focal tumors affecting one of

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the kidney poles (vs. a central lesion), and the size of the tumor must allow appropriate margins to be obtained for the tumor in question. One example for which partial nephrectomy can be indicated is in a dog with bilateral renal insufficiency and salvage of a portion of the affected kidney is felt to be important for postoperative renal function. Ideally, an incisional biopsy should be obtained preoperatively to determine whether margins anticipated from diagnostic imaging (i.e., CT and/or US) will be adequate for complete excision. If renal function is normal in the contralateral kidney, partial nephrectomy is not generally recommended due to fear of incomplete excision. Postoperative care Following nephroureterectomy, emphasis must be placed on maintaining perfusion to the remaining kidney, and

urine output should be closely monitored, ideally quantifying urine output by way of a temporary indwelling urinary catheter with a closed collection system. Functional outcome and potential complications 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; that is, a Satinksy 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 veinthrombus complex removed en bloc. The venotomy is then repaired with a simple continuous pattern of 5/0 polypropylene suture. Histologic tumor types and prognosis

Figure 11.4.  Intraoperative view of a canine renal carcinoma. A TA-30V stapling instrument is clamped across the renal artery and vein.

(a)

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, lymphoma), 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

(b)

Figure 11.5  (A) Intraoperative view of the cranial pole of a canine kidney (same case as in Figure 11.2) during partial nephrectomy. A long, straight needle has been placed through the parenchyma just proximal (relative to the tumor) to the anticipated incision line. (B) View of the remaining portion of the kidney following partial nephrectomy. The cut surface is inspected for bleeding as the Rumel tourniquet (arrow) is released.

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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 0–1,005 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). In humans, intravesicular recurrence of TCC following renal TCC is a genuine concern, as bladder tumors reportedly occur in up to 44% of patients following definitive surgical resection of upper urinary tract TCC (Raman and Scherr 2007) and underscores the necessity for regular postoperative monitoring (cystoscopy or urinary cytology). An equivalent link between primary renal TCC and secondary bladder TCC in the dog has not been appreciated at this time. Adjuvant therapy Use of chemotherapy is recommended after nephrectomy due to the high rate of metastasis. Carboplatinor doxorubicin-based protocols are commonly used. Contrary to treating most other carcinomas, use of cyclooxygenase-2 (COX-2) inhibitors should be avoided due to the potential complication of reduced renal blood flow in an animal with only one kidney.

Ureters Nephroureterectomy should be considered the most realistic surgical choice for ureteric tumors because there has been only one case of ureteral tumor without obstructive hydronephrosis and hydroureter reported (Font et al. 1993). In theory, ureteric resection and anastomosis is a possible treatment for ureteric neoplasia. There are several factors to consider before undertaking this surgery: (1) What is the functional status of the ipsilateral kidney? If the function is believed to be absent, nephroureterectomy should be performed. (2) Magnifying loupes should be available for small dogs. An operating microscope and microsurgical instruments must be available for cats. (3) There are no data available on the appropriate length of ureter to take either side of the mass to achieve tumor-free margins. Theoretically, ureteral stenting can be used as a palliative measure to alleviate an obstruction caused by a tumor. Surgical techniques Ureteric resection and anastomosis To perform the resection and anastomosis, the ureter is freed from the peritoneum. Care is taken to preserve as much of the periureteral blood supply as possible to decrease the possibility of vascular compromise. The

ureter is transected cranial and caudal to the tumor, ideally 1–2 cm from the tumor edges in cases of malignant neoplasms. The ureter is transected at an oblique angle, with the vascular side being longer. Once the tumor is removed, the avascular side can be spatulated, where it is incised longitudinally for several millimeters to increase the diameter of the lumen. One segment (either cranial or caudal) is rotated 180 degrees, and a suture is placed from the tip of one segment to the commissure of the longitudinal incision of the other segment. The suture material should be absorbable monofilament 6-0 to 4-0. For microsurgical procedures, nylon 8-0 can be used. Simple interrupted or two simple continuous suture lines, one on either side can be used to complete the anastomosis. In female dogs, it is possible to place a soft catheter through the urethra into the ureter and have the tip of the catheter be cranial to the anastomosis site. A cystotomy is done to feed the catheter into the ureter. Connecting the catheter to a urine collection system allows monitoring of urine output by the kidney, for which the ureter was operated on. It also minimizes the urine contacting the suture site, which can optimize healing. Tension at the anastomosis site should be avoided. To help alleviate the tension, psoas cystopexy and/or renal descensus can be done. Psoas cystopexy is performed by placing two to three nonabsorbable sutures from the craniolateral wall of the bladder into the psoas fascia or muscle. The sutures in the psoas are placed at a craniocaudal level, which places gentle tension on the bladder cranially. To perform renal descensus, the ipsilateral kidney is completely mobilized from its peritoneal attachments. The kidney is gently pushed caudally and medially to place mild tension on its vascular pedicle. Two to three nonabsorbable sutures are placed into the capsule and small amount of renal parenchyma of the caudal pole and the body wall to maintain the kidney in this position. Postoperative care Intravenous fluids are continued in the postoperative period to promote urine production. Urine production is monitored. Proper analgesia is provided. Functional outcome and potential complications Potential complications following ureteric resection and anastomosis include ureteric occlusion/stenosis with postrenal obstruction and ureteric urine leakage. Obstruction may not manifest itself as reduced urine output if the contralateral kidney is normal. It is likely there will be some degree of preexisting hydronephrosis on the affected side, thus this must be accounted for when examining renal anatomy and assessing dilation

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after surgery. Urine leakage can be diagnosed by detecting free abdominal fluid and comparing the urea and creatinine concentration of this fluid to serum levels. Urea in leaked urine normalizes quickly to match serum levels, whereas the larger molecule creatinine tends to remain in the peritoneal cavity longer, maintaining a level much higher than serum. Histologic tumor types and prognosis for ureteral tumors Ureteral neoplasia is very rare, with only 16 reported cases up to 2010. Eleven are benign—leiomyomas (2), transitional cell papillomas (2), fibropapilloma (1), fibroepithelial polyps (6)—and are more commonly located in the proximal ureter. Malignant tumors are uncommon, that is, sarcoma (2), leiomyosarcoma (1), mast cell tumor (1), TCC (1), and are more commonly located in the distal ureter. In one case of fibroepithelial polyp located in the distal ureter 4 cm from the trigone, ureteral resection and ureteroneocystostomy was performed (Reichle et al. 2003). A case of ureteric mast cell tumor has been reported with a 1 cm segment of thickened ureter as it entered the trigone. The left ureter and bladder wall surrounding the left ureteral papilla were resected and left ureteroneocystostomy performed (Steffey et al. 2004). Surgical treatment for all other reported cases of ureteric neoplasia has been nephroureterectomy. Prognosis for benign lesions is excellent. Animals with malignant tumors managed by nephroureterectomy have been euthanized at 5 months (mast cell tumor), 6 months (sarcoma), 8 months (sarcoma), and have been alive at 10 months (TCC) and 2 years (leiomyosarcoma). Adjuvant therapy No adjunctive chemotherapy or radiotherapy has been reported in cases of ureteric neoplasia.

Bladder Surgical techniques Partial cystectomy Up to 70% of the bladder wall can be excised without the need for urinary diversion, provided the ureteral papillae are not compromised. Following caudal laparotomy, the sublumbar chain of nodes should first be inspected. If any doubt existed on preoperative imaging regarding whether or not the draining lymph nodes were positive for metastatic disease, they should be dissected free of the retroperitoneal fat and submitted for histopathology. The medial iliac lymph nodes are the largest of the chain and are found just cranial to the

Figure 11.6.  Metastatic carcinoma to the sublumbar lymph nodes.

branching of the external iliac artery off the aorta. The benefit of removing obviously metastatic lymph nodes has not been defined in TCC (unlike apocrine gland adenocarcinoma [Hobson et al. 2006]) (Figure 11.6), but theoretically, reducing the volume of tumor in a patient may play a role in increasing patient longevity. Removal and histopathology of grossly normal lymph nodes, however, is used more as a staging tool; that is, it helps the clinician to understand more about an individual patient’s tumor and may influence treatment decisions. Recent experimental work on using nearinfrared fluorescent imaging (NIRFI) in dogs with spontaneous bladder cancer has shown it to be successful at identifying in real time sentinel lymph nodes that were confirmed histologically to harbor metastases (Knapp et al. 2007). The bladder should be exteriorized and packed off from the abdominal wound with laparotomy gauzes. The bladder is handled and manipulated using finegauge monofilament mattress stay sutures. Once the tumor is identified through the wall, the bladder is entered with a margin of 1–3 cm from the palpable edge of the mass (depending on location and size of tumor and size of bladder) with a stab incision from a scalpel blade (Figure 11.7). This first incision is then extended with Metzenbaum scissors to become the edge of the excision. Even when the cystectomy cut is planned through grossly normal tissue, histologically incomplete margins may be present in up to 50% of dogs with TCC (Stone et al. 1996) (Figure 11.8). If the proposed surgical margin surrounding the mass encroaches on one or both of the ureteric margins, a decision needs to be made to either spare the natural opening and likely suffer an incomplete margin or excise the ureteric

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Figure 11.7.  Intraoperative view of a canine urinary bladder TCC following cystotomy. The location of this tumor in the bladder apex allowed a wide excision (3 cm).

Figure 11.8.  Excised section of a canine bladder wall with multifocal TCC. The two small arrows point to TCC lesions that were completely excised (approximately 1–2 cm surgical margins), and the larger arrow points to a very small TCC nodule for which the surgical margins were incomplete. The two smaller nodules were discovered unexpectedly during the partial cystectomy. Note the pinning of the bladder to a piece of cardboard to flatten the specimen minimizes tissue shrinkage that occurs with formalin fixing and facilitates inking.

opening as part of the resection (Figure 11.9) and reimplant one or both ureters (Stone et al. 1996). The ureter is transected at least 2 cm from the bladder serosa in case carcinoma cells are present within the submucosa of the terminal ureter (Saulnier-Troff et al. 2008). A stay suture is placed in the wall of the remaining ureter, mosquito forceps are bluntly forced through intact bladder mucosa

Figure 11.9.  View of a canine TCC of the trigone through a ventral cystotomy incision just prior to mass excision. Due to proximity to the ureteral orifice and lateralized nature of this tumor, the excision included a portion of the bladder wall containing the associated ureter. A red rubber catheter is placed in each of the ureters.

and used to draw the suture and cut end of the ureter through into the bladder. The transposition is completed with three to four simple interrupted sutures of 4/0 or 5/0 monofilament absorbable suture material (e.g., poliglecaprone 25) (Figure 11.10). Saulnier-Troff and colleagues (2008) have recently described a technique to treat dogs with lower urinary tract obstruction due to malignant neoplasia. In two dogs, the bladder neck was resected, including the trigone and proximal urethra, but the neurovascular pedicles to the bladder and urethra were preserved, thereby preserving lower urinary tract function and maintaining continence (Saulnier-Troff et al. 2008). The urethral remnant was then anastomosed to the body of the bladder over a Foley catheter. The ureters entered the bladder in the center of the tumor in both dogs, and so a bilateral transplantation (neoureterocystostomy) was performed moving them to the bladder apex. In the cases described, one dog with a trigonal rhabdomyosarcoma was euthanized due to a solitary lung metastasis at 280 days after surgery. Another dog with trigonal TCC had at least one metastatic lesion in the body wall at 131 days, which grew to invade the bladder and ureters; the dog died from renal failure (with bilateral hydronephrosis) at 580 days. Partial thickness resection of the bladder wall may also be performed via a submucosal dissection to excise benign mucosal lesions such as polypoid cystitis (Figure 11.11) or to debulk select TCCs that are causing urethral obstruction and cannot be resected by other

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Figure 11.10.  Following excision of the mass in Figure 11.9 with approximately 1–2 cm margins (taking care not to encroach on the contralateral ureteral orifice), ureteral transection was performed approximately 2 cm proximal to the bladder serosa. The ureter was then tunneled through a stab incision in the bladder wall near the bladder apex, spatulated, and then the ureteral mucosa was sutured (in this case 5-0 absorbable monofilament suture) to the bladder mucosa to reconstruct a new ureteral orifice. Margins were assessed to be complete on histopathologic evaluation.

Bladder wall closure is routine. In the above example, a two-layer closure was performed with a continuous modified Gambee suture pattern on the first layer and a continuous Lembert pattern on the second layer. In most cases of bladder tumor excision, the defect in the wall can be repaired in one or two layers in a simple continuous pattern of a fine-gauge monofilament material (e.g., 4-0 to 2-0 poliglecaprone 25). Following small resections, a one-layer closure may be sufficient, but the authors favor a two-layer closure to repair larger cystectomies. A simple continuous appositional pattern has been shown to be equal biomechanically and histologically to continuous Cushing suture pattern in rats with experimentally induced inflammation of the urinary bladder (Hildreth et al. 2006). Following closure of the bladder, the laparotomy gauzes should be removed, the abdomen lavaged to remove any blood clots and residual tumor cells, and instruments and gloves changed to minimize the chance of incisional seeding of tumor cells (Figure 11.12). Laparotomy closure is routine. Total cystectomy Canine TCC typically occurs in the area of the trigone, and partial trigonal excision with neoureterocystostomy or trigonal excision with preservation of the neurovascular supply (Saulnier-Troff et al. 2008) is not always possible with advanced disease. In such cases, complete cystectomy has been described, along with urinary diversion procedures such as ureterocolonic and ureterourethral/preputial/vaginal anastamosis (Kadosawa et al. 2006). With the latter procedure, the distal ends of both

Figure 11.11.  A CO2 laser is being used to dissect deep into the bladder submucosa in a dog with polypoid cystitis. In this case, multiple polyps were removed to palliate clinical signs associated with hematuria. The submucosal defects were closed with absorbable monofilament suture.

means (Josel et al. 2002). In the case of multiple polyps throughout the bladder, such a technique allows preservation of the bladder size. Ideally, the submucosal defect is then closed primarily with absorbable monofilament suture.

Figure 11.12.  Ventral view of a dog with TCC of the bladder following cystotomy. Incisional seeding resulted from the surgery and has caused a mass to develop within the body wall and subcutaneous tissues (between the two arrows).

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ureters are transected with a comfortable margin, spatulated, and together are anastomosed to the remaining portion of the proximal urethra, prepuce, or vagina. The authors have also performed a combined total cystectomy and prostatectomy in a dog with extensive TCC involving the trigone and prostatic urethra (Figure 11.13). In this case the transacted ends of the ureters were spatulated and anastomosed to the distal portion of the penis (which was tunneled through the body wall, Figure 11.14). In these patients, postoperative urinary incontinence happens uniformly, and the dogs are

typically managed in diapers. The prognosis following total cystectomy in 14 dogs was reportedly 6 months (Kadosawa et al. 2006). Postoperative care Following partial cystectomy, an indwelling catheter is often placed for the first 24 hours and intravenous fluids administered at a daily maintenance rate to keep the bladder deflated and flush out blood clots, particularly when large portions of the bladder wall have been resected. Frequent walks (every 2–4 hours) are helpful to patients that are not postoperatively catheterized. Functional outcome and potential complications

Figure 11.13.  Bladder, prostate, and pelvic portion of the urethra from a dog with TCC involving the trigone, ureteral orifices, and prostatic urethra (length of tissue involved between white arrows).

(a)

The functional outcome resulting from partial cystectomy is usually good to excellent. Partial cystectomy results in minimal urine storage capacity and pollakiuria in over 50% cases (Stone et al. 1996). Pollakiuria is usually a transient situation, and urine capacity and frequency of urination approaches normal within a few weeks in the majority of dogs (Stone et al. 1996). Even with large resections, return to acceptable function occurs over time, with most animals being able to hold urine overnight by 3 months after surgery (Kyles and Stone 1988). Complications following total cystectomy with diversion to the urethra include uroperitoneum, ureteric stricture, and total urinary incontinence. Techniques to divert urine to the colon have also been described (Stone et al. 1988), and complications include neurologic

(b)

Figure 11.14  (A) Intraoperative image following complete cystectomy/prostatectomy/removal of the pelvic urethra and spatulation of the transected ureteric ends prior to urethral anastomosis (different case from that in Figure 11.13). The dorsal aspect of both ureters has been sutured together with fine monofilament absorbable suture to form a single ureter. This image shows the appearance of the conjoined ureters just prior to suturing the ventral aspect. (B) This intraoperative image shows the anastomosis (blue arrow) of the ureters (white arrows) and the distal urethra (yellow arrow) just prior to abdominal wall closure. The cut edge of the distal penile urethra was tunneled through the body wall and the anastomosis performed intraabdominally.

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disease (possibly from hyperammonemia, metabolic acidosis, and uremia), hyperchloremic metabolic acidosis, urine scald around the anus/perineum, matting of the fur, need for frequent opportunities to eliminate (4 hours recommended), and pyelonephritis. Six out of 10 dogs had confirmed metastatic lesions at time of death (Stone et al. 1988). Histologic tumor types and prognosis Bladder tumours in dogs and cats are usually malignant; in one report, only 3% in dogs were benign (Glickmann et al. 1989). The most frequently recognized malignant neoplasm is TCC (Osborne et al. 1968), and these tumors can range in appearance from small papillary types to solid, ulcerated, deeply invading tumors. The second most frequently recognized malignant neoplasm is the squamous cell carcinoma, thought to arise from squamous metaplasia of TCC arising in areas of transitional cell hyperplasia, or papilloma. Other rarely reported histologic types include adenocarcinoma, fibrosarcoma, leiomyosarcoma, and hemangiosarcoma (Norris et al. 1992). The most frequently diagnosed benign tumor is the papilloma (Osbourne et al. 1968). Other benign tumors such as fibromas and leiomyomas are much rarer. A study of 122 dogs showed that dogs that had the bulk of their macroscopic disease excised via cystotomy for palliation as well as diagnosis survived significantly longer (median 350 days) than dogs that had no surgery (median 207 days), and surgical debulking improved prognosis, regardless of tumor location within the bladder (Josel et al. 2002). Although this was not a randomized study it suggests surgical debulking as part of a multimodality approach may have a role to play in even advanced cases of TCC. Partial-thickness intraluminal debulking to alleviate clinical signs of obstruction can also be considered as a palliative and diagnostic measure. Reports of partial cystectomy in the cat show up to 45% of cats have trigonal tumors, and of all cats that undergo curative-intent partial cystectomy, up to 75% will suffer a local recurrence (Wilson et al. 2007). Median survival of all 20 cats in this study (regardless of treatment options) was 261 days. Adjuvant therapy Piroxicam is a nonselective COX inhibitor affecting both COX-1 and COX-2 and has been investigated as a drug to treat canine bladder cancer. In a study of 34 dogs with bladder TCC, 2 had complete remission, 4 had partial remissions, and disease stabilized in 18. The median survival was 181 days (Knapp et al. 1994). The therapy was generally well tolerated, and the pet owners

subjectively noted an improved quality of life (increased activity and alertness). Piroxicam to treat TCC is administered at 0.3 mg/kg SID (Knapp et al. 1994). This dose rate can still produce signs of gastrointestinal irritation (anorexia, vomiting, melena), and this occurred in 6 dogs (17%) of those investigated. The concurrent use of misoprostol (2–5 mcg/kg BID/TID), a prostaglandin E1 analog, may prevent these gastric side effects. Misoprostol may also diminish the nephrotoxicity associated with nonsteroidal anti-inflammatory drugs (Weir et al. 1991). Two dogs in the study were found to have renal changes consistent with this drug toxicity on postmortem. Cisplatin as a single agent has been reported to have some success against TCC. Partial responses (at least 50% decrease in tumor volume) or stable disease or minimal responses were achieved in 39%–75% of cases (Shapiro et al. 1988; Moore et al. 1990; Chun et al. 1996), and median survival times ranging from 130 to 180 days have been recorded (Moore et al. 1990; Chun et al. 1996). In one study, dogs with only a small reduction in tumor volume still had significantly longer survival times (Chun et al. 1996). This suggests that palliation of signs and longer survival times are possible even in the absence of complete responses. A common complication of cisplatin therapy is nephrotoxicity, and underlying renal pathology secondary to bladder cancer may further exacerbate azotemia (although azotemia actually diminished in two dogs treated with cisplatin (Moore et al. 1990)). Carboplatin, relatively non-nephrotoxic compared with cisplatin, was not found to be an effective treatment as a single agent in 14 dogs with TCC in one study (Chun et al. 1997). Mitoxantrone has been used therapeutically in canine bladder cancer, where one of six dogs was reported to have benefited (Ogilvie et al. 1991). A carboplatin and piroxicam combination has demonstrated some antitumor activity against canine TCC of the bladder; of 14 dogs, 5 showed partial remission and disease stabilized in 5. The duration of remission in dogs with a partial response was 95–310 days, but the overall median survival time (93 days) was shorter than that reported with the use of piroxicam alone (181 days) (Knapp et al. 1997). The combination of cisplatin and piroxicam has been evaluated, and although the response was better to this drug combination than to cisplatin alone (median survival time 246 days), the severe nephrotoxicity still excludes its routine use, with 12 of 14 dogs in one study having renal toxicity (Knapp et al. 2000). When cisplatin was given at 50 mg/m2 (then dropped to 40 mg/m2) in conjunction with piroxicam, median survival time was 307 days, but there was only a 7% response rate and moderate to severe renal and

Urinary Tract  377

gastrointestinal toxicity was seen in 5 and 8 dogs, respectively (Greene et al. 2007), prompting the recommendation that this protocol could not be recommended given the minimal efficacy and high toxicity. Forty-eight dogs with TCC were prospectively treated with mitoxantrone and piroxicam, and a measurable response rate of 35% was achieved, with a subjective improvement occurring in 75% of treated dogs. Median survival time with this combination was 350 days, with diarrhea and azotemia being the most common treatment complications (Henry et al. 2003).

Urethra Tumors of the urethra can be amendable to surgical excision depending on the location and extent of the length of urethra involved. Tumors that involve the cranial aspect of the urethra are more problematic because their excision might lead to urinary incontinence. As mentioned in the partial cystectomy section, resection of the bladder neck and proximal urethra while preserving the neurovascular pedicles to the bladder and urethra has been described, thereby preserving lower urinary tract function and maintaining continence (Saulnier-Troff et al. 2008). For tumors that are located in the midportion of the urethra and that are relatively small, a resection and anastomosis of the urethra might be possible. For tumors that are located at the caudal aspect of the urethra or that are too large to allow an anastomosis, a resection followed by an urethrostomy can be performed. The length of urethra remaining after the resection will dictate the type of urethrostomy. When the urethra is long enough in the male dog, a prescrotal urethrostomy is performed. If the urethra is shorter, a scrotal or perineal urethrostomy is performed. When dealing with an even shorter urethral remnant, a transpelvic (Bernarde and Viguier 2004) or prepubic urethrostomy is performed. In female dogs, it is possible to transplant the remaining urethra more cranially in the vagina by performing a vagino-urethroplasty. Palliative procedures to alleviate an obstruction caused by a urethral tumor include tube cystostomy, urethral stenting, and transurethral resection. Surgical techniques Urethral resection with vagino-urethroplasty A large surgical clip from the xiphoid to the anus is made to allow the vulva to be contained within the surgical field. Prior to surgery, an indwelling transurethral Foley catheter is placed to help identification of the urethra during surgery. A caudal laparotomy is made extending from midway between the umbilicus and pubic brim to

just cranial to the vulva. This is extended sharply through the linea alba into the abdomen and from the pubic brim caudally. Cutting diathermy is used to elevate and retract the gracilis muscles for 5 mm either side of the pubic symphysis. Self-retaining retractors can be used to improve exposure of the symphysis, and a midline symphysiotomy is made with an oscillating saw. The pelvic canal is opened sufficiently by either by Finochietto spreaders or Gelpis retractors to allow easy access to the urethra. Alternatively, creating a ventral window in the pubis is possible with osteotomies into both obturator forminae from the pubic brim and then connecting the foraminae across the midline. After urethral resection and vagino-urethroplasty, the bony window can be reduced and stabilized with cerclage wires into predrilled holes. The urethra is identified and traced caudally to its opening into the vagina. Umbilical tape passed dorsal to the urethra helps in manipulation of the urethra. Care should be taken when dissecting around the proximal urethra to avoid the pudendal nerves running just lateral to the urethra. The affected urethra is typically thicker and firmer than normal urethra, and soft-tissue attachments along the length of the diseased segment are freed (while keeping some distance from the tumor), including a margin of normal urethra 2–3 cm cranially. A transverse urethrotomy at the cranial margin is performed leaving the Foley catheter intact, and the tip of the Foley is withdrawn from the bladder. The caudal urethra is reflected caudally, and using the Foley catheter as a guide, the caudal urethra and a cuff of normal vaginal wall surrounding the urethral papilla are resected. The tube of resected urethra then slides off the Foley. The Foley catheter is cleaned with a moistened gauze, and gloves and instruments are changed. The bulb of the Foley catheter is then reintroduced into the bladder and reinflated. The Foley now acts as a guide for reconstruction of the vagino-urethroplasty (Figure 11.15). The vagino-urethroplasty is performed using onelayer interrupted sutures of monofilament absorbable material. The cut edge of the urethra is sutured to the cut edge of the vagina. Because the diameter of the defect in the vagina is typically larger than the diameter of the urethra, the vaginal defect is partially closed caudally until the diameter of the defect matches that of the urethra. Alternatively, if the urethra is too short to reach the defect in the vagina, this defect is closed, and a stoma is created in the vagina more cranially where the urethra will be anastomosed to the vagina. Sutures are typically preplaced, beginning on the deeper side of the anastomosis to ensure accurate apposition of mucosal surfaces. The sutures pass submucosally to avoid having suture

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and recrudescence of clinical signs such as stranguria and hematuria should be closely monitored and investigated. Histologic tumor types and prognosis

Figure 11.15.  Vagino-urethroplasty being performed on a dog with TCC of the caudal urethra. The caudal urethra and papilla have been resected, and the Foley reintroduced back into the cranial urethral remnant (cranial left, caudal right). Blue stay sutures are in the vaginal wall. The urethral and vaginal wounds are brought together for suture approximation.

Urethral tumors are usually either TCC or squamous cell carcinoma (SCC). Resection of the caudal urethra and creation of a new stoma into the vagina has been described for neoplasia in five dogs and granulomatous urethritis in one dog. The cases with neoplasia were two dogs with urethral myxosarcoma, two with urethral leiomyoma, and one with TCC. In these cases, up to 50% of the urethra and the papilla were resected. The dog with TCC had a local recurrence at 4 months, but the other five were all symptom free at least 12 months after surgery (White et al. 1996). It is not known, especially regarding TCC, whether this represents an improvement in outcome over medical management alone. There is a single case report of proximal urethral resection and vesicourethral reconstruction in a cat with TCC (Takagi et al. 2005). Adjuvant therapy

material within the urethral lumen. Polydioxanone or poliglecaprone 25 size 3-0 or 4-0 is used. The symphysiotomy is repaired with cerclage wire through holes drilled in the pubis.

There are no studies specifically reporting the outcome following chemotherapy in dogs with urethral TCC. All information is extrapolated from studies involving the bladder (see earlier).

Postoperative care

Palliative procedures

The transurethral Foley catheter is left in situ for 7–10 days, and the bladder is emptied intermittently rather than being connected to a closed drainage system to prevent dragging and tension on the urethral repair from the urinary bag. The dog is towel walked until comfortable to rise unaided, and analgesia is a priority. Use of the alpha-adrenergic phenylpropanolamine may be necessary to increase urethral tone to ensure urinary continence.

Tube cystostomy

Functional outcome and potential complications Outcome depends on the extent of urethra resected, stability of the symphysiotomy repair, accuracy of urethra-vaginal reconstruction, and frequency of tumor recurrence within the urethra. Some degree of temporary urinary incontinence is occasionally seen due to the degree of dissection and tissue manipulation, but this usually improves as the inflammation resolves. Delayed union of the symphysiotomy will result in continued discomfort when rising and walking. Although the intention of surgery remains curative and wide margins are attempted, tumor recurrence remains the most likely and most serious complication,

For tumors that involve the urethra or trigone of the bladder and that cause an obstruction, placing a cystostomy tube can be a palliative solution to allow emptying of the bladder by the owners. Although the complication rate can be close to 50%, they can be maintained for up to a year. Please see the section on the prostate in Chapter 10 for further details and surgical technique. Urethral stenting Recently, palliative urethral stenting has been described to manage malignant urethral obstructions in 12 dogs (Weisse et al. 2006). Using fluoroscopic guidance, either balloon-expandable metallic stents or self-expanding metallic stents were inserted within the urethra at the level of the obstruction and extending 1 cm proximally and distally to the obstruction. Seven dogs had a good to excellent outcome, three had a fair outcome, and two had a poor outcome. Survival times from stent placement ranged from approximately 6 days to 105 days, and in 83% dogs the cause of death was not associated with lower urinary tract obstruction. Palliative urethral stenting offers relief to dogs with urinary obstruction due to neoplastic infiltrative disease

Urinary Tract  379 Table 11.1.  Stent sizes available. Expanded Stent Diameter (mm)

Figure 11.16.  CT image of a urethral stent (small arrow; large arrow points to bladder) in the pelvic urethra placed to alleviate urinary obstruction.

(Figure 11.16). It does not address local disease as such, only the clinical signs, and the gold standard therapies for urethral neoplasia should still be discussed, including systemic chemotherapy. Prior to stenting, most patients undergo urethroscopy and cystoscopy to ensure disease is predominantly confined to the urethra. Cases with a large bladder/trigonal component, or cases that extend out of the urethral papilla, present additional problems. The former is an increased risk of incontinence after stenting and the latter an increased risk of persistent stranguria and discomfort from the stent pressing into the submucosa of the vaginal vault. Stent sizing is the first step after endoscopy. This typically involves inserting a Foley catheter under anesthesia into the distal urethra, increasing pressure in the bladder by applying caudal abdominal compression, and performing a fluoroscopic retrograde urethrogram to maximally distend the urethra. This not only identifies the length of the narrowing and its position within the urethra but also helps identify the maximal achievable width under pressure. The stent chosen is typically 10% larger than the maximal distension and then rounded up to an available diameter. The stents used commonly are self-expanding and made of nitinol (e.g., VetStent–Urethra, Infiniti Medical, Menlo Park, CA, USA) and are laser cut from a single piece of material. Deployment requires real-time fluoroscopic imaging because once deployment has started, urethral stents cannot be constrained and repositioned if position is suboptimal. At the time of publication, there are several stent sizes available (Table 11.1). Ideally, sizing should be followed immediately by “offthe-shelf ” deployment, but if the stent needs to be

6 6 8 8 10 10 10 12 12

Expanded Stent Length (mm)

Stent Introducer Delivery System

40 60 40 60 40 60 80 60 80

6F–75 cm 6F–75 cm 6F–75 cm 6F–75 cm 6F–75 cm 6F–75 cm 6F–75 cm 7F–85 cm 7F–85 cm

ordered, then an indwelling Foley can be placed and the patient recovered. The principles of stenting are easily learned, but just as with tracheal stenting, the consequences of misplacing a stent can be disastrous. With long urethral constrictions, especially in males along the prostatic urethra, two stents might be required. Occasionally, phenoxybenzamine might be required to reduce urethral spasm and the discomfort associated with a stent, or phenylpropanolamine if the stent overdilates the bladder neck and causes a low-grade urinary incontinence. Stenting offers only temporary relief. Ultimately, the TCC will continue to grow and infiltrate between the holes in the stent, filling the lumen once more and resulting in urinary obstruction. For more information, see also the section on the prostate in Chapter 10. Transurethral resection Transurethral resection (TUR), evolved from use in human medicine to treat urethral narrowing secondary to benign prostatic hyperplasia in men, has been described to manage urethral TCC in female dogs (Liptak et al. 2004). TUR was, however, associated with novel complications due to difficulty passing the cystoscope through the papilla of small dogs and the tumorassociated decrease in size and distensibility of the canine urethra because the patients present with significantly more advanced disease than their human counterparts. The authors concluded that electrosurgical TUR cannot be recommended because of a high intraoperative and postoperative complication rate with no improvement in patient outcome compared to historical reports of tube cystostomy.

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For more information, see also the section on the prostate in Chapter 10. Radiation Various options for radiation therapy (XRT) to treat lower urinary tract carcinomas have been described. Reports dating back to 1987 show that XRT has been used successfully to control canine bladder TCC and prostatic carcinoma (Withrow et al. 1989; Anderson et al. 2002); however, irradiation of lower urinary tract tumors poses several unique challenges. These include the difficulty in tumor localization and proximity of the tumor to dose-limiting structures such as the ureters and colon. Complications of therapy include cystitis and fibrosis as well as irritation to surrounding organs (McCaw and Lattimer 1988; Poirier et al. 2004). These sequelae can significantly detract from the patient’s quality of life, and successful use of XRT for the treatment of canine carcinoma requires careful delivery of the radiation dose. Factors to consider when designing radiation protocols include the volume of bladder, urethra, or prostate to be irradiated; the total dose to be delivered; the dose per fraction to be used; and the dose to surrounding tissues. To date, two different methods of delivering the prescribed radiation dose have been described: intraoperative radiotherapy (IORT), in which the bladder and/or prostate is exteriorized and single large doses (10–40 Gy) are given (Kinsella et al. 1988; McCaw and Lattimer 1988; Withrow et al. 1989; Anderson et al. 2002), or fractionated treatments where multiple smaller doses (3–5.75 Gy) in 6–12 fractions are given to equal total doses of 30–48 Gy (Arthur et al. 2008). These studies have shown tumor responses, but treatment-related toxicity, including colon perforation and stenosis of the ureters, has been reported with IORT. Other major deterrents to the use of radiation in treating lower urinary tract carcinomas are the need to perform surgery in the radiation facility in order to exteriorize the bladder or prostate (as in IORT) and the need for laborious contrast studies and urinary catheterization to ensure uniform bladder size as well as lesion localization with fractionated treatments. A new application of stereotactic radiosurgery (SRS) recently described includes the treatment of lower urinary tract tumors, especially TCC of the urethra and/ or bladder (Bacon et al. 2010), and TCC and adenocarcinoma of the prostate. CT in conjunction with SRS allows precise lesion localization followed by a highly conformal dose delivery to the tumor with minimal exposure to surrounding tissues. In a modification of the technique previously described for appendicular osteosarcoma (Farese et al. 2004), a modified bite-plate

Figure 11.17.  Stereotactic radiosurgery (SRS) treatment plan for a dog with urethral TCC (cranial left, caudal right). The blue isodose line represents a dose of 25 Gy. A Foley catheter can be seen in the urethra and bladder neck, and a small Steinmann pin (driven into an iliac wing not visible in this image) and resulting metal artifact (arrow) can be seen dorsal to the sacrum.

fiducial array is temporarily attached to the pelvis using four Steinman pins in the iliac wings, allowing precise anatomical referencing of the pelvic canal (Figure 11.17). As an added advantage, the CT, fiducial array attachment, and SRS are all performed under a single anesthetic procedure. Although still early in the course of follow-up, all nine female dogs with urethral TCC that were treated have had promising results regarding local control. Obstruction was relieved in all dogs, with dogs dying of metastatic disease or disease progression outside the radiation field. Urethral stricturing from the radiation was confirmed in one dog and presumed in another, and this or disease progression outside the radiation field resulted in 33% of dogs requiring urethral stenting. All dogs were also treated with daily piroxicam and three times weekly mitoxantrone, and the overall survival time ranged from 81 to 658 days. It is important to note that SRS, like any radiation, is a local treatment, and the goal of SRS, fundamentally, is to offer local disease control in the urethra and move the emphasis of survival onto chemotherapy.

Urinary Tract  381

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with transitional cell carcinoma of the bladder. Proceedings of the 26th Annual Conference, Veterinary Cancer Society, Callaway Gardens, GA, October, 2006, p. 66. Kinsella, T.J., W.F. Sindelar, A.M. DeLuca, et al. 1988. Tolerance of the canine bladder to intraoperative radiation therapy: An experimental study. Int J Radiat Oncol Biol Phys 14(5):939–946. Kiser, G.C., M. Totonchy, and J.M. Barry. 1986. Needle tract seeding after percutaneous renal adenocarcinoma aspiration. J Urol 136:1292–1293. Klein, M.K., G.L. Cockerell, C.K. Harris, et al. 1987. Canine primary renal neoplasms: A retrospective review of 54 cases. J Am Anim Hosp Assoc 24:443–452. Knapp, D.W., L.G. Adams, A.M. Degrand, et al. 2007. Sentinel lymph node mapping of invasive urinary bladder cancer in animal models using invisible light. Eur Urol 52(6):1700-1708. Knapp, D.W., N.W. Glickman, W.R. Widmer, et al. 2000. Cisplatin versus cisplatin combined with piroxicam in a canine model of human invasive urinary bladder cancer. Cancer Chemother Pharmacol 46(3):221–226. Knapp, D.W., R.C. Richardson, T.C. Chan, et al. 1994. Piroxicam therapy in 34 dogs with transitional cell carcinoma of the urinary bladder. J Vet Intern Med 8:273–278. Knapp, D.W., B.R. Schmidt, and W.R. Widmer. 1997. Preliminary results of carboplatin/piroxicam therapy in canine transitional cell carcinoma. Proceedings of the 17th Annual Conference of the Veterinary Cancer Society, p. 89. Dec. 3–6, Chicago, IL. Kyles, A.E. and A.S. Stone. 1998. Urinary bladder. In Current Techniques in Small Animal Surgery, 4th edition, pp. 451–453. M. Joseph Bojrab, editor. New York: Williams and Wilkins. Laluha, P., P. Grest, S. Eichenberger, et al. 2006. Leiomyoma of a kidney in a dog: A rare diagnosis. Schweiz Arch Tierheilkd 148(6):303–307. Lamb, C., N. Trower, and S. Gregory. 1996. Ultrasound-guided catheter biopsy of the lower urinary tract: Techniques and results in 12 dogs. J Small Anim Pract 37:413–416. Léveillé, R., D.S. Biller, B.P. Partington, et al. 1992. Sonographic investigation of transitional cell carcinoma of the urinary bladder in small animals. Vet Radiol Ultrasound 33:103–107. Liptak, J., S. Brutscher, E. Monnet, et al. 2004. Transurethral resection in the management of urethral and prostatic neoplasia in 6 dogs. Vet Surg 33:505–516. Locke, J.E. and L.G. Barber. 2006. Comparative aspects and clinical outcomes of canine renal hemangiosarcoma. J Vet Intern Med 20(4):962–967. McCaw, D.L. and J.C. Lattimer. 1988. Radiation and cisplatin for treatment of canine urinary bladder carcinoma: A report of two case histories. Vet Radiol 29(6):264–268. Moore, A., A. Cardona, W. Shapiro, et al. 1990. Cisplatin for treatment of transitional cell carcinoma of the urinary bladder or urethra. A retrospective study of 15 dogs. J Vet Intern Med 4:148–152. Norris, A.M., E.J. Laing, V.E. Valli, et al 1992. Canine bladder and urethral tumors: A retrospective study of 115 cases (1980–1985). J Vet Intern Med 6:145–153. Nyland, T.G., S.T. Wallack, and E.R. Wisner. 2002. Needle-tract implantation following US-guided fine-needle aspiration biopsy of transitional cell carcinoma of the bladder, urethra, and prostate. Vet Radiol Ultrasound 43:50–53. Ogilvie, G., J. Obradovich, R. Elmslie, et al. 1991. Efficacy of mitoxantrone against various neoplasms in dogs. J Am Vet Med Assoc 225:1567–1572; 198:1618–1621. Osborne, C.A., D.G. Low, V. Perman, et al. 1968. Neoplasms of the canine and feline urinary bladder: Incidence, etiologic factors, occurrence, and pathologic features. Am J Vet Res 29:2041–2055.

382  Veterinary Surgical Oncology Poirier, V.J., L.J. Forrest, W.M. Adams, et al. 2004. Piroxicam, mitoxantrone, and coarse fraction radiotherapy for the treatment of transitional cell carcinoma of the bladder in 10 dogs: A pilot study. J Am Anim Hosp Assoc 40:131–136. Raffan, E., A. Kipar, P.J. Barber, et al. 2007. Transitional cell carcinoma forming a perirenal cyst in a cat. J Small Anim Pract 49(3): 144–147. Raman, J.D. and D.S. Scherr. 2007. Management of patients with upper urinary tract transitional cell carcinoma. Nature Clin Pract Urol 4(8):432–443. Reichle, J.K., R.A. Peterson, M.B. Mahaffey, et al. 2003. Ureteral fibroepithelial polyps in four dogs. Vet Radiol Ultrasound 44:433–437. Saulnier-Troff, F., V. Busoni, and A. Hamaide. 2008. A technique for resection of invasive tumors involving the trigone area of the bladder in dogs: Preliminary results in two dogs. Vet Surg 37(5): 427–437. Shapiro, W., B.E. Kitchell, T.W. Fossum, et al. 1988. Cisplatin for treatment of transitional cell and squamous cell carcinomas in dogs. J Am Vet Med Assoc 193:1530–1533. Slywotzky, C. and M. Maya. 1994. Needle tract seeding of transitional cell carcinoma following fine-needle aspiration of a renal mass. Abdom Imaging 19:174–176. Smith, E.H. 1991. Complications of percutaneous abdominal fineneedle biopsy. Review. Radiology 178:253–258. Steffey, M., K.M. Rassnick, B. Porter, et al. 2004. Ureteral mast cell tumor in a dog. J Am Anim Hosp Assoc 40:82–85. Stewart, G.D., S.V. Bariol, K.M. Grigor, et al. 2005. A comparison of the pathology of transitional cell carcinoma of the bladder and upper urinary tract. Br J Urol Int 95:791–793.

Stone, E.A., T.F. George, S.D. Gilson, et al. 1996. Partial cystectomy for urinary bladder neoplasia: Surgical technique and outcome in 11 dogs. J Small Anim Pract 37(10):480–485. Stone, E.A., S.J. Withrow, R.L. Page, et al. 1988. Ureterocolonic anastomosis in ten dogs with transitional cell carcinoma. Vet Surg 17(3):147–153. Takagi, S., T. Kadosawa, T. Ishiguro, et al. 2005. Urethral transitional cell carcinoma in a cat. J Small Anim Pract 46(10):504–506. Weir, M.R., D.K. Klassen, P.S. Hall, et al. 1991. Minimization of indomethacin-induced reduction in renal function by misoprostol. J Clin Pharmacol 19:729–735. Weisse, C., A. Berent, K. Todd, et al. 2006. Evaluation of palliative stenting for management of malignant urethral obstructions in dogs. J Am Vet Med Assoc 229(2):226–234. White, R.N., J.V. Davies, and S.P. Gregory. 1996. Vagino-urethroplasty for treatment of urethral obstruction in the bitch. Vet Surg 25(6):503–510. Wilson, H.M., R. Chun, V.S. Larson, et al. 2007. Clinical signs, treatments, and outcome in cats with transitional cell carcinoma of the urinary bladder: 20 cases (1990–2004). J Am Vet Med Assoc 231(1):101–106. Wisner, E.R. and R.E. Pollard. 2004. Trends in veterinary cancer imaging. Vet Comp Oncol 2:49–74. Withrow, S.J., E.L. Gillette, P.J. Hoopes, et al. 1989. Intraoperative irradiation of 16 spontaneously occurring canine neoplasms. Vet Surg 18(1):7–11.

12 Eyelids, eye, and orbit B. Duncan X. Lascelles, Michael Davidson

Introduction Neoplasia affecting either the adnexa (eyelids, conjunctiva, nictitans, or sclera), uveal tract (iris, ciliary body, choroid), and orbit are relatively common in dogs and cats. The clinical significance and appropriate treatment of these tumors varies considerably depending on the anatomical location, species (dog vs. cat), age of the patient, and whether the neoplasia is primary or metastatic. However, any tumor of the orbit, adnexa, or eye can have devastating consequences for an animal’s vision, appearance, and comfort, and as such, they demand appropriate evaluation and treatment. Important differences in biological behavior of these neoplasms exist between the two species with most primary canine ocular/periocular tumors having a benign behavior, whereas most primary feline tumors are malignant. As would be expected, most tumors occur in older animals, with notable exceptions including eyelid histiocytomas and infectious papillomas in dogs, oncogene-related neoplasia in cats, and certain forms of iris melanoma in dogs. Adnexal neoplasia (such as eyelid neoplasia), when benign, becomes clinically important when it reaches a size, or is in a location, that physically irritates the conjunctiva and cornea and causes discomfort. Intraocular benign neoplasia becomes clinically significant when distortion of the uveal tissue or displacement of the lens occurs, and will generally culminate in secondary glaucoma due to obstruction to aqueous humor outflow. Malignant adnexal or intraocular neoplasia has its most important effects by being locally invasive to surrounding tissues, and/or in causing secondary glaucoma. Orbital neoplasia is generally malignant, locally invasive, and results in progressive

exophthalmos, globe deviation, and protrusion of the nictitans. All ocular and periocular tumors, regardless of their expected microscopic morphology and biological behavior, should routinely be biopsied to confirm the diagnosis.

Clinical Workup and Biopsy Principles A thorough ophthalmological evaluation should be performed in cases of orbital and ocular neoplasia. This is usually best performed by a veterinary ophthalmologist, who is also best positioned to perform diagnostic and biopsy procedures, especially for intraocular neoplasia. Masses that involve cranial nerves within the orbit (II, III, IV, VI, and ophthalmic branch of V) may lead to abnormal globe position or mobility, cranial nerve defects such as blindness, reduced pupillary light reflexes, and reduced corneal sensation. Indentation of the posterior sclera by masses may be visualized by ophthalmoscopy. Masses that impinge on the optic nerve sheath may induce papilloedema. Impression smears generally are poorly diagnostic for most adnexal tumors, although they may allow tentative diagnosis of mast cell tumors. Fine-needle aspirate (FNA) may be more diagnostic; however, excisional biopsy is the diagnostic modality of choice, especially for small masses. If this is performed, the position of the mass must be documented in detail, preferably through a combination of diagrams and photographs. In general, excisional biopsy is often required and is used for a definitive diagnosis of small orbital tumors. Large orbital tumors are evaluated with an incisional biopsy. The authors prefer to obtain the biopsy information and then proceed to the appropriate staging (both local and

Veterinary Surgical Oncology, First Edition. Edited by Simon T. Kudnig, Bernard Séguin. © 2012 by John Wiley & Sons, Ltd. Published 2012 by John Wiley & Sons, Ltd.

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distant). Local evaluation (including advanced imaging) of the tumor should always be performed as near to the time of surgical treatment as possible, and ideally before biopsy so that there is no distortion from the biopsy procedure and to help determine the best way to biopsy the tumor. Orbital tumors that are retrobulbar can be biopsied by several means, depending on the size and exact location. Large tumors may create a bulge caudolateral to the lateral canthus or in the oral cavity, typically caudal to the most caudal molar. In these instances, an incisional biopsy can be done with a surgical blade, making a small skin or mucosal incision over the bulging area and sharply and bluntly dissecting carefully to the tumor to acquire the sample. Smaller tumors that are deeper can be biopsied with a needle-core instrument (Trucut biopsy needle). Ultrasound can be helpful to guide the needle. Depending on the location of the tumor, the needle can be inserted caudolateral to the lateral canthus, between the dorsal border of the zygomatic arch and eyeball aiming caudoventrally, or intraorally caudal to the most caudal molar. Surgical exploration of the orbit might be necessary to get a biopsy sample. Further staging is performed by assessing lymph node and distant extension of the neoplasia. 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 addition, all local lymph nodes and node centers should be evaluated. Three-view thoracic radiographs (right and left lateral projections and either dorsoventral or ventrodorsal projection) or helical computed tomography (CT) scans should be performed to evaluate lung metastasis. CT scans are considerably more sensitive in detecting pulmonary metastatic lesions compared to radiographs.

Imaging Techniques Local evaluation may involve regional skull radiographs, which include open mouth, intraoral, oblique lateral, and ventrodorsal or dorsoventral projections. 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. Because of this, and the fact that all the superimposed structures make interpretation of skull radiographs difficult, other imaging modalities are now recommended for imaging of orbital tumors. CT scans are generally preferred to magnetic resonance imaging (MRI) if bone detail is required; MRI scans are preferred if there is extensive

soft tissue involvement. This information is important for planning the definitive surgical procedure (or radiation therapy if indicated). B-scan (brightness scan) ultrasonography may be used to identify intraocular neoplasms that cannot be directly visualized (for example as a result of secondary hyphema from the neoplasm), or to characterize the location and extent of intraocular neoplasia that can be visualized. Highresolution ultrasonography (ultrasound biomicroscopy), is also available and may be useful in identifying and characterizing intraocular neoplasia in very early states.

Eyelid Neoplasia Surgical techniques Benign tumors that are not removed may grow and eventually cause irritation of the globe. Surgical excision and/or cryotherapy of benign lesions are the treatments of choice. The latter offers the advantage of being performed in a sedated patient under local anesthesia and the option to repeat the procedure with local recurrence. Secondary chalazion should be excised and curetted at the time of tumor treatment. Larger or malignant neoplasia of the eyelid generally requires surgical excision. Preservation of eyelid structure and function is an important consideration when choosing treatment of eyelid neoplasms. If the structure and function of the eyelid is substantially altered, corneal exposure, irritation, and ulceration may result. Obviously, early removal of eyelid tumors makes complete removal with margins more likely to be possible. Surgical resection A full-thickness wedge resection (V-lid resection) of the eyelid tumor should be performed with a 2 mm margin (for benign tumors) of excision where possible. Surgical resection of malignant mast cell tumors of the canine eyelid poses a particular problem since, for eyelid tumors, it is impossible to achieve the 2 cm margin of excision recommended as surgical treatment for grade 1 and 2 mast cell tumors of the skin (Fulcher et al. 2006; Simpson et al. 2004; Weisse et al. 2002). Other modalities, or surgical resection combined with adjunctive therapy, may be required in such cases. Particularly aggressive mast cell tumors may require radical excision including exenteration. Basic principles of oncologic surgery should be followed. Appropriate instrumentation and magnification are required. In general, up to one-third of the eyelid margin may be excised in dogs with primary closure without significant alteration in the eyelid. In cats, which have more tightly opposed eyelids, only 20%–25% of the

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Figure 12.1.  A wedge (A) or rectangular four-sided (B) excision may be performed for eyelid masses. (Illustrations by Dave Carlson)

eyelid can be resected before additional blepharoplasty techniques are needed. Upper eyelid function is more critical to preserve than that of the lower eyelid. The lower lacrimal puncta should be preserved if possible. Precise eyelid margin apposition (with wedge resections), or reestablishing some type of mucocutaneous junction at the lid margin (with other blepharoplasty procedures), is critical in order to maintain normal eyelid function and avoid corneal or conjunctival damage. Selection of appropriate suture size, suture pattern, and management of suture tags is likewise necessary to avoid postoperative corneal or conjunctival injury. Closure of eyelid surgical wounds is performed in two layers, namely the deep tarsoconjunctival layer and the superficial muscle/skin layer. The suture bites in the deep layer should not penetrate the palpebral conjunctiva. A 5-0 or 6-0 absorbable suture is used for the deep layer, and similar-sized absorbable or nonabsorbable suture is used for the skin layer. In general, nonabsorbable (nylon) is preferred for skin closure as suture reaction is minimal and end cosmesis is better; however the temperament of the dog or cat (and need for suture removal) may make absorbable suture a more practical option for the skin. Closure is performed from the fornix to the eyelid margin. A figure-eight suture is recommended for closure of the eyelid margin; and care should be taken to ensure the eyelid margin is opposed without notching. The remainder of the surgical wound is closed with simple interrupted sutures. Suture ends can be left long and incorporated into sutures away from the lid margin to prevent corneal contact of the suture ends.

V-plasty and four-sided excision A wedge (Figure 12.1A) or rectangular four-sided (Figure 12.1B) excision may be performed for eyelid masses involving less than 30% of the lid margin in dogs or less than 20%–25% of the lid margin in cats. The incisions should be 2 to 3 mm away from the mass regardless of technique used. The defect is closed in two layers as described above. The four-sided excision allows for resection with adequate margins on a larger mass with maximal preservation of the eyelid margin. The defect is closed in two layers (Figure 12.2). With either resection, the height of the triangle (incision away from the lid margin) should be 2 times that of the base (amount of lid margin resected). If excision of the mass requires more extensive resection of the eyelid margin, a more complex reconstruction procedure is needed. Advancement flaps, rotational flaps, mucocutaneous subdermal plexus flaps (lip-tolid), cross-lid flaps, bucket handle techniques, and free oral mucosal grafts should be performed by an ophthalmologist or surgeon with experience in blepharoplasty procedures. Advancement flap The vertical pedicle advancement is the most easily performed reconstruction technique. As with all reconstructive procedures, conjunctival transposition is needed to line the graft and create a smooth hairless eyelid margin. Conjunctiva may be transposed from the adjacent palpebral conjunctiva by dissection and advancement, from the third eyelid as a rotational graft, or from the oral mucosa as a free graft. For preparation

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Figure 12.2.  Two-layer closure for an eyelid defect. (A) Upper eyelid full-thickness defect after excision of an eyelid mass. (B) The tarsoconjunctival layer is closed with a simple continuous suture pattern from the fornix to the eyelid margin, taking care not to penetrate the palpebral conjunctiva with the suture bites. (C) The eyelid margin is aligned and apposed with a figure-eight suture. (D) The remaining skin incision is closed in a simple interrupted suture pattern. (Illustrations by Dave Carlson)

of the pedicle, parallel diverging incisions twice the length of the defect are made coming away from the defect (Figure 12.3). Burrow’s triangles may be excised at the base of the incision as needed to prevent dog-ears; however, excision of these results in a more extensive scar, requiring a larger dose of follow-up local therapy such as resection or radiation therapy if the resection was not clean. After undermining the skin from subcutaneous attachments, the graft is advanced into the defect with the leading edge 0.5–1.0 mm beyond the adjacent eyelid margin to account for postoperative contraction. Sutures are placed at the eyelid margin first to maintain alignment and then along the incisional lines to complete the closure. Typically, 5-0 nylon is used for the skin, placing the suture knots at the two sides of the lid margin slightly distal to the margin to avoid suture contact with cornea. This suture line is created without tension to allow for contraction with healing and to

prevent cicatricial entropion. Conjunctiva should be advanced from the donor site to line the graft and should be sutured to the eyelid margin with 6-0 or 7-0 absorbable suture, using interrupted mattress sutures or simple interrupted sutures with the knots rotated to the skin surface and suture tags cut short. Rotational flap The principles of the rotational flap are very similar to the advancement flap. The graft is simply created in a different anatomical location (Figure 12.4). Semicircular flap The semicircular flap involves a rotational and sliding component and can be used for closure of both medial and lateral eyelid defects that involve up to 60% of the eyelid margin. It is a one-stage procedure, which has the advantage of replacement of the central eyelid region

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Figure 12.3.  Advancement graft. (A) Proposed skin incisions following tumor excision. Note the Burrow’s triangle at the dorsal aspect (see text). (B) Eyelid defect closed with advancement graft. (Illustrations by Dave Carlson)

(a)

(b)

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Figure 12.4.  Rotation flap. Medial canthus is to the right of the picture. (A) large tumor of the lower eyelid (arrow). Skin marker has been used to delineate proposed skin incisions. (B) The tumor has been excised and the rotation flap has been created (arrow). (C) The flap has been rotated to reconstruct the eyelid.

with normal tissue at the eyelid margin, obviating the need for mucosal grafts. It is performed by incising away from the lateral extent of the defect, as shown in Figure 12.5. The length of the incision should be approximately the length of the eyelid. The lateral canthus is freed, and the flap is undermined with care taken to remain in a superficial plane to avoid damage to the palpebral nerves and vessels. The flap is then advanced into the defect, and a two-layer closure is performed medially. A small triangular area of tissue will need to be removed at the base of the defect, as well as at the site of advancement at the lateral canthus (see Figure 12.5). The lateral canthus is re-formed, making sure to place the graft such that there is minimal tension in the lateral direction. Mucocutaneous subdermal plexus flaps (lip-to-lid) A more extensive rotational flap for reconstruction of lower eyelid defects is the mucocutaneous subdermal

plexus flap from the upper lip (Figure 12.6). This flap provides a mucocutaneous margin to replace excised eyelid margin as well as a central muscular layer that offers more normal thickness and rigidity (Pavletic et al. 1982). The direction of the hair in the graft will course opposite the normal periocular skin. Bucket handle or bridge flap The bucket handle or bridge flap technique uses a fullthickness skin and conjunctiva flap from the opposite eyelid while preserving the normal eyelid margin of the donor lid (Figure 12.7). The technique is generally used only for upper lid defects. The flap is tunneled below the donor eyelid margin, across the surface of the cornea, and sutured into the donor site to restore the eyelid margin of the opposite lid. This procedure, and the cross-lid variation (Munger and Gourley 1981), are twostage techniques that limit the vision during healing and require a second anesthetic event. The second surgical

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Figure 12.5.  Semicircular flap technique. Medial canthus is to the left. (A) Dotted white lines show proposed skin incisions. Two triangles of skin are removed, one at the base of the eyelid defect and one at the tip of the incision at the lateral canthus. (B) The flap has been advanced and sutured into the defect. (Illustrations by Dave Carlson)

Figure 12.6.  Mucocutaneous subdermal plexus flaps (lip-to-lid). (A) A full-thickness rotational graft is prepared from the caudal upper lip and adjacent buccal region. (B) Using a bridging incision, the pedicle is rotated into position. (C) The donor site is closed. (Illustrations by Dave Carlson)

procedure is typically performed 4–6 weeks later to allow the donor site to establish an adequate vascular supply. Functional and cosmetic results are good with these techniques. Postoperative care Postoperative care for most blepharoplasty procedures should include standard perioperative pain management and measures to prevent self-mutilation, such as an Elizabethan collar. In the author’s experience, these procedures are associated with minimal postoperative discomfort, and most animals require an Elizabethan collar for only 2–5 days. Suture removal is typically performed 10–14 days postoperatively. Cryosurgery Cryosurgery may be performed on small eyelid tumors, in cases for which anesthetic risk is high, or in

conjunction with surgical cytoreduction (Vestre 1984). However, lesions should always be biopsied at the time of, or prior to, cryosurgery. For suspected sebaceous adenomas, papillomas, or melanomas, the biopsy is generally done at the same time as the cryosurgery; this also reduces the tumor load to freeze. Very often, the appearance, position, and characteristics of the mass make it highly likely it is a papilloma or melanoma. Obviously, oncologic surgical principles would suggest it is better to perform a biopsy before any definitive treatment. Following histopathological evaluation, the treatment plan can be modified as necessary. For suspected malignant or aggressive eyelid neoplasia, a biopsy is performed and evaluated prior to any treatment, and a treatment plan is developed. In one study, cryosurgery was associated with better cosmetic results than surgical excision, and there was no statistically significant difference in recurrence rates (Roberts et al. 1986). However, when

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Figure 12.7.  Bucket handle flap. (A) The bucket handle flap is prepared by making a full-thickness incision 5 mm from the eyelid margin, parallel to the eyelid margin, with the length of the incision matching the length of the defect to be filled. Full-thickness incisions are then made coming from the ends of the incision parallel to the eyelid, and extend dorsally or ventrally, depending on the lid involved. (B) The haired flap is pulled under the donor eyelid margin, and across the cornea, and sutured into the defect on the recipient side. A temporary tarsorrhaphy is performed to ensure the flap is not damaged. The flap is left to heal for 2–3 weeks. (C) On the recipient side, the flap is divided and trimmed so as to be 1 mm longer than the defect (to allow for contraction). Conjunctiva is undermined and advanced over the cut edge (making sure there is no tension) and sutured in place, ensuring there is a smooth, hairless eyelid margin. The donor site is closed. During this procedure, an excess of donor tissue will be removed in the second stage. (Illustrations by Dave Carlson)

used for the treatment of malignant melanoma or mast cell tumor, cryotherapy is not generally considered curative. This example underscores the importance of performing a biopsy prior to making any decisions about treatment. The general principles of cryosurgery have been described (Holmberg 1980; Farris and Vestre 1982; Rickards 1980). Careful use of cryotherapy around the eyelid is indicated to prevent scarring and distortion of the eyelid. A chalazion clamp is useful for positioning of the eyelid during freezing and provides local hemostasis that facilitates maximal cellular destruction (Figure 12.8). For small, benign eyelid tumors such as sebaceous adenomas, the freezing is continued until there is a visible ice ball 1–2 mm beyond the visible margin of the tumor. For larger or malignant eyelid neoplasms, thermocouples placed within and adjacent to the mass are useful to monitor the necessary freezing time. If thermocouples are not used, in general, the ice ball should extend 5 mm beyond the margins of the mass. A double rapid-freeze/ slow-thaw cycle is used. Cytoreduction of large masses should be performed so that they are flush with the skin level before application of cryotherapy. Postoperative care Postoperatively, moderate inflammation, followed by tissue necrosis and eschar formation and depigmentation in the treated area are expected (Holmberg 1980), and owners should be educated about the expected

Figure 12.8.  Cryosurgery is performed on a tumor of the lower eyelid. A chalazion clamp (small arrow) has been placed around the tumor, and the cryotherapy probe (large arrow) is applied to the tumor.

changes. Repigmentation of the surgical site often occurs over a period of several months. Histologic tumor types and prognosis Eyelid tumors are common in dogs, and two reports indicate that benign tumors outnumber malignant tumors by a ratio of three to one. However, these reports may substantially underestimate the prevalence of benign tumors as they are less likely to be biopsied. Epithelial tumors outnumber mesenchymal tumors to a ratio of

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five to one. By far the most common tumor of the eyelid is the meibomian (sebaceous) adenoma (accounting for 44%–60% of all canine eyelid tumors), followed by benign melanoma (17%–20% of cases), and papilloma, both viral and nonviral (11%–17% of cases) (Gwin et al. 1976; Krehbiel and Langham et al. 1975; Roberts et al. 1986). Other less common benign eyelid neoplasia includes fibroma and histiocytoma. Malignant eyelid neoplasia is less common and can include mast cell tumor, sebaceous adenocarcinoma, basal cell carcinoma, squamous cell carcinoma (SCC), and fibrosarcoma. With the exception of viral papilloma and histiocytoma, they usually affect dogs older than 9 years of age. In the cat, the most common eyelid tumor is SCC (65% of cases), with white or sparsely pigmented cats being predisposed. Concurrent pinnal or nasal SCC may be present. It is generally locally invasive and late to metastasize. Other eyelid neoplasms, which tend to be malignant, include basal cell carcinoma, mast cell tumor, fibrosarcoma, and uncommonly, lymphoma. Adnexal squamous cell carcinoma in the cat tends to be very locally invasive and can be very challenging to treat as surgical excision alone has a high recurrence rate. Extensive cryosurgery, intralesional chemotherapy, and photodynamic therapy are options. The usefulness of local radiation therapy is limited by the collateral side effects on the globe, and when this modality is used, enucleation or exenteration may be necessary. Depending on the stage at which SCC is treated, the prognosis is often guarded. Other types of malignant neoplasia of the eyelid are generally treated by surgical excision, with a grafting procedure if the eyelid margin is involved. Presenting signs and differential diagnosis In dogs, sebaceous adenomas arise from the meibomian glands and present as focal masses on the eyelid margin. This slow-growing tumor may be pigmented or nonpigmented, often has a cobblestone surface, and may be associated with a secondary chalazion (swelling of the eyelid and palpebral conjunctiva from obstruction of the gland’s sebaceous secretions with secondary granulomatous inflammation) (Figure 12.9). Sebaceous adenomas can generally be distinguished from other benign eyelid neoplasia as the former arise from the eyelid margin (at the punctal opening of the meibomian gland) and often have an associated swelling in the palpebral conjunctiva, whereas other eyelid neoplasias generally arise from the cutaneous surface of the eyelid. Because they arise from the lid margin, adenomas are eventually associated with ocular discomfort due to corneal and conjunctival irritation, keratitis, or corneal ulceration. Papillomas, benign melanoma, and other types of eyelid tumors present as focal, erosive, or infiltrative masses of

Figure 12.9.  Sebaceous adenoma of the lower eyelid in a dog.

varying size (Figure 12.10). Benign eyelid neoplasia (other than sebaceous adenomas) may not require treatment unless they are of sufficient size to contact the globe or interfere with normal eyelid function. Histiocytic-type mast cell tumors in cats (in particular the Siamese breed) may require no treatment, as these tumors may regress spontaneously. Prognosis The prognosis following removal of benign eyelid tumors is very good, although some (in particular canine sebaceous adenoma) carry a substantial risk of local recurrence. The prognosis following removal of malignant eyelid tumors depends on the tumor type and stage of malignancy. Because of its low rate of metastasis, early SCC in dogs carries a favorable prognosis. Invasive SCC has a more guarded prognosis, as it may be difficult to achieve adequate margins of excision. Malignant melanoma of the eyelids may be associated with metastasis and therefore carries a guarded prognosis in both species. Other therapies External beam radiotherapy is rarely used in the treatment of eyelid neoplasia because of the sensitivity of the eye to radiation. Brachytherapy using radioactive gold198 seeds has been used successfully in the treatment of feline eyelid SCC (Hardman and Stanley et al. 2001) and in the treatment of canine eyelid mast cell tumors. Chemotherapy is indicated for lymphoma involving the eyelids and in conjunction with surgical resection for mast cell tumors.

Conjunctival, Nictitans, and Scleral Neoplasia Surgical techniques For third eyelid adenocarcinoma, the treatment of choice is removal of the entire third eyelid because of

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(b)

(c)

Figure 12.10.  Benign tumors of the eyelid in dogs. (A) benign melanoma; (B) histiocytoma; (C) papillomas.

the risk of local invasion. Amputation of the third eyelid is performed by exteriorization of the third eyelid and sharp excision of the entire cartilage and gland. Conjunctiva and deeper layers should be closed with 4-0 to 6-0 absorbable suture to help prevent orbital fat prolapse and maintain normal globe position. If appropriate margins cannot be achieved, or local invasion is extensive, exenteration should be considered. If the tumor has invaded the orbit, then exenteration or partial orbitectomy is required. For conjunctival melanoma, wide surgical excision (as wide as is possible, preserving the globe) in combination with cryosurgery is appropriate. Limbal melanomas should generally be treated early, particularly in young dogs where more rapid growth is sometimes seen and in cats where metastasis has been reported. Surgical excision early in the course of growth offers the best prognosis for the eye. This is accomplished with a partial thickness conjunctivo-sclerectomy (and keratectomy if the cornea is involved), using a no. 64 Beaver blade and a sharp, lamellar dissection. Sclerectomies and keratectomies should be performed using an operating microscope and by an experienced veterinary ophthalmic surgeon. Cryosurgery, Nd:YAG laser, or CO2 laser ablation may be used in conjunction with surgical resection or as the sole treatment. Tissue grafts may be necessary if deep or full-thickness resection of the sclera is necessary (Sullivan et al. 1996). Histologic types and prognosis Neoplasia of the conjunctiva, nictitans, and sclera is much less common than that involving the eyelid. In the dog, the conjunctiva (including that covering the nictitans) may develop hemangiomas or, less commonly, hemangiosarcomas, melanoma (usually benign), SCC, and lymphoma. Adenocarcinoma of the gland of the nictitans is the most commonly reported neoplasm of that tissue (Wilcock and Peiffer et al. 1988). These are

generally aggressive and locally invasive in the dog, and metastatic disease has been reported in the cat. Conjunctival or nictitans neoplasia is generally treated with surgical excision alone, with adjuvant therapy used in selected cases. Neoplasia of the conjunctiva must be distinguished from pseudoneoplastic or inflammatory nodules, especially an immune-mediated inflammation known as nodular granulomatous episclerokeratitis (NGE). In the cat, the only common conjunctival neoplasia is SCC, where the same considerations as with eyelid involvement apply. The only common tumor of the sclera is a melanoma arising from the limbal region, (epibulbar melanoma, limbal melanoma, limbal melanocytoma). In dogs, these are almost exclusively benign, slow-growing neoplasms that relatively late in the course of the growth can invade the cornea and adjacent iridocorneal angle and cause corneal opacity or secondary glaucoma. German shepherd dogs may be predisposed (Giuliano et al. 1999). In cats, limbal melanoma is also usually benign, but metastatic disease has been reported in one case (Betton et al. 1999). Melanoma arising from the conjunctiva at sites other than the limbus is uncommon in dogs and cats, and the behavior appears to be different from that of limbal/ epibulbar melanoma. The third eyelid is most commonly affected. In dogs, conjunctival melanomas may be aggressive, and in cats conjunctival melanoma is malignant in the majority of cases, with local and distant metastasis likely. Presenting signs and differential diagnosis Conjunctival and third eyelid tumors usually present as visible masses or erosive lesions. Melanoma usually presents as a dark mass. Secondary conjunctivitis may be present. Masses or swelling on the surface of the globe need to be distinguished from NGE, necrotizing scleritis/ keratitis, corneal or conjunctival cysts, foreign bodies,

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and globe perforation with iris prolapse. Limbal melanoma with intraocular extension must be distinguished from a uveal melanoma with extraocular extension.

Enucleation is the removal of the globe and the third eyelid. Either the subconjunctival or transpalpebral enucleation techniques can be used. The latter approach resects more tissue, but removal of all the palpebral conjunctiva and lacrimal gland is easier to accomplish. The subconjunctival approach is simpler, with less tissue resected, but the surgeon has to ensure that the residual bulbar conjunctiva (which is distal to the perilimbal incision) and all the palpebral conjunctiva are removed. Chronic drainage from the surgical site can occur if all the conjunctiva and glandular tissue is not removed. The transpalpebral approach is similar to that used for exenteration, but only the globe is removed.

traction be placed on the globe, which should be avoided (especially in cats), to avoid stretching and damage to the optic chiasm and contralateral optic nerve. The remaining bulbar conjunctiva, palpebral conjunctiva and nictitans are removed with blunt and sharp dissection, beginning at the lateral canthotomy site and extending medially. After removal, the surgeon should palpate the base of the nictitans to ensure that the entire gland of the third eyelid is included in the resection. Finally, a 2–3 mm strip of eyelid margin and adjacent skin is removed with sharp (scissor) dissection, again proceeding from lateral to medial. The caruncle (firmly attached skin at the medial canthus) is removed from the underlying lacrimal bone with scalpel dissection to allow for symmetrical end-to-end closure of the wound and to avoid a dimple. The wound is closed using a three-layer technique (deep fascial layer, subcutaneous layer and skin). To prevent postoperative concavity of the surgical site, from contraction and atrophy, two techniques may be used. A crisscross of nonabsorbable suture can be placed across the orbital rim, anchored to the orbital septum fascia. This supports the overlying skin and subcutaneous tissues. Alternatively, a 13–18 mm polymethylmethacrylate sphere may be placed in the orbit to obliterate dead space. The deep fascial layer is closed over the prosthesis using 5-0 absorbable suture. Five to seven simple interrupted sutures, working from the central wound to peripheral wound, are used, and the surgeon should ensure that facial tissue and not orbital fat is engaged. Proper closure of the fascial layer is critical to prevent anterior migration of the prosthetic sphere. The subcutaneous and skin are closed to complete the procedure.

Subconjunctival enucleation

Transpalpebral enucleation

As illustrated in Figure 12.11, a lateral canthotomy is made (1–2 cm), and a 360-degree conjunctival and subconjunctival incision (peritomy) is made 5 mm distal to the limbus to allow the majority of the conjunctiva to be removed. Posterior blunt and sharp scissor dissection is performed between the outer layer of the sclera and the fascia and extraocular muscles. The attachments of the main extraocular muscles are identified with a muscle hook or lacrimal cannula and the tendon resected near the globe. The retractor bulbi muscle is resected from its broad attachment posterior to the equator of the globe. Some surgeons prefer to clamp and ligate the optic nerve and associated vessels. The authors prefer to place slight traction and rotation on the globe and use a curved scissor to (blindly) cut the optic nerve. We have found that hemorrhage is minimal and generally easy to control with temporary gauze packing of the orbit. This curved scissor method does not require excessive

As in Figure 12.12, the skin is incised about 5 mm around the closed lid margins, and dissection continues toward the orbital rim, without puncturing the conjunctiva before continuing the dissection down to and along the outer surface of the globe as for the lateral subconjunctival approach. This plane of dissection removes the palpebral conjunctiva and nictitans. After excising the optic nerve and excising the caruncle, wound closure is similar to the subconjunctival approach.

Prognosis Third eyelid adenocarcinoma is locally invasive rather than metastatic and has a good prognosis if treated early. However, metastatic disease associated with third eyelid adenocarcinoma has been reported in the cat. Conjunctival melanoma has a guarded prognosis in dogs and a poor prognosis in cats, in view of the risk of local recurrence and of metastasis. Limbal melanoma in dogs has a good prognosis following surgical removal. In cats the prognosis is also good, but distant metastasis has been reported.

Eye Neoplasia Surgical techniques Enucleation

Exenteration Exenteration is removal of the globe, eye adnexa, and all the orbital contents, and it should be reserved for benign neoplasms involving the orbit. The lids are sutured closed, and then an incision is made around the lid margins. Different from enucleation, the plane of dissection is outside the extraocular muscles. Care is taken during the dissection not to damage the medial orbital

Figure 12.11.  Subconjunctival approach to enucleation, left eye. (A) A lateral canthotomy is performed with heavy scissors. (B) A 360-peritomy is performed 5 mm posterior to the limbus, and blunt and sharp dissection is extended posteriorly. (C) The tendon attachments to all extraocular muscles are identified (a muscle hook or lacrimal cannula facilitates this step), and the attachment excised close to the globe. The broad attachments of the retractor bulbi muscle are also excised. (D) Gentle traction and rotation is applied to the globe to allow introduction of a curved scissor. The optic nerve and associated vessels are excised blindly. Any hemorrhage is controlled by gauze packing the orbit for 1–2 minutes. (E) The palpebral conjunctiva and nictitans are excised. (F) A 2 to 3 mm strip of eyelid margin is excised with scissors, and the attachment of the caruncle to the underlying bone is excised with a scalpel. (Illustrations by Dave Carlson)

393

Figure 12.12.  Transpalpebral enucleation, left eye. (A) A sharp incision is made around the palpebral fissure through the skin. A lid plate or tongue depressor may be used behind the lids for support. (B) The lid margins are sutured together and the ends are left long to allow for traction. An Allis tissue forceps or similar instrument may also be used for this purpose. (C, D) The subcutaneous tissues are dissected to identify the extraocular muscle attachments, which are isolated and incised close to the sclera. (E) The optic nerve and associated vessels are transected with curved scissors. (Illustrations by Dave Carlson)

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wall and not to place excessive traction on the optic nerve. Hemostasis is achieved using ligation, hemoclips, and pressure. The caudal orbit is carefully evaluated for disease extension, and further biopsies of suspect tissue is taken if indicated. Because all the orbital contents have been removed, support of the overlying skin and subcutaneous tissues can be provided by a crisscross of nonabsorbable suture placed across the orbital rim, anchored to the orbital septum fascia. A prosthetic sphere is generally not used due to possibility of local recurrence of disease or the need for adjuvant local radiation therapy. Postoperative care Dogs and cats should be maintained on IV fluids in the postoperative period until they can drink sufficiently. Appropriate analgesia is provided. An outline of approaches to perioperative analgesia is provided at the end of this chapter. The outlined approach would be appropriate for exenteration (and orbitectomy), with the pain associated with enucleation being appropriately controlled using parenteral opioids and local anesthetic injected into the surgical site with a block of the optic nerve. Additionally, an NSAID should be administered unless contraindicated. Histologic tumor types and prognosis Primary anterior uveal neoplasia Melanoma is the most common primary, intraocular neoplasia in both dogs and cats. Unlike humans, where the choroid is generally affected, the anterior uveal tract (iris and ciliary body) is the most common site of involvement. In dogs, anterior uveal melanomas generally manifest as brown to black nodular lesions that protrude from the iris or ciliary body and demonstrate progressive, generally slow growth. When of sufficient size, they may cause secondary glaucoma, corneal edema, lens luxation, and uncommonly, intraocular hemorrhage. Diagnosis is made based on appearance, and if the intraocular tissue cannot be visualized, by ultrasonography. Although these tumors are generally seen in older animals, an iris melanoma with a presumed heritable basis has recently been identified in a large group of related young Labrador retriever dogs (Donaldson et al. 2006). Uveal melanomas in dogs are overwhelmingly benign in the sense that they do not metastasize to distant organs. In the largest retrospective study to date, only 6% had evidence of metastasis. A high mitotic index on microscopic examination was the strongest correlate to the likelihood of metastasis. As a result of their slow growth and benign behavior, these tumors are often monitored without treatment until

they result in secondary complications, at which time enucleation is curative. Other treatment options, especially for small primary intraocular neoplasia, include surgical resection (via intraocular surgery), laser ablation (diode or Nd:YAG lasers), and photodynamic therapy. Of these, diode laser therapy is most widely available. Prognosis depends on the stage at which these are treated and the experience of the laser surgeon. If primary surgical resection of the mass or enucleation is used, all tissue should be submitted for histopathological evaluation. In cats, melanomas (also the most common primary intraocular neoplasia) generally present as a multifocal, coalescing area of iris pigmentation, and the term “diffuse iris melanoma” has been used to describe this condition. Diffuse iris melanomas must be distinguished from other benign melanocytic changes in the iris, including benign iris melanosis and iris darkening due to chronic uveitis. Melanomas generally are raised above the iris surface and often have pigment exfoliation into the anterior chamber. Biomicroscopic examination by an experienced ophthalmologist may be necessary to diagnose early iris melanoma in cats. Unlike dogs, retrospective studies suggest that up to 50%–60% of these tumors metastasize (Patnaik and Mooney et al. 1988). A recent study also documented a statistically significant, shorter life span, presumably from metastatic disease, in cats with iris melanoma versus age-matched cats (Kalishman et al. 1998), and early enucleation was recommended. However, these tumors often exhibit very slow growth (months to even years to progress over the entire iris) and a long interval between detection (or even enucleation) and the onset of metastatic disease. As a result, there is considerable controversy in how best to treat these tumors. Some ophthalmologists recommend monitoring until secondary glaucoma ensues (this is the most common adverse sequela), whereas others, including the authors, recommend early enucleation once a diagnosis is reasonably certain. There is some evidence in two studies reported in the literature that early enucleation may lessen the likelihood of metastasis, but this point is still uncertain. The second most common (and only other common primary intraocular neoplasia) is an adenoma or adenocarcinoma arising from the ciliary body epithelium. This tumor can occur in dogs and cats, is often a nonpigmented nodule arising in the ciliary body and protruding through the pupil, and exhibiting slow growth and benign (nonmetastatic) behavior. Treatment options and philosophies are similar to anterior uveal melanomas. A rare congenital tumor, termed a medulloepithelium and arising from the ciliary body, has also been described in dogs.

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Previously traumatized feline eyes are also at risk for development of a primary ocular sarcoma (also called posttraumatic sarcoma) (Dubielzig et al. 1990). Often, a long latent period of 1–10 years between a history of trauma and onset of clinical signs is reported. Most cases appear to be associated with lens capsule rupture, and many veterinary pathologists feel the tumor arises from the lens epithelia that has undergone a neoplastic transformation to fibroblastic cell type. The tumors progressively fill the ocular cavity, invade and extend outside the sclera, and late in the course, invade the central nervous system locally and regionally metastasize. Mortality rate appears to exceed 90%. Early enucleation, exenteration, or orbitectomy are the only available treatments, and because of this high mortality rate, many clinicians recommend surgical removal of traumatized feline eyes that are blind, even if nonpainful, to prevent tumor development. The choice of enucleation, exenteration, or more radical orbitectomy will depend on the individual case. The priority is to remove all tumor cells and prevent local recurrence. Secondary anterior uveal neoplasia Although uncommon, virtually any malignant neoplasia can metastasize to the uveal tract, most commonly the anterior uvea. Generally, the disease is evident in other organs, but occasionally, clinical signs in the eye (nodule formation, hemorrhage, secondary glaucoma), may be the presenting complaint. The primary importance in these cases is in distinguishing primary versus metastatic ocular neoplasia. As the two can appear similar, it is important to perform a thorough physical examination and appropriate diagnostic tests to determine if it is primary versus secondary. The most common secondary ocular neoplasia is lymphoma and some reports suggest that up to 35% of dogs with multicentric lymphoma have ocular manifestations. In dogs, the most common manifestation is in the anterior uvea and mimics signs of anterior uveitis, including diffuse iridal thickening, aqueous flare, hypopyon, low intraocular pressure, and, occasionally, secondary glaucoma. In dogs, ocular involvement has been exclusively seen with multicentric disease, and the diagnosis is generally not difficult. Occasionally, the eye will be the predominate organ involved, and anterior chamber paracentesis may be useful to establish a (cytologic) diagnosis, but this is the rare exception. One study suggests that ocular involvement with lymphoma results in a poorer prognosis than if the eye is not involved, with these dogs having a life expectancy of 60%–70% that of dogs presenting without ocular signs (Krohne et al. 1994). In cats, uveal lymphoma may present as either a diffuse thickening of the iris, a nonpigmented nodule on

the iris or ciliary body, or be multifocal to diffuse retinal and choroidal lymphoblastic infiltration, manifesting as retinal hemorrhage, retinal edema, or retinal detachment. While feline ocular lymphoma is usually associated with other organ involvement, there is recent evidence that a form of primary ocular lymphoma may exist in cats and that this type of neoplasia may be associated with a better survival prognosis. Surgical removal of small secondary intraocular tumors, or enucleation may sometimes be used in the treatment of metastatic neoplasia; however, other organ involvement and prognosis often negate the benefit of treating the ocular site.

Orbital Neoplasia Surgical techniques Orbitectomy Orbitectomy is used in the surgical treatment of malignant tumors of the orbit, the zygomatic arch, or extension of caudal maxillary, nasal/sinus tumors or mandibular vertical ramus tumors into the orbit. The exact location and extent of the tumor will dictate the extent of excision. Total and partial orbitectomy has been described (O’Brien et al. 1996), and the general approach has been divided into superior (removal of the caudodorsal part of the maxillary bone and the dorsal and medial parts of the frontal bone), inferior (removal of the caudoventral parts of the maxillary bone, the lacrimal bone, the zygomatic bone, and the ventral part of the palatine bone), and total orbitectomies. In the first two procedures, the globe may be preserved. Total orbitectomy involves a combination of these two approaches, and usually the globe is removed. When disease extends into the sphenoid bone and temporal bone, complete resection is not likely to be possible. In addition, for disease that extends up to the surface of a bone, such as the temporal bone, the resection, even if it appears grossly clean, must be considered “cytoreductive,” with tumor cells left behind, however aggressive the rest of the resection is! It may be possible to remove the bone that the tumor extends up to, but partial craniectomies are not easily performed at the base of the brain or base of the orbital fossa. The exact surgical approach depends on the type and location of the tumor. Minimum margins of at least 2 cm, and preferably 3 cm, are recommended for malignant cancers such as SCC, malignant melanoma, and fibrosarcoma in the dog. If possible, SCC in the cat should be treated with surgical margins greater than 2 cm because of high local recurrence rates. However, these margins are rarely possible without significant morbidity because of the extent of the tumor. Lesser

Eyelids, Eye, and Orbit  397

margins may result in acceptable rates of local tumor control, especially if combined with appropriate adjunctive therapy. Prior to embarking on such surgery, biopsy is mandatory. Tumor staging is important and should include an evaluation of local lymph nodes and thoracic radiographs, CT scan, and abdominal ultrasonographic evaluation. 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. Although the bony resection is generally easily planned and visualized, particular care should be paid to the resection of soft tissues, ensuring appropriate margins are obtained. Cat and dog skulls should be available for intraoperative orientation and planning. The plane of resection should be well

outside the mass, and tissues should be removed en bloc, rather than piecemeal. Total orbitectomy with removal of the eye The goal of this total orbitectomy is to perform an osteotomy of the maxilla laterally continuous with the frontal bone dorsally combined with an osteotomy of the maxilla ventrally (intraorally) and frontal bone medial to the eye continuous into the lateral aspect of the palatine bone (see Figure 12.13). An osteotomy of the zygomatic bone completes the osteotomies necessary to remove the bony margins of the orbit en bloc with the eye and structures within the orbit. The patient is placed in lateral recumbency. A gauze is placed in the oropharynx to prevent blood from going into the trachea and esophagus (it must removed at the end of surgery). A skin incision in performed over the laterodorsal aspect of the maxilla from the level of

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Figure 12.13.  Photographs depicting the portion of the skull that is excised with a total orbitectomy including removal of the eye. (A) Lateral view, (B) frontal view, (C) caudal view, (D) ventral view. (Photographs courtesy of Dr. Bernard Séguin and technical assistance from Jill Bartlett)

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the infraorbital foramen rostrally, around the eye, and continues caudally, just past the level of the orbital ligament (Lascelles et al. 2003). Any biopsy tract is removed en bloc with the tumor, so the skin incision will also go around any previous biopsy incision. The skin is undermined and elevated from the maxilla rostrally. It is also undermined and elevated medially along the dorsal aspect of the incision to allow exposure of the frontal bone and laterally to allow exposure of the frontal and zygomatic bones. The incision continues deeper to transect the underlying musculature along the proposed site for the osteotomy for the maxilla laterally and dorsally and the frontal bone to expose the bones. The muscles incised include levator nasolabialis over the maxilla and frontalis and interscutularis over the frontal bone. The vein angularis oculi can be encountered medial to the eye and can be ligated and divided. An intraoral approach is also performed. The oral mucosa is incised medial and parallel to the maxillary teeth, from about the level of the infraorbital foramen to the caudal aspect of the maxilla. Another mucosal incision is performed lateral to the maxillary teeth along the gum line for the same distance. The medial and lateral mucosal incisions are made to meet caudal to the most caudal molar. The incision in the oral mucosa lateral to the teeth is made to communicate with the skin incision lateral to the maxilla for the entire length of the oral mucosa incision by undermining under the skin and the muscles of the upper lip (such as levator labii maxillaris). A periosteal elevator is used to elevate the remaining muscle attachments to the maxillary and frontal bones and the periosteum along the line of the proposed osteotomy. The infraorbital artery and vein can be ligated just as it comes out of the infraorbital foramen and divided, and the infraorbital nerve can be transected (bupivacaine can be injected into the nerve first) at the same level. This completes the lateral and dorsal approaches. The muscles overlying the lateral aspect of the orbital ligament are transected, namely the frontalis and retractor anguli muscles. The attachment of the masseter muscle, superficial and middle layers, is transected or elevated from the ventral aspect of the zygomatic arch cranially. The deep layer of the masseter muscle is also transected at midbody or close to its mandibular attachment. Typically, the osteotomy of the zygomatic bone and frontal bone at its lateral aspect are made just caudal to the orbital ligament. An incision can be made in the periosteum of the zygomatic bone in the dorsoventral direction, and the periosteum is elevated. The osteotomy of the zygomatic bone can be performed at this point in time. The temporalis muscle overlying the portion of the frontal bone is incised and elevated from the bone to

expose the proposed area for the osteotomy. For the osteotomy medial to the eye, the muscle pterygoideus medialis is elevated from the lateral aspect of the palatine bone. This is a tight area and should be done delicately so as to not damage the major blood vessels that are at the ventromedial aspect of the orbit. It is sometimes possible to identify these large vessels, namely the maxillary artery and pterygoid, ophthalmic and palatine plexi, clamp them or occlude them with hemostatic clips. If it is not possible at this point, the vessels will be ligated or clipped once all the osteotomies are performed and the orbit is starting to be pulled away from the remaining skull. At this point, the medial approach has been completed. The remaining osteotomies can now be performed. It is best to perform most osteotomies with a power oscillating saw. It is best to keep the medial osteotomy (lateral aspect of frontal and palatine bones) for last because if there is severe hemorrhage, it typically occurs while making this osteotomy. When it does occur, the only way to get to the bleeding vessel might be to remove the orbit very rapidly and place a hemostat on the bleeding vessel. If other osteotomies remain to be done, the patient may exsanguinate in the meantime. The osteotomy in the dorsolateral aspect of the maxilla and dorsal aspect of the frontal bone can be made first. This is very safe to perform, and the osteotomy will penetrate into the frontal sinus caudally. Rostrally, the osteotomy at the lateral aspect of the maxilla is typically performed just rostral to the carnassial tooth (premolar 4) in the dog, although variation will be present depending on the breed, particularly brachicephalic dogs. It is best to remain just rostral to the lateral edge of the infraorbital foramen to avoid lacerating the vessels within the canal and create severe bleeding (the infraorbital artery and vein were previously ligated just as they came out of the foramen). The next osteotomy to be performed is the intraoral one, medial to the teeth. The osteotomy connects with the lateral maxillary one rostrally and extends to the edge of the maxilla caudally, just lateral to the palatine bone. The last osteotomy to perform is the medial one. It is best to start at the caudodorsal aspect. The caudal end of the dorsal osteotomy comes around in the frontal bone laterally, usually just caudal to the zygomatic process of the frontal bone. The osteotomy is then aimed toward the caudal edge of the maxilla where the intraoral osteotomy was performed. The goal is to avoid the optic canal, orbital fissure, and rostral and caudal alar foramens of the sphenoid bone and to connect the medial osteotomy with the intraoral one. While at the dorsocaudal aspect of the osteotomy in the frontal bone, it is fine to use the power saw, but once the osteotomy gets deeper, close to the lateral aspect of

Eyelids, Eye, and Orbit  399

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Figure 12.14.  (A) Surgical site following total orbitectomy. Large arrow points to the nasal turbinates, and small arrow points to the frontal sinus. (B) Orbital specimen removed from the dog. (Photographs courtesy of Dr. Bernard Séguin)

the palatine bone, it is safer to use an osteotome and mallet to complete the osteotomy. This completes all the osteotomies, and now only soft tissue attachments remain to the bony orbital margins and orbital content. The orbit is gently pulled out of the skull. Excessive traction should be avoided (especially in cats) to avoid stretching and damage to the optic chiasm and contralateral optic nerve. The remaining muscle attachments are transected. The nerves caudal to the eye, namely the optic, oculomotor, trochlear, and abducent nerves, and branches of the trigeminal and facial nerves, are transected. If the major blood vessels have not yet been occluded, they are addressed at this point in the surgery. The maxillary artery and pterygoid, ophthalmic, and palatine plexi are clamped, transected, and ligated. Other smaller blood vessels are also ligated, occluded with hemostatic clip, or cauterized as appropriate. The final soft tissue attachments are transected, and the orbit can be fully removed from the skull (Figure 12.14). One of the most important aspects of the closure after a total or inferior orbitectomy is to recreate the division between the oral and nasal cavities. This is accomplished in a fashion similar to a caudal maxillectomy. A flap of mucosa is created from the lip. The flap is created by undermining the labial mucosa to include the mucosa and submucosa. The flap is elevated from the incision site along the previous gum line, and it is apposed with the mucosa of the palate. It is important to undermine sufficient tissue to prevent the overlying skin being drawn excessively medially, resulting in a poor cosmetic result. The flap is sutured into position with a two-layer closure, with the first layer consisting of simple interrupted sutures preplaced through holes predrilled in the bone of the hard palate. The labial and oral mucosas are opposed using a simple interrupted or continuous suture pattern. Absorbable monofilament suture material size 3-0 to 2-0 can be used. Leaving a significant amount of dead space at the orbitectomy site is

unavoidable. The muscles are reapposed as best as can be, and the subcutaneous tissues and skin are closed routinely. It is also unavoidable that the nasal cavity and frontal sinus will communicate with the orbitectomy site. Many variations to the technique are possible to accommodate tumor excision depending on the location and size of the tumor. If the tumor extends lateral to the orbit, portions of the masseter muscle and temporal muscle are removed en bloc. The approach can be combined with an approach to the ventral part of the vertical ramus of the mandible or to the temporomandibular joint, and these areas can be excised along with the zygomatic arch and the tumor. If the maxilla is involved, a larger segment of the maxilla can be removed by making the osteotomy of the maxilla more rostral. If necessary, resections can be combined with craniectomies. If a craniectomy is performed, a temporalis flap is used to protect the exposed brain during the closure. Superior orbitectomy The superior orbitectomy differs mostly from the total orbitectomy in that there is no intraoral approach. (See Figure 12.15.) Therefore, only one skin incision is performed on the dorsal aspect of the maxilla and frontal bone. This incision does not need made as rostral, and if the eye is preserved, the skin incision remains medial to the eye. The dorsal osteotomy involves only the frontal bone or some of the maxilla but remaining dorsal to the infraorbital foramen. This osteotomy comes laterally to the rim of the orbit. The osteotomy medial to the eye does not go as ventrally as with the total orbitectomy. Instead, this osteotomy joins the dorsal osteotomy from its caudal aspect to its rostral aspect. The ventral aspect of the medial osteotomy will often be at the level of the lacrimal bone. Enucleation is performed if the eye or its neurovascular supply, or a substantial percentage of the eyelid, is infiltrated with tumor or is in close proximity

400  Veterinary Surgical Oncology

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Figure 12.15.  Photographs depicting the portion of the skull that is excised with a superior orbitectomy. (A) Lateral view, (B) frontal view, (C) caudal view, (D) ventral view. (Photographs courtesy of Dr. Bernard Séguin and technical assistance from Jill Bartlett)

to the tumor border. If an enucleation is performed, the skin incision will be made around the eye. Inferior orbitectomy In order to achieve an inferior orbitectomy, the intraoral approach is necessary. (See Figure 12.16.) However, compared to the total orbitectomy, the dorsolateral osteotomy in the maxilla ends caudally at the rostro­ medial aspect of the orbital rim, at about the level of the lacrimal bone. The osteotomy medial to the eye therefore begins at the level of the lacrimal bone and is aimed at the caudal edge of the maxilla intraorally, cutting the lateral aspect of the palatine bone. The osteotomy of the zygomatic arch can be performed rostral to the orbital ligament if tumor location and size allows. In this instance, again, enucleation is performed if the eye or its neurovascular supply, or a substantial percentage of the eyelid, is infiltrated with tumor or is in close proximity to the tumor border.

Because the oral cavity is penetrated, the division between the oral and nasal cavities must be reestablished with the closure as described in the total orbitectomy section. Postoperative care Dogs and cats should be maintained on IV fluids in the postoperative period until they can drink sufficiently. Appropriate analgesia is provided. A feeding tube, such as esophagostomy or gastrostomy tube, can be placed at the time of surgery if the animal is not eating well prior to surgery. Suggested pain management options for orbitectomies and exenterations are as follows. 1. Fentanyl patch placed the day prior to surgery (3–4 mcg/kg/hr). 2. Intravenous NSAID (provided there are no contraindications) once at induction or following full

Eyelids, Eye, and Orbit  401

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Figure 12.16.  Photographs depicting the portion of the skull that is excised with an inferior orbitectomy. (A) Lateral view, (B) frontal view, (C) caudal view, (D) ventral view. (Photographs courtesy of Dr. Bernard Séguin and technical assistance from Jill Bartlett)

recovery if hemorrhage expected (e.g., carprofen: 4 mg/kg [dogs]; meloxicam: 0.1 mg/kg [dogs and cats]). 3. Bupivicaine infraorbital/maxillary nerve blocks at induction if appropriate (depending on the location of the tumor). Blocks of the orbital nerve can be performed prior to transection. Care with the use of local anesthetic if brain tissue is exposed. 4. For dogs use a continuous rate postoperative IV infusion of a. hydromorphone (0.005–0.02 mg/kg/hr), fentanyl (2–4 mcg/kg/hr), or morphine (0.1 mg/kg/hr) b. medetomidine (1–2 mcg/kg/hr) c. lidocaine (25–30 mcg/kg/min) d. ketamine (2 mcg/kg/min) 5. For cats use a continuous rate postoperative infu­ sion of a. hydromorphone (0.005–0.01 mg/kg/hr), fentanyl (2–4 mcg/kg/hr), or morphine (0.05 mg/kg/hr) (watch for opioid-induced hyperthermia, and if

seen, switch to buprenorphine, 20 mcg/kg every 8–12 hr) b. medetomidine (1–4 mcg/kg/hr) c. ketamine (0.1–0.5 mg/kg/hr); for the first 12–24 hr. 6. Extended “at home” analgesic medication includes a. oral NSAID for 10–14 days postoperatively at approved dose (cats: suggest meloxicam 0.1 mg/ kg once on day 1 [perioperative dose], 0.05 mg/kg every 24 hr for 4 days, 0.025 mg/kg each every 24 hr for 4 days, then every other day) b. opioid or opioid derivative for 7–10 days: Tramadol 4 mg/kg PO, BID-QID for dogs; transmucosal buprenorphine (per os), 10–20 mcg/kg twice daily for cats; fentanyl patch (cats or dogs) Cosmetic and functional outcome, potential complications Owners should be educated on the postoperative appearance of their pets following such extensive surgeries

402  Veterinary Surgical Oncology

(Figures 12.17, 12.18, 12.19, 12.20). Immediately following surgery, there can be extensive bruising and swelling, and if extensive tissue is resected, the face will have a “sunken in” appearance. Immediately after surgery, if the nasal cavity has been penetrated, the skin over the surgical site will move substantially with each breath,

Figure 12.17.  Immediate postoperative appearance of a dog following an extensive orbitectomy for a multilobular osteochondrosarcoma based around the vertical ramus and involving the orbital tissues. Surgery involved resection of the vertical ramus, zygomatic arch, dorsal orbital rim and frontal sinus, and caudal maxilla and ventromedial orbit, as well as exenteration. Residual bleeding postoperatively caused the bruising. The only late complication was pain on mouth opening due to impingement of the base of the vertical ramus on taut intraoral mucosa. Further bone resection and mobilization of a tension-free intraoral mucosal flap resolved the problem.

(a)

but this is self-limiting and usually resolves within a week to 10 days. Functional outcome is generally good to excellent. Such radical surgeries are well tolerated by dogs and cats (O’Brien et al. 1996; Lascelles et al. 2003), although there is relatively little information on cats. The main intraoperative complications are that of blood loss and the potential for compromise of central nervous system function when craniectomies are performed. The most common healing complication occurs in cases in which an extensive caudal maxillectomy combined with orbitectomy has been performed, and there is little mucosa to close the oral cavity and divide it from the area of the orbital fossa. Dehiscence can occur and

Figure 12.18.  Appearance of a dog 1 week following orbitectomy (caudal maxillectomy, zygomectomy, and exenteration) for an oral malignant melanoma.

(b)

Figure 12.19.  (A, B) Appearance of a dog 1 month after hemimaxillectomy and total orbitectomy of the right side for an ossifying fibroma. (Photographs courtesy of Chelsie DeWald)

Eyelids, Eye, and Orbit  403

indicated are the general means of treatment, if pursued. Prognosis will very much depend on the tumor type. The one study of orbitectomies found that the diseasefree interval had not been reached by 456 days for 24 dogs and 6 cats that were operated on for sarcomas (n = 23), SCC (n = 5), and benign osteomas (n = 2) (O’Brien et al. 1996).

References

Figure 12.20.  Appearance of a cat 2 weeks after total orbitectomy for a fibrosarcoma. (Photographs courtesy of Bernard Séguin)

may require large tension-free intraoral flaps at a later stage to close the defect. Frequent reexamination of the surgical site is recommended; however, if dehiscence occurs, further surgery is generally delayed several days until the full extent of dehiscence is known. Other complications reported with orbitectomy include infection and conjunctivitis, strabismus, and loss of vision when the eye is preserved (O’Brien et al. 1996). Histologic tumor types and prognosis Neoplasia involving the orbit or periorbital region is reasonably common in both dogs and cats. In both species, more than 90% of orbital tumors are malignant. In dogs, the majority of orbital tumors are primary, whereas in cats secondary causes predominate. Variable but usually slowly progressive exophthalmos, protrusion of the nictitans, deviation of the globe (strabismus), pain on opening the mouth, and occasionally visual and pupillary light reflex deficits (from optic nerve damage) are typical signs in both species. Orbital neoplasia may be primary (tissues within the orbit), extension from adjacent tissues (especially the nasal and paranasal sinuses and oral cavity), or metastatic. The first two categories are the most common. In cats, SCC from extension from the oral cavity is the most common tumor type. Fibroma and fibrosarcoma, osteosarcoma, lymphoma, optic nerve meningioma, (nasal) adenocarcinoma, mastocytoma, and multilobular osteoma have been reported in the dog. Surgical resection (orbitectomies or exenteration, or combinations of these) followed by radiation therapy if

Betton, A., L.N. Healy, R.V. English, et al. 1999. Atypical limbal melanoma in a cat. J Vet Intern Med 13:379–381. Donaldson, D., J. Sansom, T. Scase, et al. 2006. Canine limbal melanoma: 30 cases (1992–2004). Part 1. Signalment, clinical and histological features, and pedigree analysis. Vet Ophthalmol 9:115–119. Dubielzig, R.R., J. Everitt, J.A. Shadduck, et al. 1990. Clinical and morphologic features of post-traumatic ocular sarcomas in cats. Vet Pathol 27:62–65. Farris, H.E., Jr., and W.A Vestre. 1982. Veterinary cryosurgery. Cryobiology 19:228–230. Fulcher, R.P., L.L. Ludwig, P.J. Bergman, et al. 2006. Evaluation of a two-centimeter lateral surgical margin for excision of grade I and grade II cutaneous mast cell tumors in dogs. J Am Vet Med Assoc 228:210–215. Giuliano, E.A., R. Chappell, B. Fischer, et al. 1999. A matched observational study of canine survival with primary intraocular melanocytic neoplasia. Vet Ophthalmol 2:185–190. Gwin, R.M., R.D. Alsaker, and K.N. Gelatt. 1976. Melanoma of the lower eyelid of a dog. Vet Med Small Anim Clin 71:929– 931. Hardman, C. and R. Stanley. 2001. Radioactive gold-198 seeds for the treatment of squamous cell carcinoma in the eyelid of a cat. Aust Vet J 79:604–608. Holmberg, D.L. 1980. Cryosurgical treatment of canine eyelid tumors. Vet Clin North Am Small Anim Pract 10:831–836. Kalishman, J.B., R. Chappell, L.A. Flood, et al. 1998. A matched observational study of survival in cats with enucleation due to diffuse iris melanoma. Vet Ophthalmol 1:25–29. Krehbiel, J.D. and R.F. Langham. 1975. Eyelid neoplasms of dogs. Am J Vet Res 36:115–119. Krohne, S.G., N.M. Henderson, R.C. Richardson, et al. 1994. Prevalence of ocular involvement in dogs with multicentric lymphoma: Prospective evaluation of 94 cases. Vet Comp Ophthalmol 4:127–135. Lascelles, B.D., M.J. Thomson, W.S. Dernell, et al. 2003. Combined dorsolateral and intraoral approach for the resection of tumors of the maxilla in the dog. J Am Anim Hosp Assoc 39:294–305. Munger, R.J. and I.M. Gourley. 1981. Cross lid flap for repair of large upper eyelid defects. J Am Vet Med Assoc 178:45–48. O’Brien, M.G., S.J. Withrow, R.C. Straw, et al. 1996. Total and partial orbitectomy for the treatment of periorbital tumors in 24 dogs and 6 cats: A retrospective study. Vet Surg 25:471–479. Patnaik, A.K. and S. Mooney. 1988. Feline melanoma: A compara­ tive study of ocular, oral, and dermal neoplasms. Vet Pathol 25:105–112. Pavletic, M.M., L.A. Nafe, and A.W. Confer. 1982. Mucocutaneous subdermal plexus flap from the lip for lower eyelid restoration in the dog. J Am Vet Med Assoc 180:921–926. Rickards, D.A. 1980. Cryosurgery in small animal ophthalmology. Vet Clin North Am Small Anim Pract 10:471–480.

404  Veterinary Surgical Oncology Roberts, S.M., G.A. Severin, and J.D. Lavach. 1986. Prevalence and treatment of palpebral neoplasms in the dog: 200 cases (1975– 1983). J Am Vet Med Assoc 189:1355–1359. Simpson, A.M., L.L. Ludwig, S.J. Newman, et al. 2004. Evaluation of surgical margins required for complete excision of cutaneous mast cell tumors in dogs. J Am Vet Med Assoc 224:236–240. Sullivan, T.C., M.P. Nasisse, M.G. Davidson, et al. 1996. Photocoagulation of limbal melanoma in dogs and cats: 15 cases (1989–1993). J Am Vet Med Assoc 208:891–894.

Vestre, W.A. 1984. Cryosurgical techniques in veterinary ophthalmology. Compend Contin Educ Practicing Vet 6:481–490. Weisse, C., F.S. Shofer, and K. Sorenmo. 2002. Recurrence rates and sites for grade II canine cutaneous mast cell tumors following complete surgical excision. J Am Anim Hosp Assoc 38:71–73. Wilcock, B. and R. Peiffer, Jr. 1988. Adenocarcinoma of the gland of the third eyelid in seven dogs. J Am Vet Med Assoc 193: 1549–1550.

13 Endocrine system Bernard Séguin, Lisa Brownlee, Peter J. Walsh

Pituitary Tumors Clinical workup and biopsy principles Pituitary tumors are recognized clinically either because the dog has clinical signs of hyperadrenocorticism (HAC) or is having neurological signs, with altered state of consciousness (obtundation, stupor), seizures, ataxia, pacing, circling, head pressing, or blindness being the most common (Bailey and Page 2007; Niebauer 2003). In dogs with macroadenomas of the pituitary gland, clinical signs of endocrinopathy precede neurological signs in 50%, neurological signs are detected first in 10%–20%, and clinical signs of the endocrinopathy and neurological signs are detected simultaneously in 20%–30% (Bailey and Page 2007; Feldman and Nelson 2004c). This section is not intended to be a comprehensive review of the tests used to diagnose HAC and differentiate between the possible etiologies for neurological signs but rather to be a brief overview. The reader unfamiliar with the intricacies of interpreting these tests is directed to endocrinology textbooks. In dogs with clinical signs and a complete blood count (CBC), chemistry panel, and urinalysis results compatible with Cushing’s syndrome, screening tests are necessary to confirm the diagnosis of hyperadrenocorticism. Three tests are commonly used: urine cortisol/creatinine ratio, low-dose dexamethasone suppression test (LDDS), and adrenocorticotropic hormone (ACTH) stimulation test. Briefly, the urine cortisol/creatinine ratio is very sensitive but not specific. Any stressful environment or situation can transiently elevate the ratio. Therefore, the test may be best performed by having the owner collect a urine sample at home in the morning. It is, however, a useful test to rule out HAC: If the test result is normal,

the dog is not likely to have HAC. Some tumors of the adrenal cortex produce intermediates other than cortisol that will not be detected by the urine cortisol/creatinine ratio test. The ACTH stimulation test as a screening test for HAC is more specific but less sensitive than the LDDS, particularly for adrenal-dependent hyperadrenocorticism (ADH). Once the diagnosis of hyperadrenocorticism is confirmed, a test to differentiate between pituitary-dependent hyperadrenocorticism (PDH) and ADH is necessary. Three tests can be performed: endogenous ACTH concentration, high-dose dexamethasone suppression test (HDDS), and abdominal ultrasonog­ raphy. Measuring endogenous ACTH concentration requires special handling of the sample (Feldman and Nelson 2004c). Abdominal ultrasonography is a great test to add weight to the overall clinical and laboratory picture but should not be used alone (Feldman and Nelson 2004c). Results that support PDH are suppression of plasma cortisol concentration with HDDS, increased or high normal endogenous ACTH con­ centration, and bilateral normal-sized or enlarged adrenal glands that maintain, in general, normal shape. If the dog is presented for neurological signs, a full neurological workup should be undertaken and should include advanced imaging (computed tomography [CT] or magnetic resonance imaging [MRI]) of the brain. In the absence of an endocrinopathy, a nonfunctional tumor may be present, sometimes referred to as null cell adenoma (Niebauer 2003). Biopsy of the pituitary is not performed prior to the definitive surgery (hypophysectomy) because of the difficulty and associated risks. Furthermore, the decision to perform hypophysectomy is based on the presence of clinical signs and size of the lesion and not on

Veterinary Surgical Oncology, First Edition. Edited by Simon T. Kudnig, Bernard Séguin. © 2012 by John Wiley & Sons, Ltd. Published 2012 by John Wiley & Sons, Ltd.

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histological type of the tumor. Stereotactic biopsy of the pituitary gland has been reported in cadaver specimens (Giroux et al. 2002). Imaging techniques Imaging of the skull is imperative prior to hypophysectomy because the location of the pituitary with respect to anatomical landmarks used during surgery (such as the hamular processes of the pterygoid bone) is inconsistent among dogs of different breeds and even among dogs of the same breed (Niebauer 2003; Meij et al. 1997). CT and MRI are the techniques of choice to image the intracranial central nervous system and specifically the pituitary gland. Studies to date have used CT to plan for the hypophysectomy but MRI would be suitable (Niebauer 2003; Meij et al. 1997, 1998). The resolution limit reported for lesions within the pituitary had been reported to be approximately 5–6 mm on CT and 3–4 mm on MRI (Niebauer 2003; Feldman and Nelson 2004c). However, this is likely to change as the technology for both modalities improves. It is now reported that today’s modern CT units allow identification of abnormalities of the pituitary gland as small as 1–2 mm in diameter (Auriemma et al. 2009). A recent study has concluded that low-field MRI (0.2 Tesla) and dynamic CT imaging of the pituitary gland provided comparable information on the presence of the pituitary adenomas in dogs with PDH and therefore were equally diagnostic. Although there were differences between CT and MRI measurements for pituitary dimensions and brain area, the pituitary height-to-brain area ratio (P/B ratio) was not different (Auriemma et al. 2009). Pituitary microadenomas, which do not alter the size or shape of the pituitary gland, may be more challenging to identify with either CT or MRI. On routine-contrast CT, microadenomas of the pituitary gland often are indistinguishable from non tumorous pituitary tissue because of isoattenuation. Dynamic CT has been shown to be able to detect these microadenomas (van der Vlugt-Meijer et al. 2003). Dynamic CT is the rapid injection of contrast medium with sequential scans of the area of interest, namely the pituitary gland in this instance. Dynamic CT of the pituitary gland can reveal the site of the microadenoma by detecting distortion of the neurohypophyseal flush (Auriemma et al. 2009). In 36 of 55 dogs, dynamic CT allowed identification of a distinct enhancement of the neurohypophysis described as a pituitary flush. In 24 of these 36 dogs, the pituitary flush was displaced, indicating the presence of an adenoma in the adenohypophysis. In 19 dogs, there was a diffusely abnormal contrast-enhancement pattern. Overall, in 45 out of 55 dogs with PDH, the pituitary gland appeared to be abnormal based on the size or

contrast-enhancement pattern using dynamic CT (van der Vlugt-Meijer et al. 2003). Including a dynamic series of scans in the CT protocol would allow detection of dogs that are candidates for the removal of only the adenohypophysis (van der Vlugt-Meijer et al. 2003). When CT or MRI is unavailable, the use of radiographic markers and sinus venography can be used to locate the pituitary gland (Niebauer 2003). This is not ideal as size of the lesion or pituitary gland cannot be determined with this modality, and size can be both a determinant factor in the feasibility of hypophysectomy and is a prognostic factor for outcome (see section on outcome). In proceeding with hypophysectomy when performing sinus venography, it is estimated that 15%– 20% of cases will have a nonresectable or partially resectable macrotumor in the absence of neurological signs (Niebauer 2003). In the presence of neurological signs, the hypophysectomy should not be performed without advanced imaging (Niebauer 2003). When using the sinus venography approach, the procedure is more time-consuming because it involves three steps: surgical placement of radiographic markers, cavernous sinus venography, and hypophysectomy. Only the sinus venography will be described here. The other two steps are described in the surgical techniques section. For the right-handed surgeon, it is easier to place radiographic markers to the right of midline. Because the cavernous sinus will enhance unilaterally during the venogram and the radiographic markers and the venogram need to be ipsilateral, the right angularis oculi vein is catheterized. The vein is located just ventral to the ventral eyelid, and it is catheterized while the dog is under anesthesia. A cut down to the vein is performed, and the catheter is sutured to the skin after placement. After surgical placement of the radiographic markers (see surgical techniques section), the animal is placed in sternal recumbency in preparation for the venogram, with the head extended and the mandible parallel to the film. A gauze tourniquet is applied around the neck to compress the external jugular veins. The contrast medium is injected, and a single dorsoventral view is taken while the last milliliter of contrast agent is administered. The hypophysis is outlined by the cavernous sinus and the rostral intercavernous sinus (which is located just caudal to the hypophysis). Filling of some of the venous structures on the contralateral side will frequently occur (Niebauer 2003). Surgical techniques Locating the exact anatomic position of the pituitary gland is paramount. The gland is incompletely surrounded by blood vessels (cavernous sinuses laterally and rostral intercavernous sinus caudally), which are in

Endocrine System  407

(a)

(b)

Figure 13.1.  (A, B) Skull photographs showing the hamular process of each pterygoid bone (arrows).

close proximity to it. If these vessels are punctured during surgery, it can lead to early abortion of the surgical procedure and even fatal intracranial hemorrhage. Using the CT or MRI images or results of the sinus venogram with radiographic markers will allow the surgeon to identify the exact location to perform the ostectomy of the sphenoid bone in order to be right “on top” of the pituitary gland. Using CT images, the size of the pituitary gland is measured. Knowing the thickness of the images, it is possible to derive the position of the ostectomy with respect to the hamular processes of the pterygoid bone (Figure 13.1) and the flattening of the outer lamina of the sphenoid bone, from rostral to caudal on the midline. The flattening occurs caudal to the intersphenoid ridge (Niebauer 2003; Meij et al. 1997). The gland sits in the sella turcica, and knowing where to perform the ostectomy ventral to it is a challenge. Because the venous ring is incomplete rostrally, enlargement of the ostectomy site beyond the edges of the pituitary gland is only possible in the rostrocaudal axis for a short distance rostrally. Transphenoidal hypophysectomy when CT has been performed As described by Niebaur and Meij (Niebauer 2003; Meij et al. 1997), the dog is positioned in sternal recumbency with the head tilted upward. An inverted U-shaped metal bar is placed at the end of the operating table, and the head is suspended from the bar with the maxillary

Figure 13.2.  Drawing showing the positioning of the dog on the surgery table. The dog is positioned in sternal recumbency with the head tilted upward. An inverted U-shaped metal bar is placed at the end of the operating table, and the head is suspended from the bar with the maxillary canine teeth “hooked” on the horizontal part of the bar. (Illustration by Dave Carlson)

canine teeth “hooked” on the horizontal part of the bar (Figure 13.2). As well, the operating table is tilted approximately 40 degrees so the head is lifted above the heart. The mandible can be opened with tape or gauze attached to the table. The endotracheal tube is large enough to allow adequate movement of anesthetic gases but sized smaller than usual to help keep the surgery field clear, and it is tied to the mandible to that effect. Although not a sterile procedure through this approach, the contamination is minimized by still using strict aseptic technique, avoiding touching the instruments to the oral mucosa, tongue, and teeth. This sternal positioning aids the surgeon with the pituitary gland “falling” toward the ostectomy site and debris of bone, blood, and irrigation fluid draining away from the surgical site. Through the oral cavity, a midline incision is performed through the central two-thirds of the soft palate. The soft palate is retracted, and this exposes the nasopharyngeal mucoperiosteum of the sphenoid bone. An

408  Veterinary Surgical Oncology

incision is made on midline, and the edges of the mucoperiosteum are retracted. Care is taken to avoid damaging the nerves and vessels entering the pterygoid canal caudolaterally, and excessive lateral reflection and elevation of the mucoperiosteum increases the likelihood of postoperative keratitis sicca. Minor hemorrhage from various veins perforating the compact sphenoid bone is to be expected. One of the vessels can be seen arising from midline, and this is the emissary vein. If identified, this vein serves as an excellent initial landmark. Ideally, by following this vein through the sphenoid bone, the center of the pituitary gland is found. However the emissary vein is an inconsistent finding and will disappear as bone drilling proceeds. The emissary vein, therefore, should not be relied upon, and other landmarks are necessary to identify the pituitary gland. Irrigation and suction of the site help visualization, and use of bone wax helps stop bleeding from the cancellous bone. After drilling through the cancellous bone, the white dorsal lamellar bone comes into view. An outline of the bluetinged cavernous sinuses and the pink oval pituitary can be seen through the transparent bone shelf if the ostectomy site is located appropriately. An operating microscope (at least 3× magnification) is then used. With a small ball-tipped hook, the thin bony shelf is penetrated over the center of the pituitary. The hole in the dorsal cortical bone is enlarged with a neurosurgical bone punch until it is about 5–6 mm in width and length, being very careful not to penetrate the cavernous sinuses laterally. The ventral dura is now the last layer covering the pituitary gland. A crosswise incision is made in the dura with a no. 11 scalpel blade. Cerebrospinal fluid will drain. A fine blunt-tipped hook can be used to break dural attachments and vascular bridges. At the caudal aspect of the pituitary, the small caudal hypophyseal arteries penetrate the gland. These are branches of the caudal intercarotid artery, which connects the two internal carotid arteries. The pituitary can be grasped with appropriate neurosurgical forceps and extracted. Delicate extraction usually results in a clean avulsion at the level of the infundibular stalk. Additional cerebrospinal fluid may leak from the third ventricle, and self-limiting bleeding may occur. In the presence of macroadenoma, a fine blunt instrument such as a tenotomy hook can be used to free the gland from sellar adhesions. This facilitates protrusion of the pituitary and consequently partial or complete resection. To assess complete excision of the pituitary or the mass, the surgeon should have an unobstructed view of the pulsating remnant of the avulsed infundibular stalk, opening into the third ventricle. Delicate probing of the sella turcica for tissue remnants can also be done with a ball-pointed hook.

The ostectomy site can be covered with an absorbable gelatin sponge to help stop the bleeding. Closing of the ostectomy site can be done with bone wax or a muscle graft harvested from the soft palate incision. The muscle graft is preferred because bone wax can cause foreign body reaction or in extreme cases might lead to local osteomyelitis (Niebauer et al. 1990). The small graft of muscle, about 3–4 mm in diameter, is sutured into the ostectomy site to the mucoperiosteum with one or two sutures. An autologous fat graft can also be used instead. The mucoperiosteum is closed with sutures. The soft palate is closed in two layers with absorbable suture material in a simple interrupted pattern. The dorsal mucosa facing the nasopharynx is sutured first, and the ventral mucosa facing the oropharynx is sutured last. Transsphenoidal hypophysectomy when sinus venography has been performed As described by Niebauer (2003), before performing the sinus venogram, radiographic markers are placed surgically as an aid to correctly identify the anatomical location of the pituitary gland during the approach. Special dental instruments and implants are necessary to perform this procedure: a slow-speed dental drill and drill bits and self-threading screws of 0.425 mm diameter. The dog is placed in dorsal recumbency. The surgeon is seated at end of the surgery table, facing the dog. The dog’s mouth is opened as wide as possible with a speculum, and the maxilla is fixed to the table, making the palate approximately parallel to the table. An approach to the sphenoid bone is done as described in the earlier section. A larger area of the sphenoid bone is exposed, however, but damage to the vessels and nerves entering the pterygoid canal caudalaterally is avoided. The approximate location of the ostectomy is envisioned at the caudal tip of the hamular processes. Using the dental drill, three nonperforating holes are made to a depth of about 2 mm into the exposed sphenoid bone. The holes are placed on a rostrocaudal line, 3–4 mm to the right of midline, with the center hole being at the level of the caudal tip of the hamular processes, and each other hole being 4–5 mm caudal and cranial to it, respectively. The small screws are inserted into the holes and broken off flush with the bone surface. The screws will therefore remain permanently in the bone. After placement of the screws, a chlorhexidine-soaked gauze is placed over the exposed bone and the venogram is performed as described earlier. After the venogram, the ostectomy is performed as described by Meij in the preceding section. However, the venogram is used to identify the location of the hypo­ physis, and this is taken in relation to the three radiographic markers. At surgery, accurate measurements

Endocrine System  409

relative to the screws, derived from the radiographs, are used to identify the location of the ostectomy necessary to approach the pituitary gland accurately and safely. Intracranial transtemporal approach The intracranial transtemporal approach to the pituitary has been used experimentally (Niebauer 2003). This approach may be indicated for resection of macroadenomas and suprasellar or parasellar pituitary tumors, but this has not been evaluated clinically. The dog is placed in sternal recumbency and the head is elevated while avoiding compression of the jugular veins. The cranial vault is approached routinely through the rostrotentorial route unilaterally, with the temporal muscle reflected as far ventrally as feasible. The cranial osteotomy involves a large area of the temporal bone, extending as close to the base of the skull as possible. The dura is incised and cerebrospinal fluid is allowed to drain. The intracranial pressure is lowered with hyperventilation. Gravity can be used to facilitate exposure of the base of the brain by rotating the head 100 degrees to 140 degrees into an inverted position, allowing the brain to pull away from the base of the skull. The head remains elevated relative to the heart. Malleable brain spatulas can be carefully used to retract the temporal lobe of the brain. Excessive retraction can cause postoperative neurological deficits. Even without retraction, gravity and decreased intracranial pressure can allow an adequate view of the infundibular stalk. The occulomotor nerve may bisect the area but does not obstruct the access to the pituitary with appropriate neurosurgical instruments. Careful blunt dissection of the vascular and connective tissue attachments of the hypophysis is performed. With this approach, the arteries of the circle of Willis are at risk for iatrogenic laceration. Hemostasis must be meticulous as in any intracranial surgery. Closure is a routine by attachment of the temporal muscle only. Dura closure and replacement of the bone flap are unnecessary. Ventral paramedian approach and use of a Cavitron ultrasonic aspirator CT was used in the study by Axlund and colleagues (2005) in which the technique was developed to determine the location of the pituitary with respect to the hamuli processes of the pterygoid bone. The dog is placed in dorsal recumbency. A right paramedian incision is made between the larynx and the rami of the mandible to expose the confluence of the digastricus and mylohyoideus muscles. The external maxillary vein and hypoglossal nerve are identified and protected. The dissection plane between the digastricus and mylohyoideus muscles is developed to expose the medial surface

of the palatine tonsillar fold. The palatine tonsillar fold is identified by placing a blunt-tipped probe through the mouth and placing the tip directly into the fossa. The probe is angled ventrally, which allows tenting of the mucosa. The tip of the probe can be observed by the surgeon and marks the center point of the mucosal incision. A 3 cm incision is made into the tonsillar fold, and the palatine tonsil is excised, creating a stoma that allows access to the pharynx. With the tongue retracted, a 2 cm median incision is made in the soft palate, extending 1 cm rostral and caudal to the hamulus of the pterygoid bone. Mucoperiosteal elevation over the pterygoid bone is performed to expose and visualize the intersphenoid suture and the presphenoid and basisphenoid bones. A pneumatic drill and burr are used to create a 1.0 × 0.5 cm partial thickness defect on the midline of the sphenoid bone, positioned directly ventral to midpoint of the pituitary gland as determined by the CT. The remaining inner cortical bone portion of the sphenoid bone is removed with a 1 mm upper-biting rongeur, exposing the dura mater overlying the hypophysis. A cruciate incision is made in the dura mater using a no. 11 blade, avoiding the cavernous sinuses laterally and the intercavernous sinus caudally. The hypophysis is extirpated to the level of the stalk using a Cavitron ultrasonic aspirator (CUSA). The tip of the CUSA is placed through the incision in the dura until it contacts the pituitary tissue. The power setting is gradually increased until the pituitary tissue begins to liquefy, at which point the setting is secured. The entire gland is deemed aspirated when the infundibular recess of the third ventricle is seen and all grossly visible pituitary had been removed from the fossa. The bleeding is controlled with bone wax, absorbable gelatin sponges, and bipolar electrocautery. The defect in the sphenoid bone is packed with absorbable gelatin, and the mucoperiosteum is apposed but not sutured. The soft palate tissue is apposed with two layers of absorbable sutures, and then the oral mucosa, subcutaneous tissues and skin are closed. Postoperative care Food should be withheld for approximately 24 hours postoperatively, but water should be offered as soon as the dog is awake (Meij et al. 1998, 2002). Intravenous fluid with a balanced solution is given until the patient is eating and drinking well. Analgesics such as fentanyl, hydromorphone, or oxymorphone are administered parenterally while in the hospital, and tramadol can be administered orally once at home. Electrolytes, particularly sodium and potassium, central venous pressure, and plasma osmolality are monitored. Antibiotic therapy

410  Veterinary Surgical Oncology

is continued for 7–10 days postoperatively (Niebauer 2003; Meij et al.1997, 1998). Hormone supplementation is required for dogs after hypophysectomy. Immediately after surgery, hydrocortisone (sodium phosphate or sodium succinate) at 1 mg/ kg every 6 hr is administered intravenously, and desmopressin acetate (a vasopressin analog) at 4 µg is administered as a drop into the conjunctival sac every 8. As soon as the dog is eating and drinking, oral supplementation is initiated with cortisone acetate (1 mg/kg every 12 hr) and thyroxine sodium (15 µg/kg every 12 hr). Over a period of 4 weeks, the dose of cortisone acetate is gradually decreased to 0.25 mg/kg every 12 hr orally. Desmopressin (0.01%) is administered for 2 weeks, one drop into the conjunctival sac every 8 hr (Meij et al. 2002). Cosmetic and functional outcome, potential complications There are no concerns regarding cosmetic appearance from the transsphenoidal approach. The main perioperative and long-term complications are as follows: (1) temporary and mild postoperative hypernatremia (most cases), (2) temporary reduction or cessation of tear production leading to keratoconjunctivitis sicca due to neuropraxia of the lacrimal gland innervation, (3) prolonged (20%) or permanent (10%) diabetes insipidus due to decreased availability of vasopressin (antidiuretic hormone), and (4) secondary hypothyroidism due to insufficient supplementation of thyroxine. Elevated plasma sodium levels usually normalize once the dog is drinking water. The keratoconjunctivitis sicca typically resolves with a median of 10 weeks. In dogs with prolonged diabetes insipidus, desmopressin has been discontinued after a median of 4 months, but some dogs require lifelong treatment with 1–2 drops of desmopressin (Meij et al. 2002). Other complications include extensive trauma to the brain and hemorrhage (Axlund et al. 2005). The hemorrhage can be fatal. Formation of nasopharyngeal blood clots causing obstruction to breathing can also occur. Dehiscence of the soft palate is an additional complication that can be of significant importance as it can lead to aspiration pneumonia (Niebauer 2003). The dehiscence usually occurs 2–4 days postoperatively. Local osteomyelitis of the sphenoid bone can occur when bone wax is used in the ostectomy site and if there was severe contamination (Niebauer 2003). Complete removal of the pituitary gland is very difficult with any of the surgical techniques. Although all cell types from the adenohypophysis can be found in the remnant tissue of the sella turcica in most dogs

following hypophysectomy (ACTH, α-MSH, LH, and TSH), only ACTH-containing cells appear to remain functional (Axlund 2005; Meij et al. 2002). The reason for the seemingly specific durability of ACTH-producing cells is unclear but may be because of the number and location of corticotrophs in the anterior lobe. The corticotrophs are concentrated in the centroventral and rostral portions of the pars distalis, and the rostral part is the most difficult to visualize and remove during hypophysetomy (Axlund et al. 2005). In one study, treatment failures included procedurerelated deaths (12 of 150 dogs) and incomplete hypophysectomy (9 of 150 dogs) (Hanson et al. 2005). Postoperative reduction of tear production was present in 58 eyes in 47 dogs, but it was often reversible. The decreased tear production remained until death in 11 eyes of 10 dogs. Central diabetes insipidus occurred more frequently (62%) in dogs with enlarged pituitaries (pituitary height [P]-to-brain area [B] ratio [P/B] higher than 0.31 × 10−2 mm−1) than in dogs with nonenlarged pituitaries (44%) (equal to or less than 0.31 × 10−2 mm−1) (Hanson et al. 2005). The size limit of an operable pituitary tumor is debatable. It has been postulated that a pituitary mass confined to the sella turcica can undergo hypophysectomy with a favorable prognosis. Once the mass expands dorsally into the infundibulum and impinges on adjacent neural structures, hypophysectomy may be not be technically feasible and carries an unfavorable prognosis (Niebauer 2003). In a study evaluating 181 dogs, the 1-year, 2-year, 3-year, and 4-year estimated survival rates were 86%, 83%, 80%, and 79%, respectively. The 1-year, 2-year, 3-year, and 4-year disease-free fraction were 90%, 77%, 72%, and 62%, respectively. Increased age, pituitary size, and basal plasma ACTH concentration were risk factors for shorter postoperative survival times. Thickness of the sphenoid bone, mean preoperative urinary cortisol/creatine ratio, pituitary size, and plasma αmelanocyte-stimulating hormone (α-MSH) concentration were risk factors for recurrence after transsphenoidal hypophysectomy for pituitary-dependant hyperadrenocorticism. Urinary cortisol/creatine ratios measured at 6–10 weeks after surgery can be used as a guide for predicting the risk of tumor recurrence (Hanson et al. 2007). Histologic tumor types Most tumors are functional adenomas of the adenohypophysis. Pituitary adenocarcinomas are uncommon (