Current Surgical Therapy [14 ed.] 9780323796835

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current surgical therapy

current surgical therapy 14

th

edition

John L. Cameron

MD, FACS, FRCS(Eng)(Hon), FRCS(Ed)(Hon), FRCSI (Hon) The Alfred Blalock Distinguished Service Professor Department of Surgery Johns Hopkins University School of Medicine Baltimore, Maryland

Andrew M. Cameron MD, PhD, FACS

Professor Director, Department of Surgery Chief, Division of Transplantation Johns Hopkins University School of Medicine Baltimore, Maryland

ELSEVIER

1600 John F. Kennedy Blvd. Ste. 1600 Philadelphia, PA 19103-2899 CURRENT SURGICAL THERAPY, FOURTEENTH EDITION Copyright © 2023 by Elsevier Inc. All rights reserved.

ISBN: 978-0-323-79683-5

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Notices

Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary. Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility. With respect to any drug or pharmaceutical products identified, readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of practitioners, relying on their own experience and knowledge of their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions. To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein.

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Contributors Ariane M. Abcarian, MD Attending Surgeon Division of Colon and Rectal Surgery Cook County Health Assistant Professor Department of Surgery Rush University Medical Center Chicago, Illinois Management of Hemorrhoids Herand Abcarian, MD, FACS Professor of Surgery University of Illinois Hospital and Health Sciences System John H. Stroger Jr. Hospital of Cook County Chicago, Illinois Management of Hemorrhoids Mohamad A. Abdulhai, MD Colon and Rectal Surgeon Department of Surgical Oncology Banner MD Anderson Cancer Center Phoenix, Arizona Surgical Management of Colon Cancer Christopher J. Abularrage, MD Associate Professor Division of Vascular Surgery and Endovascular Therapy Johns Hopkins Hospital Baltimore, Maryland Diabetic Foot Ali F. AbuRahma, MD, FRCS, FACS, RVT, RPVI Professor and Chief Vascular and Endovascular Surgery Director, Vascular Fellowship and Residency Programs Department of Surgery Robert C. Byrd Health Sciences Center West Virginia University Medical Director, Vascular Laboratory Charleston Area Medical Center Charleston, West Virginia Femoropopliteal Occlusive Disease Zachary T. AbuRahma, DO Assistant Professor of Vascular Surgery Charleston Area Medical Center West Virginia University Charleston, West Virginia Femoropopliteal Occlusive Disease

David B. Adams, MD Distinguished University Professor Emeritus Department of Surgery Medical University of South Carolina Charleston, South Carolina Pancreas Divisum and Other Variants of Dominant Dorsal Duct Anatomy Laura M. Adams, MD Associate Physician and Surgeon Department of Surgery UC San Diego La Jolla, California Endocrine Changes with Critical Illness Reid B. Adams, MD S. Hurt Watts Chair and Professor Department of Surgery University of Virginia Charlottesville, Virginia Management of Liver Hemangioma Adeseye Adekeye, MD, PhD Assistant Professor Department of Surgery Thomas Jefferson University Philadelphia, Pennsylvania Advances in Neoadjuvant and Adjuvant Therapy for Early-Stage Breast Cancer Gina L. Adrales, MD, MPH, FACS Associate Professor Department of Surgery Johns Hopkins School of Medicine Baltimore, Maryland Management of Inguinal Hernia Gillian M. Ahrendt, MD Resident Department of Orthopaedic Surgery University of Pittsburgh School of Medicine Pittsburgh, Pennsylvania Management of Primary Sclerosing Cholangitis Steven A. Ahrendt, MD Professor Department of Surgery Division of Surgical Oncology University of Colorado Denver, Colorado Management of Primary Sclerosing Cholangitis

Nita Ahuja, MD, MBA, FACS Professor and Chair Department of Surgery Yale School of Medicine Professor Department of Pathology Yale–New Haven Hospital New Haven, Connecticut Management of Adrenal Cortical Tumors Venkata S. Akshintala, MD Assistant Professor Division of Gastroenterology Johns Hopkins University School of Medicine Baltimore, Maryland Management of Hepatic Encephalopathy Mohammad Al Efishat, MD, FSSO Complex Surgical Oncology, HPB Fellow Department of Surgery Johns Hopkins Hospital Baltimore, Maryland Management of Intrahepatic, Perihilar, and Distal Extrahepatic Cholangiocarcinoma Hasan B. Alam, MD Loyal and Edith Davis Professor and Chair Department of Surgery Northwestern University Feinberg School of Medicine Surgeon-in-Chief Northwestern Memorial Hospital Chicago, Illinois Initial Assessment and Resuscitation of the Trauma Patient Vance L. Albaugh, MD, PhD Assistant Professor of Metabolic Surgery Metamor Institute Pennington Biomedical Research Center Staff Surgeon Metabolic and Bariatric Surgery Franciscan Missionaries of Our Lady Baton Rouge, Louisiana Cardiovascular Disease Risk Reduction After Bariatric Surgery

v

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CONTRIBUTORS

Katherine Albutt, MD, MPH Assistant Professor Division of Trauma, Emergency Surgery, and Surgical Critical Care Massachusetts General Hospital Boston, Massachusetts Current Management of Rectal Injury Yewande Alimi, MD, MHS Assistant Professor Department of Surgery Georgetown University School of Medicine Washington, DC Loss of Domain in Abdominal Wall Reconstruction Wilson M. Alobuia, MD, MS General Surgery Resident Stanford University Stanford, California Management of Pheochromocytoma Ranim Alsaad, MD General Surgery Resident Johns Hopkins Hospital Baltimore, Maryland Ischemic Colitis Pregnancy and Breast Cancer Management Emanuela Silva Alvarenga, MD Clinical Associate Staff Colon and Rectal Surgery Cleveland Clinic Florida Weston, Florida Rectovaginal Fistula John C. Alverdy, MD, FACS, FSIS Sara and Harold Lincoln Thompson Professor of Surgery Executive Vice Chair Department of Surgery The University of Chicago Pritzker School of Medicine Chicago, Illinois Management of Acute Necrotizing Pancreatitis Avani Amin, MD Instructor of Medicine Division of Hospital Medicine Section of Palliative Medicine Johns Hopkins University School of Medicine Baltimore, Maryland Surgical Palliative Care Ciro Andolfi, MD, FACS Pediatric Surgeon Department of Surgery The University of Chicago Pritzker School of Medicine Chicago, Illinois, Pediatric Surgeon Department of Surgery Les Hôpitaux Civils de Colmar Colmar, France Management of Cysts, Tumors, and Abscesses of the Spleen

Lauren Antognoli, MD Surgical Resident Luminis Health Anne Arundel Medical Center Annapolis, Maryland Management of Primary Chest Wall Tumors Pathik Aravind, MD Resident Physician Yale University School of Medicine New Haven, Connecticut Treatment Trends in Locally Recurrent and Metastatic Breast Cancer Margaret W. Arnold, MD Program Director General Surgery MedStar Baltimore Baltimore, Maryland; Associate Professor Department of Surgery Georgetown School of Medicine Washington, DC Treatment of Claudication Chady Atallah, MD Assistant Professor Department of Surgery Johns Hopkins Medical Institutions Baltimore, Maryland Management of Radiation-Induced Injury to the Small and Large Bowel Management of Pruritus Ani Andrea L. Axtell, MD, MPH Surgical Fellow Division of Thoracic Surgery Massachusetts General Hospital Boston, Massachusetts Management of Tracheal Stenosis Nilofer Azad, MD Associate Professor Department of Gastrointestinal Oncology Johns Hopkins Medical Institutions Baltimore, Maryland Neoadjuvant and Adjuvant Therapy for Colorectal Cancer Omaira Azizad, MD Assistant Professor Anesthesiology and Pain Management University of Texas Southwestern Medical Center Dallas, Texas ERAS Protocols for General Surgery Alison M. Bales, MD Fellow Department of Surgery Indiana University Indianapolis, Indiana Management of Pulmonary Parenchymal Injury

Adrian Barbul, MD Professor Department of Surgery Vanderbilt University Medical Center Professor Department of Surgery Nashville Veterans Affairs Hospital Nashville, Tennessee Is Nasogastric Intubation Necessary After Alimentary Tract Surgery? Philip S. Barie, MD, MBA, MCCM, FSIS, FIDSA, FACS, MAMSE Professor Emeritus of Surgery Division of Trauma, Burns, Critical and Acute Care Weill Cornell Medical College New York, New York Burn Wound Management Emilie C. Barnes, MD Department of Surgery University of North Carolina Chapel Hill, North Carolina Management of Tumors of the Anal Region Stephen L. Barnes, MD, FACS Chair, Hugh E Stephenson Department of Surgery University of Missouri Columbia, Missouri Abdomen That Will Not Close Erica Barnett, BA MD Candidate Department of Surgery Harvard Medical School Boston, Massachusetts Management of Acute Cholangitis Reva Basho, MD Assistant Professor Medical Oncology Cedars-Sinai Medical Center Director, Women’s Cancer Research Ellison Institute for Transformative Medicine Los Angeles, California Molecular Targets in Breast Cancer Gary A. Bass, MD, MSc, MBA, PhD, FEBS (EmSurg) Assistant Professor Division of Traumatology, Surgical Critical Care, and Emergency Surgery University of Pennsylvania Philadelphia, Pennsylvania Acute Kidney Injury in the Injured and Critically Ill Richard J. Battafarano, MD, PhD Associate Professor and Chief Division of Thoracic Surgery Johns Hopkins Medical Institutions Baltimore, Maryland Management of Paraesophageal Hernia Repair

C ontributors

Solange Bayard, MD General Surgery NewYork-Presbyterian/Weill Cornell Medicine New York, New York Surgical Management of the Axilla Marshall S. Bedine, MD Assistant Professor Department of Medicine Division of Gastroenterology and Hepatology Johns Hopkins Medical Institutions Baltimore, Maryland Management of Acute Colonic Pseudo-Obstruction (Ogilvie’s Syndrome) Kevin E. Behrns, MD Chief Medical Officer and Professor Department of Surgery University of Florida Leesburg, Florida Genetic Testing and High-Risk Pancreatic Cancer Screening Lauren Beliveau, MD Vascular Fellow Baylor Heart and Vascular Hospital Dallas, Texas Brachiocephalic Reconstruction Elizabeth R. Benjamin, MD, PhD Associate Clinical Professor Department of Surgery Emory University Trauma Medical Director Grady Memorial Hospital Atlanta, Georgia Management of Traumatic Liver Injury David Berger, MD Associate Professor General and Gastrointestinal Surgery Harvard Medical School Massachusetts General Hospital Boston, Massachusetts Management of Acute Cholangitis James H. Black III, MD, FACS David Goldfarb MD Professor of Surgery Vascular Surgery and Endovascular Therapy Johns Hopkins School of Medicine Chief, Vascular Surgery and Endovascular Therapy Johns Hopkins Hospital Baltimore, Maryland Management of Thoracic and Thoracoabdominal Aortic Aneurysms Alex B. Blair, MD Surgical Resident Johns Hopkins Hospital Baltimore, Maryland Management of Gastric Adenocarcinoma

Shivanand Bomman, MD Gastroenterology Research Fellow Center for Digestive Health Virginia Mason Franciscan Health Seattle, Washington Pancreatic Ductal Disruptions Leading to Pancreatic Fistula, Pancreatic Ascites, or Pancreatic Pleural Effusion Morgan Bonds, MD Assistant Professor Department of Surgery University of Oklahoma Health Sciences Center Oklahoma City, Oklahoma Management of Gallstone Ileus Marylise Boutros, MD, FRCSC, FACS Associate Professor Department of Surgery McGill University Attending Surgeon Colorectal Surgery Jewish General Hospital Montreal, Quebec Management of Clostridioides Difficile Colitis Justin Brilliant, MD Resident Physician Johns Hopkins Hospital Baltimore, Maryland Management of Refractory Ascites L.D. Britt, MD, MPH, DSc (Hon), FACS, FCCM Henry Ford Professor and Edward J. Brickhouse Chairman Department of Surgery Eastern Virginia Medical School Norfolk, Virginia Blunt Abdominal Trauma Sacha P. Broccard, MD Resident Mayo Clinic Jacksonville, Florida Surgical Management of the Polyposis Syndromes Malcolm V. Brock, MD Professor Division of Thoracic Surgery Johns Hopkins Medical Institutions Baltimore, Maryland Esophageal Function Tests Mediastinal Masses Ryan C. Broderick, MD Assistant Professor Department of Surgery Division of Minimally Invasive Surgery UC San Diego La Jolla, California Management of Acute Cholecystitis

vii

Stephen R. Broderick, MD, MPHS Assistant Professor Department of Surgery Johns Hopkins Medical Institutions Baltimore, Maryland Management of Barrett’s Esophagus Lawrence B. Brown, MD, MPH, MHS General Surgery Resident Johns Hopkins University Baltimore, Maryland Gastrointestinal Tubes for Feeding and Decompression Jill C. Buckley, MD Professor Department of Urology UC San Diego Health System San Diego, California Renal and Ureteral Traumatic Injuries Corinne Bunn, MD Resident Loyola University Medical Center Chicago, Illinois Buerger’s Disease (Thromboangiitis Obliterans) Mark S. Burke, MD, FACS Attending Surgeon Plastic and Reconstructive Surgery Erie County Medical Center Buffalo, New York Breast Reconstruction Following Mastectomy: Considerations, Techniques, and Outcomes, Part 2 Richard A. Burkhart, MD Associate Professor Departments of Surgery and Oncology Johns Hopkins Hospital and Johns Hopkins University Baltimore, Maryland Intraductal Papillary Mucinous Neoplasms of the Pancreas Michael S. Burnim, MD Fellow Division of Pulmonary and Critical Care Medicine Johns Hopkins University School of Medicine Baltimore, Maryland COVID-19 and Health Care Delivery in a Pandemic William Reece Burns, MD Assistant Professor Department of Surgery Johns Hopkins School of Medicine Baltimore, Maryland Management of Intrahepatic, Perihilar, and Distal Extrahepatic Cholangiocarcinoma

viii

CONTRIBUTORS

Errol L. Bush, MD, FACS Surgical Director Advanced Lung Disease and Transplant Program Associate Professor Division of Thoracic Surgery Johns Hopkins University Baltimore, Maryland Extracorporeal Membrane Oxygenation for Respiratory Failure Ronald W. Busuttil, MD, PhD Distinguished Professor Emeritus and Executive Chair Department of Surgery Founding Chief Division of Liver and Pancreas Transplantation David Geffen School of Medicine at University of California Los Angeles Los Angeles, California Management of Budd-Chiari Syndrome Jo Buyske, MD CEO and President American Board of Surgery Adjunct Professor Department of Surgery University of Pennsylvania Perelman School of Medicine Philadelphia, Pennsylvania The American Board of Surgery Certifying (Oral) Examination Kristine E. Calhoun, MD Professor Director of Medical Student Surgical Education University of Washington School of Medicine Seattle, Washington Ductal and Lobular Carcinoma in situ of the Breast Nicholas A. Calotta, MD Resident Physician Plastic and Reconstructive Surgery Johns Hopkins School of Medicine Baltimore, Maryland Nonmelanoma Skin Cancers Management of Cutaneous Melanoma Richard P. Cambria, MD Robert R. Linton Professor of Vascular and End-Vascular Surgery Harvard Medical School Division of Vascular and Endovascular Surgery St. Elizabeth Medical Center Boston, Massachusetts Open Repair of Abdominal Aortic Aneurysms Endovascular Treatment of Abdominal Aortic Aneurysms

Melissa S. Camp, MD, MPH Assistant Professor Department of Surgery Johns Hopkins Hospital Baltimore, Maryland Breast Implant-Associated Anaplastic Large Cell Lymphoma

Timothy D. Chilton, DO Resident Physician Vascular and Endovascular Surgery St. Louis University St. Louis, Missouri Management of Infected Grafts

Yilin (Linda) Cao, MD Resident Physician Department of Radiation Oncology and Molecular Radiation Sciences Johns Hopkins University School of Medicine Baltimore, Maryland Neoadjuvant and Adjuvant Therapy for Colorectal Cancer

Walter Cholewczynski, MD Associate Chairman of Surgery Director of Surgical Critical Care Department of Surgery Bridgeport Hospital Bridgeport, Connecticut; Clinical Assistant Professor Department of Surgery Yale School of Medicine New Haven, Connecticut Antibiotics in Surgical Critical Care

Ned Z. Carp, MD Barbara Brodsky Chief of Surgery and Chair Department of Surgery Lankenau Medical Center Wynnewood, Pennsylvania Management of Male Breast Cancer

Michael A. Choti, MD, MBA Chief, Department of Surgery Banner MD Anderson Medical Center Phoenix, Arizona Surgical Management of Colon Cancer

Fabio Casciani, MD Department of Surgery University of Pennsylvania Perelman School of Medicine Philadelphia, Pennsylvania Management of Complications After the Whipple Procedure Elliot L. Chaikof, MD, PhD Johnson and Johnson Professor of Surgery Department of Surgery Harvard Medical School Chair, Roberta and Stephen R. Weiner Department of Surgery Beth Israel Deaconess Medical Center Boston, Massachusetts Popliteal and Femoral Artery Aneurysm Ahmed Chatila, MD Fellow Department of Gastroenterology and Hepatology University of Maryland Baltimore, Maryland Pneumatosis Intestinalis and the Importance for the Surgeon Sophia Y. Chen, MD, MPH Resident Physician Johns Hopkins University School of Medicine Baltimore, Maryland Management of Radiation-Induced Injury to the Small and Large Bowel Albert Chi, MSE, MD Associate Professor Division of Trauma, Critical Care, and Acute Care Surgery Oregon Health & Science University Portland, Oregon Fluid and Electrolyte Therapy

Joani Christensen, MD Assistant Professor Department of Surgery Washington University in St. Louis School of Medicine St. Louis, Missouri Lymphedema Adrienne N. Christopher, MD Resident Physician Thomas Jefferson University Hospital Clinical Research Fellow Division of Plastic Surgery University of Pennsylvania Hospital Philadelphia, Pennsylvania Use of Various Meshes in Hernia Repair Anna Chudnovets, MD General Surgery Specialist Department of Surgery Johns Hopkins Medical Institutions Baltimore, Maryland Preoperative Bowel Preparation: Is It Necessary? Jose R. Cintron, MD Chairman, Division of Colon and Rectal Surgery (Retired) John H. Stroger Hospital of Cook County Associate Professor (Retired) University of Illinois College of Medicine at Chicago Chicago, Illinois Surgical Management of Constipation Bryan M. Clary, MD, MBA Professor and Chair Department of Surgery UC San Diego San Diego, California Management of Acute Cholecystitis

C ontributors

Jordan M. Cloyd, MD Surgical Oncologist Department of Surgery Ohio State University Columbus, Ohio Management of Colorectal Liver Metastases Christine S. Cocanour, MD, FACS, FCCM Professor Department of Surgery Division of Trauma UC Davis Sacramento, California Catheter Sepsis in the Intensive Care Unit Raul Coimbra, MD, PhD Surgeon-in-Chief Division of Trauma, Surgical Critical Care, and Burns Riverside University Health System Medical Center Riverside, California; Professor Department of Surgery Loma Linda University Loma Linda, California Chest Wall Trauma, Hemothorax, and Pneumothorax Salih Colakoglu, MD Assistant Professor Plastic and Reconstructive Surgery Johns Hopkins Hospital Baltimore, Maryland Breast Reconstruction Following Mastectomy: Indications, Techniques, and Results, Part 1 Julie A. Conyers, MD, MBA, FACS Surgeon, Trauma Acute Care Surgery UC Health Colorado Springs, Colorado; Chief Medical Officer Pikes Peak Regional Hospital Woodland Park, Colorado Endoscopic Therapy for Esophageal Variceal Hemorrhage Edward E. Cornwell III, MD, FACS, FCCM, FWACS (Hon.) The LaSalle D. Leffall Jr. Professor Department of Surgery Howard University Hospital Washington, DC Injured Spleen Gregory A. Coté, MD, MS Professor Department of Medicine Division of Gastroenterology and Hepatology Oregon Health & Science University Portland, Oregon Pancreas Divisum and Other Variants of Dominant Dorsal Duct Anatomy

Chris Cribari, MD, FACS Associate Clinical Professor Department of Surgery University of Colorado Medical Director Acute Care Surgery UC Health Medical Group Loveland, Colorado Septic Response and Management Patricia A. Cronin, MD, BAO, BCh, BMedSci, FRCS, FACS Assistant Professor Division of Surgical Oncology and Endocrine Surgery Mayo Clinic Arizona Phoenix, Arizona Margins: How to and How Big? Patrick Crosby, MD General Surgery Resident Johns Hopkins Hospital Baltimore, Maryland Metabolic Changes Following Bariatric Surgery Alisa Cross, MD Associate Professor Department of Surgery University of Oklahoma Oklahoma City, Oklahoma Surgeon’s Use of Ultrasound in the Trauma and Critical Care Settings

Whitney A. Davidson, MD Faculty, Department of Surgery Mercy NWA Rogers, Arkansas Management of Primary Chest Wall Tumors Katherine deAngeli, MD Fellow Mount Sinai Hospital New York, New York Genetic Counseling and Testing Sarah E. Deery, MD, MPH Vascular Surgeon Division of Vascular and Endovascular Therapy Maine Medical Center Portland, Maine; Clinical Assistant Professor Tufts University School of Medicine Boston, Massachusetts Management of Recurrent Carotid Artery Stenosis Daniel J. Delitto, MD, PhD Assistant Professor Department of Surgery Stanford University Stanford, California Genetic Testing and High-Risk Pancreatic Cancer Screening

Steven C. Cunningham, MD, FACS Director of Pancreatic and Hepatobiliary Surgery Department of Surgery Ascension Saint Agnes Hospital and Cancer Institute Baltimore, Maryland Management of Common Bile Duct Stones

Tom R. DeMeester, MD Professor and Chairman Emeritus Department of Surgery University of Southern California, Los Angeles Los Angeles, California New Approaches to Gastroesophageal Reflux Disease (LINX)

Hasan Dani, MD Brady Urological Institute Department of Urology Johns Hopkins Hospital Baltimore, Maryland Urologic Complications of Pelvic Fracture

Daniel T. Dempsey, MD, MBA Professor Emeritus Department of Surgery University of Pennsylvania Pennsylvania, Philadelphia Benign Gastric Ulcer Management of Duodenal Ulcers

Alan Dardik, MD, PhD Professor Surgery and Cellular and Molecular Physiology Vice Chair, Faculty Affairs Yale School of Medicine New Haven, Connecticut; Attending, Vascular Surgery Department of Surgery VA Connecticut Healthcare Systems West Haven, Connecticut Raynaud’s Phenomenon Halley Darrach, MD Medical Student Plastic and Reconstructive Surgery Johns Hopkins School of Medicine Baltimore, Maryland Lymphedema

ix

Isabel S. Dennahy, MD General Surgery Resident Johns Hopkins Hospital Baltimore, Maryland Total Pancreatectomy and Islet Autotransplantation for Chronic Pancreatitis Daniel L. Dent, MD Vice Chair for Education Department of Surgery Chair, Department of Medical Education UT Health San Antonio Long School of Medicine San Antonio, Texas The American Board of Surgery Certifying (Oral) Examination

x

CONTRIBUTORS

Danielle K. DePeralta, MD Assistant Professor Surgical Oncology Northwell Health New York, New York Management of Malignant Liver Tumors Niraj M. Desai, MD Assistant Professor Department of Surgery Johns Hopkins University School of Medicine Baltimore, Maryland Transplantation of the Pancreas Melissa Louise DeSouza, MD Surgeon Foregut and Bariatric Surgery The Oregon Clinic Portland, Oregon Management of Disorders of Esophageal Motility Lauren M. DeStefano, MD Breast Surgical Oncologist Department of Surgery Cedars-Sinai Medical Center Los Angeles, California Ductal and Lobular Carcinoma in situ of the Breast Laurence P. Diggs, MD Chief Resident Rutgers Robert Wood Johnson University School of Medicine New Brunswick, New Jersey Management of Gastrointestinal Stromal Tumors Conor Dillon, DO Instructor, General Surgery Homer Stryker School of Medicine Western Michigan University Kalamazoo, Michigan Surgical Site Infections Joseph DiNorcia, MD Associate Professor Recanati/Miller Transplantation Institute Icahn School of Medicine at Mt. Sinai New York, New York Management of Budd-Chiari Syndrome Gerard M. Doherty, MD Moseley Professor and Chair of Surgery Harvard Medical School Surgeon-in-Chief and Crowley Family Chair Brigham and Women’s Hospital Boston, Massachusetts Nontoxic Goiter James M. Donahue, MD Associate Professor Department of Surgery University of Alabama at Birmingham Birmingham, Alabama Management of Esophageal Perforation

Joy Zhou Done, MD, MHS Resident Johns Hopkins Baltimore, Maryland PET Scanning in the Management of Colorectal Cancer Treatment Trends in Locally Recurrent and Metastatic Breast Cancer Jay J. Doucet, MD, MSc, FACS, FRCSC Professor Department of Surgery UC San Diego San Diego, California Endocrine Changes with Critical Illness Quan-Yang Duh, MD Professor and Chief Section of Endocrine Surgery UC San Francisco Attending Surgeon VA Medical Center San Francisco, California Management of Thyroid Nodules Mark D. Duncan, MD, FACS Associate Professor Division of Surgical Oncology Johns Hopkins Medical Institutions Associate Professor Department of Oncology Miller Coulson Academy of Clinical Excellence Baltimore, Maryland Management of Gastric Adenocarcinoma Mark A. Eckardt, MD Surgical Resident Yale School of Medicine New Haven, Connecticut Management of Adrenal Cortical Tumors Barish H. Edil, MD Professor and Chair Department of Surgery University of Oklahoma Oklahoma City, Oklahoma Management of Gallstone Ileus David T. Efron, MD Professor Department of Surgery University of Maryland Shock Trauma Center Medical Director and Chief of Trauma RA Cowley Shock Trauma Center University of Maryland School of Medicine Baltimore, Maryland Emergency Department Resuscitative Thoracotomy Jonathan E. Efron, MD Professor of Surgery and Urology Johns Hopkins University Baltimore, Maryland Management of Toxic Megacolon

Anne P. Ehlers, MD, MPH Senior Fellow University of Washington Seattle, Washington Endoscopic Treatment of Barrett’s Esophagus Daniel L. Eisenson, MD Resident Johns Hopkins University School of Medicine Baltimore, Maryland Management of Hepatic Abscess S. James El Haddi, MD, MS General Surgery Resident Oregon Health & Science University Portland, Oregon Fluid and Electrolyte Therapy Mohamad El Moheb, MD General Surgery Resident University of Virginia Charlottesville, Virginia; Postdoctoral Research Fellow Massachusetts General Hospital Boston, Massachusetts Use of Opioids in the Postoperative Period Ramy El-Diwany, MD, PhD Resident Johns Hopkins University School of Medicine Baltimore, Maryland Management of Small Bowel Tumors James K. Elsey, MD, FACS Professor Department of Surgery Medical University of South Carolina Charleston, South Carolina Management of Abdominal Aortic Aneurysm with Concomitant Nonvascular Abdominal Pathology Joel Elterman, MD, FACS Associate Clinical Professor Department of Surgery University of Colorado School of Medicine Anschutz Medical Campus Fort Collins, Colorado; Trauma and Acute Care Surgery Medical Center of the Rockies Loveland, Colorado Septic Response and Management Zachary Obinna Enumah, MD, MA General Surgeon Johns Hopkins Hospital Baltimore, Maryland Tenets of Damage Control Acid-Base Disorders David M. Euhus, MD Professor Department of Surgery Johns Hopkins University Baltimore, Maryland Pregnancy and Breast Cancer Management

C ontributors

Douglas B. Evans, MD Donald C Ausman Family Foundation Professor and Chair Department of Surgery Medical College of Wisconsin Milwaukee, Wisconsin Palliative Interventions for Patients with Operable and Advanced Pancreatic and Periampullary Cancer Mikael A. Fadoul, MD Resident Physician Department of Vascular and Endovascular Surgery Cooper University Hospital Camden, New Jersey Endovascular Management of Vascular Injuries Peter J. Fagenholz, MD Associate Professor Division of Trauma, Emergency Surgery, and Critical Care Massachusetts General Hospital Associate Professor Harvard Medical School Boston, Massachusetts Current Management of Rectal Injury Marissa Famularo, DO Integrated Vascular Resident Vascular Surgery Cooper University Hospital Camden, New Jersey Endovascular Management of Vascular Injuries Sandy Hwang Fang, MD Associate Professor Department of Surgery Oregon Health & Sciences University Portland, Oregon Preoperative Bowel Preparation: Is It Necessary? PET Scanning in the Management of Colorectal Cancer Alik Farber, MD, MBA Chief Division of Vascular and Endovascular Surgery Associate Chair for Clinical Operations Department of Surgery Boston Medical Center Professor of Surgery and Radiology Boston University School of Medicine Boston, Massachusetts Management of Peripheral Arterial Thromboembolism Genevieve Fasano, MD, MS Resident NewYork-Presbyterian/Weill Cornell Medicine New York, New York Surgical Management of the Axilla

David V. Feliciano, MD, FACS, MAMSE Clinical Professor Department of Surgery University of Maryland School of Medicine Attending Surgeon Emeritus Shock Trauma Center University of Maryland Medical Center Baltimore, Maryland Penetrating Abdominal Trauma David J. Feller-Kopman, MD, FACP Professor Department of Medicine Geisel School of Medicine at Dartmouth Hanover, New Hampshire; Chief, Pulmonary and Critical Care Medicine Dartmouth-Hitchcock Medical Center Lebanon, New Hampshire Tracheostomy Kirkpatrick Beekman Fergus, MD, MAS Resident Physician UC San Francisco San Francisco, California Management of Chronic Ulcerative Colitis Carlos Fernandez-del Castillo, MD Professor Department of Surgery Massachusetts General Hospital Boston, Massachusetts Rare and Unusual Pancreatic Tumors Alessandro Fichera, MD, FACS, FASCRS Surgery Safety and Quality Officer Division Chief, Colorectal Surgery Baylor University Medical Center Dallas, Texas Surgical Management of Crohn’s Colitis Surgical Management of Fecal Incontinence John P. Fischer, MD, MPH Assistant Professor Division of Plastic Surgery University of Pennsylvania Pennsylvania, Philadelphia Use of Various Meshes in Hernia Repair Adam Fish, MD Resident Physician Department of Interventional Radiology Yale School of Medicine New Haven, Connecticut Vena Cava Filters P. Marco Fisichella, MD, MBA, FACS Associate Professor Department of Surgery Harvard Medical School Associate Chief of Surgery Department of Surgery West Roxbury VA Boston, Massachusetts Management of Cysts, Tumors, and Abscesses of the Spleen

xi

James W. Fleshman Jr., MD, FACS, FASCRS Chairman, Department of Surgery Baylor University Medical Center Clinical Professor Texas A&M College of Medicine Dallas, Texas Surgical Management of Crohn’s Colitis Katherine L. Florecki, MD Assistant Professor Department of Surgery Division of Acute Care Surgery Johns Hopkins University School of Medicine Baltimore, Maryland Ventilator-Associated Pneumonia Post–Intensive Care Syndrome Yuman Fong, MD The Sangiacomo Family Chair in Surgical Oncology City of Hope National Medical Center Duarte, California Cystic Disease of The Liver Zhi Ven Fong, MD, MPH Complex General Surgical Oncology Fellow Department of Surgery Massachusetts General Hospital Boston, Massachusetts Ablation of Colorectal Carcinoma Liver Metastases Diagnosis and Management of Autoimmune Pancreatitis Ryan B. Fransman, MD Trauma Surgery University of Maryland Shock Trauma Center Baltimore, Maryland Emergency Department Resuscitative Thoracotomy Julie A. Freischlag, MD, FACS, FRCSEd(Hon), DFSVS Professor, Vascular and Endovascular Surgery Wake Forest University School of Medicine Chief Executive Officer Atrium Health Wake Forest Baptist Dean, Wake Forest University School of Medicine Winston-Salem, North Carolina; Chief Academic Officer Atrium Health Enterprise Charlotte, North Carolina Thoracic Outlet Syndrome Christopher Frost, MD Resident Physician Plastic and Reconstructive Surgery Johns Hopkins Hospital Baltimore, Maryland Nerve Injury and Repair

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CONTRIBUTORS

Alodia Gabre-Kidan, MD, MPH Assistant Professor Department of Surgery Johns Hopkins School of Medicine Baltimore, Maryland Management of Rectal Prolapse Vivian Gahtan, MD Chair, Department of Surgery Stritch School of Medicine Loyola University Staff Physician Department of Surgery Edward Hines Jr. VA Hospital Maywood, Illinois Buerger’s Disease (Thromboangiitis Obliterans) Susan Galandiuk, MD Price Endowed Professor of Surgery Director, Price Institute of Surgical Research Director, Division of Colon and Rectal Surgery Program Director, Division of Colon and Rectal Surgery Hiram C. Polk Jr, MD, Department of Surgery University of Louisville Louisville, Kentucky Management of Diverticular Disease of the Colon Samuel M. Galvagno Jr., DO, PhD, MS, FCCM Professor of Anesthesiology R. Adams Cowley Shock Trauma Center Executive Vice Chair, Anesthesiology University of Maryland School of Medicine Baltimore, Maryland; Colonel, Air Force Reserve USAF Pentagon Arlington, Virginia Management of Diverticular Disease of the Colon Airway Management in the Trauma Patient Raisa Gao, DO Instructor, General Surgery Homer Stryker MD School of Medicine Western Michigan University Kalamazoo, Michigan Surgical Site Infections Brian T. Garibaldi, MD Associate Professor Pulmonary and Critical Care Medicine Johns Hopkins University School of Medicine Baltimore, Maryland COVID-19 and Health Care Delivery in a Pandemic

Danon E. Garrido, MD Assistant Professor Vascular and Endovascular Surgery University of Mississippi Medical Center Jackson, Mississippi Balloon Angioplasty and Stents in Carotid Artery Occlusive Disease Susan L. Gearhart, MD, MEHP Associate Professor of Colorectal Surgery Director, Colorectal Surgery Fellowship Program Johns Hopkins University School of Medicine Baltimore, Maryland Gastrointestinal Tubes for Feeding and Decompression Mary L. Gemignani, MD, MPH Attending Surgeon Program Director, Breast Surgery Fellowship Breast Service Department of Surgery Memorial Sloan Kettering Cancer Center New York, New York Breast Cancer: Surgical Therapy Christos Georgiades, MD, PhD Professor Radiology and Radiological Sciences Director, Interventional Oncology Johns Hopkins University Baltimore, Maryland Transjugular Intrahepatic Portosystemic Shunt Transhepatic Interventions for Obstructive Jaundice Zachary German, MD Medical Student Wake Forest School of Medicine Winston-Salem, North Carolina Thoracic Outlet Syndrome Bruce L. Gewertz, MD Chair and Surgeon in Chief Department of Surgery Cedars-Sinai Medical Center Los Angeles, California Takayasu’s Arteritis Omar M. Ghanem, MD, FACS Assistant Professor Department of Surgery Mayo Clinic Rochester, Minnesota Diagnosis and Management of Motility Disorders of the Stomach and Small Bowel in the Current Era Joseph S. Giglia, MD Professor Interim Chief of Vascular Surgery Department of Surgery University of Cincinnati College of Medicine Cincinnati, Ohio Atherosclerotic Renal Artery Stenosis

Armando E. Giuliano, MD, FACS, FRCSEd Chief, Surgical Oncology Department of Surgery Cedars-Sinai Medical Center Clinical Professor Department of Surgery UCLA School of Medicine Los Angeles, California Molecular Targets in Breast Cancer Ablative Techniques in the Treatment of Benign and Malignant Breast Disease Natalia O. Glebova, MD, PhD Vascular Surgeon Mid-Atlantic Permanente Medical Group Rockville, Maryland Tibioperoneal Arterial Occlusive Disease Ana Gleisner, MD, PhD Associate Professor Department of Surgery University of Colorado Aurora, Colorado Management of Benign Liver Tumors Lee A. Goeddel, MD, MPH Assistant Professor Department of Anesthesiology and Critical Care Medicine Johns Hopkins University School of Medicine Assistant Professor Biomedical Engineering Johns Hopkins Whiting School of Engineering Baltimore, Maryland Perioperative Optimization Eric M. Goldberg, MD Associate Professor Department of Medicine and Gastroenterology University of Maryland School of Medicine Baltimore, Maryland Pneumatosis Intestinalis and the Importance for the Surgeon Reyna Gonzalez, MD, MS Emergency General Surgery Medical Director Riverside University Health Systems Moreno Valley, California Glucose Control in the Postoperative Period Amy V. Gore, MD Assistant Professor Department of Surgery Rutgers New Jersey Medical School Newark, New Jersey Management of Intraabdominal Infections

C ontributors

Jeremy Goverman, MD Assistant Professor Department of Surgery Harvard Medical School MGH Trustee’s Fellow in Burns Division of Burns Massachusetts General Hospital Medical Staff Shriners Hospital for Children Boston, Massachusetts Medical Management of the Burn Patient Miral Sadaria Grandhi, MD Associate Professor Director of Hepatobiliary Surgery Department of Surgery, Division of Surgical Oncology Program Director of the Complex General Surgical Oncology Fellowship Program Rutgers Cancer Institute of New Jersey Rutgers Robert Wood Johnson Medical School New Brunswick, New Jersey Management of Gastrointestinal Stromal Tumors Management of Echinococcal Cyst Disease of the Liver Michael D. Grant, MD Breast Surgeon Department of Surgery Baylor University Medical Center Dallas, Texas A Surgeon’s Practical Guide to Breast Imaging Richard J. Gray, MD Professor Division of Surgical Oncology and Endocrine Surgery Mayo Clinic Scottsdale, Arizona Margins: How to and How Big? Jonathan B. Greer, MD Assistant Professor Department of Surgery Johns Hopkins University School of Medicine Baltimore, Maryland Small Bowel Diverticulosis Management of Hepatic Abscess Mahip Grewal, BA Medical Student NYU Grossman School of Medicine NYU Langone Health New York, New York Biomarker Guided Surgical Management of Hepatobiliary and Pancreatic Tumors Chassidy Grimes, MD Resident Rush University Medical Center Chicago, Illinois Anal Stenosis

Traci M. Grucz, PharmD, BCCCP Clinical Pharmacy Specialist Department of Pharmacy Johns Hopkins Hospital Baltimore, Maryland Ventilator-Associated Pneumonia Matthew D. Grunwald, MD Physician Fellow Department of Gastroenterology Maimonides Medical Center New York, New York Use of Esophageal Stents Jose G. Guillem, MD, MPH, MBA Chief, Division of GI Surgery Department of Surgery University of North Carolina Chapel Hill, North Carolina Management of Colonic Volvulus Management of Tumors of the Anal Region Rebecca L. Gunter, MD, MS Associate Staff Colorectal Surgery Cleveland Clinic Foundation Cleveland, Ohio Management of Pilonidal Disease NavYash Gupta, MD, FACS Associate Professor Department of Surgery Director, Venous Program Vascular Surgery Cedars-Sinai Medical Center Los Angeles, California Takayasu’s Arteritis Joseph R. Habib, MD Department of Surgery University of Maryland Medical Center Baltimore, Maryland Biomarker Guided Surgical Management of Hepatobiliary and Pancreatic Tumors Mehran Habibi, MD, MBA Assistant Professor Department of Surgery Johns Hopkins University Baltimore, Maryland Treatment Trends in Locally Recurrent and Metastatic Breast Cancer Edward R. Hagen, MD General/Colon and Rectal Surgery Traverse General Surgery and Trauma Care Traverse City, Michigan Anal Condyloma

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Jafar Haghshenas, DO Clinical Assistant Professor Department of Surgery University of Illinois Chicago, Illinois; Attending Surgeon Department of Trauma Surgery and Surgical Critical Care Advocate Christ Medical Center Oak Lawn, Illinois Venous Thromboembolism: Prevention, Diagnosis, and Treatment Pegge M. Halandras, MD Associate Professor Division of Vascular Surgery and Endovascular Therapy Loyola University Chicago Stritch School of Medicine Maywood, Illinois Buerger’s Disease (Thromboangiitis Obliterans) James P. Hamilton, MD Associate Professor Director of Hepatology Division of Gastroenterology and Hepatology Department of Medicine Johns Hopkins University School of Medicine Baltimore, Maryland Management of Refractory Ascites Muhammad Hammami, MD Fellow Gastroenterology and Hepatology University of Maryland School of Medicine Baltimore, Maryland Pneumatosis Intestinalis and the Importance for the Surgeon Britta Jean Han, MD, MS Resident Physician Washington University School of Medicine St. Louis, Missouri Management of Recurrent Inguinal Hernia Misop Han, MD, MS Professor Departments of Urology and Oncology Johns Hopkins Medicine Baltimore, Maryland Urologic Complications of Pelvic Fracture Guy Handley, MD Assistant Professor Division of Infectious Disease and International Medicine Morsani College of Medicine Tampa, Florida Antifungal Therapy in the Surgical Patient John W. Harmon, MD Professor General Surgery Johns Hopkins University Baltimore, Maryland Management of Small Bowel Tumors

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CONTRIBUTORS

Andrew Harris, MD Resident Physician Department of Orthopaedic Surgery Johns Hopkins University Baltimore, Maryland Spine and Spinal Cord Injuries

Joseph M. Herman, MD, MSc, MSHCM Director of Clinical Research Radiation Oncology Northwell Health Cancer Institute Lake Success, New York Intraoperative Radiation for Pancreatic Cancer

James E. Harris Jr. MD Chair, Department of Surgery Johns Hopkins Hospital Howard County General Columbia, Maryland Acid-Base Disorders

Sean Hickey, MD Instructor Department of Surgery Massachusetts General Hospital Boston, Massachusetts Cold-Induced Injuries and Hypothermia

Jon M. Harrison, MD Surgical Resident GI and General Surgery Massachusetts General Hospital Boston, Massachusetts Rare and Unusual Pancreatic Tumors

Caitlin W. Hicks, MD, MS Associate Professor Division of Vascular Surgery and Endovascular Therapy Johns Hopkins University School of Medicine Baltimore, Maryland Diabetic Foot Management of Ruptured Abdominal Aortic Aneurysms

Christine Haugen, MD, PhD Resident Johns Hopkins Hospital Baltimore, Maryland Hemodialysis Access Surgery Elliott R. Haut, MD, PhD Associate Professor Anesthesiology/Critical Care Medicine and Emergency Medicine Division of Acute Care Surgery Johns Hopkins University School of Medicine Baltimore, Maryland Venous Thromboembolism: Prevention, Diagnosis, and Treatment Pancreatic and Duodenal Injuries Dana Hayden, MD, MPH, FACS, FASCRS Associate Professor Department of General Surgery Rush University Medical Center Chicago, Illinois Anal Stenosis Jin He, MD, PhD Associate Professor Department of Surgery Johns Hopkins University School of Medicine Baltimore, Maryland Vascular Reconstruction During the Whipple Operation Fernando A.M. Herbella, MD Associate Professor Department of Surgery Federal University of Sao Paulo Sao Paulo, Brazil Management of Zenker’s Diverticulum

Michael G. House, MD Professor Department of Surgery Chief, Division of Surgical Oncology Indiana University School of Medicine Indianapolis, Indiana Management of Mallory-Weiss Syndrome David B. Hoyt, MD Professor Emeritus and Chair Department of Surgery University of California, Irvine Irvine, California; Immediate Past Executive Director American College of Surgeons Chicago, Illinois Chest Wall Trauma, Hemothorax, and Pneumothorax Yinin Hu, MD Assistant Professor Department of Surgery University of Maryland Baltimore, Maryland Surgical Management of Thyroid Cancer

David Hindin, MD, MS Fellow Division of General Surgery Stanford University Stanford, California Loss of Domain in Abdominal Wall Reconstruction

Nadia Ijaz, MBBS, MS Geriatric Medicine Fellow Division of Internal Medicine University of Maryland Baltimore, Maryland Coagulation Issues and the Trauma Patient

O. Joe Hines, MD Professor and Interim Chair Department of Surgery David Geffen School of Medicine at the University of California, Los Angeles Los Angeles, California Management of Pancreatic Necrosis

Kenji Inaba, MD Professor of Surgery, Anesthesia, and Emergency Medicine Department of Surgery University of Southern California Los Angeles, California Management of Diaphragmatic Injuries

Jessie Ho, MD General Surgery Resident Northwestern University Chicago, Illinois Initial Assessment and Resuscitation of the Trauma Patient Richard A. Hodin, MD Professor Department of Surgery Harvard Medical School Boston, Massachusetts Management of Enterocutaneous Fistulas Abraham P. Houng, MD, FACS Assistant Professor Department of Surgery Weill Cornell Medical College New York, New York Burn Wound Management

Gabriel D. Ivey, MD Assistant Professor Department of Surgery Division of Surgical Oncology Johns Hopkins University School of Medicine Baltimore, Maryland Intraductal Papillary Mucinous Neoplasms of the Pancreas Lisa K. Jacobs, MD, MSPH Associate Professor Departments of Surgery and Oncology Johns Hopkins University Baltimore, Maryland Role of Stereotactic Biopsy in Management of Breast Disease Claire Janssen, MD Fellow Vascular Surgery UC San Diego San Diego, California Aortoiliac Occlusive Disease

C ontributors

Ammar A. Javed, MD Assistant Professor of Surgery NYU Langone Health New York, New York Biomarker Guided Surgical Management of Hepatobiliary and Pancreatic Tumors Management of Pancreatic Pseudocyst Amballur David John, MD Assistant Professor Anesthesia and Critical Care Johns Hopkins University Baltimore, Maryland Management of Postoperative Delirium Eric K. Johnson, MD, FACS, FASCRS Professor Colorectal Surgery Cleveland Clinic Foundation Cleveland, Ohio Management of Pilonidal Disease Wali Rashad Johnson, MD, MPH General Surgery Resident Vanderbilt University Medical Center Nashville, Tennessee Is Nasogastric Intubation Necessary After Alimentary Tract Surgery? Fabian M. Johnston, MD, MHS Associate Professor of Surgery Johns Hopkins University Baltimore, Maryland Familial Gastric Cancer Management of Peritoneal Surface Malignancies Ronald C. Jones, MD Chief Emeritus of Surgery Baylor Scott & White Health Dallas, Texas A Surgeon’s Practical Guide to Breast Imaging Bellal Joseph, MD, FACS Professor and Chief of Surgery University of Arizona Tucson, Arizona Use of Resuscitative Endovascular Balloon Occlusion of the Aorta in Resuscitation of the Trauma Patient Girish P. Joshi, MBBS, MD, FFARCSI Professor Anesthesiology and Pain Management UT Southwestern Medical Center Dallas, Texas ERAS Protocols for General Surgery Haytham Kaafarani, MD, MPH Associate Professor of Surgery Massachusetts General Hospital Harvard Medical School Boston, Massachusetts Use of Opioids in the Postoperative Period

Anthony N. Kalloo, MD Chairman Department of Medicine Maimonides Medical Center New York, New York Use of Esophageal Stents Lewis J. Kaplan, MD, FACS, FCCM, FCCP Professor Department of Surgery Division of Trauma, Critical Care, and Emergency Surgery University of Pennsylvania Perelman School of Medicine Section Chief, Surgical Critical Care Department of Surgery Corporal Michael J Crescenz VA Medical Center Philadelphia, Pennsylvania Acute Kidney Injury in the Injured and Critically Ill Shkala Karzai, MD Breast and Endocrine Surgeon Department of Surgery WestMed Medical Group Rye, New York Adrenal Incidentaloma Primary Hyperparathyroidism Vikram S. Kashyap, MD, FACS Frederik Meijer Chair Meijer Heart and Vascular Institute Vice President, Cardiovascular Health Spectrum Health Grand Rapids, Michigan Upper Extremity Arterial Occlusive Disease Mark Katlic, MD, FACS Chair, Department of Surgery Sinai Hospital of Baltimore Baltimore, Maryland Achalasia of the Esophagus Michael G. Kattah, MD, PhD Assistant Professor Department of Medicine Division of Gastroenterology UC San Francisco San Francisco, California Management of Chronic Ulcerative Colitis Krista L. Kaups, MD, MSc Professor of Clinical Surgery Department of Surgery UCSF Fresno Fresno, California Glucose Control in the Postoperative Period Yasaman Kavousi, MD Clinical Vascular Fellow Division of Vascular Surgery and Endovascular Therapy Johns Hopkins Hospital Baltimore, Maryland Management of Thoracic and Thoracoabdominal Aortic Aneurysms Diabetic Foot

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Qingwen Kawaji, MD, ScM Surgical Resident Medstar Health Baltimore, Maryland Treatment of Claudication Khaled M. Kebaish, MD, FRCS Professor of Orthopaedic Surgery Johns Hopkins University Baltimore, Maryland Spine and Spinal Cord Injuries Electron Kebebew, MD Professor and Chief Department of Surgery Stanford University Stanford, California Management of Pheochromocytoma Scott R. Kelley, MD, FACS, FASCRS Consultant, Colon and Rectal Surgery Mayo Clinic Rochester, Minnesota Surgical Management of the Polyposis Syndromes Kaitlyn Kennard, MD Breast Surgical Oncology Fellow Siteman Cancer Center Washington University in St. Louis St. Louis, Missouri Management of Male Breast Cancer Alistair J. Kent, MD, MPH Assistant Professor Trauma, Critical Care, and Emergency General Surgery Johns Hopkins School of Medicine Baltimore, Maryland Abdominal Compartment Syndrome and Management of the Open Abdomen Rachel G. Khadaroo, MD, PhD, FRCSC Professor of Surgery University of Alberta Edmonton, Alberta A Practical Approach to Surgery in the Frail Elderly Ali H. Khalifeh, MD Vascular Surgeon Cleveland Clinic Cleveland, Ohio Management of Vascular Injuries Maria Abou Khalil, MD, MSc, FRCSC Colorectal Surgery Fellow McGill University Montreal, Quebec Management of Clostridioides difficile Colitis

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CONTRIBUTORS

Hamza Khan, MD Post-Doctoral Research Fellow Department of Surgery Johns Hopkins University Baltimore, Maryland Esophageal Function Tests Familial Gastric Cancer Mediastinal Masses Maryam Ali Khan, MD Research Fellow Division of Vascular Surgery UC San Diego San Diego, California Aortoiliac Occlusive Disease Sameer Khan, MD Clinical Fellow Gastroenterology and Hepatology Johns Hopkins Hospital Laurel, Maryland Obstructive Jaundice: The Role of Endoscopic Intervention Mouen A. Khashab, MD Associate Professor of Medicine Director of Therapeutic Endoscopy Department of Gastroenterology and Hepatology Johns Hopkins Medical Institutions Baltimore, Maryland Enteral Stents in the Treatment of Colonic Obstruction Dmitriy O. Khodorskiy, MD Assistant Director of Advanced Therapeutic Endoscopy Maimonides Medical Center Clinical Assistant Professor Department of Medicine State University of New York Downstate Medical Center New York, New York Use of Esophageal Stents Mohammad R. Khreiss, MD Associate Professor Department of Surgery University of Arizona Tucson, Arizona Pancreatic Neuroendocrine Tumors of the Pancreas Excluding Gastrinoma Jina Kim, MD Endocrine Surgeon Inova Health System Falls Church, Virginia Management of Hyperthyroidism Joseph Kim, MD Internal Medicine University of Maryland Baltimore, Maryland Pneumatosis Intestinalis and the Importance for the Surgeon

Karen M. Kim, MD, MS Assistant Professor Department of Cardiac Surgery University of Michigan Ann Arbor, Michigan Management of Acute Aortic Dissections Elizabeth Gherardi King, MD Assistant Professor Division of Vascular and Endovascular Surgery Boston University Boston, Massachusetts Management of Peripheral Arterial Thromboembolism Benedict Kinny-Köster, MD Postdoctoral Research Fellow Department of Surgery Johns Hopkins University School of Medicine Baltimore, Maryland; Surgical Resident Department of General, Visceral, and Transplantation Surgery Heidelberg University Hospital Heidelberg, Baden-Württemberg, Germany Vascular Reconstruction During the Whipple Operation V. Suzanne Klimberg, MD, PhD, MSHCT, MAMSE, FACS Professor and Courtney M Townsend Jr MD Distinguished Chair in General Surgery University of Texas Medical Branch in Galveston Galveston, Texas; Adjunct Professor MD Anderson Cancer Center Houston, Texas Lymphatic Mapping and Sentinel Lymphadenectomy Deepika Koganti, MD Assistant Professor Department of Surgery Emory University School of Medicine Associate Fellowship Program Director Atlanta, Georgia Management of Traumatic Liver Injury George Kokosis, MD Assistant Professor of Surgery Rush Medical College Rush University Medical Center Chicago, Illinois Lymphedema Andrew R. Kolarich, MD Diagnostic and Interventional Radiology Resident Johns Hopkins Hospital Baltimore, Maryland Transjugular Intrahepatic Portosystemic Shunt Transhepatic Interventions for Obstructive Jaundice

Richard Kozarek, MD Director Emeritus, Digestive Disease Institute Division of Gastroenterology Virginia Mason Franciscan Health Clinical Professor Department of Medicine University of Washington Seattle, Washington Pancreatic Ductal Disruptions Leading to Pancreatic Fistula, Pancreatic Ascites, or Pancreatic Pleural Effusion Ashley Krepline, MD General Surgery Resident Medical College of Wisconsin Milwaukee, Wisconsin Palliative Interventions for Patients with Operable and Advanced Pancreatic and Periampullary Cancer Swati A. Kulkarni, MD Professor Department of Surgery Northwestern University Feinberg School of Medicine Chicago, Illinois Contralateral Prophylactic Mastectomy Vivek Kumbhari, MD Assistant Professor of Medicine Director of Endoscopy Department of Medicine Bayview Medical Center Director of Bariatric Endoscopy Department of Medicine Johns Hopkins Medical Institutions Baltimore, Maryland Management of Morbid Obesity Shaun M. Kunisaki, MD, MSc Associate Professor Department of Surgery Johns Hopkins Children’s Center Baltimore, Maryland Common Pediatric Surgical Emergencies Gifty Kwakye, MD, MPH, FACS, FASCRS Associate Professor Division of Colorectal Surgery University of Michigan Ann Arbor, Michigan Management of Colorectal Polyps Mitchell R. Ladd, MD, PhD Pediatric Surgery Fellow Division of Pediatric Surgery Johns Hopkins Children’s Center Baltimore, Maryland Common Pediatric Surgical Emergencies Kelly J. Lafaro, MD, MPH Assistant Professor Department of Surgery Johns Hopkins University Baltimore, Maryland Management of Pancreatic Pseudocyst

C ontributors

Daniel A. Laheru, MD Ian T. MacMillan Professorship in Clinical Pancreatic Research Medical Oncology Johns Hopkins University School of Medicine Baltimore, Maryland Neoadjuvant and Adjuvant Therapy for Pancreatic Cancer William P. Lancaster, MD Assistant Professor Department of Surgery Medical University of South Carolina Charleston, South Carolina Gallstone Pancreatitis Julie R. Lange, MD, ScM Associate Professor Department of Surgery Johns Hopkins University School of Medicine Baltimore, Maryland Screening for Breast Cancer Anna M. Ledgerwood, MD Professor Michael and Marian Ilitch Department of Surgery Wayne State University Trauma Medical Director Trauma Services Detroit Receiving Hospital Detroit, Michigan Penetrating Neck Trauma Blunt Cardiac Injury Extremity Compartment Syndrome Christina Lee, MD Burn Surgeon Department of Surgery Cooperman Barnabas Medical Center Livingston, New Jersey Burn Wound Management Eliza J. Lee, MD Transplant Surgery Fellow Johns Hopkins Hospital Baltimore, Maryland Portal Hypertension: Role of Shunting Procedures Grace C. Lee, MD General Surgery Resident Massachusetts General Hospital Boston, Massachusetts Management of Enterocutaneous Fistulas Hanjoo Lee, MD Colorectal Surgeon Harbor-UCLA Medical Center Torrance, California Surgical Management of Crohn’s Colitis

Adam S. Levin, MD Associate Professor Orthopaedic Surgery and Oncology Johns Hopkins University Baltimore, Maryland Management of Soft Tissue Sarcomas Robert P. Liddell, MD Assistant Professor Radiology and Radiological Sciences Johns Hopkins School of Medicine Baltimore, Maryland Acute Peripheral Arterial and Bypass Graft Occlusion: Thrombolysis and Thrombectomy Heather A. Lillemoe, MD Fellow, Complex General Surgical Oncology Department of Surgical Oncology University of Texas MD Anderson Cancer Center Houston, Texas Management of Benign Biliary Strictures Keith D. Lillemoe, MD Chief, Department of Surgery Massachusetts General Hospital W. Gerald Austen Professor Department of Surgery Harvard Medical School Boston, Massachusetts Management of Benign Biliary Strictures Pamela A. Lipsett, MD, MHPE Warfield M. Firor Endowed Professorship Department of Surgery Assistant Dean of Assessment and Evaluation Johns Hopkins University School of Medicine Program Director, General Surgery and Surgical Critical Care Co-Director, Surgical Intensive Care Units Baltimore, Maryland Ischemic Colitis Post-Intensive Care Syndrome Anna Liveris, MD Assistant Professor Division of Trauma and Critical Care Services Jacobi Medical Center Albert Einstein College of Medicine New York, New York Management of Lower Gastrointestinal Bleeding David H. Livingston, MD Wesley J. Howe Professor Chief of Trauma and Surgical Critical Care Department of Surgery Rutgers New Jersey Medical School Newark, New Jersey Management of Intraabdominal Infections

xvii

Laurie Anne Loiacono, MD Associate, Critical Care Medicine Geisinger Clinics Wilkes-Barre, Pennsylvania Electrical and Lightning Injury Joseph V. Lombardi, MD Professor and Chief Vascular Surgery Cooper University Hospital Camden, New Jersey Endovascular Management of Vascular Injuries Gregory K. Low, MD Assistant Professor Department of Surgery University of Tennessee Medical Center Knoxville, Tennessee Management of Rectal Cancer Lea Lowenfeld, MD Assistant Professor Department of Surgery NewYork-Presbyterian Hospital/Weill Cornell Medical Center New York, New York Use of Strictureplasty in Crohn’s Disease Charles E. Lucas, MD Professor The Michael and Marian Ilitch Department of Surgery Wayne State University Surgeon Detroit Receiving Hospital Detroit, Michigan Penetrating Neck Trauma Blunt Cardiac Injury Extremity Compartment Syndrome Ying Wei Lum, MD, MPH Associate Professor Division of Vascular Surgery and Endovascular Therapy Johns Hopkins Hospital Baltimore, Maryland Management of Recurrent Carotid Artery Stenosis Juliet Siena Lumati, MD, MPH Complex Surgical Oncology Fellow Division of Surgical Oncology Johns Hopkins University School of Medicine Baltimore, Maryland Familial Gastric Cancer Management of Peritoneal Surface Malignancies Gray R. Lyons, MD, PhD Assistant Professor Interventional Radiology Johns Hopkins School of Medicine Baltimore, Maryland Acute Peripheral Arterial and Bypass Graft Occlusion: Thrombolysis and Thrombectomy

xviii

CONTRIBUTORS

Thomas E. MacGillivray, MD Chief of Cardiac Surgery and Thoracic Transplant Surgery Jimmy Howell Endowed Chair of Cardiac Surgery Department of Cardiovascular Surgery Houston Methodist Houston, Texas Management of Acute Aortic Dissections Thomas H. Magnuson, MD Associate Professor Department of Surgery Johns Hopkins University School of Medicine Chair, Surgeon in Chief Johns Hopkins Bayview Medical Center Baltimore, Maryland Metabolic Changes Following Bariatric Surgery Elaa Mahdi, MD, MPH General Surgery Resident Pediatric Surgery University of Rochester Rochester, New York Appendicitis: Diagnosis and Management Martin A. Makary, MD, MPH Professor of Surgery and Health Policy and Management Chief, Johns Hopkins Islet Transplantation Center Director, Minimally Invasive Pancreas Surgery Johns Hopkins Hospital Baltimore, Maryland Management of Chronic Pancreatitis Total Pancreatectomy and Islet Autotransplantation for Chronic Pancreatitis Mahmoud B. Malas, MD, MHS, RPVI, FACS Professor and Chief Division of Vascular and Endovascular Surgery Vice Chair of Surgery for Research UC San Diego La Jolla, California; Professor of Epidemiology Johns Hopkins Bloomberg School of Public Health Baltimore, Maryland Aortoiliac Occlusive Disease William C. Mallon, MD Assistant Professor Department of Radiology University of Southern California Los Angeles, California Role of Stereotactic Biopsy in Management of Breast Disease

Michele Ann Manahan, MD, MBA, FACS Professor of Clinical Plastic and Reconstructive Surgery Department of Plastic and Reconstructive Surgery Johns Hopkins Hospital Baltimore, Maryland Breast Implant-Associated Anaplastic Large Cell Lymphoma Paul N. Manson, MD Distinguished Service Professor Plastic Surgery Johns Hopkins University Baltimore, Maryland Nonmelanoma Skin Cancers Management of Cutaneous Melanoma M. Ashraf Mansour, MD, MBA Professor and Chief Cardiovascular Medicine Michigan State University College of Human Medicine Chief of Vascular Surgery Cardiovascular Health Spectrum Health Medical Group Grand Rapids, Michigan Gangrene of the Foot Nathalie Mantilla, MD Colon and Rectal Surgeon Division of Colon and Rectal Surgery John H. Stroger Jr. Hospital of Cook County Assistant Professor Department of Surgery Rush University Chicago, Illinois Surgical Management of Constipation Mariuxi C. Manukyan, MD, FACS Assistant Professor Department of Trauma Acute Care Surgery and Surgical Critical Care Johns Hopkins Hospital Baltimore, Maryland Ventilator-Associated Pneumonia James F. Markmann, MD, PhD Chief, Division of Transplant Surgery Department of Surgery Massachusetts General Hospital Claude E. Welch Professor of Surgery Harvard Medical School Boston, Massachusetts Transplantation of the Pancreas Christopher A. Maroun, MD Resident Physician Department of Otolaryngology Johns Hopkins Hospital Baltimore, Maryland Management of Solitary Neck Mass

Matthew J. Martin, MD Director of Trauma Research Division of Trauma and Acute Care Surgery Los Angeles County, USC Medical Center Los Angeles, California; Professor Department of Surgery Uniformed Services University of the Health Sciences Bethesda, Maryland Management of Traumatic Brain Injury Niels D. Martin, MD Section Chief of Surgical Critical Care Department of Surgery University of Pennsylvania Philadelphia, Pennsylvania Acute Kidney Injury in the Injured and Critically Ill Michael Martyak, MD, MS Assistant Professor Department of Surgery Eastern Virginia Medical School Norfolk, Virginia Blunt Abdominal Trauma Regina Matar, MD Research Fellow Breast Service, Department of Surgery Memorial Sloan Kettering Cancer Center New York, New York Breast Cancer: Surgical Therapy Douglas J. Mathisen, MD Thoracic Surgeon Department of Surgery Massachusetts General Hospital Boston, Massachusetts Management of Tracheal Stenosis Aarti Mathur, MD, PhD, FACS Associate Professor Departments of Surgery and Oncology Section of Endocrine Surgery Johns Hopkins University School of Medicine Baltimore, Maryland Adrenal Incidentaloma Kazuhide Matsushima, MD, FACS Assistant Professor Department of Surgery University of Southern California Los Angeles, California Management of Diaphragmatic Injuries J. Greg Mawn, MD Orthopedic Surgeon Johns Hopkins Medical Institutions Baltimore, Maryland Early Management of Pelvic Ring Disruption

C ontributors

Mary C. McCarthy, MD Professor Department of Surgery Wright State University School of Medicine Dayton, Ohio Management of Pulmonary Parenchymal Injury Patrick M. McCarthy, MD General Surgery Resident Brooke Army Medical Center San Antonio, Texas Management of Traumatic Brain Injury Katherine McDermott, MD General Surgery Resident Johns Hopkins School of Medicine Baltimore, Maryland Incisional, Epigastric, and Umbilical Hernias David W. McFadden, MD, MBA Murray-Heilig Chairman and Professor Department of Surgery University of Connecticut Farmington, Connecticut Management of Zollinger-Ellison Syndrome Sean P. McGuire, MD General Surgery Resident Indiana University Indianapolis, Indiana Management of Cystic Disorders of the Bile Ducts Christopher R. McHenry, MD, FACS Vice Chair, Department of Surgery Metro Health Medical Center Professor Department of Surgery Case Western Reserve University School of Medicine Cleveland, Ohio Management of Thyroiditis Erin E. McIntosh, MD Resident Physician Department of Surgery St. Elizabeth’s Medical Center Boston, Massachusetts Open Repair of Abdominal Aortic Aneurysms Genevieve B. Melton-Meaux, MD, PhD Professor Department of Surgery University of Minnesota Minneapolis, Minnesota Management of Colorectal Polyps Avedis Meneshian, MD Assistant Professor Department of Surgery Johns Hopkins University School of Medicine Baltimore, Maryland, Thoracic Surgeon Anne Arundel Medical Center Annapolis, Maryland Management of Primary Chest Wall Tumors

xix

Raman Menon, MD Colon and Rectal Surgery Swedish Medical Center Seattle, Washington Anal Condyloma

Peter Muscarella II, MD Gastrointestinal Surgery Niagara Falls Memorial Medical Center Niagara Falls, New York Management of Lower Gastrointestinal Bleeding

Thomas S. Metkus Jr., MD, PhD Assistant Professor Departments of Surgery and Medicine Johns Hopkins University Baltimore, Maryland Cardiovascular Pharmacology

Matthew Mutch, MD Chief, Section of Colon and Rectal Surgery Associate Professor Department of Surgery Washington University in St. Louis St. Louis, Missouri Management of Rectal Cancer

Fabrizio Michelassi, MD Lewis Atterbury Stimson Professor and Chairman Department of Surgery Weill Cornell Medical College Surgeon-in-Chief NewYork-Presbyterian Hospital/Weill Cornell Medical Center New York, New York Use of Strictureplasty in Crohn’s Disease Shruti Mony, MBBS Department of Gastroenterology and Hepatology Johns Hopkins University Baltimore, Maryland Enteral Stents in the Treatment of Colonic Obstruction Katherine A. Morgan, MD, FACS Professor and Chief Division of Gastrointestinal and Laparoscopic Surgery Medical University of South Carolina Charleston, South Carolina Gallstone Pancreatitis Ryan B. Morgan, MD Department of Surgery University of Chicago Chicago, Illinois Management of Acute Necrotizing Pancreatitis Carol D. Morris, MD, MS Division Chief, Orthopaedic Oncology Vice Chair, Clinical Operations Department of Orthopaedic Surgery Johns Hopkins Medicine Baltimore, Maryland Management of Soft Tissue Sarcomas Christopher R. Morse, MD Assistant Professor Thoracic Surgery Massachusetts General Hospital Harvard University Boston, Massachusetts Management of Acquired Esophageal Respiratory Tract Fistula Ashok Muniappan, MD Thoracic Surgeon Department of Surgery Massachusetts General Hospital Boston, Massachusetts Management of Tracheal Stenosis

Juan A. Muñoz-Largacha, MD Cardiothoracic Surgery Fellow Division of Cardiothoracic Surgery University of Alabama at Birmingham Birmingham, Alabama Management of Esophageal Perforation Arthur J. Nam, MD, MS Associate Professor Plastic and Reconstructive Surgery R Adams Cowley Shock Trauma Center Baltimore, Maryland Necrotizing Skin and Soft Tissue Infections Amol Kumar Narang, MD Assistant Professor Department of Radiation Oncology and Molecular Sciences Johns Hopkins University School of Medicine Baltimore, Maryland Intraoperative Radiation for Pancreatic Cancer Isam W. Nasr, MD Assistant Professor Department of Surgery Johns Hopkins University Baltimore, Maryland Repair of Pectus Excavatum James T. Nawalaniec, MD General Surgery Resident Massachusetts General Hospital Boston, Massachusetts Management of Acquired Esophageal Respiratory Tract Fistula Matthew A. Nehs, MD Assistant Professor Department of Surgery Brigham and Women’s Hospital Harvard Medical School Boston, Massachusetts Nontoxic Goiter Adam Nelson, MD Assistant Professor Department of Surgery University of Arizona Tucson, Arizona Use of Resuscitative Endovascular Balloon Occlusion of the Aorta in Resuscitation of the Trauma Patient

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CONTRIBUTORS

Brenda S. Nettles, DNP, MS, ACNP-BC, CNE Assistant Professor School of Nursing Acute Care Nurse Practitioner Division of Surgical Oncology Johns Hopkins Hospital Baltimore, Maryland Surgical Palliative Care Lisa Ann Newman, MD, MPH Professor, Department of Surgery NewYork-Presbyterian Hospital/Weill Cornell Medical Center Chief, Division of Breast Surgery Director, NewYork-Presbyterian Hospital Network Interdisciplinary Breast Program Medical Director and Founder International Center for the Study of Breast Cancer Subtypes Weill Cornell Medicine New York, New York Surgical Management of the Axilla Nariman Nezami, MD Associate Professor Division of Vascular and Interventional Radiology Department of Diagnostic Radiology and Nuclear Medicine University of Maryland School of Medicine Associate Professor Experimental Therapeutics Program University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center Baltimore, Maryland Transarterial Therapies for Primary and Metastatic Liver Tumors Dennis C. Nguyen, MD Assistant Professor Plastic and Reconstructive Surgery Washington University School of Medicine St. Louis, Missouri Evaluation and Management of the Patient with Craniomaxillofacial Trauma Hien T. Nguyen, MD, MBA Director of the Comprehensive Hernia Center Associate Professor Department of Surgery Johns Hopkins Medical Institutions Baltimore, Maryland Incisional, Epigastric, and Umbilical Hernias Jake A. Nicholson, DO Resident Physician Vascular Surgery Spectrum Health Michigan State University Grand Rapids, Michigan Gangrene of the Foot

Wasay Nizam, MBBS Research Associate Department of Surgery Johns Hopkins Medical Institutions Baltimore, Maryland Esophageal Function Tests Mediastinal Masses Yuri W. Novitsky, MD Director, Columbia Comprehensive Hernia Center Columbia University Medical Center Professor, Department of Surgery Columbia College of Physicians and Surgeons Chief, Division of Abdominal Wall Surgery Columbia University School of Medicine New York, New York Abdominal Wall Reconstruction Brant K. Oelschlager, MD Professor, Byers Endowed Chair in Esophageal Research Department of Surgery University of Washington Division of General Surgery University of Washington Medical Center Seattle, Washington Surgical Management of Gastroesophageal Reflux Disease Endoscopic Treatment of Barrett’s Esophagus Jennifer B. Ogilvie, MD Section Chief, Endocrine Surgery Yale School of Medicine New Haven, Connecticut Management of Adrenal Cortical Tumors John A. Olson Jr., MD, PhD William K. Bixby Professor and Chair Department of Surgery Washington University School of Medicine Surgeon-in-Chief Barnes-Jewish Hospital St. Louis, Missouri Surgical Management of Thyroid Cancer Kristofor A. Olson, MD, PhD Administrative Chief Resident Surgery and Perioperative Care The University of Texas at Austin Dell Medical School Austin, Texas Acute Mesenteric Ischemia Charles S. O’Mara, MD, MBA Professor Emeritus Department of Surgery University of Mississippi Medical Center Jackson, Mississippi Balloon Angioplasty and Stents in Carotid Artery Occlusive Disease

Tawakalitu O. Oseni, MD, MPH Assistant Professor Department of Surgery Massachusetts General Hospital Boston, Massachusetts Benign Breast Disease Greg M. Osgood, MD Associate Professor Chief, Orthopedic Trauma Department of Orthopedic Surgery Johns Hopkins University School of Medicine Baltimore, Maryland Early Management of Pelvic Ring Disruption Luis Ostrosky-Zeichner, MD, FACP, FIDSA, FSHEA, FECMM Professor and Division Chief Division of Infectious Diseases University of Texas Health Science Center at Houston Medical Director for Epidemiology Memorial Hermann Texas Medical Center Houston, Texas Antifungal Therapy in the Surgical Patient Shane Ottmann, MD Transplant Surgeon Department of Surgery Johns Hopkins Hospital Baltimore, Maryland Hepatic Malignancy: Resection Versus Transplantation Theodore N. Pappas, MD Professor Department of Surgery Duke University Durham, North Carolina Management of Asymptomatic (Silent) Gallstones Charudutt Paranjape, MD, FACS Assistant Professor Department of Surgery Harvard Medical School Trauma Emergency and Critical Care Surgeon Massachusetts General Hospital Boston, Massachusetts; Chief, General Surgery and Acute Care Surgery Mass General Brigham Newton-Wellesley Hospital Newton, Massachusetts Management of Small Bowel Obstruction

C ontributors

Adrian E. Park, MD, FRCSC Chair and Surgeon in Chief Department of Surgery Luninis Health Annapolis, Maryland; Professor Department of Surgery Johns Hopkins University School of Medicine Baltimore, Maryland Splenectomy for Hematologic Disorders Pauline K. Park, MD Professor Division of Acute Care Surgery University of Michigan Ann Arbor, Michigan Postoperative Respiratory Failure

Walter Pegoli Jr., MD Professor of Surgery and Pediatrics University of Rochester Rochester, New York Appendicitis: Diagnosis and Management Bruce A. Perler, MD, MBA Julius H. Jacobson II Professor Vice Chair for Clinical Operations Chief Emeritus, Division of Vascular Surgery and Endovascular Therapy Johns Hopkins University School of Medicine Baltimore, Maryland; Vice President American Board of Surgery Philadelphia, Pennsylvania Carotid Endarterectomy

Jessica M. Pastoriza, MD Breast Surgical Oncology Fellow Department of Surgery Johns Hopkins Hospital Baltimore, Maryland Role of Stereotactic Biopsy in Management of Breast Disease Pregnancy and Breast Cancer Management

Nancy D. Perrier, MD, FACS Walter and Ruth Sterling Endowed Professor of Surgery Surgical Oncology MD Anderson Cancer Center Houston, Texas Persistent and Recurrent Hyperparathyroidism

Purvi P. Patel, MD Assistant Professor Department of Surgery Loyola University Medical Center Chicago, Illinois Management of Traumatic Brain Injury

Benjamin Philosophe, MD, PhD Surgical Director Comprehensive Transplant Center Johns Hopkins Medical Institutions Baltimore, Maryland Liver Transplantation

Shirali T. Patel, MD, FACS Chief of General Surgery St. Agnes Baltimore, Maryland Management of Common Bile Duct Stones

Henry A. Pitt, MD Distinguished Professor Department of Surgery Rutgers Robert Wood Johnson Medical School Chief of Oncologic Quality Rutgers Cancer Institute of New Jersey New Brunswick, New Jersey Management of Echinococcal Cyst Disease of the Liver

Marco G. Patti, MD Professor Department of Surgery University of Virginia Charlottesville, Virginia Management of Zenker’s Diverticulum Timothy M. Pawlik, MD, PhD, MPH, MTS, MBA, FACS Professor and Chair Department of Surgery Ohio State University Medical Center Urban Meyer III and Shelley Meyer Chair for Cancer Research Wexner Medical Center at Ohio State University Columbus, Ohio Management of Colorectal Liver Metastases Gregory J. Pearl, MD, FACS Chair, Department of Vascular Surgery Baylor Scott & White Heart and Vascular Hospital Chief, Division of Vascular Surgery Baylor University Medical Center Clinical Professor Texas A&M Health Sciences Center Dallas, Texas Brachiocephalic Reconstruction

Jennifer K. Plichta, MD, MS Associate Professor Department of Surgery Duke University Medical Center Durham, North Carolina Inflammatory Breast Cancer Dina Podolsky, MD Assistant Professor Department of Surgery Columbia University Medical Center New York, New York Abdominal Wall Reconstruction Amani D. Politano, MD, MS Assistant Professor Vascular Surgery Oregon Health & Science University Portland, Oregon Pseudoaneurysms and Arteriovenous Fistulas

Elisa Port, MD, FACS Chief, Breast Surgery Mount Sinai Health System Professor Icahn School of Medicine at Mount Sinai New York, New York Genetic Counseling and Testing Carolyn R. Postol, DO Resident Physician Vascular Surgery Spectrum Health Michigan State University Grand Rapids, Michigan Lower Extremity Amputation Ajita S. Prabhu, MD Associate Professor Department of Surgery Cleveland Clinic Cleveland, Ohio Management of Spigelian, Obturator, and Lumbar Hernias Joshua E. Preiss, MD Fellow Cardiothoracic Surgery University of Washington Seattle, Washington Primary Tumors of the Thymus Jason D. Prescott, MD, PhD Associate Professor Department of Surgery NYU Grossman School of Medicine New York, New York Primary Hyperparathyroidism Leigh Ann Price, MD Director, Department of Surgery National Burn Reconstruction Center Assistant Professor Plastic and Reconstructive Surgery Johns Hopkins University School of Medicine Baltimore, Maryland Electrical and Lightning Injury Matthew D. Price, MD General Surgery Fellow Johns Hopkins University School of Medicine Baltimore, Maryland Management of Pruritus Ani Management of Chronic Pancreatitis Scott G. Prushik, MD Vascular Surgeon Division of Vascular and Endovascular Surgery St. Elizabeth’s Medical Center Brighton, Massachusetts Endovascular Treatment of Abdominal Aortic Aneurysm

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CONTRIBUTORS

Carla M. Pugh, MD, PhD Thomas Krummel Professor Department of Surgery Stanford University School of Medicine Stanford, California Loss of Domain in Abdominal Wall Reconstruction T. Robert Qaqish, MD Clinical Assistant Professor Thoracic Surgery University at Buffalo Buffalo, New York Achalasia of the Esophagus Zaffer Qasim, MBBS, FRCEM, EDIC Assistant Professor of Emergency Medicine and Critical Care University of Pennsylvania Perelman School of Medicine Philadelphia, Pennsylvania Prehospital Management of the Trauma Patient Jacob A. Quick, MD Associate Professor Department of Surgery University of Missouri Columbia, Missouri Abdomen That Will Not Close Amanda Radisic, MD General Surgery Resident Robert Wood Johnson University Hospital New Brunswick, New Jersey Injuries to Small and Large Bowel Shannon N. Radomski, MD Resident Department of Surgery Johns Hopkins School of Medicine Baltimore, Maryland Management of Rectal Prolapse Todd E. Rasmussen, MD Professor and Vice-Chair for Education Department of Surgery Vascular Surgeon Mayo Clinic Rochester, Minnesota Management of Vascular Injuries Abhinav V. Reddy, MD Resident Physician Radiation Oncology Johns Hopkins University School of Medicine Baltimore, Maryland Intraoperative Radiation for Pancreatic Cancer Christopher R. Reed, MD Resident Physician Department of Surgery Duke University Medical Center Durham, North Carolina Management of Asymptomatic (Silent) Gallstones

Christina Maria Regelsberger-Alvarez, DO Clinical Assistant Professor Trauma and Surgical Critical Care Brody School of Medicine East Carolina University Greenville, North Carolina Postoperative Respiratory Failure Thomas Reifsnyder, MD Johns Hopkins Bayview Medical Center Department of Surgery Johns Hopkins University Baltimore, Maryland Hemodialysis Access Surgery Linda M. Reilly, MD Professor Vascular Surgery UC San Francisco San Francisco, California Chronic Mesenteric Ischemia Taylor S. Riall, MD, PhD Professor Department of Surgery Associate Director, Oncology Services University of Arizona Cancer Center University of Arizona Tucson, Arizona Pancreatic Neuroendocrine Tumors of the Pancreas Excluding Gastrinoma John Peter Ricci, MD, FACS Assistant Professor Department of Surgery Zucker School of Medicine at Hofstra/ Northwell Hempstead, New York; Chief, Colon and Rectal Surgery Long Island Jewish Medical Center New Hyde Park, New York Management of Crohn’s Disease of the Small Bowel Anamaria J. Robles, MD Assistant Professor Department of Surgery UC Davis Sacramento, California Catheter Sepsis in the Intensive Care Unit Douglas Rodgers, MD Resident Vascular Surgery University of Cincinnati Medical Center Cincinnati, Ohio Atherosclerotic Renal Artery Stenosis Alexandra B. Roginsky, MD, FACS Assistant Professor Department of Surgery Johns Hopkins University School of Medicine Baltimore, Maryland Multiple Organ Dysfunction and Failure

Yesenia Rojas-Khalil, MD, FACS Assistant Professor Department of Surgery Baylor College of Medicine Houston, Texas Management of Large Bowel Obstruction Rae S. Rokosh, MD General Surgery Resident NYU Langone Health New York, New York Popliteal and Femoral Artery Aneurysm Riccardo Rosati, MD, FACS Professor Gastrointestinal Surgery San Raffaele Hospital Milan, Italy Management of Zenker’s Diverticulum J. Bart Rose, MD, MAS, FACS Assistant Professor Department of Surgery University of Alabama Birmingham Birmingham, Alabama Management of Biliary Dyskinesia Laura H. Rosenberger, MD, MS Associate Professor Department of Surgery Duke University Durham, North Carolina Inflammatory Breast Cancer Robert C. Ross, MD Fellow in Surgical Metabolism and Metabolic Surgery Department of Metabolic Surgery Pennington Biomedical Research Center Baton Rouge, Louisiana Cardiovascular Disease Risk Reduction After Bariatric Surgery Gedge D. Rosson, MD Associate Professor Department of Plastic and Reconstructive Surgery Johns Hopkins University School of Medicine Baltimore, Maryland Nerve Injury and Repair Breast Reconstruction Following Mastectomy: Considerations, Techniques, and Outcomes, Part I Rishi A. Roy, MD Partner and Founder Advanced Vascular and Vein Associates Jackson, Mississippi Balloon Angioplasty and Stents in Carotid Artery Occlusive Disease Grace S. Rozycki, MD, MBA Professor Department of Surgery Johns Hopkins School of Medicine Baltimore, Maryland Surgeon’s Use of Ultrasound in the Trauma and Critical Care Settings

C ontributors

Colleen M. Ryan, MD Professor of Surgery Massachusetts General Hospital Harvard Medical School Staff Surgeon Shriners Hospitals for Children-Boston Boston, Massachusetts Cold-Induced Injuries and Hypothermia Uma M. Sachdeva, MD, PhD Assistant in Surgery Division of Thoracic Surgery Massachusetts General Hospital Assistant Professor Harvard Medical School Boston, Massachusetts Multimodality Therapy in Esophageal Cancer Bethany C. Sacks, MD, MEd Associate Professor of Surgery Surgery Clerkship and Curriculum Director Associate Program Director Department of Surgery Washington University School of Medicine St. Louis, Missouri Management of Recurrent Inguinal Hernia Justin M. Sacks, MD, MBA, FACS Chief, Division of Plastic and Reconstructive Surgery Washington University School of Medicine St. Louis, Missouri Lymphedema Evaluation and Management of the Patient with Craniomaxillofacial Trauma Zeyad T. Sahli, MD General Surgery Resident University of Virginia Charlottesville, Virginia Surgical Management of Secondary and Tertiary Hyperparathyroidism Joseph V. Sakran, MD, MPH, MPA Associate Professor of Surgery and Nursing Vice Chair of Clinical Operations Department of Surgery Johns Hopkins Hospital Baltimore, Maryland; Senior Fellow Satcher Health Leadership Institute Morehouse School of Medicine Atlanta, Georgia Injuries to Small and Large Bowel David Sanders, MD, FRCPC Gastroenterology Kelowna General Hospital Kelowna, British Columbia, Canada Pancreatic Ductal Disruptions Leading to Pancreatic Fistula, Pancreatic Ascites, or Pancreatic Pleural Effusion

Michael G. Sarr, MD James C. Masson Emeritus Professor of Surgery Department of Surgery Mayo Clinic Rochester, Minnesota Diagnosis and Management of Motility Disorders of the Stomach and Small Bowel in the Current Era Robert G. Sawyer, MD Professor and Chair of Surgery Homer Stryker MD School of Medicine Adjunct Professor of Engineering and Applied Sciences Western Michigan University Kalamazoo, Michigan; Adjunct Professor Department of Surgery University of Virginia Charlottesville, Virginia Surgical Site Infections Samer Sbayi, MD, MBA, FACS Assistant Professor Department of Surgery Stony Brook University Stony Brook, New York Athletic Pubalgia Thomas M. Scalea, MD, FACS Francis X. Kelly Professor of Trauma Surgery Director of Program in Trauma Physician-in-Chief University of Maryland School of Medicine R Adams Cowley Shock Trauma Center Baltimore, Maryland Airway Management in the Trauma Patient Philip R. Schauer, MD Professor Bariatric and Metabolic Institute Cleveland Clinic Cleveland, Ohio Cardiovascular Disease Risk Reduction After Bariatric Surgery Katharina M. Scheurlen, MD, PhD Price Institute of Surgical Research Fellow Department of Surgery University of Louisville Louisville, Kentucky Management of Diverticular Disease of the Colon Dennis K. Schimpf, MD, MBA, FACS Owner Sweetgrass Plastic Surgery Charleston, South Carolina Breast Reconstruction Following Mastectomy: Considerations, Techniques, and Outcomes, Part 2

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Todd R. Schlachter, MD Assistant Professor Department of Radiology and Biomedical Imaging Yale School of Medicine New Haven, Connecticut Vena Cava Filters Sally Schonefeld, MD Vascular Fellow Department of Surgery Cedars-Sinai Medical Center Los Angeles, California Takayasu’s Arteritis Andrew Schulick, MD, MBA, FACS Division of Vascular Surgery and Endovascular Therapy Department of Surgery Johns Hopkins School of Medicine Baltimore, Maryland; Chief of Vascular Surgery Suburban Hospital Bethesda, Maryland Treatment of Varicose Veins Richard D. Schulick, MD, MBA, FACS Professor and Chair Department of Surgery University of Colorado School of Medicine Director, University of Colorado Cancer Center University of Colorado School of Medicine Aurora, Colorado Management of Benign Liver Tumors Michael A. Schweitzer, MD Associate Professor Department of Surgery Johns Hopkins University Baltimore, Maryland Management of Morbid Obesity Metabolic Changes Following Bariatric Surgery Naomi M. Sell, MD, MHS Chief Resident Physician Department of Surgery Massachusetts General Hospital Boston, Massachusetts Ablation of Colorectal Carcinoma Liver Metastases Anthony J. Senagore, MD, MS, MBA Chief Medical Officer PolyPid Inc. Summit, New Jersey Management of Large Bowel Obstruction Aamir S. Shah, MD Associate Professor Cardiothoracic and Vascular Surgery Cedars-Sinai Medical Center Los Angeles, California Takayasu’s Arteritis

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CONTRIBUTORS

Adil A. Shah, MD Fellow Department of General and Thoracic Surgery Children’s National Medical Center Washington, DC Injured Spleen Brian D. Shames, MD Chief, Division of General Surgery General Surgery Residency Program Director University of Connecticut Health Center Program Director General Surgery Residency University of Connecticut School of Medicine Farmington, Connecticut Management of Zollinger-Ellison Syndrome Ashwyn K. Sharma, MD Resident Physician Department of Surgery UC San Diego San Diego, California Proper Use of Cholecystostomy Tubes Robert Sheridan, MD Medical Director, Burn Service Shriners Hospital for Children Professor, Department of Surgery Harvard Medical School Boston, Massachusetts Medical Management of the Burn Patient Aditya S. Shirali, MD Surgical Endocrinology Fellow University of Texas MD Anderson Cancer Center Houston, Texas Persistent and Recurrent Hyperparathyroidism Artem Shmelev, MD Clinical Fellow Department of Surgery Columbia University Medical Center New York, New York Management of Common Bile Duct Stones Shmuel Shoham, MD Professor Department of Medicine Johns Hopkins University School of Medicine Baltimore, Maryland Epidemiology, Prevention, and Management of Occupational Exposure to Bloodborne Infections Jaimie T. Shores, MD Clinical Director of Hand and Upper Extremity Transplantation Assistant Professor Plastic and Reconstructive Surgery Johns Hopkins University School of Medicine Baltimore, Maryland Surgical Infections of The Hand

Jason K. Sicklick, MD, FACS Professor Departments of Surgery and Pharmacology Division of Surgical Oncology University of California San Diego Moores Cancer Center University of California San Diego Health San Diego, California Proper Use of Cholecystostomy Tubes Frederick Sieber, MD Professor Anesthesiology and Critical Care Medicine Johns Hopkins Medical Institutions Baltimore, Maryland Management of Postoperative Delirium Justin M. Simmons, DO, RPVI Vascular Surgeon Division of Vascular Surgery Spectrum Health Medical Group Clinical Instructor Department of Surgery Michigan State University College of Human Medicine Grand Rapids, Michigan Lower Extremity Amputation Sarah S. Sims, MD Endocrine Surgeon Department of Surgery Caremount Medical Poughkeepsie, New York Management of Thyroid Nodules Vikesh K. Singh, MD, MSc Professor of Medicine Division of Gastroenterology Director of Pancreatology Johns Hopkins University School of Medicine Director of Endoscopy Johns Hopkins Hospital Baltimore, Maryland Management of Hepatic Encephalopathy Obstructive Jaundice: The Role of Endoscopic Intervention Matthew R. Smeds, MD Professor Department of Surgery Division of Vascular and Endovascular Surgery Saint Louis University St. Louis, Missouri Management of Infected Grafts John Nikolhaus Smith, MD Chief Fellow Department of Cardiology Johns Hopkins Hospital Baltimore, Maryland Cardiovascular Pharmacology

Thomas J. Smith, MD, FACP Director of Palliative Medicine Johns Hopkins University Medical Institutions Professor of Oncology and Palliative Medicine Sidney Kimmel Comprehensive Cancer Center Johns Hopkins Baltimore, Maryland Surgical Palliative Care Thomas W. Smith Jr., MD, MS Professor Department of Pathology UMass Chan Medical School Worcester, Massachusetts Contralateral Prophylactic Mastectomy Anthony Sorrentino, MD General Surgery Resident NYU Langone New York, New York Surgical Management of Gallbladder Cancer Julie Ann Sosa, MD, MA Leon Goldman MD Distinguished Professor and Chair Department of Surgery Affiliated Faculty Philip R. Lee Institute for Health Policy Studies UC San Francisco San Francisco, California Management of Hyperthyroidism Konstantinos Spaniolas, MD, FACS, FASMBS Professor Department of Surgery Stony Brook University Stony Brook, New York Athletic Pubalgia Jason Sperry, MD, MPH Andrew B. Peitzman Professor of Surgery Section Chief, Trauma and General Surgery University of Pittsburgh Pittsburgh, Pennsylvania Nutrition Therapy in the Critically Ill Surgical Patient Scott R. Steele, MD, MBA Chairman, Department of Colorectal Surgery Cleveland Clinic Professor Cleveland Clinic Lerner College of Medicine of Case Western Reserve University Cleveland, Ohio Management of Pilonidal Disease Jonathan M. Stem, MD Assistant Professor Department of Surgery University of North Carolina School of Medicine Chapel Hill, North Carolina Management of Colonic Volvulus

C ontributors

Jane Stevens, MD, MSN House Officer General Surgery Oregon Health & Science University Portland, Oregon Fluid and Electrolyte Therapy Kent Allen Stevens, MD, MPH Associate Professor Department of Surgery Chief, Division of Acute Care Surgery Trauma Medical Director Director, Johns Hopkins Global Surgery Initiative Johns Hopkins Medical Institutions Baltimore, Maryland Tenets of Damage Control David P. Stonko, MD, MS Resident Physician in Surgery Johns Hopkins Hospital Baltimore, Maryland Management of Ruptured Abdominal Aortic Aneurysms Michael B. Streiff, MD Professor of Medicine Department of Medicine (Hematology) Johns Hopkins Medical Institutions Baltimore, Maryland Coagulation Issues and the Trauma Patient Sarah Stringfield, MD Assistant Professor Department of Surgery Texas A&M School of Medicine Colorectal Surgeon Department of Surgery Baylor University Medical Center Dallas, Texas Surgical Management of Fecal Incontinence David S. Strosberg, MD Assistant Professor Department of Surgery (Vascular) Yale University New Haven, Connecticut Raynaud’s Phenomenon Amanda Su, MD Clinical Fellow Gastroenterology and Hepatology Johns Hopkins Hospital Baltimore, Maryland Management of Hepatic Encephalopathy Madhu Subramanian, MD Assistant Professor Johns Hopkins University School of Medicine Baltimore, Maryland Pancreatic and Duodenal Injuries

Visakha Suresh, MD Resident Physician Department of Plastic and Reconstructive Surgery Johns Hopkins School of Medicine Baltimore, Maryland Surgical Infections of The Hand Srinivas M. Susarla, DMD, MD, MPH, FACS, FAAP Associate Professor Oral and Maxillofacial Surgery University of Washington School of Dentistry Associate Professor Surgery (Plastic) University of Washington School of Medicine Seattle, Washington Evaluation and Management of the Patient with Craniomaxillofacial Trauma Whitney Sutton, MD General Surgery Resident MedStar Georgetown University Hospital Washington, DC Adrenal Incidentaloma Lee L. Swanstrom, MD Professor Institute for Image Guided Surgery IHU Strasbourg Strasbourg, Alsace, France; Professor Department of Surgery Oregon Health & Science University Portland, Oregon Management of Disorders of Esophageal Motility Mark A.Talamini, MD Chair, Department of Surgery Chief, Surgical Services Stony Brook Medicine Stony Brook, New York Management of Crohn’s Disease of the Small Bowel Vernissia Tam, MD, MS General Surgery Resident University of Pittsburgh Pittsburgh, Pennsylvania Management of Fissure-In-Ano Nicola Tamburini, MD Department of Surgery Sant’Anna University Hospital Ferrara, Italy Management of Cysts, Tumors, and Abscesses of the Spleen Li Ting Tan, MBBS General Surgery Resident Johns Hopkins University School of Medicine Baltimore, Maryland Ventilator-Associated Pneumonia

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Kenneth K.Tanabe, MD Professor Department of Surgery Harvard Medical School Co-Chief, Division of Gastrointestinal and Oncologic Surgery Department of Surgery Massachusetts General Hospital Boston, Massachusetts Ablation of Colorectal Carcinoma Liver Metastases Rebecca Tang, MD General Surgery Resident Massachusetts General Hospital Boston, Massachusetts Management of Acute Cholangitis Julia Tchou, MD, PhD, FACS Director, Breast Surgery Research, Director, Breast Surgery Fellowship Professor of Clinical Surgery University of Pennsylvania Philadelphia, Pennsylvania Advances in Neoadjuvant and Adjuvant Therapy for Early-Stage Breast Cancer Pedro G.Teixeira, MD Associate Professor Division Chief, Vascular Surgery Surgery and Perioperative Care University of Texas at Austin Austin, Texas Acute Mesenteric Ischemia Jeffrey Thiboutot, MD Assistant Professor Pulmonary and Critical Care Medicine Johns Hopkins University Baltimore, Maryland Tracheostomy Jon S.Thompson, MD Professor Department of Surgery University of Nebraska Medical Center Omaha, Nebraska Management of Short Bowel Syndrome Lucas W.Thornblade, MD, MPH Assistant Professor of Clinical Surgery Division of Surgical Oncology UC San Francisco–East Bay Highland Hospital Oakland, California Cystic Disease of The Liver Amy J.Thorsen, MD Clinical Associate Professor Department of Surgery University of Minnesota Minneapolis, Minnesota Management of Anorectal Abscess and Fistula

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CONTRIBUTORS

Crisanto M.Torres, MD Assistant Professor of Surgery BU School of Medicine Trauma and Acute Care Surgeon Intensivist Boston Medical Center Boston, Massachusetts Injuries to Small and Large Bowel Abdominal Compartment Syndrome and Management of the Open Abdomen Susan Tsai, MD, MHS Professor of Surgical Oncology Department of Surgery Medical College of Wisconsin Milwaukee, Wisconsin Management of Periampullary Cancers Palliative Interventions for Patients with Operable and Advanced Pancreatic and Periampullary Cancer Yvonne Tsitsiou, MBBS, BSc (Hon) Department of Radiology Division of Vascular and Interventional Radiology Johns Hopkins University School of Medicine Baltimore, Maryland Charing Cross Hospital Imperial NHS Healthcare Trust Imperial College London London, United Kingdom Transjugular Intrahepatic Portosystemic Shunt Transhepatic Interventions for Obstructive Jaundice Eric Tsung, MD Acute Care Surgeon Trauma, Critical Care Acute Care Surgery, Burns Yale–New Haven Health Bridgeport Hospital Bridgeport, Connecticut Antibiotics in Surgical Critical Care Anthony Tufaro, MD, DDS, FACS Professor and Interim Chief Department of Surgery Division of Plastic Surgery and Surgical Oncology Case Western Reserve University Cleveland, Ohio Nonmelanoma Skin Cancers Management of Cutaneous Melanoma

Brooks V. Udelsman, MD, MHS Cardiothoracic Fellow Department of Surgery Yale–New Haven Hospital New Haven, Connecticut Multimodality Therapy in Esophageal Cancer Marissa Vane, MD, MSc Department of Surgery Maastricht UMC+ Maastricht, Limburg, Netherlands Ablative Techniques in the Treatment of Benign and Malignant Breast Disease George Velmahos, MD, PhD John F. Burke Professor of Surgery Harvard Medical School Division Chief of Trauma, Emergency Surgery, and Surgical Critical Care Massachusetts General Hospital Boston, Massachusetts Management of Small Bowel Obstruction Jack P. Vernamonti, MD Surgical Research Fellow Pediatric Surgery University of Michigan Ann Arbor, Michigan Postoperative Respiratory Failure Charles M.Vollmer Jr., MD Professor, Chief of Gastrointestinal Surgery Department of Surgery University of Pennsylvania Philadelphia, Pennsylvania Management of Complications after the Whipple Procedure Halley Vora, MD Department of Surgical Oncology Loma Linda University Loma Linda, California Benign Breast Disease Peter S.Vosler, MD, PhD, FACS Assistant Professor Department of Otolaryngology-Head and Neck Surgery Johns Hopkins University Baltimore, Maryland Management of Solitary Neck Mass

Kiara A.Tulla, MD Abdominal Transplant Fellow Department of Surgery Johns Hopkins Medicine Baltimore, Maryland Liver Transplantation

Christi M. Walsh, MSN, CRNP Department of Surgery Johns Hopkins Hospital Management of Chronic Pancreatitis Total Pancreatectomy and Islet Autotransplantation for Chronic Pancreatitis

Kelly H.Tunder, DO Complex Abdominal Wall Surgeon Department of Surgery St. Luke’s Medical Center Advocate Aurora, Milwaukee, Wisconsin Abdominal Wall Reconstruction

Xuanji Wang, MD, MS General Surgery Resident Loyola University Medical Center Maywood, Illinois Inflammatory Breast Cancer

Andrew L. Warshaw, MD, FACS, FRCSEd (Hon), MAMSE Emeritus Surgeon-in-Chief Massachusetts General Hospital W. Gerald Austen Distinguished Professor of Surgery Harvard Medical School Physician Director Network Development and Integration Mass General Brigham Boston, Massachusetts Diagnosis and Management of Autoimmune Pancreatitis Philip J. Wasicek, MD Resident Department of Plastic Surgery University of Pittsburgh Pittsburgh, Pennsylvania Necrotizing Skin and Soft Tissue Infections Sharon R. Weeks, MD Abdominal Transplant Surgeon Department of Surgery Johns Hopkins School of Medicine Baltimore, Maryland Hepatic Malignancy: Resection Versus Transplantation Roi Weiser, MD Breast Surgical Oncology Fellow Department of Surgery University of Texas Medical Branch Galveston, Texas International Surgical Oncology Fellow Department of Surgical Oncology University of Texas MD Anderson Cancer Center Houston, Texas Lymphatic Mapping and Sentinel Lymphadenectomy Clifford R. Weiss, MD Professor of Radiology Radiologic Science and Biomedical Engineering Department of Radiology/Division of Interventional Radiology Johns Hopkins University School of Medicine Medical Director of Johns Hopkins Center for Bioengineering Innovation and Design Department of Biomedical Engineering Johns Hopkins University School of Medicine and the Whiting School of Medicine Baltimore, Maryland Transarterial Therapies for Primary and Metastatic Liver Tumors Eric G. Weiss, MD Chief Academic Officer Education Center, Chairman Regional Education Institute Cleveland Clinic Florida Weston, Florida Rectovaginal Fistula

C ontributors

Matthew J. Weiss, MD, MBA Deputy Physician-in-Chief Director of Surgical Oncology Northwell Health Cancer Institute Lake Success, New York Management of Malignant Liver Tumors Ethel D. Weld, MD, PhD Assistant Professor of Medicine Infectious Diseases Clinical Pharmacology Johns Hopkins University School of Medicine Baltimore, Maryland Epidemiology, Prevention, and Management of Occupational Exposure to Bloodborne Infections Jennine H. Weller, MD, PhD General Surgery Resident Johns Hopkins Hospital Baltimore, Maryland Repair of Pectus Excavatum Adam S. Weltz, MD, FACS Attending Surgeon Associate Professor Department of Surgery Anne Arundel Medical Center Annapolis, Maryland Splenectomy for Hematologic Disorders Russel N. Wesson, MBChB Assistant Professor Division of Transplantation Johns Hopkins Hospital Baltimore, Maryland Portal Hypertension: Role of Shunting Procedures Steven D. Wexner, MD, PhD (Hon), FACS, FRCS(Eng), FRCS(Ed), FRCSI(Hon), Hon FRCS(Glasg) Director, Digestive Disease Center Chair, Department of Colorectal Surgery Cleveland Clinic Florida Weston, Florida; Clinical Affiliate Professor Division of Surgery Charles E. Schmidt College of Medicine Florida Atlantic University Boca Raton, Florida; Clinical Professor Herbert Wertheim College of Medicine Florida International University Miami, Florida Management of Clostridioides Difficile Colitis Glenn J.R. Whitman, MD Professor Division of Cardiac Surgery Johns Hopkins School of Medicine Co-Director, CVSICU Johns Hopkins Hospital Director, Cardiac Surgery Quality and Safety Johns Hopkins Health System Baltimore, Maryland Cardiovascular Pharmacology

David R. Whittaker, MD, FACS, RPVI Associate Professor Vascular and Endovascular Surgery Johns Hopkins University School of Medicine Bethesda, Maryland Treatment of Varicose Veins Elizabeth C. Wick, MD Professor Division of General Surgery UC San Francisco San Francisco, California Management of Chronic Ulcerative Colitis Fatima G. Wilder, MD, MS Cardiothoracic Surgery Fellow General Surgeon Johns Hopkins University School of Medicine Baltimore, Maryland Management of Esophageal Cancer Extracorporeal Membrane Oxygenation for Respiratory Failure Austin D. Williams, MD, MSEd Assistant Professor Department of Surgical Oncology Fox Chase Cancer Center Philadelphia, Pennsylvania Management of Male Breast Cancer Timothy K. Williams, MD Associate Professor Vascular and Endovascular Surgery Wake Forest Baptist Health Winston-Salem, North Carolina Thoracic Outlet Syndrome James E. Wiseman, MD, MBA Department of Surgery University of Arizona College of Medicine Tucson, Arizona Management of Inguinal Hernia Michael W. Witthaus, MD Reconstructive Urology Fellow UC San Diego San Diego, California Renal and Ureteral Traumatic Injuries Aric Wogsland, MD Fellow Vascular Surgery and Endovascular Therapy University Hospitals Cleveland Medical Center Case Wester Reserve University Cleveland, Ohio Upper Extremity Arterial Occlusive Disease Christopher L. Wolfgang, MD, PhD Chief, Hepatobiliary and Pancreatic Surgery NYU Grossman School of Medicine NYU Langone Health System New York, New York Surgical Management of Gallbladder Cancer

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Daniel J. Wong, MD, MHS General Surgery Resident Beth Israel Deaconess Medical Center Boston, Massachusetts Popliteal and Femoral Artery Aneurysm Virginia L. Wong, MD, FACS Associate Professor Vascular Surgery University Hospitals Cleveland Medical Center Case Western Reserve University Cleveland, Ohio Management of Aneurysms of the Extracranial Carotid and Vertebral Arteries Upper Extremity Arterial Occlusive Disease Douglas E. Wood, MD, FACS, FRCSEd The Henry N. Harkins Professor and Chair Department of Surgery University of Washington Seattle, Washington Primary Tumors of the Thymus Cameron D. Wright, MD Professor Department of Surgery Massachusetts General Hospital Harvard Medical School Boston, Massachusetts Management of Spontaneous and Secondary Pneumothorax Clement Wu, MBBS, MRCP, MMed, MCI Consultant Gastroenterologist Department of Gastroenterology and Hepatology Singapore General Hospital Singapore Enteral Stents in the Treatment of Colonic Obstruction Lawrence W. Wu, MD Resident Department of Medicine Johns Hopkins Hospital Baltimore, Maryland Neoadjuvant and Adjuvant Therapy for Pancreatic Cancer Stephen C.Yang, MD Professor of Surgery and Oncology The Arthur B. and Patricia B. Modell Endowed Chair in Thoracic Surgery Department of Surgery Division of Thoracic Surgery Johns Hopkins Medical Institutions Baltimore, Maryland Management of Esophageal Cancer Linda Ye, MD Resident Physician Department of Surgery David Geffen School of Medicine at University of California Los Angeles Los Angeles, California Management of Pancreatic Necrosis

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CONTRIBUTORS

Heather L.Yeo, MD, MHS Assistant Professor Department of Surgery NewYork-Presbyterian/Weill Cornell Medical Center Associate Professor of Population Health Sciences Healthcare Policy and Research Weill Cornell Medical Center New York, New York Management of Fissure-In-Ano Stephanie Young, MD, MPH Complex General Surgical Oncology Fellow Department of Surgical Oncology John Wayne Cancer Institute Santa Monica, California Management of Periampullary Cancers Victor M. Zaydfudim, MD, MPH Associate Professor Section of Hepatobiliary and Pancreatic Surgery Division of Surgical Oncology University of Virginia Charlottesville, Virginia Management of Liver Hemangioma

Martha A. Zeiger, MD Professor and Chair Department of Surgery University of Virginia School of Medicine Charlottesville, Virginia Surgical Management of Secondary and Tertiary Hyperparathyroidism Michael E. Zenilman, MD Professor Department of Surgery Weill Cornell Medicine Chief, Department of Surgery New York Methodist Hospital New York, New York A Practical Approach to Surgery in the Frail Elderly Jay Zhu, MD Assistant Professor of Surgery University of New Mexico School of Medicine Albuquerque, New Mexico Surgical Management of Gastroesophageal Reflux Disease

Maaz K. Zuberi, MD Chief Resident Department of General Surgery Howard University College of Medicine Washington DC Injured Spleen Nicholas J. Zyromski, MD Professor Department of Surgery Indiana University School of Medicine Indianapolis, Indiana Management of Cystic Disorders of the Bile Ducts

Preface The first edition of Current Surgical Therapy was published in 1984. The textbook has thus been in existence for almost 40 years, and this is the fourteenth edition. In each edition, we have updated the material to reflect the continuing evolution of the field of general surgery. The textbook continues to be perhaps the most popular surgical book in the field, and as long as it fulfills a need, we plan to continue the publication every 3 years. It has been a special privilege and honor for the two editors to be able to review contributions from surgeons around the country and, indeed, from around the world, on what they believe is the current surgical therapy for essentially all common general surgical topics. It is an enjoyable task and keeps two surgeons who care for surgical patients current on all general surgical topics. As with prior editions, nearly every chapter has been written by a new author. All authors have contributed their specific and personal thoughts on the current surgical therapy of the disease about which they are experts. Therefore, to obtain a broad view of the topic, the reader may want to review the contributions of the other experts in the past two or three editions of Current Surgical Therapy. As with the past editions, disease presentation, pathophysiology, and diagnosis are discussed only briefly, with the emphasis on current surgical therapy. When an operative procedure is discussed, an effort has been made to include brief and concise descriptions with figures and diagrams when possible. Current Surgical Therapy is written for surgical residents, fellows, and fully trained surgeons in private practice or in an academic setting. Many have told us that it is an excellent textbook to review before taking the general surgical

boards or recertifying. Medical students have also given us feedback that they believe the text is of value to them. However, Current Surgical Therapy is not written principally for medical students. We believe a more classic surgical textbook with substantial sections on disease presentation, diagnosis, and pathophysiology is more appropriate for medical students. We remain grateful to the many surgeons throughout the country, as well as to the international surgeons, who participated in creating this textbook. Most of the potential authors whom we solicit respond enthusiastically to the opportunity to present their expert views. Their efforts obviously are what make this textbook a success. In addition, we could not have compiled this textbook without the herculean efforts of Ms. Irma Silkworth, who has been involved with virtually all of these editions. Ms. Katie DeFrancesco at Elsevier has also has been a terrific help and stands out in the publishing industry. Both editors continue to enjoy and thrive in our chosen profession of general surgery. In recruiting medical students into our specialty over the past 40 years, we have used the statement, “If you pick a profession you love, you never have to work the rest of your life.” In our view, that profession is surgery. Finally, we would like to dedicate this edition, as with the others, to the surgical house staff and fellows at Johns Hopkins Hospital, who are “the best of best.” Andrew M. Cameron, MD John L. Cameron, MD

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Contents The American Board of Surgery Certifying (Oral) Examination The American Board of Surgery Certifying (Oral) Examination  1 Jo Buyske, MD, and Daniel L. Dent, MD

Stomach Benign Gastric Ulcer   81 Daniel T. Dempsey, MD, MBA

Management of Duodenal Ulcers   86 Daniel T. Dempsey, MD

Esophagus Esophageal Function Tests   3 Wasay Nizam, MBBS, Hamza Khan, MD, and Malcolm V. Brock, MD

Surgical Management of Gastroesophageal Reflux Disease  7 Jay Zhu, MD, and Brant K. Oelschlager, MD

New Approaches to Gastroesophageal Reflux Disease (LINX)  14 Tom R. DeMeester, MD

Management of Barrett’s Esophagus   19 Stephen R. Broderick, MD, MPHS

Endoscopic Treatment of Barrett’s Esophagus   24 Anne P. Ehlers, MD, MPH, and Brant K. Oelschlager, MD

Management of Paraesophageal Hernia Repair   29 Richard J. Battafarano, MD, PhD

Management of Zollinger-Ellison Syndrome   92 David W. McFadden, MD, MBA, and Brian D. Shames, MD

Management of Mallory-Weiss Syndrome   98 Michael G. House, MD

Management of Gastric Adenocarcinoma   100 Alex B. Blair, MD, and Mark D. Duncan, MD

Familial Gastric Cancer   107 Hamza Khan, MD, Juliet Siena Lumati, MD, and Fabian M. Johnston, MD

Management of Gastrointestinal Stromal Tumors   111 Laurence P. Diggs, MD, and Miral Sadaria Grandhi, MD

Gastrointestinal Tubes for Feeding and Decompression  119 Lawrence B. Brown, MD, MPH, MHS, and Susan L. Gearhart, MD

Management of Morbid Obesity   123 Michael A. Schweitzer, MD, and Vivek Kumbhari, MD

Management of Zenker’s Diverticulum   34 Fernando A.M. Herbella, MD, Riccardo Rosati, MD, and Marco G. Patti, MD

Achalasia of the Esophagus   39 T. Robert Qaqish, MD, and Mark Katlic, MD

Management of Disorders of Esophageal Motility   45 Melissa Louise DeSouza, MD, and Lee L. Swanstrom, MD

Management of Esophageal Cancer   54 Fatima G. Wilder, MD, and Stephen C. Yang, MD

Multimodality Therapy in Esophageal Cancer   59 Brooks V. Udelsman, MD, MHS, and Uma M. Sachdeva, MD, PhD

Use of Esophageal Stents   65 Matthew D. Grunwald, MD, Anthony N. Kalloo, MD, and Dmitriy O. Khodorskiy, MD

Management of Esophageal Perforation   74 Juan A. Muñoz-Largacha, MD, and James M. Donahue, MD

Small Bowel Management of Small Bowel Obstruction   129 Charudutt Paranjape, MD, and George Velmahos, MD

Management of Crohn’s Disease of the Small Bowel   134 John Peter Ricci, MD, and Mark A. Talamini, MD

Use of Strictureplasty in Crohn’s Disease   138 Lea Lowenfeld, MD, and Fabrizio Michelassi, MD

Management of Small Bowel Tumors   144 Ramy El-Diwany, MD, PhD, and John W. Harmon, MD

Small Bowel Diverticulosis   149 Jonathan B. Greer, MD

Diagnosis and Management of Motility Disorders of the Stomach and Small Bowel in the Current Era   152 Omar M. Ghanem, MD, and Michael G. Sarr, MD

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CONTENTS

Management of Short Bowel Syndrome   161 Jon S. Thompson, MD

Management of Enterocutaneous Fistulas   166 Grace C. Lee, MD, and Richard A. Hodin, MD

Management of Radiation-Induced Injury to the Small and Large Bowel   171 Sophia Y. Chen, MD, MPH, and Chady Atallah, MD

Neoadjuvant and Adjuvant Therapy for Colorectal Cancer   259 Yilin (Linda) Cao, MD, and Nilofer Azad, MD

Management of Colorectal Polyps   263 Gifty Kwakye, MD, MPH, and Genevieve B. Melton, MD, PhD

Management of Peritoneal Surface Malignancies   267 Fabian M. Johnston, MD, and Juliet Siena Lumati, MD

Management of Lower Gastrointestinal Bleeding   274 Anna Liveris, MD, and Peter Muscarella II, MD

Large Bowel Preoperative Bowel Preparation: Is It Necessary?   177

Appendicitis: Diagnosis and Management   281 Elaa Mahdi, MD, MPH, and Walter Pegoli Jr., MD

Anna Chudnovets, MD, and Sandy Hwang Fang, MD

Management of Diverticular Disease of the Colon   181 Katharina M. Scheurlen, MD, and Susan Galandiuk, MD

Management of Chronic Ulcerative Colitis   186 Kirkpatrick Beekman Fergus, MD, Michael G. Kattah, MD, PhD, and Elizabeth C. Wick, MD

Management of Toxic Megacolon   190 Jonathan E. Efron, MD

Surgical Management of Crohn’s Colitis   194 Hanjoo Lee, MD, Alessandro Fichera, MD, and James W. Fleshman Jr., MD

Ischemic Colitis  200 Ranim Alsaad, MD, and Pamela A. Lipsett, MD, MHPE

Management of Clostridioides Difficile Colitis   204 Marylise Boutros, MD, Maria Abou Khalil, MD, and Steven D. Wexner, MD, PhD (Hon)

Management of Large Bowel Obstruction   209 Anthony J. Senagore, MD, MS, MBA, and Yesenia Rojas-Khalil, MD

Enteral Stents in the Treatment of Colonic Obstruction  215 Shruti Mony, MBBS, Clement Wu, MBBS, and Mouen Khashab, MD

Management of Acute Colonic Pseudo-Obstruction (Ogilvie’s Syndrome)  226 Marshall S. Bedine, MD

Management of Colonic Volvulus   229 Jose G. Guillem, MD, and Jonathan M. Stem, MD

Management of Rectal Prolapse   232 Shannon N. Radomski, MD, and Alodia Gabre-Kidan, MD, MPH

Surgical Management of Constipation   236 Nathalie Mantilla, MD, and Jose R. Cintron, MD

Surgical Management of the Polyposis Syndromes   244 Scott R. Kelley, MD, and Sacha P. Broccard, MD

Surgical Management of Colon Cancer   251 Mohamad A. Abdulhai, MD, and Michael A. Choti, MD

PET Scanning in the Management of Colorectal Cancer   255 Joy Zhou Done, MD, and Sandy H. Fang, MD

Anorectal Management of Hemorrhoids   287 Ariane M. Abcarian, MD, and Herand Abcarian, MD

Management of Fissure-In-Ano   295 Vernissia Tam, MD, MS, and Heather L. Yeo, MD, MHS

Management of Anorectal Abscess and Fistula   298 Amy J. Thorsen, MD

Anal Stenosis  307 Chassidy Grimes, MD, and Dana Hayden, MD

Management of Pruritus Ani   311 Matthew D. Price, MD, and Chady Atallah, MD

Surgical Management of Fecal Incontinence   313 Sarah Stringfield, MD, and Alessandro Fichera, MD

Rectovaginal Fistula  319 Eric G. Weiss, MD, and Emanuela Silva Alvarenga, MD

Anal Condyloma  327 Edward P. Hagen, DO, and Raman Menon, MD

Management of Pilonidal Disease   331 Rebecca L. Gunter, MD, MS, Eric K. Johnson, MD, and Scott R. Steele, MD

Pneumatosis Intestinalis and the Importance for the Surgeon  337 Joseph Kim, MD, Ahmed Chatila, MD, Muhammad Hammami, MD, and Eric Goldberg, MD

Management of Rectal Cancer   340 Gregory K. Low, MD, and Matthew Mutch, MD

Management of Tumors of the Anal Region   346 Emilie C. Barnes, MD, and Jose G. Guillem, MD

Liver Cystic Disease of the Liver   351 Lucas W. Thornblade, MD, MPH, and Yuman Fong, MD

Management of Echinococcal Cyst Disease of the Liver   355 Miral Sadaria Grandhi, MD, and Henry A. Pitt, MD

CONTENTS

Management of Liver Hemangioma   363 Victor M. Zaydfudim, MD, MPH, and Reid B. Adams, MD

Management of Benign Liver Tumors   368 Richard D. Schulick, MD, MBA, and Ana Gleisner, MD, PhD

Management of Malignant Liver Tumors   375 Danielle K. DePeralta, MD, and Matthew J. Weiss, MD, MBA

Hepatic Malignancy: Resection Versus Transplantation   380 Sharon R. Weeks, MD, and Shane E. Ottmann, MD

Management of Colorectal Liver Metastases   384 Jordan M. Cloyd, MD, and Timothy M. Pawlik, MD, MPH, PhD

Ablation of Colorectal Carcinoma Liver Metastases   391 Naomi M. Sell, MD, MHS, Zhi Ven Fong, MD, PhD, and Kenneth K. Tanabe, MD

Management of Hepatic Abscess   396 Daniel L. Eisenson, MD, and Jonathan B. Greer, MD

Transarterial Therapies for Primary and Metastatic Liver Tumors  401 Nariman Nezami, MD, and Clifford R. Weiss, MD

xxxiii

Management of Common Bile Duct Stones   476 Artem Shmelev, MD, Shirali T. Patel, MD, and Steven C. Cunningham, MD

Management of Acute Cholangitis   481 Rebecca Tang, MD, Erica Barnett, BA, and David Berger, MD

Management of Benign Biliary Strictures   486 Heather A. Lillemoe, MD, and Keith D. Lillemoe, MD

Management of Cystic Disorders of the Bile Ducts   491 Sean P. McGuire, MD, and Nicholas J. Zyromski, MD

Management of Primary Sclerosing Cholangitis   497 Gillian M. Ahrendt, MD, and Steven A. Ahrendt, MD

Management of Intrahepatic, Perihilar, and Distal Extrahepatic Cholangiocarcinoma  501 Mohammad Al Efishat, MD, and William Reece Burns, MD

Biomarker Guided Surgical Management of Hepatobiliary and Pancreatic Tumors   509 Mahip Grewal, BA, Joseph R. Habib, MD, and Ammar A. Javed, MD

Surgical Management of Gallbladder Cancer   516 Anthony Sorrentino, MD, and Christopher L. Wolfgang, MD, PhD

Management of Gallstone Ileus   521

Portal Hypertension Portal Hypertension: Role of Shunting Procedures   413 Eliza J. Lee, MD, and Russel N. Wesson, MBChB

Liver Transplantation  417 Benjamin Philosophe, MD, PhD, and Kiara A. Tulla, MD

Endoscopic Therapy for Esophageal Variceal Hemorrhage   427

Morgan Bonds, MD, and Barish H. Edil, MD

Transhepatic Interventions for Obstructive Jaundice   523 Andrew R. Kolarich, MD, Yvonne Tsitsiou, MBBS, and Christos Georgiades, MD, PhD

Obstructive Jaundice: The Role of Endoscopic Intervention  532 Sameer Khan, MD, and Vikesh K. Singh, MD, MSc

Julie A. Conyers, MD

Transjugular Intrahepatic Portosystemic Shunt   434 Andrew R. Kolarich, MD, Yvonne Tsitsiou, MBBS, and Christos Georgiades, MD, PhD

Management of Refractory Ascites   442 Justin Brilliant, MD, and James P. Hamilton, MD

Management of Hepatic Encephalopathy   447 Amanda Su, MD, Venkata S. Akshintala, MD, and Vikesh K. Singh, MD, MSc

Management of Budd-Chiari Syndrome   451 Joseph DiNorcia, MD, and Ronald W. Busuttil, MD, PhD

Pancreas Management of Acute Necrotizing Pancreatitis   539 Ryan B. Morgan, MD, and John C. Alverdy, MD

Gallstone Pancreatitis  546 Katherine A. Morgan, MD, and William P. Lancaster, MD

Pancreas Divisum and Other Variants of Dominant Dorsal Duct Anatomy  549 David B. Adams, MD, and Gregory A. Coté, MD, MS

Diagnosis and Management of Autoimmune Pancreatitis   556

Gallbladder and Biliary Tree Management of Asymptomatic (Silent) Gallstones   457 Theodore N. Pappas, MD, and Christopher R. Reed, MD

Management of Biliary Dyskinesia   460 J. Bart Rose, MD

Management of Acute Cholecystitis   462 Ryan C. Broderick, MD, and Bryan M. Clary, MD

Proper Use of Cholecystotomy Tubes   467 Ashwyn K. Sharma, MD, and Jason K. Sicklick, MD

Zhi Ven Fong, MD, MPH, and Andrew L. Warshaw, MD

Management of Pancreatic Necrosis   561 Linda Ye, MD, and O. Joe Hines, MD

Management of Pancreatic Pseudocyst   568 Ammar A. Javed, MD, and Kelly J. Lafaro, MD, MPH

Pancreatic Ductal Disruptions Leading to Pancreatic Fistula, Pancreatic Ascites, or Pancreatic Pleural Effusion   574 David Sanders, MD, Shivanand Bomman, MD, and Richard Kozarek, MD

Management of Chronic Pancreatitis   582 Matthew D. Price, MD, Christi M. Walsh, MSN, CRNP, and Martin A. Makary, MD, MPH

xxxiv

CONTENTS

Genetic Testing and High-Risk Pancreatic Cancer Screening  587 Daniel J. Delitto, MD, PhD, and Kevin E. Behrns, MD

Management of Periampullary Cancers   589 Stephanie Young, MD, MPH, and Susan Tsai, MD, MHS

Management of Complications after the Whipple Procedure  599 Fabio Casciani, MD, and Charles M. Vollmer Jr., MD

Vascular Reconstruction During the Whipple Operation  606 Benedict Kinny-Köster, MD, and Jin He, MD, PhD

Palliative Interventions for Patients with Operable and Advanced Pancreatic and Periampullary Cancer   609

Incisional, Epigastric, and Umbilical Hernias   671 Hien T. Nguyen, MD, MBA, and Katherine McDermott, MD

Management of Spigelian, Obturator, and Lumbar Hernias   678 Ajita S. Prabhu, MD

Athletic Pubalgia  686 Samer Sbayi, MD, MBA, and Konstantinos Spaniolas, MD

Abdominal Wall Reconstruction   693 Dina Podolsky, MD, Kelly H. Tunder, DO, and Yuri W. Novitsky, MD

Loss of Domain in Abdominal Wall Reconstruction    702 Yewande Alimi, MD, David Hindin, MD, and Carla M. Pugh, MD, PhD

Use of Various Meshes in Hernia Repair   708 Adrienne N. Christopher, MD, and John P. Fischer, MD, MPH

Ashley Krepline, MD, Susan Tsai, MD, MHS, and Douglas B. Evans, MD

Neoadjuvant and Adjuvant Therapy for Pancreatic Cancer  615 Lawrence W. Wu, MD, and Daniel A. Laheru, MD

Rare and Unusual Pancreatic Tumors   620 Jon M. Harrison, MD, and Carlos Fernandez-del Castillo, MD

Intraductal Papillary Mucinous Neoplasms of the Pancreas  627 Gabriel D. Ivey, MD, and Richard A. Burkhart, MD

Pancreatic Neuroendocrine Tumors of the Pancreas Excluding Gastrinoma  632 Mohammad R. Khreiss, MD, and Taylor S. Riall, MD, PhD

Intraoperative Radiation for Pancreatic Cancer   638 Amol Kumar Narang, MD, Joseph M. Herman, MD, MSc, MSHCM, and Abhinav V. Reddy, MD

Transplantation of the Pancreas   641 Niraj M. Desai, MD, and James F. Markmann, MD, PhD

Total Pancreatectomy and Islet Autotransplantation for Chronic Pancreatitis  646 Isabel S. Dennahy, MD, Christi Walsh, MSN, CRNP, and Martin A. Makary, MD, MPH

Breast Benign Breast Disease   717 Halley Vora, MD, and Tawakalitu O. Oseni, MD

Screening for Breast Cancer   720 Julie R. Lange, MD, ScM

Role of Stereotactic Biopsy in Management of Breast Disease  724 Jessica M. Pastoriza, MD, William C. Mallon, MD, and Lisa K. Jacobs, MD, MSPH

Molecular Targets in Breast Cancer   728 Reva K. Basho, MD, and Armando E. Giuliano, MD

Breast Cancer: Surgical Therapy   733 Regina Matar, MD, and Mary L. Gemignani, MD, MPH

Pregnancy and Breast Cancer Management   740 Jessica M. Pastoriza, MD, Ranim Alsaad, MD, and David M. Euhus, MD

Ablative Techniques in the Treatment of Benign and Malignant Breast Disease   746 Marissa Vane, MD, MSc, and Armando E. Giuliano, MD, FACS, FRCSEd

Lymphatic Mapping and Sentinel Lymphadenectomy   749 Roi Weiser, MD, and V. Suzanne Klimberg, MD, PhD, MSHCT

Spleen Splenectomy for Hematologic Disorders   651 Adam S. Weltz, MD, and Adrian E. Park, MD

Management of Cysts, Tumors, and Abscesses of the Spleen  656 P. Marco Fisichella, MD, Nicola Tamburini, MD, and Ciro Andolfi, MD

Surgical Management of the Axilla   756 Genevieve Fasano, MD, Solange Bayard, MD, and Lisa Ann Newman, MD, MPH

Inflammatory Breast Cancer   762 Jennifer K. Plichta, MD, MS, Xuanji Wang, MD, MS, and Laura H. Rosenberger, MD, MS

Ductal and Lobular Carcinoma in situ of the Breast   768 Lauren M. DeStefano, MD, and Kristine E. Calhoun, MD

Hernia Management of Inguinal Hernia   663 James E. Wiseman, MD, MBA, and Gina L. Adrales, MD, MPH

Management of Recurrent Inguinal Hernia   668 Britta Jean Han, MD, MS, and Bethany C. Sacks, MD, MEd

Advances in Neoadjuvant and Adjuvant Therapy for EarlyStage Breast Cancer   770 Julia Tchou, MD, PhD, and Seye Adekeye, MD, PhD

Treatment Trends in Locally Recurrent and Metastatic Breast Cancer  773 Joy Zhou Done, MD, Pathik Aravind, MD, and Mehran Habibi, MD

CONTENTS

Management of Male Breast Cancer   779 Austin D. Williams, MD, MSEd, Kaitlyn Kennard, MD, and Ned Z. Carp, MD

xxxv

Cardiovascular Disease Risk Reduction After Bariatric Surgery  884 Robert C. Ross, MD, Vance L. Albaugh, MD, PhD, and Philip R. Schauer, MD

A Surgeon’s Practical Guide to Breast Imaging   782 Michael D. Grant, MD, and Ronald C. Jones, MD

Genetic Counseling and Testing   786 Katherine deAngeli, MD, and Elisa Port, MD

Contralateral Prophylactic Mastectomy   787 Thomas W. Smith Jr., MD, MS, and Swati A. Kulkarni, MD

Margins: How to and How Big?   791 Patricia A. Cronin, MD, and Richard J. Gray, MD

Breast Reconstruction Following Mastectomy: Considerations, Techniques, and Outcomes, Part 1   795 Salih Colakoglu, MD, and Gedge Rosson, MD

Breast Reconstruction Following Mastectomy: Considerations, Techniques, and Outcomes, Part 2   800 Mark S. Burke, MD, and Dennis K. Schimpf, MD

Breast Implant-Associated Anaplastic Large Cell Lymphoma   805 Melissa S. Camp, MD, and Michele Ann Manahan, MD, MBA

Skin and Soft Tissue Nonmelanoma Skin Cancers   895 Nicholas Calotta, MD, Paul N. Manson, MD, and Anthony Tufaro, MD, DDS

Management of Cutaneous Melanoma   903 Nicholas Calotta, MD, Paul N. Manson, MD, and Anthony Tufaro, MD, DDS

Management of Soft Tissue Sarcomas   912 Adam S. Levin, MD, and Carol D. Morris, MD, MS

Management of Solitary Neck Mass   924 Christopher A. Maroun, MD, and Peter S. Vosler, MD, PhD

Surgical Infections of the Hand   931 Visakha Suresh, MD, and Jaimie T. Shores, MD

Nerve Injury and Repair   937 Christopher Frost, MD, and Gedge D. Rosson, MD

Necrotizing Skin and Soft Tissue Infections   946

Endocrine Glands Adrenal Incidentaloma  809 Whitney Sutton, MD, MHS, Shkala Karzai, MD, and Aarti Mathur, MD, PhD

Management of Adrenal Cortical Tumors   815 Mark A. Eckardt, MD, Jennifer B. Ogilvie, MD, and Nita Ahuja, MD, MBA

Management of Pheochromocytoma   824 Wilson M. Alobuia, MD, MS, and Electron Kebebew, MD

Management of Thyroid Nodules   834 Quan-Yang Duh, MD, and Sarah S. Sims, MD

Nontoxic Goiter  837 Matthew A. Nehs, MD, and Gerard M. Doherty, MD

Management of Thyroiditis   841 Christopher R. McHenry, MD

Management of Hyperthyroidism   846 Jina Kim, MD, and Julie Ann Sosa, MD, MA

Surgical Management of Thyroid Cancer   853 Yinin Hu, MD, and John A. Olson Jr., MD, PhD

Primary Hyperparathyroidism  860 Shkala Karzai, MD, and Jason D. Prescott, MD, PhD

Persistent and Recurrent Hyperparathyroidism   867

Philip J. Wasicek, MD, and Arthur J. Nam, MD, MS

Chest Wall, Mediastinum, and Trachea Management of Spontaneous and Secondary Pneumothorax  951 Cameron D. Wright, MD

Management of Primary Chest Wall Tumors   955 Whitney A. Davidson, MD, Lauren Antognoli, MD, and Avedis Meneshian, MD

Mediastinal Masses  961 Hamza Khan, MD, Wasay Nizam, MBBS, and Malcolm V. Brock, MD

Primary Tumors of the Thymus   971 Joshua E. Preiss, MD, and Douglas E. Wood, MD, FRCSEd

Management of Tracheal Stenosis   975 Andrea L. Axtell, MD, MPH, Douglas J. Mathisen, MD, and Ashok Muniappan, MD

Management of Acquired Esophageal Respiratory Tract Fistula  982 James T. Nawalaniec, MD, and Christopher R. Morse, MD

Repair of Pectus Excavatum   987 Jennine H. Weller, MD, PhD, and Isam W. Nasr, MD

Aditya S. Shirali, MD, and Nancy D. Perrier, MD

Surgical Management of Secondary and Tertiary Hyperparathyroidism  873 Zeyad T. Sahli, MD, and Martha A. Zeiger, MD

Metabolic Changes Following Bariatric Surgery   879 Patrick Crosby, MD, Thomas H. Magnuson, MD, and Michael A. Schweitzer, MD

Vascular Surgery Open Repair of Abdominal Aortic Aneurysms   993 Erin E. McIntosh, MD, and Richard P. Cambria, MD

Endovascular Treatment of Abdominal Aortic Aneurysms   998 Richard P. Cambria, MD, and Scott G. Prushik, MD

xxxvi

CONTENTS

Management of Ruptured Abdominal Aortic Aneurysms  1004 David P. Stonko, MD, MS, and Caitlin W. Hicks, MD, MS

Management of Abdominal Aortic Aneurysm with Concomitant Nonvascular Abdominal Pathology   1009 James K. Elsey, MD

Management of Thoracic and Thoracoabdominal Aortic Aneurysms  1012 Yasaman Kavousi, MD, and James H. Black III, MD

Management of Acute Aortic Dissections   1019 Karen M. Kim, MD, MS, and Thomas E. MacGillivray, MD

Carotid Endarterectomy  1025 Bruce A. Perler, MD, MBA

Management of Recurrent Carotid Artery Stenosis   1031 Sarah E. Deery, MD, MPH, and Ying Wei Lum, MD

Balloon Angioplasty and Stents in Carotid Artery Occlusive Disease  1037 Danon E. Garrido, MD, Rishi A. Roy, MD, and Charles S. O’Mara, MD, MBA

Management of Aneurysms of the Extracranial Carotid and Vertebral Arteries  1044 Virginia L. Wong, MD

Brachiocephalic Reconstruction  1049 Gregory J. Pearl, MD, and Lauren Beliveau, MD

Upper Extremity Arterial Occlusive Disease   1057 Aric Wogsland, MD, Virginia L. Wong, MD, and Vikram S. Kashyap, MD

Aortoiliac Occlusive Disease   1064 Maryam Ali Khan, MD, Claire Janssen, MD, and Mahmoud B. Malas, MD, MHS

Femoropopliteal Occlusive Disease   1075 Zachary T. AbuRahma, DO, and Ali F. AbuRahma, MD

Tibioperoneal Arterial Occlusive Disease   1083 Natalia O. Glebova, MD, PhD

Popliteal and Femoral Artery Aneurysm   1092 Rae S. Rokosh, MD, Daniel J. Wong, MD, MHS, and Elliot L. Chaikof, MD, PhD

Treatment of Claudication   1097 Qingwen Kawaji, MD, and Margaret W. Arnold, MD

Pseudoaneurysms and Arteriovenous Fistulas   1102 Amani D. Politano, MD, MS

Management of Peripheral Arterial Thromboembolism  1108 Alik Farber, MD, and Elizabeth Gherardi King, MD

Acute Peripheral Arterial and Bypass Graft Occlusion: Thrombolysis and Thrombectomy   1115 Gray R. Lyons, MD, and Robert P. Liddell, MD

Management of Infected Grafts   1119 Timothy D. Chilton, DO, and Matthew R. Smeds, MD

Atherosclerotic Renal Artery Stenosis   1126 Douglas Rodgers, MD, and Joseph S. Giglia, MD

Raynaud’s Phenomenon  1133 David S. Strosberg, MD, and Alan Dardik, MD, PhD

Thoracic Outlet Syndrome   1137 Timothy K.Williams, MD, Zachary German, BSPH, and Julie A. Freischlag, MD

Diabetic Foot  1143 Yasaman Kavousi, MD, Caitlin W. Hicks, MD, MS, and Christopher J. Abularrage, MD

Gangrene of the Foot   1148 Jake A. Nicholson, DO, and M. Ashraf Mansour, MD

Buerger’s Disease (Thromboangiitis Obliterans)   1155 Corinne Bunn, MD, MS, Pegge M. Halandras, MD, and Vivian Gahtan, MD

Takayasu’s Arteritis  1158 Sally Schonefeld, MD, NavYash Gupta, MD, Aamir Shah, MD, and Bruce L. Gewertz, MD

Acute Mesenteric Ischemia   1160 Kristofor A. Olson, MD, PhD, and Pedro G. Teixeira, MD

Chronic Mesenteric Ischemia   1167 Linda M. Reilly, MD

Hemodialysis Access Surgery   1175 Christine Haugen, MD, PhD, and Thomas Reifsnyder, MD

Venous Thromboembolism: Prevention, Diagnosis, and Treatment  1182 Jafar Haghshenas, DO, and Elliott R. Haut, MD, PhD

Vena Cava Filters   1185 Todd R. Schlachter, MD, and Adam Fish, MD

Treatment of Varicose Veins   1192 Andrew Schulick, MD, and David R. Whittaker, MD

Lymphedema  1204 Joani Christensen, MD, George Kokosis, MD, Halley Darrach, MD, and Justin M. Sacks, MD, MBA

Lower Extremity Amputation   1209 Justin M. Simmons, DO, and Carolyn R. Postol, DO

Trauma and Emergency Care Initial Assessment and Resuscitation of the Trauma Patient  1215 Jessie Ho, MD, and Hasan B. Alam, MD

Prehospital Management of the Trauma Patient   1223 Zaffer Qasim, MBBS

Use of Resuscitative Endovascular Balloon Occlusion of the Aorta in Resuscitation of the Trauma Patient   1231 Adam Nelson, MD, and Bellal Joseph, MD

Airway Management in the Trauma Patient   1236 Samuel M. Galvagno Jr., DO, PhD, and Thomas M. Scalea, MD

CONTENTS

Surgeon’s Use of Ultrasound in the Trauma and Critical Care Settings  1243 Alisa Cross, MD, and Grace F. Rozycki, MD, MBA

Emergency Department Resuscitative Thoracotomy   1252 Ryan B. Fransman, MD, and David T. Efron, MD

Management of Traumatic Brain Injury   1257 Purvi P. Patel, MD, Patrick M. McCarthy, MD, and Matthew J. Martin, MD

Chest Wall Trauma, Hemothorax, and Pneumothorax   1264 Raul Coimbra, MD, PhD, and David B. Hoyt, MD

Management of Pulmonary Parenchymal Injury   1270 Alison M. Bales, MD, and Mary C. McCarthy, MD

Blunt Abdominal Trauma   1275 L.D. Britt, MD, MPH, and Michael Martyak, MD

Penetrating Abdominal Trauma   1288 David V. Feliciano

Management of Diaphragmatic Injuries   1293 Kazuhide Matsushima, MD, and Kenji Inaba, MD

Management of Traumatic Liver Injury   1299 Elizabeth R. Benjamin, MD, PhD, and Deepika Koganti, MD

Pancreatic and Duodenal Injuries   1305 Madhu Subramanian, MD, and Elliott R. Haut, MD, PhD

Injuries to the Small and Large Bowel   1314 Crisanto M. Torres, MD, Amanda Radisic, MD, and Joseph V. Sakran, MD, MPH, MPA

Current Management of Rectal Injury   1318 Katherine Albutt, MD, MPH, and Peter J. Fagenholz, MD

Injured Spleen  1320 Adil A. Shah, MD, Maaz K. Zuberi, MD, and Edward E. Cornwell III, MD

Renal and Ureteral Traumatic Injuries   1326 Michael W. Witthaus, MD, and Jill C. Buckley, MD

Tenets of Damage Control   1335 Zachary Obinna Enumah, MD, PhD, MA, and Kent Allen Stevens, MD, MPH

Early Management of Pelvic Ring Disruption   1339 J. Greg Mawn, MD, and Greg M. Osgood, MD

Urologic Complications of Pelvic Fracture   1348 Hasan Dani, MD, and Misop Han, MD, MS

Spine and Spinal Cord Injuries   1351 Khaled M. Kebaish, MD, FRCS, and Andrew Harris, MD

Evaluation and Management of the Patient with Craniomaxillofacial Trauma  1357 Dennis C. Nguyen, MD, Srinivas M. Susarla, DMD, MD, MPH, and Justin M. Sacks, MD

Penetrating Neck Trauma   1365 Anna M. Ledgerwood, MD, and Charles E. Lucas, MD

Blunt Cardiac Injury   1370 Anna M. Ledgerwood, MD, and Charles E. Lucas, MD

xxxvii

Abdominal Compartment Syndrome and Management of the Open Abdomen   1374 Crisanto M. Torres, MD, and Alistair J. Kent, MD, MPH

Abdomen That Will Not Close   1387 Stephen L. Barnes, MD, and Jacob A. Quick, MD

Management of Vascular Injuries   1393 Ali H. Khalifeh, MD, and Todd E. Rasmussen, MD

Endovascular Management of Vascular Injuries   1405 Joseph V. Lombardi, MD, Mikael A. Fadoul, MD, and Marissa Famularo, DO

Extremity Compartment Syndrome   1411 Charles E. Lucas, MD, and Anna M. Ledgerwood, MD

Burn Wound Management   1418 Christina Lee, MD, Philip S. Barie, MD, MBA, and Abraham P. Houng, MD, MSE

Medical Management of the Burn Patient   1422 Robert Sheridan, MD, and Jeremy Goverman, MD

Cold-Induced Injuries and Hypothermia   1428 Sean Hickey, MD, and Colleen M. Ryan, MD

Electrical and Lightning Injury   1433 Leigh Ann Price, MD, and Laurie Anne Loiacono, MD

Preoperative and Postoperative Care ERAS Protocols for General Surgery   1443 Omaira Azizad, MD, and Girish P. Joshi, MBBS, MD

Fluid and Electrolyte Therapy   1449 S. James El Haddi, MD, MS, Jane Stevens, MSN, MD, and Albert Chi, MD

Common Pediatric Surgical Emergencies   1457 Mitchell R. Ladd, MD, PhD, and Shaun M. Kunisaki, MD, MSc

A Practical Approach to Surgery in the Frail Elderly  1463 Rachel G. Khadaroo, MD, PhD, FRCSC, and Michael E. Zenilman, MD

Perioperative Optimization  1468 Lee A. Goeddel, MD, MPH

Is Nasogastric Intubation Necessary After Alimentary Tract Surgery?  1472 Wali Rashad Johnson, MD, MPH, and Adrian Barbul, MD, FACS

Surgical Site Infections   1474 Raisa Gao, DO, Conor Dillon, DO, and Robert G. Sawyer, MD

Management of Intraabdominal Infections   1480 Amy V. Gore, MD, and David H. Livingston, MD

Epidemiology, Prevention, and Management of Occupational Exposure to Bloodborne Infections   1486 Ethel D. Weld, MD, PhD, and Shmuel Shoham, MD

Antifungal Therapy in the Surgical Patient   1491 Guy Handley MD, and Luis Ostrosky-Zeichner, MD

xxxviii

CONTENTS

Use of Opioids in the Postoperative Period   1501 Mohamad El Moheb, MD, and Haytham Kaafarani, MD, MPH

Management of Postoperative Delirium   1507 Amballur David John, MD, and Frederick Sieber, MD

Surgical Critical Care COVID-19 and Health Care Delivery in a Pandemic   1513 Michael S. Burnim, MD, and Brian T. Garibaldi, MD

Surgical Palliative Care   1517 Avani Amin, MD, Brenda S. Nettles, DNP, ACNP-BC, and Thomas J. Smith, MD

Cardiovascular Pharmacology  1522 John Nikolhaus Smith, MD, Thomas S. Metkus Jr., MD, PhD, and Glenn J.R. Whitman, MD

Glucose Control in the Postoperative Period   1528 Reyna Gonzalez, MD, and Krista L. Kaups, MD

Postoperative Respiratory Failure   1531 Christina Maria Regelsberger-Alvarez, DO, Jack P. Vernamonti, MD, and Pauline K. Park, MD

Ventilator-Associated Pneumonia  1537 Katherine L. Florecki, MD, MPH, Li Ting Tan, MBBS, Traci M. Grucz, PharmD, BCCP, and Mariuxi C. Manukyan, MD

Extracorporeal Membrane Oxygenation for Respiratory Failure  1541 Fatima G. Wilder, MD, MS, and Errol L. Bush, MD

Tracheostomy  1548 Jeffrey Thiboutot, MD, and David J. Feller-Kopman, MD

Acute Kidney Injury in the Injured and Critically Ill   1554 Gary A. Bass, MD, MSc, MBA, PhD, Niels D. Martin, MD, and Lewis J. Kaplan, MD

Acid-Base Disorders  1564 Zachary Obinna Enumah, MD, PhD, MA, and James E. Harris Jr., MD

Catheter Sepsis in the Intensive Care Unit   1568 Anamaria J. Robles, MD, and Christine S. Cocanour, MD

Septic Response and Management   1572 Chris Cribari, MD, and Joel Elterman, MD

Multiple Organ Dysfunction and Failure   1576 Alexandra B. Roginsky, MD

Antibiotics in Surgical Critical Care   1582 Walter Cholewczynski, MD, and Eric Tsung, MD

Endocrine Changes with Critical Illness   1592 Laura M. Adams, MD, and Jay J. Doucet, MD, MSc, FRCSC

Nutrition Therapy in the Critically Ill Surgical Patient  1597 Jason Sperry, MD

Coagulation Issues and the Trauma Patient   1604 Nadia Ijaz, MD, and Michael B. Streiff, MD

Post–Intensive Care Syndrome   1615 Pamela A. Lipsett, MD, MHPE, and Katherine L. Florecki, MD

Index  1621

Video Contents Enteral Stents in the Treatment of Colonic Obstruction Uncovered self-expandable metal stent (USEMS) in malignant colonic stricture process

Management of Spigelian, Obturator, and Lumbar Hernias Laparoscopic obturator repair Laparoscopic lumbar hernia repair Reverse transversus abdominis release (reverse TAR) Mesh fixation utilizing bone anchors

Management of Spontaneous and Secondary Pneumothorax Normal lung sliding Absence of lung sliding with no shimmering appearance of bright pleural line

Acute Mesenteric Ischemia Acute embolic mesenteric ischemia in the setting of chronic SMA atherosclerosis and IMA occlusion following open exploration, resection, and SMA endarterectomy

xxxix

The American Board of Surgery Certifying (Oral) Examination

The American Board of Surgery Certifying (Oral) Examination Jo Buyske, MD, and Daniel L. Dent, MD

PRINCIPLE The American Board of Surgery (ABS) was founded in 1937, with a mission to protect the public and enhance the profession. At the time, the standards for becoming a surgeon were vague and inconsistent. Some people did a Halstedian residency. Some apprenticed themselves to surgeons. Others did internships and then were self-taught, or they skipped formal training altogether. The public had no way to distinguish the training or skill of these practitioners. The ABS and the certification process was a way to set standards for the profession and to provide a testimonial to patients that their surgeon was qualified. Certification by the ABS is the culmination of surgical training. It is a testimonial to quality, knowledge, and judgment based on several distinct components. First, training in an Accreditation Council for Graduate Medical Education (ACGME)-accredited training program is a prerequisite for certification in nearly all cases. Second, candidates must meet the standards of training as set by the ABS, including things like passing knowledge and skills tests in laparoscopy (FLS), endoscopy (FES), trauma (ATLS), and cardiovascular events (ACLS). Candidates must meet case minimums both in the early years of training to “prepare the soil” and also during the chief year to demonstrate maturation. There are time requirements, and required observations of both clinical and operative skills. Third is a knowledge exam, the Qualifying Examination. The Qualifying or written examination is a 300-plus question, computer-based multiple choice exam designed to test foundational knowledge.1 Finally, after all of these other qualifications have been met, the Certifying, or oral examination, is a test of judgment and applied knowledge. The two tests measure different assets, and candidates’ performance is not predictable across the two exams. That is to say, doing well on one exam does not predict doing well on the other exam. They measure different attributes, and each one is important to fulfill the ABS mission of serving the public and the profession.2 The Certifying Examination consists of a series of carefully created scenarios. The scenarios are the tool that supports the examiners in their charge, which is to “evaluate a candidate’s clinical skills in organizing the diagnostic evaluation of common surgical problems and determining appropriate therapy. Emphasis is placed on candidates’ ability to use their knowledge and training to “safely, effectively and promptly manage a broad range of clinical problems.” Additionally, “Technical details of operations may also be evaluated, as well as issues related to a candidate’s ethical and humanistic qualities.”3

CONTENT The content of the Certifying Examination is generally aligned with the ABS SCORE Curriculum Outline. The majority of the exam will focus on topics that are listed among the core content of the curriculum. The remainder of the exam will be on complications of these basic scenarios or may be taken from the advanced portion of the curriculum.4 While each exam roster contains 12 cases, the content for the exam comes from 13 question-writing committees. There is some overlap of the content between committees. For example, a case of septic shock secondary to a colonic perforation from an incarcerated hernia could have been put forward as content from the colorectal, hernia, or critical care committees. Each roster of cases is reviewed for breadth of content and consistency of difficulty relative to historical performance of the individual questions so exam difficulty is consistent across all rosters. Because the candidate will also be tested as to baseline surgical knowledge on the qualifying (written) exam, it is not generally expected that the candidate will be asked to regurgitate basic surgical facts. With that said, the candidate can expect that some questions may include a list of questions asking how the candidate’s management plan might change in the face of variations of patient presentation or pathologic findings, or in the setting of intraoperative or postoperative complications. This should not necessarily be interpreted as meaning that the candidate is off track, but rather is a way of probing the candidate’s skill and judgment in managing a variety of situations.

PROCESS The Certifying Examination consists of three exam sessions that each last 30 minutes. In each session, the candidate will be presented with four case scenarios. Two examiners are used in each session to help ensure the validity of the exam. All examiners are in active practice, currently certified by the ABS, and participating in the ABS Continuous Certification Program. All of the examiners have taken the certifying exam themselves, some of them more than once. Examiners are all volunteers, and they do not receive any financial compensation for their service.5–7 The examiners will typically alternate in presenting the case information to the candidate. In presenting the case scenarios, the goal of the examiners is to provide a clear description of each case. It is the intent of the examiners to provide sufficient information at each step in the case so the candidate may make pertinent decisions on how to progress in the workup and treatment of the patient. The COVID-19 pandemic presented a new challenge for the administration of the Certifying Examination. The inability to administer the exam in person created a need to administer the exam in a virtual format. In the 2020–2021 academic year, the exam was administered with all candidates and examiners participating virtually. This necessitated some modifications to the timing of the exam, specifically that each room was given an extra 5 minutes in case of 1

2

The American Board of Surgery Certifying (Oral) Examination

technical difficulties. The time allotted to answering questions did not change; if the extra time was not needed, then there was simply a short break between sessions. The candidates found the experience to be fair and the vast majority support keeping the exam in a virtual format going forward.8

PREPARATION The ideal preparation for the Certifying Examination is to have successfully provided evidence-based care for each condition that will be covered during the exam. Surgical residency, as currently structured by the parameters of the ACGME, Residency  Review Committee (RRC), and ABS, provides strong foundation for the exam. Given the breadth of general surgery, however, it is likely that candidates will encounter scenarios they have not seen in training. Before taking the exam, candidates are encouraged to practice taking oral exams with colleagues who have successfully completed the examination process as the concise oral presentation of decision making benefits from repetition and practice. In doing so, the candidate should practice case scenarios over a wide range of pathologic conditions. Specific recommendations for preparing for the exam include the following: ■ Practice clarity of communication with regard to explaining the ■

■

■

■

decision-making process. Practice anatomic descriptions of common procedures (e.g., inguinal herniorrhaphy) as verbalizing operative anatomy can be challenging in a high-stakes setting. Recognize that the goal of the exam is to convey how one would actually safely manage a patient, not to try to guess what the examiners want to hear. Plan for management of complications and consequences of treatment decisions. For example, in appropriately selected patients with colon pathology, it may be appropriate to perform primary anastomosis. However, the candidate should also know how to handle the potential consequence of an anastomotic leak. Conversely, if the candidate initially chooses to manage the patient with a colostomy, it is reasonable to expect that the candidate can also manage ostomy ischemia and parastomal hernia. Recognize that the exam is not a multiple-choice exam and that each case discussion is an ongoing conversation. As the case evolves, the optimal management evolves with it. For example, it may be appropriate to initially manage a patient nonoperatively but then convert to operative management if the patient’s condition changes.

ASSESSMENT Examiners receive standardized training before giving an exam. This includes practice scoring, implicit bias training, and team review of the scenarios. In addition, examiners routinely get formative feedback from observers and their co-examiners. Finally, examiner scoring patterns are evaluated from a psychometric perspective, looking at patterns of consistency and severity as well as any evidence of bias.9 ■ Each examiner records a score for each case to maximize the

number of independent observations that contribute to the candidate’s total score. A total score that reflects the ability to safely care for the broad array of cases that are presented over the course of the exam is considered a passing grade. There is no preset pass or fail rate for the exam. On each scenario, candidates may be given a passing grade, a failing grade, or an equivocal grade. The equivocal grade is given when the examiners do not have enough

information to give a passing grade, such as when the candidate spends more time asking questions than answering them, or when the candidate makes multiple noncritical errors while also making a number of correct management choices. The examiners are charged with assessing the following characteristics of the candidate’s performance: ■ Demonstrates an organized approach and solid rationale for

planned actions.

■ Rapidly determines and interprets key findings in a clinical

presentation.

■ Effectively and efficiently uses clinical knowledge to solve clinical

problems; effectively addresses key management points.

■ Avoids errors and critical fails (omission and commission) asso-

ciated with the case.

■ Recognizes personal limitations in knowledge and expertise

when diagnosing and treating clinical problems.

■ Reacts in a prompt but flexible manner to alterations in the

patient’s course (e.g., disease or treatment complications).

■ Overall, demonstrates appropriate surgical judgment, clinical

reasoning skills, and problem-solving ability.2,3

In answering the examiners’ questions, candidates should be able to not only state what they would do, but also concisely explain how and why they would provide the stated care.5

SUMMARY The ABS Certifying Examination is an assessment of a surgeon’s thought processes in managing surgical conditions. Board certification is the culmination of targeted training in accredited programs, meeting specific training requirements in order to be eligible for the exam process, and then passing a written foundational knowledge exam and an oral exam of judgment delivered by trained surgical examiners. The process serves as a testimonial that board-certified surgeons have met the standards established by the profession.

Suggested Readings 1. The American Board of Surgery. Training and Certification. General Surgery Qualifying Examination (QE) https://www.absurgery.org/default. jsp?certgsqe. 2. Kopp J, Ibanez B, Jones A, et  al. Association between American Board of Surgery General Surgery Initial Certification and risk of receiving severe disciplinary actions against medical licenses. JAMA Surg. 2020;155(5):e200093. 3. The American Board of Surgery. Training and Certification. General Surgery Qualifying Examination (QE). https://www.absurgery.org/ default.jsp?certcehome. 4. The American Board of Surgery. Training and Certification. SCORE Curriculum Outline for General Surgery. https://www.absurgery.org/ default.jsp?scre_booklet. 5. The American Board of Surgery. Training and Certification. Taking the CE—What to Expect. https://www.absurgery.org/default.jsp?certce_ whattoexpect. 6. The American Board of Surgery. Training and Certification, CE Candidate Video. https://www.absurgery.org/default.jsp?certce_video. 7. The American Board of Surgery. Training and Certification. FAQs. htttp://www.absurgery.org/default.jsp?faq_gsce. 8. Chen H, Tseng JF, Chaer R, et al. Outcomes of the First Virtual General Surgery Certifying Exam of the American Board of Surgery. Ann Surg. 2021;274(3):467–472. 9. Ong TQ, Kopp JP, Jones AT, Malangoni MA. Is there gender bias on the American Board of Surgery General Surgery Certifying Examination? J Surg Res. 2019;237:131–135.

Esophagus

Esophageal Function Tests Wasay Nizam, MBBS, Hamza Khan, MD, and Malcolm V. Brock, MD

T

he esophagus is a muscular, tubelike structure located in the posterior mediastinum. It spans from the posterior oropharynx to the cardia of the stomach with three functional regions: the upper esophageal sphincter (UES), esophageal body, and lower esophageal sphincter (LES). With the aid of peristalsis and coordinated relaxation/contraction of sphincters, the esophagus allows the transport of food boluses to the stomach and prevents the reflux of corrosive stomach contents. Assessment of esophageal motility requires evaluating its structural integrity, peristalsis, and synchronized pressure changes of the sphincters. The diagnostic tools assessing these functions are termed esophageal function tests. Utilizing pressure sensors, these tests provide a dynamic demonstration of esophageal motility and an assessment of alternating pressures within the LES. Patients presenting with dysphagia, reflux, or non-cardiac chest pain should undergo endoscopic or radiologic examination first to rule out structural lesions such as malignancy. Once these are ruled out, functional disorders secondary to esophageal dysmotility are considered (Box 1). This chapter will review commonly used tests, such as manometry and esophageal pH monitoring. Esophageal integrity may be evaluated both directly and indirectly by endoscopy or radiologic tools, respectively. These modalities will also be discussed in depth in subsequent chapters along with details on management of esophageal dysmotility disorders such as achalasia.

ESOPHAGEAL MANOMETRY Esophageal manometry remains the gold standard for assessing esophageal motility. This test permits evaluation of the contractility and coordination of esophageal muscles. It measures a series of pressure events along the esophageal length and presents them as curves of amplitude over time. Originally developed in the 1950s, esophageal manometry underwent numerous modifications before becoming the state-of-the-art diagnostic tool it is today. Briefly, all versions of the manometer contain a series of sensors placed on a thin catheter that transduce intraluminal esophageal pressure into electrical signals that are then displayed as pressure waves. The original version was based on a pneumo-hydraulic system that has since been replaced by a solid-state catheter that provides a faster response and requires less technical expertise. Conventional manometry utilizes information from sensors placed at fixed locations (∼5 cm) along the length of the catheter. This catheter is placed transnasally into the esophagus with its distal

tip in the stomach. Characteristics of the pressure waveform after a swallowing event allow for the recognition of the UES, the esophageal body, the LES, and the gastric cardia (Fig. 1). However, conventional manometry has several limitations including: (1) widely spaced sensors that preclude information on motor activity less than 5 cm apart, (2) unidirectional sensors unable to record pressures accurately in an asymmetrical lumen, and (3) false pressure readings during swallowing because of the tendency of the sphincters to move cephalad, dislodging the catheter. To overcome these challenges, manometry systems have evolved to utilize more sensors (20–36) placed 1 cm apart that also record circumferentially. As a result, data on various pressure points are gathered and plotted using computer software as a smooth contour plot giving a high-resolution manometry (HRM) image. Readings are presented in color-coded spatiotemporal pressure graphs called esophageal pressure topography (EPT) or Clouse plots, named after Ray Clouse, who established the technique. These topographical plots represent time on the x-axis, location of the pressure wave on the y-axis, and color denoting pressure (Fig. 2). With the advent of HRM, a smooth continuous pressure wave along the esophagus in real-time is now available. This led to advances in our understanding of many esophageal motor diseases that were previously puzzling, such as achalasia. A standard protocol for esophageal manometry conduction has been outlined in version 4.0 of the Chicago Classification. The original classification scheme, proposed in 2009 by the International HRM Working Group, was in response to rapid advances in HRM technology. But the scheme became so clinically useful that

BOX 1  Indications and Contraindications for Esophageal Function Tests Indications • Noncardiac chest pain or heartburn with no improvement from acid suppression and no explanation on radiologic or endoscopic examination • Nonobstructive dysphagia or odynophagia that is unexplained • Evaluating esophageal peristalsis before foregut surgery • Localizing LES to place impendence probe in preparation of pH monitoring study • Evaluating dysphagia after foregut surgery • Workup of scleroderma Contraindications • Esophageal mass causing obstruction • Abnormal nasal-oropharyngeal anatomy precluding catheter placement • Nonresponsive patients unable to follow commands • Patients on anticoagulation with high risk of bleeding 3

4

Esophageal Function Tests

Water-perfused catheter with 5 channels placed 5 cm apart

Pressure, mm Hg

Cricopharyngeal sphincter

%

cm

10

1

30

6

50

11

70

16

90

21

80 60 40 20

Length

Esophageal body

Fifth channel with 4 sensors at the same level

Resp. FIG. 1  Esophageal manometry showing a transnasally placed catheter that records a normal waveform progression. Newer solid-state catheters have sensors placed 1 cm apart.

100 18

Lower esophageal sphincter Time

FIG. 2  Clouse plot showing a peristaltic wave after swallowing in a healthy individual. (From Baldwin D, Puckett Y. Esophageal manometry. Updated Sep 28, 2021. In: StatPearls. Treasure Island, FL: StatPearls Publishing; 2021. https://www.ncbi.nlm.nih.gov/books/NBK559237/.)

it helped accelerate esophageal HRM’s current position as the stateof-the-art diagnostic tool that has thoroughly replaced conventional line tracing. Before the procedure, patients are obliged to fast for a minimum of 4 hours, and then the procedure begins with patients in

the supine position for 10 wet (5-mL) swallows spaced 30 seconds apart. This is followed by a single multiple rapid swallow sequence (five 2-mL swallows, 2–3 seconds apart) that can be repeated up to three times. Following this, the patient is placed upright and given

E so p h ag us

five additional wet swallows and one rapid drink challenge (200 mL of water ingested as fast as possible). More provocative testing may include the utilization of a solid swallow test, a solid test meal, or even pharmacologic provocation. Pressure sensors within the body of the catheter then record intraluminal pressure that is transmitted to an external recording device. Clouse plots generated from HRM are interpreted with consideration of the following five metrics: 1. Integrated relaxation pressure (IRP): the average deglutitive relaxation pressure in a 4-second window beginning at UES relaxation 2. Distal contractile integral: the product of amplitude, duration, and length of the distal esophageal contraction 3. Distal latency: the interval between UES relaxation and the contractile deceleration point 4. Peristaltic breaks 5. Pressurization patterns Information from these indices may be applied toward the diagnoses of esophageal motility disorders. The Chicago Classification broadly divides these disorders into disorders of esophagogastric junction (EGJ) outflow or of peristalsis. A useful algorithm presented in the classification then allows for the delineation of specific disorders, based on manometry findings (Fig. 3). HRM is the preferred diagnostic tool when evaluating esophageal motor function, especially when radiologic or endoscopic studies are unable to explain the patient’s symptoms. It is safe, with a low-risk profile of complications that is similar to those of nasogastric tube placement, namely, gagging, oropharyngeal discomfort, epistaxis, and rarely aspiration or perforation. Diet can be resumed immediately following removal of the catheter because only topical nasal

5

anesthesia is used. It is an outpatient procedure requiring no sedation, and patients can drive home afterward. It is important, however, that patients stop H2-blockers, proton pump inhibitors, opioids, nitrates, and calcium channel blockers before the study to avoid any interference with testing. Furthermore, it must be remembered that patients with a history of esophageal surgery, peptic stricture, or those with a current hiatal hernia are prone to false readings.

ESOPHAGEAL pH MONITORING Acid reflux into the esophagus may be assessed with intraluminal pH monitoring. This can be performed with catheter-based devices or a wireless device (Bravo probe, Medtronic, Minneapolis, MN). Catheter-based devices are inserted transnasally, with the distal pH probe located approximately 5 cm above the LES. This device is then left in situ for 24 hours with patients instructed to record meals, symptoms, and periods of sleep by pressing buttons on a recorder. A wireless device is placed endoscopically in the distal esophagus and attached to the esophageal mucosa with a clip. This device then transmits information to a recorder. As there is no external component to this method, patient activities, dietary patterns, and comfort levels are more natural. Furthermore, because this is a single device, pH levels are only assessed at a single level, rather than across the length of the esophagus. pH monitoring is used to determine whether or not acid exposure to the esophagus is physiologic. Data gathered from the probe are correlated with symptoms, patient positioning, and relation to meals. The information from the device is then used to calculate a composite pH or DeMeester score. Scores of 14.72 (95th percentile of normal) or greater are considered abnormal. The components of the DeMeester score include the following:

FIG. 3  Esophageal motility disorders on high-resolution manometry: Chicago classification version 4.0 Hierarchical Classification Scheme. EGJOO, Esophagogastric junction outflow obstruction; FLIP, functional lumen imaging probe; IBP, intrabolus pressurization; IRP, integrated relaxation pressure; LES, lower esophageal sphincter; MRS, multiple rapid swallows; PEP, pan-esophageal pressurization; RDC, rapid drink challenge; TBE, timed barium esophagram. (From Yadlapati R, Kahrilas PJ, Fox MR, et al. Esophageal motility disorders on high-resolution manometry: Chicago classification version 4.0. Neurogastroenterol Motil. 2021;33:e14058.)

6

Esophageal Function Tests

Swallow

Bolus movement upward

Bolus movement downward

Bolus entry

FIG. 4  Impedance testing showing (A) normal downward movement of the bolus after swallowing and (B) reflux of the swallowed bolus.

1. 2. 3. 4. 5. 6.

A

Percent total time pH 5 years) and ≥2 risk factors for esophageal adenocarcinoma (age ≥50 y, male, white, elevated BMI, smoking history)

Screening endoscopy

Diagnosis of BE (Confirmed with EGD and biopsy)

Incidental finding of BE on endoscopy performed for other reasons

Control GERD with PPI

No dysplasia

High-grade dysplasia (HGD)

Low-grade dysplasia

Consider repeat EGD with biopsy within 1 year of initial diagnosis

No dysplasia

No dysplasia

Repeat EGD and biopsy every 3-5 years (consider 1-3 years based on risk)

Follow HGD algorithm

Repeat EGD with biopsy in 3-6 months

Annual surveillance for 2 years

Follow protocol for no dysplasia

Confirmed lowgrade dysplasia

Consider endoscopic ablation versus surveillance every 6-12 months

Progression to HGD

Follow HGD algorithm

Long-term GERD management with PPI or antireflux surgery is mandatory LongFIG. 3  Management of Barrett’s esophagus. BE, Barrett’s esophagus; BMI, body mass index; EGD, esophagogastroduodenoscopy; GERD, gastroesophageal reflux; PPI, proton pump inhibitor.

E so p h ag us

23

High-grade dysplasia (HGD) or suspected intramucosal cancer (IMC)

Multidisciplinary discussion recommended

No visible lesion

Endoscopic ablation (every 8 weeks) until eradication

Endoscopic resection for removal and staging

Esophagectomy*

Repeat EGD with biopsy every 3 months for 1 year, then every 6 months for 1 year, then annually thereafter

Long-term GERD management with PPI or antireflux surgery *Reasons to consider esophagectomy in biopsy proven HGD:      

Visible lesion

Poor prognostic risk factors of the lesion: large size (>2-3 cm), lymphovascular invasion, multifocality Patient prefers surgery Unable to comply with the repeat endoscopic treatments and surveillance Inability to eradicate HGD and/or adenocarcinoma or progression of disease Failed ablation techniques End-stage esophageal function (due to motility disorder, stricture, obstructed hiatal hernia)

HGD/stage T1a

Endoscopic ablation for residual metaplastic disease (every 8 weeks)

Esophagectomy*

Stage T1b

Esophagectomy with lymphadenectomy

Repeat EGD with biopsy every 3 months and annually thereafter

Long-term GERD management with PPI or antireflux surgery

FIG. 4  Management of high-grade dysplasia and intramucosal cancer (IMC). EGD, Esophagogastroduodenoscopy; GERD, gastroesophageal reflux; PPI, proton pump inhibitor.

allow for preservation of the esophagus. However, there remains a role for esophagectomy in select patients with BE (Figs. 3 and 4).

Suggested Readings Johnson CS, Louie BE, Wille A, et  al. The durability of endoscopic therapy for treatment of Barrett’s metaplasia, dysplasia, and mucosal cancer after Nissen fundoplication. J Gastrointest Surg. 2015;19(5):799–805. Maret-Ouda J, Konings P, Lagergren J, Busselaers N. Antireflux surgery and risk of esophageal adenocarcinoma: a systematic review and meta-analysis. Ann Surg. 2016;263(2):251–257.

Oelschlager BL, Barreca M, Chang L, Oleynikov D, Pellegrini CA. Clinical and pathologic response of Barrett’s esophagus to laparoscopic antireflux surgery. Ann Surg. 2003;238(4):458–464. Parasa S, Vennalaganti S, Gaddam S, et al. Development and validation of a model to determine risk of progression of Barrett’s esophagus to neoplasia. Gastroenterology. 2018;154(5):1282–1289. Shaheen NJ, Falk GW, Iyer PG, Gerson LB. ACG Clinical guideline diagnosis and management of Barrett’s esophagus. Am J Gastroenterol. 2016;111(1):30–50.

24

Endoscopic Treatment of Barrett’s Esophagus

Endoscopic Treatment of Barrett’s Esophagus Anne P. Ehlers, MD, MPH, and Brant K. Oelschlager, MD

B

arrett’s esophagus (BE) is a disease characterized by the gradual replacement of the normal stratified squamous epithelium of the esophagus with columnar, intestinal metaplasia (Figs. 1 and 2). This transformation is due to chronic exposure to gastric contents, often within the context of gastroesophageal reflux disease (GERD). Patients at risk for BE are screened with endoscopy and biopsy. The major concern with BE is that it is a precursor lesion for esophageal adenocarcinoma (EAC), a disease with poor prognosis and poor long-term survival. In addition, EAC is a disease that continues to increase in incidence. Given this, identifying and eradicating BE before progression to adenocarcinoma is a top priority. In the past, patients with BE often were recommended for esophagectomy. More recently, evolving endoscopic techniques have replaced esophagectomy for many of these patients, allowing for eradication of BE with less morbidity and fewer complications.

SURVEILLANCE AND MANAGEMENT ALGORITHM Screening The primary risk factor for BE is longstanding GERD, along with male sex, age older than 50 years, and central obesity. Patients with GERD have a 10% to 15% risk of BE; increasing age and long-segment BE (>3 cm) are risk factors for progression to dysplasia. Overall, the rate of progression from BE to esophageal adenocarcinoma is low, perhaps as low as 0.12% per year. Other evidence suggests that for patients with nondysplastic BE, the annual risk of progression to EAC is 0.33% per year among all patients with BE and 0.19% per year among patients with short-segment BE (50 years, white race, central obesity, history of smoking, family history of BE or EAC). Screening for female patients is generally not recommended, except for patients with multiple risk factors, as outlined previously. Screening is generally undertaken using high-resolution endoscopy with liberal use of narrow band imaging and biopsy, but as previously stated this can be very labor and time intensive. Several novel screening modalities have been proposed to reduce this burden. One alternative is transnasal esophagoscopy, which is an office-based procedure that uses topical anesthetic to pass an endoscope through the nares and into the esophagus. Compared with traditional high-resolution endoscopy, the image quality is reduced

and the biopsies are smaller but often are sufficient for histologic analysis to allow a diagnosis of BE to be made without a formal endoscopy. A second option for screening is the Cytosponge, which is a gelatin-coated capsule attached to a string that is then swallowed by the patient. Once in the stomach, the gelatin coating dissolves leaving behind a sponge that is then retrieved by pulling on the string. As the sponge comes back through the esophagus, it picks up cells that can then be examined for abnormalities. It currently holds promise as a screening tool for BE but is not adequate to screen for EAC. Because transnasal esophagoscopy and Cytosponge are still relatively new, high-resolution endoscopy is still the gold standard for diagnosis of BE.

Surveillance Patients with confirmed BE in the absence of dysplasia or EAC should be regularly surveilled to detect disease progression. A challenge in the past has been lack of universal criteria for describing the extent of disease. To address this challenge, the Prague Criteria are a set of endoscopic data developed and validated by a working group specifically focused on esophagitis using standardized videos of endoscopies. The purpose was to improve on the previously used vague descriptions of “long” versus “short” segment disease and to facilitate communication between providers. The Prague Criteria measures the extent of disease based on circumference and maximum extent (C&M) criteria, with C being the maximum circumferential extent of disease and M the maximum length, including any isolated tongues of disease. Once a patient has been diagnosed with BE, the next step is to evaluate for any dysplasia or invasive cancer. The current recommendation is to evaluate the patient with high-resolution or high-definition white light endoscopy followed by meticulous inspection of the esophageal lumen, after both insufflation and desufflation, including inspection of the gastroesophageal junction in the retroflexed view. Some data suggest that longer inspection time is associated with better detection of dysplasia or EAC. Suspicious lesions such as erosions, ulcerations, nodules, plaques, and other mucosal or luminal abnormalities should be selectively sampled. Random biopsies are not recommended. Suspicious lesions in patients with known dysplasia are best removed via endoscopic mucosal resection (EMR), which will be described later in the chapter. Additionally, the ACG recommends against taking biopsies in areas of active, erosive esophagitis and instead suggests waiting until the patient has been treated with antisecretory agents to allow the inflammation to subside. Ongoing surveillance is dependent on the pathology determined at the time of biopsy. For patients who have BE without evidence of dysplasia, the recommendation is that they undergo repeat endoscopic surveillance every 3 to 5 years, as described previously. In cases in which biopsies are inconclusive for dysplasia, patients should be placed on an acid suppression regimen for 3 to 6 months, after which repeat endoscopy should be performed. If the biopsies are still inconclusive at that time, repeat endoscopy should be performed 12 months later. If dysplasia is diagnosed (LGD or HGD), the biopsies should be reviewed by two separate pathologists, one of whom is an expert in gastrointestinal pathology because there is a high level of interobserver variability when it comes to dysplasia. Once dysplasia is confirmed, the next steps depend on the degree of dysplasia. For LGD, endoscopic therapy is preferred for patients without significant comorbidity; however, repeat endoscopy in 12 months is acceptable in these cases. For HGD, endoscopic therapy is recommended except in the case of life-limiting comorbid conditions. Patients with a diagnosed cancer should undergo further staging workup to determine whether the cancer is resectable, and some early adenocarcinomas can be managed endoscopically. For certain young patients with long-segment multifocal HGD, recurrent HGD, or

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A

B

C

D

25

FIG. 1  Spectrum of dysplasia grading. (A) Negative for dysplasia. Although some nuclear hyperchromasia is noted, it is limited to the normal proliferative zone with evidence of surface maturation. (B) Low-grade dysplasia shows basally oriented, hyperchromatic nuclei with pseudostratification. Crypt architecture is preserved. (C) High-grade dysplasia demonstrates prominent mitotic activity, enlarged nuclei, and loss of nuclear polarity with evidence of glandular crowding. (D) This lesion shows cytoarchitectural atypia, equivalent to that of low-grade dysplasia, in the deep glands. However, given the presence of surface maturation and the stromal changes suggestive of a reparative process, it is best classified as indefinite for dysplasia. (From Hagen CE, Lauwers GY, MinoKenudson M. Barrett esophagus: diagnostic challenges. Semin Diagn Pathol. 2014;32:100–113.)

intramucosal cancer, surgery should be considered. A summary of the surveillance and treatment algorithm is provided in Figures 3 and 4.

PRINCIPLES OF ENDOSCOPIC THERAPIES The current evidence suggests that endoscopic therapy should be used for patients with BE who have LGD, HGD, and for some patients with early intramucosal (T1a) EAC because the risk of lymph node metastasis is nonexistent for LGD and HGD and is low for intramucosal EAC. Endoscopic techniques work by either removing it before development of invasive disease or destroying

abnormal tissue (ablative techniques). The intestinal metaplasia is then replaced with normal appearing squamous epithelium (Fig. 5).

ENDOSCOPIC RESECTION TECHNIQUES Endoscopic Mucosal Resection EMR is a technique that allows removal of lesions within segments of BE for complete histologic analysis, including dysplasia and superficial T1a adenocarcinoma. It offers an advantage over ablative techniques because it allows for examination of tissue specimens, rather than just destroying them. The ACG recommends EMR as the initial treatment modality for patients with nodular BE. For patients

26

Endoscopic Treatment of Barrett’s Esophagus

FIG. 2  Endoscopic image of Barrett’s esophagus. The arrows mark the esophagogastric junction, which is identified endoscopically as the most proximal extent of the gastric folds. The reddish color and velvet-like texture of the Barrett’s epithelium contrast sharply with the pale and glossy appearance of the esophageal squamous epithelium. Note that the Barrett’s columnar epithelium extends well above the esophagogastric junction to line the distal esophagus. (From Spechler SJ, Souza RF. Barrett’s esophagus. In: Sleisenger and Fordtran’s gastrointestinal and liver disease. Philadelphia: Elsevier; 2016.)

without high-risk features (submucosal invasion, poor differentiation, or lymphatic vascular invasion), EMR has 98.8% eradication rate of BE; in patients with high-risk features, the rate is 80.6%. For T1a tumors, EMR has a 91% to 98% eradication rate. There are several methods used for EMR. In the cap-assisted method, the endoscope is fitted with a transparent cap. Once located, the target lesion is sucked into the cap and a specialized electrocautery snare is used to resect the lesion. A submucosal injection can be performed to facilitate this. In the ligation-assisted method, lesions are removed using a band-ligation device attached to the tip of the endoscope. Once identified, the target lesion is again sucked into the endoscope and the band is applied around the lesion to create a pseudopolyp. Electrocautery is then used to remove the pseudopolyp. In the injection-assisted technique, the submucosal space is injected to lift the lesion and allow it to be snared and cut. One of the primary side effects of EMR is esophageal stricture, which occurs in up to 40% of patients. Typically, these lesions can be managed with endoscopic dilation or stents. EMR is often used in conjunction with radiofrequency ablation (RFA) with good effect. In a recent systematic review, EMR alone had a 33.5% risk of stricture, 7.5% risk of bleeding, and 1.3% risk of perforation compared with 10.2%, 1.1%, and 0.2%, respectively, in patients undergoing EMR in conjunction with RFA.

Endoscopic Submucosal Dissection Endoscopic submucosal dissection (ESD) is a technique that allows for complete, en bloc resection of suspicious lesions to allow for thorough histologic evaluation. When compared with EMR, it also

Flat columnar mucosa

Systematic cold biopsy

Nondysplastic BE

Indefinite for dysplasia

Confirmed LGD

Confirmed HGD

T1a EAC

Repeat EGD w/ biopsies in 3–5 years

Optimize PPI therapy repeat EGD

Endoscopic eradication therapy*

Endoscopic eradication therapy

Endoscopic eradication therapy

Confirmed

Discordant

EGD w/ biopsies in 1 year

Manage per new histology

FIG. 3  Management of nonnodular Barrett’s esophagus (BE). *Although endoscopic eradication therapy is associated with a decreased rate of progression, surveillance upper endoscopy at 1-year intervals is an acceptable alternative. This algorithm assumes that the T1a esophageal adenocarcinoma (EAC) displays favorable characteristics for endoscopic therapy, including well-differentiated histology and lack of lymphovascular invasion. HGD, High-grade dysplasia; LGD, low-grade dysplasia; PPI, proton pump inhibitor. (From Shaheen NJ, Falk GW, Iyer PG, et al. ACG Clinical Guideline: Diagnosis and Management of Barrett’s Esophagus. Am J Gastroenterol. 2016;111:30–51.)

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Endoscopically visible nodularity in BE

Endoscopic mucosal resection

Low-grade dysplasia

High-grade dysplasia

T1a EAC

Endoscopic ablative therapy*

Endoscopic ablative therapy

Favorable histology?

T1b EAC

No

Discussion at multidisciplinary oncology group

Yes Endoscopic ablative therapy FIG. 4  Management of nodular Barrett’s esophagus (BE). *Little data exist on the clinical course of patients with low-grade dysplasia (LGD) managed by endoscopic surveillance following endoscopic mucosal resection (EMR), although this is an alternative treatment strategy. Endoscopic submucosal dissection is an alternative to EMR. Favorable histology consists of no lymphatic or vascular invasion and moderate to well-differentiated disease. EAC, Esophageal adenocarcinoma. (From Shaheen NJ, Falk GW, Iyer PG, et al. ACG Clinical Guideline: Diagnosis and Management of Barrett’s Esophagus. Am J Gastroenterol. 2016;111:30–51.)

allows for complete resection of lesions, rather than having to resect lesions in a piecemeal fashion, especially for larger lesions (>1.5–2 cm). The primary indication for ESD is resection of nodular lesions within a segment of BE to allow for complete histologic evaluation. Given the relative technical difficulty of this procedure, as well as the concern for significant adverse events, it is not as widely used. The ACG recommends that ESD only be performed in centers of clinical expertise. The technique of ESD involves first marking the area of resection with coagulation. The submucosal space of the marked area is then injected with a saline solution to lift the area, and finally ESD resection knives are used to incise the mucosa and perform the submucosal dissection. Most of the available data on ESD is from Europe or Asia, but a recent multicenter study performed in the United States showed that en bloc resection occurred in 95.7% of patients with a median resection size of 45 mm. Nearly half of patients required admission after the procedure, either for routine observation or for pain control. An R0 resection was achieved in 76.1%, and the overall cure rate was 69.6%. More than two-thirds of patients in this study were found to harbor EAC in the resected specimen, resulting in histologic upstaging in more than half of all patients. Adverse events occurred in 23.9% of patients, including bleeding (6.5%), perforation (2.2%), and esophageal stricture (15.2%). All adverse events were managed endoscopically. These results were confirmed by a recent meta-analysis demonstrating that ESD has a 92.9% success rate of achieving en bloc resection, a 74.5% rate of achieving an R0 resection, and a 64.9% rate of achieving curative resection. Bleeding occurred in 1.8% of patients, and 1.5% of patients sustained esophageal perforation. Both the bleeding and perforation events were managed endoscopically. Overall esophageal stricture rate was 11.6%; these were managed

with endoscopic dilation. The total rate of immediate and delayed adverse events was 4.95%.

ENDOSCOPIC ABLATION TECHNIQUE Photodynamic Therapy Photodynamic therapy (PDT) involves administration of a systemic photosensitizing agent that is taken up preferentially by neoplastic tissues. The photosensitizing agent then produces cytotoxicity after exposure to an appropriate wavelength and power of light, specific to the photosensitizing agent. The two most widely available photosensitizing agents are Photofrin and 5-aminolevulinic acid. Randomized trial data indicate that complete ablation of HGD can be achieved in 77% of patients with PDT, and 52% of patients had complete replacement of all BE tissue with normal squamous epithelium. There is a relatively high complication rate associated with PDT. Because of its systemic administration, the photosensitizing agents can predispose to cutaneous photosensitivity similar to a sunburn in more than two-thirds of patients. Other complications include odynophagia, constipation, vomiting, noncardiac chest pain, dehydration, dysphagia, and stricture formation (up to 36% in some studies). This was the first effective ablation technique, but because of the relatively high complication rate, PDT is no longer widely used.

Argon Plasma Coagulation Argon plasma coagulation (APC) uses a beam of argon gas to conduct an electrical current, resulting in a noncontact form of thermal electrocoagulation. The depth of necrosis is relatively shallow (2–3 mm) and can be useful in conditions such as BE that involve the mucosa. In the initial randomized controlled trial (RCT) conducted by Ackroyd et al., after a median of three treatments, patients treated

28

Endoscopic Treatment of Barrett’s Esophagus

A After EMR

Band EMR

B

Argon Plasma Coagulation

C

APC catheter

Post APC necrosis

Post RFA necrosis

Radiofrequency Ablation

Circumferential RFA balloon

D

Spray Cryotherapy

Hemicircumferential ice

E Diffuser

Ice patch

Ablation Cryoballoon

Post-cryoablation effect

FIG. 5  Endoscopic techniques for eradication of esophageal early neoplasia. (A) Band endoscopic mucosal resection involves suction and ligation (banding) of a target lesion, with or without prior submucosal injection, followed by resection using snare polypectomy technique. Endoscopic photo shows the endoscopic view of the submucosa through the banding device after complete resection of well-differentiated adenocarcinoma. (B) Argon plasma coagulation (APC) involves conduction of heat energy with argon gas to the mucosa. Endoscopic image shows the APC catheter and white coagulation necrosis of treated BE mucosa. (C) Radiofrequency ablation (RFA) involves the application of a preset amount of heat energy (12 J) through electrodes on a circumferential (Halo 360) ablation catheter inflated to make contact with the esophageal mucosa. Endoscopic image of post-RFA necrosis. (D) Liquid nitrogen spray cryotherapy involves release of liquid nitrogen that expands to gas and freezes large areas of tissue to −196°C. The dosing of liquid nitrogen cryogen has varied from 15 to 20 seconds of ice, followed by a timed minimum 45 seconds of thaw, and repeated for three cycles. Endoscopic image of a hemicircumferential patch of ice on the esophageal mucosa. (E) The cryoballoon ablation system includes a portable handheld reusable controller that delivers nitrous oxide gas into a low-pressure compliant, 30 mm, oval-shaped balloon at the end of a disposable balloon catheter passed through the endoscope channel. The balloon at the end of the catheter is inflated and simultaneously cooled by the gas expansion. The cryogen is directed toward a specific location by rotation of the diffuser. Endoscopic image shows the endoscopic view through the cryoballoon with a focal ice patch and thawed treated mucosa with post cryotherapy red color change. EMR, endoscopic mucosal resection. (From di Pietro M, Canto MI, Fitzgerald RC. Endoscopic management of early adenocarcinoma and squamous cell carcinoma of the esophagus: screening, diagnosis, and therapy. Gastroenterology. 2018;154:421–436.)

with APC achieved complete macroscopic ablation 60% of the time, with the remaining patients achieving a significant decrease in the size of their BE. At the 1-year follow-up, 58% of patients had no macroscopic evidence of disease compared with only 15% in the surveillance group. At 5-year follow-up, 70% of patients in the APC group

had sustained at least a 95% reduction in the surface area of BE, and 40% had no histologic or macroscopic disease compared with only 25% and 15%, respectively, in the surveillance group. There were no early complications, and long-term complications included strictures that were managed with endoscopic dilation.

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Other reported complications include chest pain, odynophagia, ulceration, bleeding, perforation, and death. One advantage of APC is that the equipment is widely available and is relatively inexpensive. However, as noted in the RCTs, it often requires multiple treatments over time to achieve regression of disease.

Cryotherapy Cryotherapy directly destroys tissue by freezing it, resulting in both immediate and delayed tissue destruction. There are several cryotherapy systems available, but the most widely studied is liquid nitrogen. In a retrospective study of patients treated with liquid nitrogen, Shaheen et al. found that after an average of four treatments, 97% of patients had resolution of HGD, 87% had resolution of intestinal dysplasia, and 57% had resolution of intestinal metaplasia. There were no serious complications, but 3% of patients developed strictures that were managed with endoscopic dilation. At the 5-year follow-up, 93% of patients had complete resolution of high-grade dysplasia, 88% had resolution of dysplasia, and 75% had resolution of intestinal metaplasia, although some of these patients underwent “touch-up” therapy after the initial round of treatment. As with other endoscopic methods of treatment, ongoing endoscopic surveillance is required. One advantage of cryotherapy is that it can be used both as a firstline treatment for BE with dysplasia and as a second-line treatment in patients who have failed other treatments. As with other therapies, however, it often requires multiple treatments to completely eradicate disease. In a recent review of liquid nitrogen cryotherapy, the complication rate ranged from 0% to 3% with the most frequent complication being pain requiring narcotics (10% of patients), followed by stricture requiring dilation (up to 9%), then bleeding and perforation.

29

required to achieve complete eradication of dysplasia, with close follow-up following eradication. In an RCT comparing RFA with sham endoscopy, complete eradication of LGD occurred in 90.5% of patients and complete eradication of HGD occurred in 81% of patients following RFA, compared with only 22% and 19% in the sham group, respectively. Among all patients, RFA completely eradicated evidence of intestinal metaplasia in 77.4%, compared with only 2.3% in the control group. All these results were statistically significant. There is a known rate of progression to esophageal cancer, and in this study 19% of patients with HGD progressed to cancer over a 1-year timeframe. At 2-year follow-up, these results were found to be durable: complete eradication of dysplasia occurred in 95% of patients, and complete eradication of intestinal metaplasia occurred in 93% of patients; results were similar at 3-year follow-up. The primary side effects of RFA are chest pain and dysphagia lasting up to 4 days, and strictures occur in up to 8% of patients. Bleeding is rare. No deaths have been reported following RFA. RFA is the preferred therapy for nonnodular BE.

CONCLUSION The management of BE continues to evolve as new technology and more effective treatments become available. Compared with esophagectomy, endoscopic techniques have the advantage of being less invasive with fewer complications; however, in all cases, it is important to ensure that the correct technique is being used, which requires a baseline understanding of each technique. In general, patients with nodular disease should have this resected, and patients with early esophageal cancer should be referred for discussion at a multidisciplinary cancer group or tumor board to discuss alternative therapies to endoscopic ones.

Radiofrequency Ablation

Suggested Readings

The most commonly used ablative technique is RFA. Using either a balloon catheter or a focal catheter, a generator and a bipolar electrode array deliver a fixed amount of thermal energy, resulting in a uniform burn to a depth of 0.5 mm. RFA can be performed in the outpatient setting and is targeted as either a circumferential ablation (using the balloon catheter) or a focal ablation (using the focal catheter). Circumferential ablation is for circumferential segments of BE that are longer than 2 cm, whereas focal ablation is for shorter segments, or tongues, of BE. After treatment, follow-up is recommended in approximately 2 months, and often multiple sessions of RFA are

Hvid-Jensen F, Pedersen L, Drewes AM, et al. Incidence of adenocarcinoma among patients with Barrett’s esophagus. N Engl J Med. 2011;365:1375– 1383. Ning B, Abdelfatah MM, Othman MO. Endoscopic submucosal dissection and endoscopic mucosal resection for early stage esophageal cancer. Ann Cardiothorac Surg. 2017;6:88–98. Peter S, Monkemuller K. Ablative endoscopic therapies for Barrett’sesophagus-related neoplasia. Gastroenterol Clin North Am. 2015;44:337– 353. Shaheen NJ, Falk GW, Iyer PG, et al. ACG clinical guideline: diagnosis and management of Barrett’s esophagus. Am J Gastroenterol. 2016;111:30–50.

Management of Paraesophageal Hernia Repair Richard J. Battafarano, MD, PhD

T

he most common acquired diaphragmatic hernia is the hiatal hernia. Widening of the esophageal hiatus and weakening of the phrenoesophageal ligament is associated with herniation of the stomach and other intraabdominal organs through the hiatus and into the mediastinum. Many patients are noted to have hiatal hernias with minimal symptoms. However, the most common symptoms

associated with hiatal hernia are gastroesophageal reflux disease (GERD) and early satiety. Patients who develop abdominal pain after eating or who present with anemia in the setting of a hiatal hernia often have larger paraesophageal hernias with at least partial organo-axial volvulus of the stomach. Patients with these symptoms are at greater risk for the potentially lethal consequences of complete volvulus, strangulation, incarceration, and perforation. Paraesophageal hernias are classified into four types (Box 1) based on the location of the esophagogastric junction (EGJ) and the herniated abdominal contents. Type I hiatal hernias are the most common; they account for 90% to 95% of all hernias and most frequently present with GERD. Patients with type II, type III, and type IV paraesophageal hernias often present with the additional symptoms of early satiety, anemia, and postprandial abdominal or chest pain, vomiting, dysphagia, and weight loss.

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Management of Paraesophageal Hernia Repair

BOX 1  Classification of Paraesophageal Hernias Type I: The esophagogastric junction (EGJ) herniates above the diaphragm into the mediastinum (“sliding hernia”). Type II: A portion of the stomach is herniated into the mediastinum alongside a normally positioned (i.e., intraabdominal) EGJ. Type III: The EGJ is above the hiatus, and a portion of the stomach is folded alongside the esophagus. Type IV: An intraabdominal organ other than the stomach also is herniated through the hiatus.

SURGICAL INDICATIONS AND PREOPERATIVE EVALUATION The indications for surgery in patients with paraesophageal hernia depend on the severity of the patient’s symptoms and the patient’s other comorbid medical conditions. Patients with paraesophageal hernias whose symptoms are well controlled on acid suppression medications and who do not have dysphagia, weight loss, or pain may be followed closely and do not require immediate repair of the paraesophageal hernia. However, patients with other symptoms should be thoroughly evaluated before proceeding with paraesophageal hernia repair. As part of the evaluation for patient’s symptoms, many will have either a contrast esophagram (Fig. 1) or a computed tomography (CT) scan (Fig. 2) at the time of presentation. Although these two radiographic studies often complement one another, the current thin-cut CT scans, with coronal and sagittal reconstructions, are quite helpful for delineating the anatomy of the paraesophageal hernia and for determining if additional organs have also herniated into the mediastinum (type IV paraesophageal hernia). An upper endoscopy is important to determine the presence of esophagitis, gastritis, Cameron ulcers, and peptic ulcer disease and to rule out malignancy. Esophageal manometry is very important in patients with type I and type II paraesophageal hernias to assess esophageal motility, which will guide the decision for the appropriate fundoplication at the time of the paraesophageal hernia repair. The use of esophageal manometry in patients with large type III or type IV paraesophageal hernias is often quite difficult to accurately perform because the catheters often curl in the esophagus or herniated stomach, limiting the data that can be obtained. In these patients, a partial fundoplication should be performed. The use of pH testing in patients with paraesophageal hernia does not usually add significant information in patients whose EGJ is above the diaphragm. However, pH monitoring is critically important in patients who have significant symptoms of gastroesophageal reflux disease without the presence of a paraesophageal hernia.

SURGICAL TECHNIQUE Type I and type II paraesophageal hernias can almost always be successfully repaired using the laparoscopic technique. Laparoscopic repair of these hernias has been associated with decreased operative morbidity, especially when compared with thoracotomy. However, the choice of operation for large type III and type IV paraesophageal hernias is somewhat more controversial. Patients with more advanced type III and type IV paraesophageal hernias often develop dense adhesions between the hernia sac and the pericardium, lung, and even the airway itself. Dissecting the sac and its contents away from these structures often results in pneumothorax with subsequent loss of pneumoperitoneum and subsequent visualization. In addition, visualizing the structures above the level of the inferior pulmonary veins becomes much more difficult using a laparoscopic approach. In these large paraesophageal hernias, open repair using either an upper midline laparotomy or a left thoracotomy may be

Herniated stomach

Gastric Volvulus

FIG. 1  Barium esophagram showing a large paraesophageal hernia with a gastric volvulus.

more efficacious. Other relative indications for open repair rather than laparoscopic repair of paraesophageal hernias include a previous paraesophageal hernia repair (especially if mesh was used at the hiatus), extension of the paraesophageal hernia into one or both pleural spaces, and proximal extension of the paraesophageal hernia to the level of the carina.

Laparoscopic Repair of Paraesophageal Hernias Positioning of the Patient and Placement of Ports After adequate general anesthesia has been performed, a nasogastric tube is placed to decompress the stomach. Although many surgeons utilize the low lithotomy position for this procedure, we have chosen to keep the patient in the supine position with a footboard to allow the steep reverse Trendelenburg position. A total of five ports are used for the procedure: one for the camera (port 1, 10 mm); two for the operating surgeon (port 4, 10 mm; port 5, 5 mm); one for the assistant (port 2, 5 mm); and one for the liver retractor (port 3, 5 mm). The first port is usually placed in the midline approximately 14 cm below the xiphoid process and is utilized for the camera. We prefer to place this port via an open technique to minimize the risk of injuring any intraabdominal contents upon entry. The remaining ports are all carefully placed under direct vision (Fig. 3). At the completion of the procedure, the fascia around each of the two 10-mm ports is closed with absorbable suture to decrease the risk of port site hernias.

Dissection and Reduction of the Hernia Sac We begin by opening the gastrohepatic ligament up to the level of the right crus of the diaphragm. Great care is taken to identify the presence of a replaced or accessory left hepatic artery. If one of these is identified during this portion of the dissection, they are encircled

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31

Stomach Stomach Colon

Stomach Colon Diaphragm Diaphragm

Colon

Diaphragm Diaphragm

Diaphragm

A

B

C

FIG. 2  CT scans showing a type IV paraesophageal hernia.

of the procedure and greatly reduces the risk for gastric injury or perforation. With the stomach reduced into the abdomen, we mobilize the greater curvature of the stomach, dividing all of the short gastric vessels using a harmonic scalpel. Our focus on removing the entire hernia sac during the procedure often results in small tears in the pleura, creating capnothorax with associated hypotension or increased airway pressure. Reduction of the insufflation pressure and close cooperation between the surgical and anesthesia teams almost always allows completion of these procedures laparoscopically without conversion to laparotomy.

Esophageal Mobilization and Lengthening

4

5 14 cm

3

1

2

FIG. 3  Port placement for laparoscopic paraesophageal hernia repair. (From Patti MG, Fisichella PM. Laparoscopic paraesophageal hernia repair. How I do it. J Gastrointest Surg. 2009;13:1728-1732.)

with a vessel loop and gently retracted during the remainder of the dissection and creation of the fundoplication. The periesophageal tissues are then dissected away from the right crus, and the anterior and posterior vagus nerves are identified. This dissection is then continued anteriorly to dissect the sac away from the pericardium and extended to the left crus of the diaphragm. The hernia sac is then dissected away from the left crus of the diaphragm exposing the posterior aspects of both the right and left crura just above the aorta. The posterior dissection is completed allowing the herniated stomach and the hernia sac to be reduced into the abdomen, and the esophagus is encircled in the lower mediastinum with a Penrose drain. Mobilization of the hernia sac and its contents in this manner decreases the amount of force applied to the stomach during this step

The hernia sac is then resected taking great care to preserve both vagus nerves, and the EGJ is identified. The mediastinal dissection is extended proximally by dividing the small esophageal arterial branches using the harmonic scalpel. The dissection is continued up into the mediastinum to achieve at least 3 cm of intraabdominal esophagus. It is quite helpful to decrease the insufflation from 15 mm Hg to 8 mm Hg and to not utilize any caudal traction of the stomach at this time so an accurate measurement of intra-abdominal esophagus can be achieved. Once an accurate measurement of intra-abdominal esophagus has been made, the insufflation is returned to 15 mm Hg, and attention is directed toward posterior approximation of the right and left crura.

Closure of the Esophageal Hiatus Retraction of the esophagus upward and toward the patient’s left with the Penrose drain optimizes visualization of the posterior right and left crura. Interrupted 0 Ethibond sutures are placed to reapproximate the posterior right and left crura just above the aorta using a laparoscopic needle driver through the left upper quadrant 10-mm port. Although many surgeons perform intracorporeal knot tying, we prefer to utilize the Ti-KNOT. It is important to accurately space these posterior crural sutures on each crus because the left crus is often much longer than the right crus. In addition, it is important for the surgeon to carefully place these sutures, being mindful that both the aorta and inferior vena cava are in close proximity to the posterior crura. Before the last crural sutures are tied, a 52F or 56F bougie is carefully inserted down the esophagus, and there should be room for a closed grasper to easily slide between the esophagus and crura. Although there was initial enthusiasm for the use of biologic mesh for reinforcement of the crural closure, more recent studies have demonstrated that the long-term recurrence rates are

32

Management of Paraesophageal Hernia Repair

similar between cruroplasty alone versus cruroplasty with biologic mesh. However, the overall morbidity seems to be higher in patients repaired with nonabsorbable mesh.

Creation of the Fundoplication For a Nissen (360-degree) fundoplication, the 56F bougie remains in the lumen of the esophagus, and the fundus of the stomach is passed behind the esophagus, taking great care to ensure sufficient mobilization to avoid having part of the gastric fundus above the wrap. A total of three 2-0 Ethibond sutures are used to create the Nissen fundoplication. Each stitch is placed through the seromuscular wall of the stomach on the left side of the fundus, the muscular wall of the esophagus, and the right side of the fundus at 1-cm intervals. At the completion of the fundoplication, the anterior portion of the fundoplication should be approximately 2 cm in length and should sit comfortably below the hiatus. Many surgeons place sutures between the superior aspect of the wrap and the right and left sides of the crural closure, creating a gastropexy to anchor the wrap below the hiatus (Fig. 4). It is critical that the wrap is not created under tension. When the patient’s esophageal motility will not allow a Nissen fundoplication, a Toupet fundoplication (posterior 240-degree fundoplication) is created by placing a total of six 2-0 Ethibond sutures. Three are placed through the seromuscular right and left sides of the fundus and are separately sutured to the right and left sides of the muscular wall of the esophagus, leaving 120 degrees of the anterior esophageal wall uncovered (Fig. 5).

Open Repair of Large Paraesophageal Hernias Repair through an Upper Midline Laparotomy Although a number of surgeons will repair large paraesophageal hernias (type III and type IV) and reoperative paraesophageal hernias using laparoscopic and/or a combination of laparoscopic and thoracoscopic techniques, operative times are longer, and the risk for complications such as gastric or esophageal perforation is higher. For this reason, we often repair large paraesophageal hernias and

Esophagus

Wrap FIG. 4  Crural repair and total 360-degree fundoplication. (From Townsend CM, Beauchamp RD, Evers BM, Mattox KL. Sabiston Textbook of Surgery. 20th ed. Philadelphia: Elsevier; 2017.)

140˚± 20 Esophagus Wrap FIG. 5  Crural repair and partial posterior fundoplication. (From Townsend CM, Beauchamp RD, Evers BM, Mattox KL. Sabiston Textbook of Surgery. 20th ed. Philadelphia: Elsevier; 2017.)

reoperative paraesophageal hernias through a limited upper midline laparotomy. The postoperative morbidity of an upper midline laparotomy is minimal and offers a number of advantages over a difficult laparoscopic dissection. First, without utilizing insufflation, entrance into either the left or right pleural space as part of resection of the sac does not negatively affect or limit the ability to complete the procedure. Reduction of the sac and its contents from the mediastinum or the pleural space can often be performed more gently with one’s hands in comparison with using Babcock or other laparoscopic clamps, and complete resection of the sac can be accomplished in all cases. Because large paraesophageal hernias are more likely to be associated with an EGJ that does not comfortably sit 3 cm below the hiatus despite extensive proximal mobilization of the hiatus, accurate assessment of esophageal length and the creation of esophageal lengthening procedures such as a Collis gastroplasty or a fundic wedge gastroplasty are more easily performed. In reoperative cases, takedown of the adhesions from the previous repair can be more safely achieved, especially when mesh was utilized at the time of the primary repair. CT images of a representative large type III paraesophageal hernia performed through an upper midline laparotomy are shown (Fig. 6). Upper abdominal exposure is achieved using a standard bookwalter retractor system, and the steps of the operation are performed exactly as described earlier. When an esophageal lengthening procedure is necessary, it is performed over a 56F bougie using an endoscopic stapler with a closed staple height of 2 mm. A Toupet fundoplication is performed (instead of a Nissen fundoplication) to prevent postoperative dysphagia.

Repair through a Left Thoracotomy Historically, the transthoracic repair of paraesophageal hernias was the standard approach for patients with this disease led by Dr. David Skinner and Dr. Ronald Belsey. Because of the increased postoperative pain associated with a thoracotomy, procedures performed using laparoscopy or through an upper midline laparotomy are currently preferred. However, transthoracic repair of large paraesophageal hernias still has a role in the care of patients with this disease (Fig. 7).

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FIG. 6  Coronal and sagittal images of a large type III paraesophageal hernia extending up proximally in the mediastinum up to the level of the pulmonary veins.

A

C

B

FIG. 7  Sequential axial images of a large type III paraesophageal hernia extending up to the level of the pulmonary veins and into both pleural spaces in a patient who presented with bleeding from a Cameron ulcer.

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Management of Zenker’s Diverticulum

Transthoracic repair allows the surgeon to more easily divide dense adhesions between the hernia sac and its contents from the lungs and pericardium. It also allows the esophagus to be mobilized up to the level of the aortic arch behind the carina, generating maximal tension-free esophageal length. In the rare cases in which this degree of esophageal mobilization does not achieve enough length to allow the EGJ to sit comfortably below the hiatus, a Collis gastroplasty can be easily performed. Although the traditional fundoplication utilized by Skinner and Belsey was the Belsey Mark IV repair (270-degree fundoplication), this procedure can be conceptually more difficult to understand and to teach to others. Therefore, a standard Toupet fundoplication can be created in the left chest and then returned to the abdomen before tying the final two posterior crural approximation stitches to complete the repair.

POSTOPERATIVE CARE No matter which surgical approach is utilized, patients are extubated immediately after the completion of the procedure. Nasogastric tubes are not necessary for patients with type I or type II paraesophageal hernias. However, patients with type III and type IV paraesophageal hernias often have significant gastric distension and benefit from tube decompression. I obtain a contrast esophagram on the first postoperative day to ensure flow of contrast through the fundoplication and to ensure gastric emptying. Patients are discharged on full liquids and a limited soft diet until they are seen at follow-up in approximately 2 weeks. Although patients whose repair was performed through a midline laparotomy or a left thoracotomy initially have more incisional pain, complete recovery and return to work is achieved in approximately 4 weeks.

OUTCOMES Laparoscopic and open repair of paraesophageal hernias is associated with excellent recovery and long-term symptom relief. The choice between laparoscopic and open repair depends on the paraesophageal type and the patient’s previous surgical history. Many series have demonstrated a relatively high radiographic recurrence rate. However, the need for reoperation remains quite low, especially

Management of Zenker’s Diverticulum Fernando A.M. Herbella, MD, Riccardo Rosati, MD, and Marco G. Patti, MD

GENERAL CONSIDERATIONS Zenker’s diverticulum is a rare disease that occurs in the pharyngoesophageal area. It is a pulsion pseudodiverticulum because it is composed of mucosa only and not all wall layers. A large proportion of patients with esophageal diverticula are asymptomatic. Dysphagia is the most common symptom, but regurgitation, weight loss, chest pain, halitosis, and aspiration are also common complaints.

PATHOPHYSIOLOGY Pharyngoesophageal diverticulum occurs in areas of muscular gap at the transition of the cricopharyngeal, inferior constrictor of the pharynx and esophageal intrinsic muscles. Three separate weak

in patients initially treated for type I and type II paraesophageal hernias.

ACKNOWLEDGMENTS I recognize the authors of this chapter in the previous editions, as I have revised and updated their excellent work.

Suggested Readings Angeramo CA, Schlottmann F. Laparoscopic paraesophageal hernia repair: to mesh or not to mesh. Systematic review and meta-analysis. Ann Surg. 2022;275(1):67–72. Dallemagne B, Kohnen L, Perretta S, et al. Laparoscopic repair of paraesophageal hernia. Long-term follow-up reveals good clinical outcome despite high radiological recurrence rate. Ann Surg. 2011;253(2):291–296. Hietaniemi H, Ilonen I, Järvinen T, et al. Health-related quality of life after laparoscopic repair of giant paraesophageal hernia: how does recurrence in CT scan compare to clinical success?. BMC Surgery. 2020;20(1):109–116. Lidor AO, Steele KE, Stem M, et al. Long-term quality of life and risk factors for recurrence after laparoscopic repair of paraesophageal hernia. JAMA Surg. 2015;150(5):424–431. Oelschlager BK, Pellegrini CA, Hunter J, et  al. Biologic prosthesis reduces recurrence after laparoscopic paraesophageal hernia repair: a multicenter, prospective, randomized trial. Ann Surg. 2006;244(4):481–490. Oelschlager BK, Pellegrini CA, Hunter JG, et al. Biologic prosthesis to prevent recurrence after laparoscopic paraesophageal hernia repair: long-term follow-up from a multicenter, prospective, randomized trial. J Am Coll Surg. 2011;213(4):461–468. Schlottmann F, Strassle PD, Allaix ME, Patti MG. Paraesophageal hernia repair in the USA: trends of utilization stratified by surgical volume and consequent impact on perioperative outcomes. J Gastrointest Surg. 2017;21(8):1199–1205. Schlottmann F, Strassle PD, Farrell TM, Patti MG. Minimally invasive surgery should be the standard of care for paraesophageal hernia repair. J Gastrointest Surg. 2017;21(5):778–784. Schlottmann F, Strassle PD, Patti MG. Laparoscopic paraesophageal hernia repair: utilization rates of mesh in the USA and short-term outcome analysis. J Gastrointest Surg. 2017;21(10):1571–1576. Skinner DB, Belsey RH. Surgical management of esophageal reflux and hiatus hernia: long term results with 1,030 patients. J Thorac Cardiovasc Surg. 1967;53(1):33–54.

areas have been described (Laimer’s, Killian’s, and Killian-Jamieson’s triangles); however, even though there are different eponyms for the diverticula in each area, they are usually collectively called Zenker’s diverticulum and are similarly treated because of their proximity and pathophysiology (Fig. 1). An altered motility of the upper esophageal sphincter is necessary to create a high-pressure zone and force the mucosa through these areas of weakness. Gastroesophageal reflux disease (GERD) is associated in up to 95% of patients, and this association may be related to esophageal longitudinal muscles reflex contraction and consequent widening of the gap between pharyngeal constrictors and cricopharyngeal muscles, or upper esophageal sphincter spasm. The incidence of cancer in a diverticulum is almost negligible.

DIAGNOSIS Upper digestive endoscopy is usually performed to diagnose the diverticulum and to rule out malignancy and associated diseases. Endoscopists should be aware of the possibility of this diagnosis to prevent missing small diverticula or causing perforation of large diverticula misdiagnosed as the esophageal lumen (Fig. 2).

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Inferior constrictor

Cricopharyngeus

Diverticulum Trachea

FIG. 1  Zenker’s diverticulum at the pharyngoesophageal area.

septum

diverticulum

esophageal lumen

FIG. 2  Zenker’s diverticulum at upper digestive endoscopy. FIG. 3  Barium swallow disclosing a Zenker’s diverticulum (arrow).

Barium swallow allows estimation of the size and location better than the endoscopy because the contrast distends the diverticulum (Fig. 3). Esophageal manometry may be used to diagnose the upper sphincter dysfunction, even though most experts believe that a motor disorder is always present and esophageal manometry is no more than an academic curiosity. Ambulatory pH monitoring may be indicated in patients with suspected GERD to allow planning of a combined procedure or guide medical therapy.

TREATMENT Some propose treating only symptomatic diverticula, while others advise treatment to prevent complications such as aspiration, even in the absence of symptoms. The diverticulum may be treated by: (1) myotomy of the cricopharyngeal muscle alone; (2) myotomy plus diverticulectomy; (3) myotomy plus diverticulopexy; or (4) endoscopically by division of the septum between the diverticulum and the esophagus (diverticulo-esophagostomy [Dohlman’s procedure]) (Fig. 4).

bilateral arciform incision. The layers to be dissected are: (1) skin; (2) subcutaneous tissue that is conjoined with the platysma muscle; and (3) superficial cervical fascia. After these planes are dissected, the infrahyoid muscles will be exposed. Usually there is no need to divide muscles. The sternohyoid muscle can be retracted medially and the omohyoid superiorly. The diverticulum is usually located below the omohyoid muscle. After the muscles are retracted, the esophagus is exposed. There is no need for circumferential dissection of the esophagus as it increases the risk of damage to the left recurrent laryngeal nerve located in the groove between the esophagus and the trachea. If the diverticulum is not yet identified, the esophagus should be rotated to expose the posterior side. Sometimes esophageal intubation by the anesthesiologist or intraoperative endoscopy is necessary to identify the diverticulum.

Dysmotility Treatment

SURGICAL MANAGEMENT Surgical Anatomy and Access Most surgeons prefer a left cervical incision following the medial border of the sternocleidomastoid muscle, while others opt for a

The myotomy of the cricopharyngeal muscle must always be performed based on the assumption that an upper esophageal sphincter dysfunction is part of the pathophysiology of the disease. If the neck of the diverticulum is properly dissected, the myotomy is easily performed because the diverticulum is composed entirely of mucosa,

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Management of Zenker’s Diverticulum

A

B

C

D

FIG. 4  Treatment options for Zenker’s diverticulum. (A) Myotomy of the cricopharyngeal muscle. (B) Stapled diverticulectomy. (C) Diverticulopexy. (D) Endoscopic diverticulo-esophagostomy. (From Herbella FA, Patti MG. Modern pathophysiology and treatment of esophageal diverticula. Langenbecks Arch Surg. 2012;397:29–35.)

and the interface between the muscular and mucosa layers can be effortlessly found. The myotomy must be extended about 3 cm downward onto the esophageal wall.

Diverticulum Treatment There is no need to resect small diverticula (15 mm Hg. Instantaneous pressure along the black dashed line is represented by the black line on the right side of each panel. (A) Type I achalasia: characterized by no esophageal contraction or esophageal pressurization. (B) Type II achalasia: characterized by panesophageal pressurization and no peristaltic contraction. Note that pressurization corresponds to homogeneous pressure along the spatial pressure variation plot. (C) Type III achalasia: characterized by at least 20% premature contractions, defined as distal latency (DL) less than 4.5 seconds. DL is defined as the interval between UES relaxation and the contractile deflection point (CDP), which is a pressure topographic metric that demarcates peristalsis from ampullary emptying, localized within 3 cm of the proximal LES. Note the multiple peaks corresponding to contractions along the spatial pressure variation plot. EGJ outflow obstruction may represent achalasia (D) It might also be the consequence of a mechanical obstruction (E), such as a distal esophageal stenosis. (From Kahrilas PJ, Bredenoord AJ, Gyawali CP, et al.; International High Resolution Manometry Working Group. The Chicago Classification of Esophageal Motility Disorders, v3.0. Neurogastroenterol Motil. 2015;27[2]:160–174).

and involves injecting the toxin into four quadrants of the LES. Typically, 80 to 100 units are injected (20–25 units/quadrant). Its mechanism of action involves irreversible inhibition of acetylcholine release from presynaptic terminals that eliminates the neurogenic component of the LES pressure. Therapeutic relief is short-lived, however, as new axonal growth will eventually occur, and the patient’s symptoms will recur. Patients typically report an improvement in their symptoms for up to 1 year but often require repeat endoscopic injection. Repeat injection may be associated with local inflammatory reactions and fibrosis, which limit its repetition. Chest discomfort and rash are also known side effects of the therapy. Pharmacologic therapies administered via the sublingual route before eating have also been employed in patients who are unfit for general anesthesia. These have included smooth muscle cell relaxants such as nitrates and calcium channel blockers that can lower the LES pressure. Side effects such as headaches limit the use of nitrates.

Nifedipine administered via the sublingual route (30 mg/day) is also associated with headache, orthostasis, and dizziness and has limited efficacy. Sildenafil has also been trialed and has short-lived efficacy. Its use is limited by cost and potential side effects.

Pneumatic Dilation Endoscopic dilation is the most effective nonsurgical option for achalasia. The principles of this therapy involve disruption of the circular muscle fibers of the LES as a result of dilation. Pneumatic dilators are more effective in achieving physical disruption of the muscle fibers in comparison with rigid dilators. These endoscopic procedures are performed under conscious sedation, and aspiration risk is not insignificant in this patient population because there may be retained food within the esophageal lumen. Implementation of a clear liquid diet for longer than 1 day may be advisable.

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IRP  ULN and 100% failed peristalsis or spasm

Yes

Achalasia Type I: No contractility Type II: 20% PEP Type III: 20% spasm (DL 50% ineffective swallows

Yes

Fragmented Peristalsis  >50% fragmented swallows and not ineffective

No 5

IRP normal and >40% effective swallows

Ineffective Motility (IEM)  >50% ineffective swallows

Minor disorders of peristalsis Impaired clearance

Yes

Normal

FIG. 3  The Chicago Classification version 3.0, a hierarchical analysis. The initial step involves evaluating the relaxation of the esophagogastric junction (EGJ) upon swallowing by using the integrated relaxation pressure (IRP, defined as the mean of the 4 seconds of maximal deglutitive relaxation in the 10-second window beginning at upper esophageal sphincter (UES) relaxation. If elevated (greater than upper limit of normal [ULN] of 15 mm Hg), patients should be classified as having achalasia or EGJ outflow obstruction, depending on the peristalsis. In the case of a normal IRP, peristalsis is classified based on its absence, distal latency (DL, defined as the interval between UES relaxation and the contractile deflection point, CDP, which is a pressure topographic metric that demarcates peristalsis from ampullary emptying, localized within 3 cm of the proximal lower esophageal sphincter, LES), distal contractile integral (DCI, defined as: amplitude × duration × length (mm Hg • s • cm) of the distal esophageal contraction exceeding 20 mmHg from the transition zone to the proximal margin of the LES) and fragmentation. If there are abnormalities, patients are classified as having a major or minor disorder of peristalsis. Major disorders are never observed in controls, in contrast with minor disorders. If a patient has a normal IRP and more than 50% of swallows are effective, esophageal motility is normal. (From Pandolfino JE, Kahrilas PJ. Esophageal neuromuscular function and motility disorders. In: Feldman M, Friedman LS, Brandt LJ, eds. Sleisenger and Fordtran’s Gastrointestinal and Liver Disease. 11th ed. Philadelphia: Elsevier; 2021:chap 44; Rohof WOA, Bredenoord AJ. Chicago Classification of Esophageal Motility Disorders: Lessons Learned. Curr Gastroenterol Rep. 2017;19[8]:37.)

Gastroscopy and fluoroscopy are used to guide inflation of the dilating balloon. Balloon sizes can range from 3.0 to 4.0 cm in 0.5 cm increments. A handheld manometer is used as the balloon is passed over a wire fluoroscopically. The “waist” of the balloon is created as a result of the LES and should essentially be carefully effaced during inflation. Long-lasting reduction in LES pressure typically involves dilation of the LES to 3 cm. A cautious approach should always be employed starting with the smallest balloon first. If the patient does not have symptomatic relief or there is an unsatisfactory result with dilation, it may be useful to repeat the dilation at a short interval (2–3 weeks). Esophageal perforation is the most worrisome complication of pneumatic dilation and can occur at an incidence of 1%. Some practitioners perform a water-soluble followed by barium esophagram to follow each of their dilations routinely. Most perforations are apparent within the first hour after the procedure as fever, chest pain, and subcutaneous emphysema may be indicative of an esophageal leak.

If the perforation is small, conservative measures including NPO, intravenous antibiotics and antifungals, and inpatient observation can be employed. If there is worsening fever, chest pain, or an uncontrolled leak, surgical therapy is recommended as early as possible (450). DCI, Distal contractile integral. (Courtesy The Oregon Clinic.)

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and jackhammer esophagus. Phosphodiesterase-5 inhibitors such as sildenafil, which acts by blocking degradation of nitric oxide, also can be effective. These drugs may be tolerated poorly because of lightheadedness, headache, or other side effects, and tachyphylaxis has been noted. The cost of sildenafil may be prohibitive, and effects of daily long-term use of this agent in various populations of patients are unknown. Low-dose antidepressants, including tricyclic agents and trazodone, may provide pain modulation and anxiety relief for noncardiac chest pain. As previously discussed, GERD is frequently part of the clinical syndrome of esophageal dysmotility, although its role in pathogenesis is not understood completely. A trial of PPIs is warranted and may help reduce inflammation, pain, and spasm related to abnormal esophageal acid exposure.

Endoscopic Therapy PD has been used to treat spastic esophageal motility disorders affecting the EGJ, including EGJOO, DES, and nutcracker esophagus, with variable success. In small studies, 26% to 70% of DES and nutcracker patients had a favorable response with PD, although there is concern that some of these cases may have been classified more accurately as achalasia. From the achalasia literature, there is a known risk of perforation with pneumatic dilation in the range of about 2% to 5% of cases performed by expert endoscopists. This rate of perforation is unacceptable to many endoscopists, who no longer use PD as first-line therapy. Endoscopic injection of botulinum toxin (Botox) may be temporarily effective in relief of spasm in EGJOO, DES, or jackhammer disorders. The technique for administration of botulinum toxin has not been standardized; some report injection of the EGJ alone, and others include the esophageal body. Botox to the esophageal body may be helpful in cases such as DES or jackhammer, although it is uncertain exactly where and how much drug should be injected. Infection is an uncommon but serious risk of Botox injections. One death resulting from mediastinitis has been reported in a DES case treated with Botox, although other serious adverse events have been rare. Endoscopists may elect to use EUS to guide positioning and depth of injections into the thinner-walled esophageal body. In small studies of patients with EGJOO and DES, successful relief of symptoms with botulinum toxin injections was achieved in more than 50% of patients at 6 months, with further improvement from serial on-demand treatments thereafter. This was comparable to efficacy in achalasia. Fall-off of symptom relief is present in each of these disorders with time, which may require repeat treatments or escalation to surgical intervention. Prominent symptoms and spastic features may predict early recurrence of symptoms. Botulinum toxin before surgical myotomy has been noted to cause submucosal fibrosis and increase difficulty in identifying and maintaining the proper dissection plane. Prior Botox is not an absolute contraindication to surgery, however, and may be useful as a trial to determine if a patient may respond well to surgical myotomy. Long-term studies are not available evaluating the efficacy of repeated botulinum toxin injection for spasm.

Surgical Management Surgical therapy is an option for nonachalasia esophageal motility disorders, but optimal timing and approach are controversial. Surgery generally has been reserved for medically refractory cases because outcomes are variable, somewhat unpredictable, and may be associated with surgical morbidity. As mentioned earlier, IEM patients with GERD, whether they also have dysphagia, tolerate antireflux surgery with a tailored fundoplication well, and treatment of the reflux often corrects the motility disorder as well. Classically, these patients have a partial fundoplication, most commonly a 270-degree posterior wrap (Fig. 7). Nissen fundoplication also has been shown to be well tolerated in select patients; a full wrap should be reserved for IEM patients with minimal symptoms of dysphagia before surgery and significant reflux disease. Endoluminal antireflux

FIG. 7  Completed laparoscopic 270-degree posterior Toupet fundoplication.

procedures such as Stretta (radiofrequency) and transoral incisionless fundoplication, which provide less-aggressive valve reconstructions, also may be good options for these patients. Data on surgical outcomes for EGJOO, DES, and other hypercontractile disorders are limited to a few series, mostly small and nonrandomized over the past 50 years. As diagnostic modalities have improved and disease classifications have evolved, these data become even more difficult to interpret. In general, outcomes for surgery are better for relief of chest pain and dysphagia compared with medical or endoscopic therapies. In DES, which is the most frequently studied esophageal motility disorder aside from achalasia, favorable symptomatic outcomes are reported in about 70% of cases treated with surgical myotomy via an abdominal or thoracic approach at highly skilled centers. These outcomes are notably less successful than those for surgical myotomy for achalasia, so surgery often is reserved as a last resort for patients with nonachalasia motility disorders. Symptoms of chest pain are less reliably improved than dysphagia in these patients, and prior series have reported only 50% reduction in chest pain for patients with nutcracker esophagus. Therefore, many of these patients endure long courses of medical or endoscopic therapy because there is no clear definition of “medical failure.” Surgical techniques for esophageal myotomy are varied. Traditional open surgery largely has been replaced by minimally invasive techniques, and new endoscopic options are available. Length of the esophageal body myotomy, inclusion of the EGJ in the myotomy, and addition of a concomitant antireflux procedure are variable from surgeon to surgeon. Previous authors in this text have recommended a long thoracic myotomy for the treatment of DES or other esophageal body motility disorders and have described the technique in detail (Fig. 8). Thoracic access allows myotomy extension for the full length of the esophageal body, which is not possible with laparoscopic Heller myotomy. However, thoracic myotomy has the disadvantage of requiring single lung ventilation, chest tube placement, and typically a longer length of stay. The thoracic approach is complicated further if the surgeon desires a fundoplication or extended gastric myotomy. POEM offers several advantages for esophageal myotomy and is preferred as a less invasive technique for patients with hypercontractile/spastic esophageal motility disorders. This natural orifice transluminal endoscopic surgery procedure is completely endoscopic

52

Management of Disorders of Esophageal Motility

A

B

FIG. 8  (A) Thoracic myotomy and (B) Belsey fundoplication. Courtesy Corinne Sandone. (From Cameron JL, Sandone C. Atlas of Gastrointestinal Surgery, vol 1. 2nd ed. Shelton, CT: People’s Medical Publishing; 2007.)

and incisionless. It provides the ability to tailor the length and location of the myotomy with ease because the entire affected esophageal body and EGJ are accessible. POEM allows the surgeon to produce a selective circular myotomy and avoids the risk of vagus nerve injury or disruption of the diaphragmatic crural component of the EGJ. Single lung ventilation, lateral or prone positioning, and chest tubes are not required. Moreover, postoperative pain is usually minimal. POEM was first applied clinically for achalasia by Inoue in 2008, and since then more than 4000 cases have been performed worldwide with an excellent safety profile and good clinical results, mostly for patients with achalasia. Until recently, studies of POEM for nonachalasia esophageal motility disorders included only a few such cases and have not always been stratified by subtype. POEM is also used for spastic esophageal disorders such as DES, jackhammer esophagus, and EGJOO (including cases of nutcracker esophagus and HTLES as classified before CC v3.0) with favorable results. POEM has reported success rates of more than 80% for these disorders with relatively low morbidity at expert centers. In a meta-analysis by Khan et al. examining the clinical success of POEM in spastic esophageal disorders including type III spastic achalasia, DES, and nutcracker esophagus, 179 patients were pooled for analysis from 8 observational studies. Clinical success for all types of spastic esophageal disorders was 87%. Although these studies are small, they suggest comparable outcomes for extended POEM with low morbidity compared with traditional open or laparoscopic/thoracoscopic approaches for extended esophageal myotomy. Given the subsequent weakening of peristalsis after esophageal body myotomy, it is recommended to extend the myotomy through the EGJ onto the stomach to prevent relative outflow obstruction and postoperative dysphagia, even in the setting of a normally relaxing EGJ. POEM myotomy length should be tailored based on HRM topography and endoscopic measurement of the high-pressure zone and has been extended proximally anywhere between 6 and 23 cm above the gastric cardia in such cases. POEM with variable length of myotomy was comparable to other surgical techniques for relief of dysphagia and chest pain and had less morbidity. A disadvantage of POEM is the requisite learning curve, which is about 20 cases for experienced endoscopists as demonstrated by Kurian and colleagues. GERD is also a long-term risk of POEM, currently with a 20% to 46% risk based on cumulative data. This is in fact comparable to Heller myotomy with partial fundoplication, which has a postoperative rate of GERD between 21% and 42%, depending on the fundoplication technique. Postoperative GERD is asymptomatic in one-half of patients, so routine follow-up pH testing or endoscopy is prudent. Patients identified with GERD have been treated successfully with PPIs with avoidance of long-term sequelae

of reflux thus far. POEM results in a low rate of clinically significant leak or stricture and has been shown to be safe and effective in revision after Heller myotomy, Botox, and PD. POEM does not preclude subsequent endoscopic, laparoscopic, or thoracoscopic procedures should they be required. Because of these benefits, extended myotomy by POEM should be the preferred approach for primary spastic motility disorders requiring intervention.

Peroral Endoscopic Myotomy Operative Technique Previous chapters in this and other texts have described esophageal myotomy with or without fundoplication via abdominal and thoracic approaches, so these are not repeated in detail here. POEM is performed in the operating room under general anesthesia. The procedure requires a high-definition endoscope for optimal visualization and CO2 insufflation because it has a better safety profile than room air. The patient is placed in the supine position to allow access to the abdomen or chest. For a few days before the procedure, patients are given a Nystatin rinse prophylactically to clear any Candida esophagitis related to esophageal stasis and allowed only a liquid diet for 1 day to allow clearance of retained food. A preoperative antibiotic and a single preoperative dose of intravenous steroid are administered to prevent development of mucosal edema. Upper endoscopy is performed to evaluate the anatomy, rule out Candida spp., and clear any fluid or food debris within the esophagus before proceeding. An endoscopic functional lumen imaging probe (EndoFLIP) is used to measure baseline esophageal diameter, pressure, cross-sectional area, distensibility, and compliance. An overtube is used for distal myotomy to stabilize the scope from overtorquing. No overtube is used for extended myotomy. The gastric wall is tattooed with indigo carmine 2 cm distal to the EGJ in the anterior position along the lesser curvature, marking the target for the distal extent of the myotomy. The location and extent of the myotomy and mucosotomy are calculated based on careful evaluation of the preoperative manometry and intraoperative evaluation of the high-pressure zone. An angled dissecting cap is attached to the high-definition endoscope to facilitate dissection and visualization. A mucosal lift is created with injectable saline with dilute indigo carmine in the anterior esophagus 2 to 4 cm proximal to the proximal extent of the planned myotomy (Fig. 9). An endoscopic cautery knife is used to create a 1.5-cm longitudinal mucosal incision to expose the submucosa. Using the dissecting cap, the surgeon advances the endoscope through the mucosotomy and into the submucosal plane. Once inside, spray cautery and serial injections of lifting solution are used to create a submucosal tunnel, separating the mucosa from the circular muscle. Visible vessels are coagulated with the dissecting knife or grasped with hot biopsy

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D

FIG. 9  Peroral endoscopic myotomy. (A) Entry into submucosal plane. (B) Creation of submucosal tunnel (mucosa is inferior, circular muscle is superior). (C) Myotomy of circular muscle. (D) Closure of mucosal entry site with clips. (From Inoue H, Sato H, Ikeda H, et al. Per-oral endoscopic myotomy: a series of 500 patients. J Am Coll Surg. 2015;221:256–264).

forceps. The submucosal tunnel is extended distally across the GEJ and onto the gastric wall until the distal darker blue tattoo is reached. Once satisfied with the extent of the tunnel, the endoscope is brought back, and the myotomy is created by selectively dividing the circular muscle layers. The thin longitudinal muscle layer is left intact whenever possible. Full-thickness breaches of the muscle are usually not critical as the mediastinal adventitial tissue is left intact. The myotomy is extended across the EGJ and onto the proximal gastric wall. During the procedure, exiting the tunnel to deflate insufflated gas from the stomach may be required to relieve gastric distension. Capnoperitoneum may develop in up to 30% of cases; it is often minor and self-limited but is evacuated easily with a Veress needle if abdominal overdistension or respiratory compromise develops. After the myotomy is completed, the surgeon withdraws the endoscope, checking for hemostasis. Completion endoscopy identifies any inadvertent mucosal injuries, which are treated with endoscopic clips. The EndoFLIP catheter is replaced, and measurements are compared with those obtained before surgery to ensure adequacy of the myotomy before closure. Endoscopic clips then are used to close the proximal mucosotomy in a longitudinal fashion from distal to proximal.

Postoperative Care The patient is kept NPO overnight, and a routine contrast esophagram is obtained on the first postoperative day. If no leaks or obstruction are identified, the patient is allowed clear liquids and crushed medications. The patient may be discharged on postoperative day 1 if liquids are tolerated and should maintain a puree-consistency diet for 1 week to avoid disruption of the mucosal closure clips. In most cases, postoperative pain is minimal and usually does not require narcotics.

Complications Acute postoperative complications can include intratunnel bleeding, mucosal leak or dehiscence, or mediastinitis. No deaths have been

reported. Bleeding may require transfusion and repeat endoscopy to achieve hemostasis. Mucosal leaks or dehiscence may seal with conservative management but often require repeat endoscopy and repair with additional clips or suturing. Mediastinitis is treated with antibiotics and may require percutaneous or surgical drainage. Postprocedure adverse events in the meta-analysis reported by Khan et al. for all types of spastic esophageal disorders were 14%. Most of the adverse events (74%) were managed conservatively. Five patients required prolonged hospitalization and/or an intervention for pneumothorax, pulmonary embolism, capnoperitoneum, or bleeding.

CONCLUSION There is work to be done in the realm of nonachalasia esophageal motility disorders as HRM diagnostics and treatment options evolve. To achieve the best possible outcome, therapeutic options should be considered carefully and individually tailored. Patients should be advised on expectations because treatment outcomes are somewhat unpredictable and may be disappointing in some cases. POEM is a promising, minimally invasive treatment option for hypercontractile and spastic disorders and perhaps will be considered as an early surgical intervention rather than salvage therapy, given its relative success and safety profile. For hypomotility disorders associated with GERD, partial fundoplications remain the gold standard, although Nissen fundoplication also has been shown to be well tolerated in many cases of at least partially preserved peristalsis. There also may be a role for newer endoscopic antireflux procedures, although there are insufficient data at this time to define their application for these relatively rare disorders.

ACKNOWLEDGMENT We acknowledge the work of Kristin Wilson Beard, MD, in conjunction with Lee L. Swanstrom, MD, on the comprehensive content in previous editions of this text.

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Management of Esophageal Cancer

Suggested Readings

Schlottmann F, Shaheen NJ, Madanick RD, Patti MG. The role of Heller myotomy and POEM for non-achalasia motility disorders. Dis Esophagus. 2017;30(4):1–5. Sharata A, Dunst C, Pescarus R, et al. Peroral endoscopic myotomy (POEM) for esophageal primary motility disorders: analysis of 100 consecutive patients. J Gastrointest Surg. 2015;19:161–170. Vanuytsel T, Bisschops R, Farré R, et al. Botulinum toxin reduces dysphagia in patients with nonachalasia primary esophageal motility disorders. Clin Gastroenterol Hepatol. 2013;11:1115–1121 e2. Woltman TA, Oelschlager BK, Pellegrini CA. Surgical management of esophageal motility disorders. J Surg Res. 2004;117:34–43. Yadlapati R, Kahrilas PJ, Fox MR, et  al. Esophageal motility disorders on high-resolution manometry: Chicago classification version 4.0. Neurogastroenterol Motil. 2020;33:e14058.

Almansa C, Hinder RA, Smith CD, et  al. A comprehensive appraisal of the surgical treatment of diffuse esophageal spasm. J Gastrointest Surg. 2008;12:1133–1145. Inoue H, Sato H, Ikeda H, et al. Per-oral endoscopic myotomy: a series of 500 patients. J Am Coll Surg. 2015;221:256–264. Khan MA, Kumbhari V, Ngamruengphong S, et al. Is POEM the answer for management of spastic esophageal disorders? A systematic review and meta-analysis. Dig Dis Sci. 2017;62:35–44. Roman S, Kahrilas PJ. Distal esophageal spasm. Curr Opin Gastroenterol. 2015;31:328–333. Samo S, Qayed E. Esophagogastric junction outflow obstruction: Where are we now in diagnosis and management? World J Gastroenterol. 2019;25(4):411–417.

Management of Esophageal Cancer

lumen. A notable component of the patient’s past medical history is often a long-standing history of gastroesophageal reflux disease with or without a hiatal hernia. Due to the fact that symptoms often present late, patients are typically at an advanced stage at the time of diagnosis. However, those with a history of reflux disease may be diagnosed earlier on surveillance endoscopy.

Fatima G. Wilder, MD, and Stephen C. Yang, MD

EPIDEMIOLOGY

DIAGNOSIS/STAGING

Esophageal cancer is the eighth deadliest cancer in the world as reported by the World Health Organization in 2020. The two predominant histologic types are adenocarcinoma (most common in the United States) and squamous cell carcinoma (most common worldwide). Notable risk factors include gastroesophageal reflux, smoking, alcohol consumption, nutritional deficiencies, environmental carcinogens, long-standing achalasia, and caustic injury.

Diagnosis and staging should be carried out in an expeditious manner to avoid delay in therapy, potentially compromising outcome. The eighth edition of the American Joint Committee on Cancer (AJCC) staging of epithelial cancers of the esophagus and esophagogastric junction (EGJ) presents separate classifications for clinical (cTNM), pathologic (pTNM), and postneoadjuvant (ypTNM) stage groups, and differs slightly between adenocarcinoma and squamous cell histologies (Fig. 1). Barium swallow should be the first study in the diagnostic workup of esophageal cancer, as it will provide critical information regarding the source of obstruction. However, esophagogastroduodenoscopy (EGD) remains the gold standard for evaluation and tissue diagnosis when there is a concern for malignancy. It allows for identification of anatomical location of the mass, tumor characteristics, relation to surrounding structures, and tumor grade. Evidence of Barrett’s esophagus should be characterized according to the Prague criteria.

CLINICAL PRESENTATION Commonly reported symptoms at the time of presentation include regurgitation, odynophagia, weight loss, and hematemesis. Dysphagia is the most common presenting symptom in patients with esophageal cancer. In the early phases of obstruction, patients typically compensate for their symptoms by adjusting their diet and consuming semisolid and liquid nutrition as tolerated. Dysphagia does not typically present until the tumor occludes two-thirds of the

pTNM Adenocarcinoma N0 Tis

N3

N0

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IA IB

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IIIB

IIIB

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IVA

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IIB

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T1b

IB IIA IIA IIA

IB IIA IIA IIB

B

FIG. 1  Staging of esophageal cancer, American Joint Committee on Cancer Manual, eighth edition. Pathologic stage groups (pTNM) for (A) adenocarcinoma and (B) squamous cell carcinoma. (From Rice TW, Ishwaron H, Ferguson MK, Blackstone EH, Goldstraw P. Cancer of the esophagus and esophagogastric junction: an eighth edition staging primer. J Thoracic Oncol. 2017;12[1]:36–42.)

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TABLE 1  Siewert Classification Siewert Type

Description

I

Adenocarcinoma of the lower esophagus with the epicenter located within 1 to 5 cm above the anatomic GEJ

II

True carcinoma of the cardia with the tumor epicenter within 1 cm above and 2 cm below the EGJ

III [Considered gastric cancer; utilize gastric cancer algorithm for management guidelines]

Subcardial carcinoma with the tumor epicenter between 2 and 5 cm below the EGJ, which infiltrates the EGJ and lower esophagus from below

All suspicious lesions should be biopsied simultaneously. Based on the Seattle protocol, six to eight four-quadrant biopsies of the mass utilizing standard size endoscopy forceps should be obtained along every centimeter of gross disease. If available at the time of EGD, endoscopic ultrasound (EUS) is important as an early staging modality and to determine the Siewert classification (Table 1), as location will determine optimal treatment pathways. EUS will also assess tumor invasion (T stage), presence of suspicious lymph nodes (N stage), and, at times, presence of regional metastases (M stage). The addition of fine-needle aspiration (FNA) aids in the accuracy of diagnosis. Endoscopic mucosal resection (EMR) can be considered therapeutic especially in patients with early-stage disease (T1a or T1b). This typically correlates with small, nodular lesions ≤2 cm. Focal nodules should be completely excised and sent for pathology. Tumor samples should be assessed for depth of invasion, degree of differentiation, and presence of vascular and/or lymphatic invasion. Presence of poor differentiation, deep submucosal invasion, and/or lymphovascular invasion (LVI) are associated with greater risk of lymph node involvement. Additional workup including computed tomography (CT) of the chest, abdomen, and pelvis with oral and IV contrast is indicated

55

to evaluate for metastatic disease, assess the locoregional extent of the disease, and evaluate for issues of unresectability. CT is poorly sensitive for early-stage disease, type of Siewert location, and limited in its ability to distinguish T3 from T4 lesions. However, esophageal thickening of more than 5 mm clearly is considered abnormal. Whole body 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)/CT is done to assess for metastatic disease. In patients with tumor that is at or above the carina, with no evidence of M1 disease, bronchoscopy should be performed. Symptom management in the preoperative settings includes esophageal dilation for those with obstructive symptoms. Tumor ablation with Nd:YAG laser, photodynamic therapy (PDT), and cryoablation can be utilized for long-term ablation. Expandable metal or plastic stents can also be utilized to relieve obstructive disease but should not be placed if radiation therapy is offered for local control.

STAGE-BASED TREATMENT STRATEGIES/ ALGORITHMS There are subtle differences in the treatment of esophageal cancer based on stage depending on the histology; these are briefly listed in Table 2. T1 tumors involving the mucosa and superficial submucosa may be addressed with EMR or endoscopic submucosal dissection; deeper submucosal lesions may be treated with esophagectomy. Data regarding treatment of squamous cell carcinoma with EMR are limited. Optimal management of T2N0M0 disease is somewhat controversial. Due to unreliable clinical staging modalities, a significant percentage of patients are under- and overstaged. Although historical evidence supports induction therapy for this group, there are a growing number of studies that suggest induction therapy is not beneficial in those with node-negative disease. Current NCCN guidelines suggest that, for patients who are medically fit, there are a variety of treatment possibilities including definitive chemoradiation and esophagectomy with or without induction or adjuvant therapy. Treatment selections also take into consideration low- versus high-risk lesions. cT1b-cT2, N0 low-risk lesions that are 10.000 WBC/mL) Pleural effusion on imaging*

1

• Fever (>38.5°C) • Noncontained perforation† • Respiratory distress (>O2 requirements, RR >30, need for mechanical ventilation) • Time to diagnosis >24 hours

2

• Hypotension • Malignancy

3

*Chest x-ray, esophagram, or chest CT. † Esophagram or chest CT. bpm, Beats per minute; RR, respiratory rate; WBC, white blood cells.

the most dire situations, esophageal resection and exclusion may be necessary. Regardless of the therapeutic approach chosen, initial management of patients with esophageal perforation should include close monitoring in a surgical critical care unit. Patients should be maintained nil per os (NPO), appropriately resuscitated with intravenous fluid, and started on broad-spectrum antibiotics to include fungal coverage. Adequate intravenous analgesia and a proton pump inhibitor (PPI) should be started, and early total parenteral nutritional support can be considered if a prolonged course is expected.

Nonoperative Management Criteria for nonoperative management were initially described by Cameron et al. in 1979 and further modified by Altorjay. These included early diagnosis, contained perforations or perforations draining back into the esophagus, no significant mediastinal contamination, absence of sepsis or multiorgan failure, and perforation not associated with malignancy or obstruction of the esophagus. If

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hemodynamically stable without signs of sepsis or multiorgan failure, the patient is admitted to the surgical critical care unit for 48 to 72 hours of observation. Patients should be maintained NPO with the head of the bed elevated, started on 72 hours of broad-spectrum antibiotics and a PPI, and, dependent on premorbid nutritional status, considered for parenteral nutritional support. Repeat imaging is obtained in 72 to 96 hours. If this demonstrates no evidence of free perforation, a liquid diet may be initiated. It is important to remember that these patients require close observation to ensure that they continue to meet nonoperative criteria. Should the patient’s clinical condition deteriorate as evidenced by the development of fever, leukocytosis, tachypnea, tachycardia, or mental status changes, repeat imaging and possible endoscopy are indicated.

Endoscopic Stenting with Thoracoscopic Mediastinal and Pleural Drainage For patients with evidence of free contrast extravasation into the mediastinum, endoscopic covered stent placement or endoluminal clipping to attempt to seal the perforation can be performed as an alternative to open surgical repair. It is vital to remember that this approach does not address the associated mediastinal and possible pleural contamination. For this reason, early video-assisted thoracoscopic surgery (VATS), performed either immediately after stent placement or within 1 to 2 days following the procedure, is generally required for debridement and drainage of the mediastinum and pleural cavity. At the conclusion of the VATS procedure, depending on the degree of contamination, at least one chest tube is left in the pleural space, and another (often a Blake drain) is left adjacent to the esophagus. Typically, a contrast esophagram is performed 48 hours after stent placement to determine if sealing of the esophageal perforation has occurred. If there is no evidence of extravasation, a clear liquid diet can be started and advanced to full liquids. It is advisable to leave the tube in place adjacent to the esophagus while the liquid diet is being initiated to monitor the character of the output as well as the patient’s clinical condition. On the other hand, if the esophagram shows extravasation of contrast around the stent into the mediastinum or the drainage character changes after liquids are begun, the patient should be returned to NPO status and will require placement of a jejunostomy tube. In their study, Ben-David et al. showed encouraging results in 76 patients with esophageal perforation (majority iatrogenic or spontaneous) managed with endoscopically placed metallic covered stents in addition to laparoscopic or VATS drainage and enteral feeding access placement. All patients were treated within 24 hours of initial presentation, and perforation occlusion was confirmed within 48 hours after stent placement in 68 patients (89.5%). Additionally, no need for an open esophageal procedure was required, avoiding the morbidity of a more invasive operation. However, stent placement was not without complications, with an almost 40% migration rate requiring additional intervention within the first week of placement. The ideal time for esophageal stent removal remains controversial and may depend on the size of the perforation. Some studies have shown adequate healing within 10 days for small perforations, while this process may take up to 8 weeks for larger defects. Ben-David et al. showed a mean length of 36 days from initial placement to final stent removal. In practice, waiting between 4 and 6 weeks, depending on the size of the perforation, is reasonable. Imaging confirmation of perforation healing with an esophagram should be obtained following stent removal before a liquid diet is initiated. If the perforation has not healed at the time of stent removal, the stent can be replaced for another 4 to 6 weeks.

Endoscopic Techniques The use of endoluminal stents for the management of esophageal perforations is not a new concept, and in fact the most used self-expanding metal stents (SEMS) have been available since the 1990s.

77

Technology improvement with better deployment mechanisms have also increased their use. The development of covered stents with different polymers has increased the technical and clinical success of the management of esophageal perforations and, at the same time, has decreased the rate of stent-related complications. Esophagogastroduodenoscopy (EGD) is performed to localize the defect, determine the extent of the perforation, and identify anatomic landmarks and other esophageal abnormalities. Under direct vision and with the concomitant use of fluoroscopy, a careful assessment of the landing zones and the desired diameter and length of the stent is conducted. Once this assessment is completed, the landmarks for the proximal and distal extent of the stent are marked with radio-opaque markers under fluoroscopy. A guidewire is then introduced under fluoroscopy. Figure 3 shows an endoscopic view of a perforation and subsequent stent placement. Ideally, the stent deployment will successfully cover the perforation on the first attempt, however the stent can be endoscopically repositioned to achieve complete coverage of perforation if needed. If there is evidence of incomplete radial deployment, a balloon dilation may be performed to attain complete contact between the stent and esophageal mucosa. An NGT can be placed under direct vision for gastric decompression in the acute setting. An anteroposterior and lateral chest x-ray should be obtained after stent placement to have a baseline for its location and facilitate further assessment of adequate positioning. As noted, a contrast esophagram should be obtained 48 hours after stent placement before liquids are begun. Figure 4 shows a SEMS in adequate position without evidence of contrast extravasation. Stent complications include migration, bleeding, erosion, and tissue overgrowth, among others. Migration is the most common complication reported in about 8% to 40% of cases, with less migration rates reported with the use of metallic stents compared with plastic stents. Some studies have reported endoscopic suturing or clipping to secure the stent and prevent migration with favorable results. Endoscopic suturing or clip placement may also be used to attempt to primarily repair small, early perforations. Previous reports demonstrate higher rates of closure, with an average defect size of 8 mm and higher failure rates when the lesion is greater than 13 mm. EGD is performed, and the esophageal defect is identified to confirm healthy mucosal edges for adequate clip placement. Through-thescope clips can be used for defects less than 1 cm, and an over-thescope clip system can be used for larger lesions. Suction can be used to help approximate the lesion edges and aid with better clip deployment. Even though acceptable results have been reported in the literature, this technique is not commonly used given that patients usually present with a more advanced disease process requiring more aggressive interventions.

Open Repair Currently, little data exist to guide surgeons as to whether to proceed with an open repair or choose stent placement with pleural/ mediastinal drainage. Elderly patients and those with multiple medical comorbidities are likely better served with the endoscopic/ thoracoscopic approach. Although the likelihood of success of an open repair diminishes over 24 hours from the perforation event, several reports describe successful repairs being performed for perforations beyond the 24-hour mark. Following initial resuscitation efforts, patients who remain hemodynamically labile may still undergo successful repair, although a less invasive approach has obvious advantages in these patients. Ultimately, the decision is left to surgeon judgment and experience of the surgeon and his or her team with each approach. If open repair is chosen, it is critical to identify the location of the perforation to guide the surgical approach. This may require performance of endoscopy in the operating room before incision. Whenever feasible, two-layer closure should be performed and reinforced with a pedicled buttress. In cases of delayed perforation, single-layer closure may be all that is possible.

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Management of Esophageal Perforation

A

B

FIG. 3  Endoscopic treatment of esophageal perforation. (A) Endoscopic view of a perforation in the middle third of the esophagus (arrow). (B) Endoscopic view of the stent in place. (From Chirica M, Champault A, Dray X, et al. Esophageal perforations. J Visc Surg. 2010;147[3]:e117–e128.)

A

B

FIG. 4  Esophagram. (A) Esophageal stent in adequate position covering a prior perforation. (B) Stent in place without evidence of contrast extravasation.

Thoracic Perforations Perforations of the upper and middle thirds of the esophagus are best approached through a right posterolateral thoracotomy via the fourth or fifth intercostal space. The intercostal muscle (ICM) within the interspace is harvested at this time using electrocautery to ultimately buttress the repair. The cautery tip is positioned near parallel with the surface of the superior rib to avoid injury to the neurovascular bundle. The ICM is freed from the rib to the level of the lumbar-dorsal fascia. Care must be taken to identify this landmark because further dissection risks injury to the intercostal vessels. The ICM flap is transected anteriorly after ligating or clipping the anterior aspect of the muscle to prevent bleeding. Next, the pleura is opened in the area of the perforation, and the esophagus is dissected enough to obtain clear visualization of the perforation. The edges of

the perforation should be debrided to determine the full extent of the injury. Of note, the mucosal injury may extend a greater distance than the visualized muscular injury. The esophageal mucosa is closed with running or interrupted absorbable suture (4-0 Vicryl or PDS), and the muscularis is closed with interrupted 3-0 silk sutures. The pleural side of the ICM flap is then placed in contact with the repair and secured to the muscle layer of the esophagus with multiple interrupted silk sutures. Pleural and mediastinal drainage tubes are placed at the conclusion of the operation. Perforations of the lower third of the esophagus should be approached through a left posterolateral thoracotomy in the seventh or eighth intercostal space. Although an ICM flap is generally used as a buttress, a diaphragmatic flap is also an option. A posteriorly based full-thickness diaphragmatic flap of adequate length and width can be mobilized to reach the area of primary repair. The flap is secured to the esophageal muscle with interrupted silk sutures to cover the repair. The diaphragm then is closed primarily with nonabsorbable suture. Advantages of diaphragmatic flap use include its, thickness, ease, and extent of mobility.

Cervical Perforations The preferred method of exposure for cervical esophageal perforation is a left-sided neck incision along the anterior border of the sternocleidomastoid muscle (SCM). It may be necessary to ligate the middle thyroid vein for improved exposure. The trachea and thyroid gland are retracted medially for exposure of the esophagus (Fig. 5). The retroesophageal space is entered bluntly along the prevertebral fascia, with care taken to preserve the recurrent laryngeal nerve. Blunt dissection should be continued down to the posterior mediastinum to drain all fluid collections. If the perforation is identified, the defect is repaired primarily as described earlier. A strap muscle can be used to buttress the repair. If the defect is not clearly identified, closed drainage of the area is performed.

Abdominal Perforations Patients with abdominal esophageal perforation and uncontained leak should be taken to the operating room for primary repair.

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79

Omohyoid remnant Esophagus Carotid a. Stump of middle thyroid v.

FIG. 5  Cervical esophagus exposure. Incision is made over the anterior border of the sternocleidomastoid muscle. If necessary, the middle thyroid vein and inferior thyroid artery can be ligated. Medial retraction of the trachea and thyroid gland is performed to help expose the esophagus. (From Cooke DT, Lau CL. Primary repair of esophageal perforation. Op Tech Thor Cardiovasc Surg. 2008;13[2]:126–137.)

Trachea

Perforations of the abdominal esophagus can be approached via an upper midline incision. Once debrided, the perforation should be closed primarily and buttressed with omentum or, more commonly, a fundoplication.

Nutritional Management Following Repair Traditionally, following transthoracic repair, patients were immediately repositioned for a laparotomy and underwent placement of a gastrostomy tube for gastric decompression and a jejunostomy tube for nutritional access. This has become less commonly performed over time. If patients are requiring inotropic support following the repair, spending extra time in the operating room to place these tubes is not warranted. Furthermore, if the repair is successful, oral nutrition may be able to be started within 1 week, obviating the need for the feeding tube. To promptly begin nutritional support, as an alternative to a surgical feeding tube, a Dobhoff tube may be placed at the time of the repair under direct vision before the repair has been completed. The tube can then be advanced to a post-pyloric position postoperatively to allow early initiation of enteral feeding. An NGT could also be placed at this same time to allow for gastric decompression if the surgeon feels this is necessary. Early initiation of total parenteral nutrition is another option. Regardless of the initial nutritional strategy, an esophagram is obtained approximately 5 to 7 days after surgery depending on the patient’s condition. If no leak is identified, liquids may be started and slowly advanced to a soft diet. If there is a persistent leak, this may be managed with subsequent stent placement, which may seal the leak. If the leak persists following stent placement, the patient will require jejunostomy tube placement as several weeks or more will likely be required for healing of the perforation. Although it can be difficult to maintain patience, ultimate healing is still very likely to occur following adequate mediastinal debridement, appropriate antibiotic therapy, and good nutritional support.

seen with long delays in diagnosis, or perforated cancers that cannot be stented because of the size of the perforation or tumor. In stable patients, when large defects are encountered, options like stenting followed by operative coverage of the defect with biodegradable mesh and a muscle flap, such as the serratus anterior or latissimus dorsi, can be considered. Although the healing process will take months, an intact, functional esophagus is still possible. Previous reports have described use of a T-tube to create a controlled esophageal fistula for management of very large defects. This is often cumbersome to care for postoperatively and has generally been abandoned. When repair is deemed not to be possible, esophageal exclusion is recommended over resection and immediate reconstruction. The risk of anastomotic failure in patients who are hemodynamically unstable and/or have significant mediastinal contamination is very high. Once the decision has been made to perform an esophageal exclusion procedure, the esophagus should be mobilized as much as possible in the chest. The esophagus is dived as far distally as possible near the gastroesophageal junction with a 45-mm stapler. After the chest is closed, the patient is then turned to the supine position. A left-sided neck incision is made along the anterior border of the SCM, as described for cervical esophageal perforations. The esophagus should be dissected circumferentially with care taken to avoid injury to the recurrent laryngeal and vagus nerves. Once mobilized from the prevertebral fascia and posterior mediastinum, the esophagus is elevated into the wound. It is vital to preserve as much viable esophagus as possible to aid in future reconstruction. After the esophagus has been transected, it is tunneled subcutaneously onto the left chest, and an end esophagostomy is created. A jejunostomy tube is then placed. If the surgeon wishes to place a gastrostomy tube for gastric decompression, care must be taken not to compromise the use of the stomach as a conduit for later reconstruction.

Resection with Diversion

Special Situations Malignancy

Although every attempt should be made to preserve the patient’s esophagus, there are rare instances in which this is not possible. These include long (generally >6 cm) perforations that are not amenable to stenting, a large segment of devitalized esophagus, which generally is

When esophageal perforation involves a malignancy, consideration must be given to the treatment of both problems. If drainage is adequate, placement of an esophageal stent to control contamination is favored, reserving resection and anastomosis for a later time. If the

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Management of Esophageal Perforation

patient is found to have massive contamination with hemodynamic instability not amenable to stent placement, resection, cervical esophagostomy, tube placement, and gastrostomy should be considered as described earlier.

Achalasia Patients with a known diagnosis of achalasia with perforation require special consideration. These patients may experience esophageal perforation during pneumatic dilation, at the time of myotomy, or with other previously mentioned mechanisms. Because of the elevated intraluminal pressure proximal to the esophageal sphincter, healing of the repair often is precluded. Following repair of the perforation, these patients require myotomy for adequate healing. The myotomy should be performed on the opposite side of the esophagus from the perforation.

Suggested Readings Abbas G, Schuchert MJ, Pettiford BL, et al. Contemporaneous management of esophageal perforation. Surgery. 2009;146(4):749–755; discussion 755–756. Axtell AL, Gaissert HA, Morse CR, et  al. Management and outcomes of esophageal perforation. Dis Esophagus. 2022;35(1):doab039.

Ben-David K, Behrns K, Hochwald S, et al. Esophageal perforation management using a multidisciplinary minimally invasive treatment algorithm. J Am Coll Surg. 2014;218(4):768–774. Fadoo F, Ruiz DE, Dawn SK, Webb WR, Gotway MB. Helical CT esophagography for the evaluation of suspected esophageal perforation or rupture. AJR Am J Roentgenol. 2004;182(5):1177–1179. Kaman L, Iqbal J, Kundil B, Kochhar R. Management of esophageal perforation in adults. Gastroenterology Res. 2010;3(6):235–244. Kamarajah SK, Bundred J, Spence G, Kennedy A, Dasari BVM, Griffiths EA. Critical appraisal of the impact of oesophageal stents in the management of oesophageal anastomotic leaks and benign oesophageal perforations: an updated systematic review. World J Surg. 2020;44(4):1173–1189. Norton-Gregory AA, Kulkarni NM, O’Connor SD, Budovec JJ, Zorn AP, Desouches SL. CT Esophagography for evaluation of esophageal perforation. Radiographics. 2021;41(2):447–461. Rausa E, Asti E, Aiolfi A, Bianco F, Bonitta G, Bonavina L. Comparison of endoscopic vacuum therapy versus endoscopic stenting for esophageal leaks: systematic review and meta-analysis. Dis Esophagus. 2018;31(11). Schweigert M, Sousa HS, Solymosi N, et al. Spotlight on esophageal perforation: A multinational study using the Pittsburgh esophageal perforation severity scoring system. J Thorac Cardiovasc Surg. 2016 Apr;151(4):1002– 1009. Watkins JR, Farivar AS. Endoluminal therapies for esophageal perforations and leaks. Thorac Surg Clin. 2018;28(4):541–554.

Stomach

Benign Gastric Ulcer Daniel T. Dempsey, MD, MBA

B

enign gastric ulcer is a discrete macroscopic wound in the luminal surface of the stomach, extending into the submucosa or muscularis propria and rarely to the serosa of the organ. It is generally believed to start as a mucosal defect that remains unrepaired and deepens because of an imbalance between gastric mucosal defenses and aggressive luminal forces, primarily acid and pepsin. The early natural history of benign gastric ulcer is poorly understood, but most patients presenting to a surgeon with this problem are believed to have had the ulcer for weeks or months or even years. However, gastric ulcers related to drugs (nonsteroidal antiinflammatory drugs [NSAIDs] or cocaine) or stress may form and create clinical problems more rapidly. Most gastric ulcers are caused by (or strongly associated with) Helicobacter pylori infection, NSAID use (including aspirin), smoking, or physiologic or psychological stress. There are undoubtedly other factors that play a role in ulcer formation and healing, such as abnormalities in locoregional gastric blood flow, gastroduodenal motility, or duodenogastric reflux. It is likely that microscopic defects occur commonly in the surface epithelial layer of the gastric mucosa. These are repaired by a process of rapid restitution, restoring an intact layer of surface epithelial cells (SECs). Numerous mucosal defenses are necessary for this local healing process to occur, lest luminal acid and pepsin enter the lamina propria, causing further tissue damage. The mucus secreted by the SECs forms a physiologic bandage over the denuded mucosa, while healthy SECs move in from the periphery to reconstitute an intact epithelial layer. Mucosal blood flow is augmented during this process. Prostaglandins are important mediators. The causes of gastric ulcer described above interfere with these mucosal defenses. NSAIDs and aspirin block prostaglandin production. Smoking decreases mucosal blood flow. Helicobacter causes chronic mucosal inflammation, priming the lamina propria with inflammatory cells and mediators, which interfere with local defenses. These inflammatory cells are probably upregulated when the mucosal layer breaks, exposing them to acid and pepsin. Helicobacter infection also interferes with acid and gastrin secretion. Severe physiologic or psychologic stress can interfere with mucosal blood flow, gastric motility, and acid secretion.

TYPES OF BENIGN GASTRIC ULCER Johnson initially defined three types of gastric ulcer (Fig. 1). Type 1 ulcers are the most common benign gastric ulcer. They typically occur at or near the angularis incisura on the lesser curvature of the stomach where the parietal cell containing body transitions to the gastric antrum (locus minoris resistentiae). Type 1 gastric ulcers are

not associated with gastric acid hypersecretion, and thus vagotomy has not traditionally been part of the surgical treatment. Type 2 ulcers usually occur in the distal stomach and are associated with duodenal ulcer disease, either active or chronic. Type 3 ulcers occur in the prepyloric region. Pathophysiologically, type 2 and 3 gastric ulcers are believed to resemble duodenal ulcers, and thus truncal vagotomy to ameliorate acid hypersecretion has been part of the surgical treatment. Recently two additional types of gastric ulcer have been described, resulting in a “modified Johnson classification” (Table 1). Type 4 gastric ulcer occurs high on the lesser curvature near the gastroesophageal (GE) junction. Excision of type 4 ulcers may get close to the esophagus, requiring Roux reconstruction (Csendes operation). Type 5 gastric ulcers are believed to be drug induced and typically occur toward the greater curvature, making them amenable to simple wedge resection. Neither type 4 nor 5 gastric ulcers are believed to be associated with acid hypersecretion, so vagotomy is probably unnecessary.

SURGICAL OPTIONS FOR GASTRIC ULCER When operating on a patient with gastric ulcer, the choice of operation depends on a variety of technical and clinical factors, which will be discussed further below. Fundamentally, operations for gastric ulcer fall into two categories: those that excise the ulcer and those that do not (Table 2). If the ulcer is not excised, it must be biopsied to rule out cancer. Formal gastric resection with anastomosis is avoided in unstable patients. Before embarking on resection, it is prudent to assess during surgery whether the ulcer involves the pancreas, portal triad, or celiac artery or branches. For low-risk patients with distal gastric ulcers, distal gastrectomy with (type 2 and 3 ulcers) or without (type 1 ulcers) truncal vagotomy is the treatment of choice. Reconstruction consists of Billroth 1 gastroduodenostomy or Billroth 2 gastrojejunostomy (Fig. 2). The latter may be preferred when there is concomitant duodenal ulcer disease (type 2 gastric ulcer). With both types of reconstruction, we prefer to do the anastomosis to the greater curvature side of the gastric remnant. Roux reconstruction is much preferred with small gastric remnants when the gastrojejunostomy is close to the GE junction, but it should be avoided with large gastric remnants. For low-risk patients with high gastric ulcers (type 4), distal subtotal gastrectomy and in-continuity excision of the high lesser curvature ulcer can be considered, with reconstruction via Roux-en-Y esophagogastrojejunostomy (Csendes procedure) if resection encroaches on the gastric cardia (Fig. 3). For type 4 ulcers that are more distally located (or type 1 ulcers that are unusually proximal), a more limited distal gastric resection and lesser curvature extension can be performed, with reconstruction by gastrojejunostomy (Billroth 2 or Roux) (Pauchet procedure). Simple wedge resection is a good option for type 5 gastric ulcers, but it is difficult to perform for prepyloric ulcers (type 2 and 3), juxtacardial 81

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Benign Gastric Ulcer

TABLE 2  Choice of Operation for Gastric Ulcer by Type*

Type I lesser curve

Type II combined gastric and duodenal

Gastric Ulcer Type

Option 1 (Resect Ulcer) Option 2 (Biopsy Ulcer)

1

Distal gastrectomy

Vagotomy and drainage (with or without wedge excision)

2

Distal gastrectomy and vagotomy

Vagotomy and drainage

3

Distal gastrectomy and vagotomy

Vagotomy and drainage

4

Csendes or Pauchet procedure

Kelling-Madlener procedure, or vagotomy and drainage

5

Wedge resection

Patch/oversew

Type III prepyloric

*Simple patch or oversew with biopsy is a reasonable option for all types of gastric ulcer in unstable patients.

INDICATIONS FOR OPERATION

Type IV juxtoesophageal

Type V drug related

FIG. 1  Types of gastric ulcer. (From Matthews JB, Silen W. Operations for peptic ulcer disease and early operative complications. In: Sleisenger MH, Fordtran JS, eds. Gastrointestinal disease. Philadelphia: Saunders; 1993.)

TABLE 1  Modified Johnson Classification Type

Location

Acid Hypersecretion

I

Lesser curvature, incisura

No

II

Body of stomach, incisura, and duodenal ulcer (active or healed)

Yes

III

Prepyloric

Yes

IV

High on lesser curve, near gastroesophageal junction

No

V

Anywhere (medication induced)

No

Most patients with benign gastric ulcer never see a surgeon. They present to primary care or gastrointestinal (GI) practices or emergency departments, with complaints of upper abdominal pain, nausea, vomiting, or iron deficiency anemia. These complaints are evaluated with upper endoscopy with or without upper GI radiology. If a gastric ulcer is diagnosed, it is aggressively biopsied to rule out gastric cancer. If biopsy and cytology specimens are benign, the patient is treated with acid suppression, and the causative factors discussed above (H. pylori, NSAIDs, smoking) are eliminated if possible. Then the upper endoscopy is repeated in 2 to 3 months to document ulcer healing and to perform repeat biopsy. With this approach, the likelihood of misdiagnosing a gastric adenocarcinoma or lymphoma as a benign gastric ulcer is 1%. If helicobacter is eradicated, NSAID and aspirin use is stopped, and smoking is eliminated, almost all gastric ulcers will heal with a 2- to 3-month course of proton pump inhibitor therapy, and recurrence or nonhealing is unusual. But, if helicobacter infection, NSAID or aspirin use, or smoking persists, recurrent gastric ulcer is the rule after the cessation of acid suppression. It is doubtful that definitive operation can completely nullify this fact, although recurrence of peptic ulceration (gastric or marginal ulcer or both) may be delayed after operation. For optimal results after operation for gastric ulcer, it is very important to strive for and document after surgery the absence of helicobacter infection, NSAID use, and smoking. Vagotomy or long-term acid suppressive medication may prevent recurrent peptic ulcer in some patients, and clearly patients having operation for gastric ulcer who require long-term NSAIDs or aspirin should receive long-term acid-suppressive medication. Selective COX-2 inhibitors should be considered in patients with ulcers requiring NSAIDs because these may have a lower risk of peptic ulceration.

PERFORATED GASTRIC ULCER ulcers (type 4), and ulcers on the lesser curvature. For type 2 and 3 gastric ulcers that are left in situ, truncal vagotomy and gastrojejunostomy (with ulcer biopsy) may be a reasonable alternative to distal gastric resection. Similarly, for type 4 gastric ulcers, distal gastrectomy without ulcer excision (but with ulcer biopsy) can be considered (Kelling-Madlener operation).

The most common indication for operation in benign gastric ulcer is perforation. Patients with gastric ulcer perforation present with acute abdominal pain and tenderness, usually with signs of peritoneal irritation (i.e., rebound tenderness and referred rebound tenderness). Because of the severity and acuteness of the symptoms, these patients most commonly present to the emergency department

S TO M AC H

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FIG. 2  Three types of reconstruction after distal gastrectomy. (A) Billroth I: A gastroduodenostomy is performed toward the greater curvature. (B) Billroth II: A gastrojejunostomy is created to reestablish the alimentary transit. Several variations may be observed in this type of reconstruction. (C) Roux-en-Y: To prevent biliopancreatic reflux into the stomach, a 50-cm to 60-cm Roux limb is anastomosed to the stomach with the biliopancreatic limb brought in 50 to 60 cm distal to the gastrojejunostomy. (Modified from Ginsburg GG, Kochman ML, Norton ID, Gostout CJ. Clinical gastrointestinal endoscopy. 2nd ed. Philadelphia: Elsevier, 2011.)

A

B

C

FIG. 3  Operations for a type 4 gastric ulcer. (A) Pauchet procedure. (B) Kelling-Madlener procedure. (C) Csendes procedure (esophagogastrojejunostomy). (Modified from Seymour NE. Operations for peptic ulcer and their complications. In: Feldman M, Scharschmidt BF, Sleisenger MH, eds. Gastrointestinal disease. Philadelphia: Saunders; 1998.)

where computed tomography (CT) scanning reveals free intraperitoneal air, usually with free fluid as well. If water-soluble oral contrast has been administered, the scan often reveals extravasation from the stomach. Gastric wall thickening is difficult to evaluate on CT if the stomach is collapsed. Simple upright chest radiography usually shows free air under the diaphragm, but this classic radiologic finding may be absent in 20% of patients with perforated gastric ulcer. Intravascular volume depletion is the rule, so fluid resuscitation begins with 1 to 2 L of isotonic fluid. Induction of general anesthesia in the patient with severe hypovolemia may result in cardiovascular collapse and cardiac arrest. Intravenous antibiotics (cefazolin and fluconazole) are administered. Careful insertion of a nasogastric (NG) tube before surgery for gastric decompression is prudent, especially if water-soluble oral contrast has recently been administered

or if imaging shows gastric distention. Operation is planned to occur usually within 2 hours of presentation. Rarely, nonoperative treatment is indicated if the patient is clinically stable, without signs and symptoms of sepsis, and with good radiologic evidence that the perforation has sealed. Operation may be done open or laparoscopically. Copious irrigation of the soiled peritoneal cavity is performed with 5 to 10 L of warm saline. The entire anterior surface of the stomach is inspected. If no perforation is seen, the lesser sac is entered through the gastrocolic omentum and irrigated and the posterior stomach inspected. If still no perforation is found, it may be along the greater or lesser curvatures. If the patient is hemodynamically unstable or a poor operative risk, the perforated gastric ulcer should be biopsied and closed, either with a Graham (omental) patch or with a wedge resection of

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TABLE 3  Choice of Operation for Gastric Ulcer by Indication Indication

Option 1

Option 2

Option 3

Perforation

Patch or wedge excision

Patch or wedge excision with vagotomy and drainage

Distal gastrectomy*

Bleeding

Oversew or wedge excision

Oversew with vagotomy and drainage

Distal gastrectomy*

Obstruction

Vagotomy and distal gastrectomy

Vagotomy and gastrojejunostomy

Nonhealing/Intractability

Distal gastrectomy (with vagotomy for type 2 and 3)

Wedge excision with vagotomy and drainage

*Consider addition of vagotomy for type 2 and 3 gastric ulcer.

TABLE 4  Rockall Score to Assess Rebleeding and Mortality Risk in Upper Gastrointestinal Bleeding Variable

0 Points

1 Point

2 Points

Age (yr)

80

Shock

None

P >100; BP >100 systemic

BP 2 cm) perforated gastric ulcers may be too big to securely patch with omentum and thus may require resection. If resection is deemed hazardous, it may be possible to achieve closure by anastomosing the perforation to a Roux limb (mucosa to mucosa). Before closure of the abdomen, the NG tube is positioned appropriately in the stomach and secured to the nose. We test the repair with both air insufflation and methylene blue via the NG tube. If postoperative reinsertion of the prematurely pulled NG is deemed a risk to the ulcer repair or suture line, it should be sutured or “bridled” to the nose before leaving the operating room. After surgery antibiotics are continued until the patient is fever free with a normal white blood cell count. Once GI function has returned, gastrografin swallow is performed before the initiation of a liquid diet. Leakage at the repair site is managed without surgery, if adequately drained and the patient is doing well. Otherwise, early reoperation is necessary, the primary goal of which is to achieve adequate drainage of the leak, and enteral access for proximal decompression (e.g., gastrostomy) and feeding distally (e.g., jejunostomy).

BLEEDING GASTRIC ULCER Although still a common reason for hospitalization, bleeding gastric ulcer is increasingly less common as an indication for operation. This is likely due to the increasing effectiveness of medical and endoscopic treatment for bleeding gastric ulcer. The most common cause of GI bleeding in hospitalized patients is peptic ulcer, and annually in the United States a few thousand patients die of peptic

ulcer bleeding. About half of these patients succumb to bleeding gastric ulcer. Essentially all the deaths from bleeding ulcer occur in patients with risk factors for persistent or recurrent bleeding. Thus, it is important to identify this high-risk group, which represents about one-quarter of patients admitted to the hospital with bleeding peptic ulcer. Risk assessment tools have been developed for this, such as the Rockall score (Table 4). None of these tools can predict with 100% accuracy who does and does not have a life-threatening ulcer bleed, but they are useful as guides. Patients with a Rockall score of 0 to 1 are very unlikely to have a life-threatening GI hemorrhage, whereas patients with a score from 9 to 11 may very well succumb to the bleed. In general, patients at high risk present with hematemesis, hypotension, or the requirement for multiple units of blood transfusion. These patients require early surgical consultation. Urgent upper endoscopy often shows high-risk endoscopic features, such as active bleeding or visible vessel in the ulcer base. Such patients should have endoscopic hemotherapy consisting of cautery, injection of epinephrine, and application of clips. Intravenous acid suppression and fluid resuscitation are important. Rebleeding can usually be managed with repeat endoscopic therapy, but angiography with possible embolization should also be considered. In the occasional patient in whom these modalities fail, operation should be considered. In general, candidates for operation for bleeding gastric ulcer have been transfused more than a few units of blood, have recurrent or refractory hemorrhagic shock, or have ulcer erosion into a large artery such as the left gastric or splenic artery. The operative mortality rate is around 25%. Biopsy and oversewing of the bleeding ulcer is the appropriate operation for high risk or hemodynamically unstable patients. Wedge resection should be considered for bleeding ulcers on the greater curvature or free wall of the proximal stomach. Formal resection should be reserved for good risk and hemodynamically stable patients. Rebleeding is more common when the ulcer is not resected, but ultimate hospital mortality is similarly high in patients who are initially managed with oversewing and those initially managed with

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resection. Postoperative bleeding might respond to angiographic embolization.

OBSTRUCTING GASTRIC ULCER The most common cause of gastric outlet obstruction in the adult patient is cancer (pancreatic, duodenal, or gastric). So, when considering operation for obstructing distal gastric ulcer, the surgeon must ask whether the patient might have malignant obstruction. Whereas upper endoscopy, biopsy, contrast radiography, endoscopic ultrasound, CT, or magnetic resonance imaging may all be reassuring that the obstruction is benign, misdiagnosis, although rare, remains a real possibility. The classic operation for obstructing gastric ulcer is vagotomy and distal gastrectomy, but vagotomy and gastrojejunostomy may be an acceptable alternative. The latter procedure has a lower operative mortality risk, and, in the event of severe dumping, the gastrojejunostomy is potentially reversible if gastric outlet patency can be maintained. However, distal gastrectomy confirms the absence of cancer. Vagotomy should be performed because obstructing gastric ulcers are likely to be Johnson type 2 or 3 lesions.

NONHEALING GASTRIC ULCER (INTRACTABILITY) Operation for nonhealing gastric ulcer should be unusual today because our understanding of ulcer pathophysiology is more complete than ever. Acid suppression, eradication of helicobacter, elimination of NSAIDs, and smoking cessation should heal the ulcer. So why would the gastric ulcer persist? Could it be cancer? Is the patient noncompliant? Is there unrecognized gastric stasis or enterogastric reflux? Are there important factors in ulcer pathogenesis that we have not discovered yet? These are all important questions for the surgeon to consider before operating on a patient for nonhealing gastric ulcer. Furthermore, it must be recognized that patient noncompliance and unknown pathophysiologic factors may predispose to ulcer recurrence or poor functional results after gastrectomy for nonhealing ulcer. This may be particularly problematic in thin patients who are easy to operate on but who have insufficient nutritional reserves in the event of a poor functional outcome. In the event that operation for nonhealing ulcer is necessary, the ulcer should be excised either with distal gastrectomy or wedge resection. This both excludes cancer and resects the vulnerable part of the stomach. If distal gastrectomy, the classic operation, is performed, then vagotomy should be added for type 2 and 3 gastric ulcers. If the ulcer is wedged out, then vagotomy and drainage should be added.

MARGINAL AND RECURRENT ULCER Ulcers that occur at or near the gastroenterostomy are termed marginal ulcers. They may occur on either side of the anastomosis. When on the distal side, they are generally believed to be due to acid/peptic injury to small bowel mucosa, which is ill equipped to defend itself against unbuffered gastric juice. This occurs more commonly in Roux gastrojejunostomy because the anastomosis is devoid of the buffering effects of duodenal contents, which help protect a Billroth 2 anastomosis. When on the proximal side of the anastomosis, the ulcer is generally thought to be due to ischemia, stasis, foreign body (suture), bile reflux, or the circumstances that led to the gastric ulcer in the first place (recurrent ulcer). Marginal ulcer complicates Rouxen-Y gastric bypass in about 8% of patients, and presently this is the most common cause of marginal ulcer, which may also complicate gastrojejunostomy for cancer or ulcer. The medical treatment of marginal ulcer is identical to gastric ulcer: acid suppression, eradication of helicobacter, elimination of

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NSAIDs, and smoking cessation. Indications for operation are also identical to those for gastric ulcer: perforation, bleeding, obstruction, and intractability. The realization that reoperation for recurrent or marginal ulcer puts the patient at increased risk (and closer to total gastrectomy) underscores the importance of patient education and good management after the first ulcer operation, which includes minimizing the risk factors for ulcer recurrence. In addition to elimination of helicobacter, NSAIDs, and smoking, we consider every patient who has had an operation for gastric ulcer a candidate for lifelong acid suppression, unless the patient has had a vagotomy. Perforated marginal ulcer may be treated with simple patch closure, which is certainly appropriate in high-risk and unstable patients. It may also be the preferred treatment in patients with Roux-en-Y gastric bypass because resection may necessitate esophagojejunostomy. In stable low-risk patients with perforated gastrojejunostomy after distal gastric resection, resection of the anastomotic region (segmental jejunal resection with additional gastrectomy) is preferred. The addition of truncal vagotomy may be considered. If the remaining gastric remnant is 30% or less, reconstruction should be Roux gastrojejunostomy to avoid bile reflux esophagitis. If the remaining remnant is larger than 30%, reconstruction should be via Billroth 1 or 2 technique to minimize recurrence of marginal ulceration. If the original operation was a simple loop gastrojejunostomy, consideration may be given to reversal (if the gastric outlet is patent) or distal gastrectomy with Billroth 1 or 2 reconstruction. Bleeding marginal ulcer can usually be managed without surgery with the help of endoscopic hemostatic techniques or angiographic embolization, unless the ulcer has eroded into a named visceral vessel such as the splenic, left gastric, or middle colic artery. Those patients requiring emergency operation may have torrential bleeding and often present with a less impressive “herald bleed.” Whereas gastroenterotomy and transluminal oversewing of the bleeding vessel may prove adequate, resection of the anastomotic region may be expeditious and safer. Postoperative angiographic embolization might complement the operation. Marginal ulcers associated with obstruction or intractability should be treated with elective resection of the anastomosis, followed by Roux or Billroth reconstruction, depending on how close the anastomosis is to the GE junction.

Suggested Readings Abubaker A, Ahmed BH, Nussbaum MS. Surgery for peptic ulcer disease. In: Yeo CJ et al, ed. Shackelford’s Surgery of the Alimentary Tract. 8th ed.; 2019. Byrge N, Barton RG, Enniss TM, Nirula R. Laparoscopic versus open repair of perforated gastroduodenal ulcer: a National Surgical Quality Improvement Program analysis. Am J Surg. 2013;206:957–963. Laine L. Upper gastrointestinal bleeding due to a peptic ulcer. NEJM. 2016;374:2367–2376. Lanas A, Chan FKL. Peptic ulcer disease. Lancet. 2017;390:613–624. Lightner AL, Brunicardi FC. The management of benign gastric ulcers. In: Cameron JL, Cameron AM, eds. Current Surgical Therapy. 12th ed.; 2017. Roses RE, Dempsey DT.Stomach, in Schwartz’s Principles of Surgery. In: Brunicardi, et al (eds), 11th ed. McGraw Hill. Schroder VT, Pappas TN, Vaslef SN, et al. Vagotomy/drainage is superior to local oversew in patients who require emergency surgery for bleeding peptic ulcers. Annals of Surgery. 2014;259:1111–1118. Soreide K, Thorsen K, Harrison EM, et  al. Perforated peptic ulcer. Lancet. 2015;386:1288–1298. Sverden E, Mattsson F, Lindstrom D, et al. Transcatheter arterial embolization compared with surgery for uncontrolled peptic ulcer bleeding—a population based cohort study. Annals of Surgery. 2019;269:304–309. Wang YR, Richter JE, Dempsey DT. Trends and outcomes of hospitalizations for peptic ulcer disease in the United States, 1993 to 2006. Annals of Surgery. 2010;251:51–58. Wilhelmsen M, Moller MH, Rosenstock S. Surgical complications after open and laparoscopic surgery for perforated peptic ulcer in a nationwide cohort. Br J Surg. 2015;102:382–387.

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Management of Duodenal Ulcers

Management of Duodenal Ulcers Daniel T. Dempsey, MD

INTRODUCTION Duodenal ulcer is an acute or chronic localized wound of the duodenal mucosa caused by acid/peptic injury. Superficial ulcers involve the submucosa; deeper ulcers involve the muscularis propria or the serosa and may penetrate posteriorly or perforate anteriorly. Common predisposing factors are Helicobacter pylori infection, use of nonsteroidal antiinflammatory drugs (NSAIDs) or aspirin, smoking, and stress. Less common causative factors include gastrinoma (Zollinger-Ellison syndrome), radiation, Crohn’s disease, cocaine, and gastroduodenal dysmotility. The most common symptoms of duodenal ulcer are abdominal pain, nausea, vomiting, and anemia. The reasons for hospitalization resulting from duodenal ulcer are (in decreasing order) upper gastrointestinal (GI) bleeding, perforation, obstruction, and intractability. Peptic ulcer is the most common cause of clinically significant upper GI bleeding requiring hospitalization, but nowadays very few of these patients require operation. Currently the most common indication for operation in duodenal ulcer patients is perforation. Surgery for bleeding and obstruction is less common, and surgery for medically intractable duodenal ulcer is very uncommon. The operative (90-day) mortality rate for emergency peptic ulcer surgery is about 30%. After surgery for duodenal ulcer, recurrent ulcer can be minimized if all of the following conditions are met: eradication of H. pylori infection, diligent and permanent avoidance of NSAIDs and aspirin, and long-lasting abstention from smoking. If compliance with these management principles cannot be followed, eventual ulcer recurrence is likely. Testing for H. pylori infection should be performed in all patients with active peptic ulcer disease or a history of peptic ulcer disease unless previous cure of H. pylori infection has been documented. Testing should also be strongly considered if long-term aspirin or NSAIDs are required. All patients who test positive should be treated. Testing for H. pylori infection should be performed in all patients with peptic ulcer, mucosa-associated lymphoid tissue (MALT), early gastric cancer, and those on long-term aspirin or NSAID regimens (Box 1). With the appropriate 10- to 14-day multidrug regimen (which takes into account local antibiotic resistance and recent antibiotic usage) and patient compliance, H. pylori eradication will be confirmed in about 85% of patients who undergo a urea breath test, fecal antigen test, or endoscopic biopsy (H. pylori serology should not be used to test for cure of H. pylori infection). Consultation with a gastroenterologist or infectious diseases specialist with an interest and expertise in H. pylori treatment and cure should be considered. If medically indicated, daily aspirin for cardiovascular prophylaxis may be taken safely, provided a daily proton pump inhibitor (PPI) is also taken. It is not unreasonable to consider long-term PPI treatment (e.g., omeprazole 20 mg before breakfast) for all patients who have required hospitalization for duodenal ulcer unless a vagotomy has been performed, particularly in patients for whom the above conditions cannot be assured. It is unclear whether definitive duodenal ulcer surgery (e.g., vagotomy and drainage; vagotomy and antrectomy [V/A]) is as effective in preventing ulcer recurrence as it was in the past. The acid suppressive effect of vagotomy may be no more profound than a properly taken PPI, but admittedly the former does not depend on patient compliance. Clearly, the concept that a more complex surgery is better should be used carefully and sparingly today in ulcer surgery, particularly during emergency surgery, which now is far more common than elective surgery. Gastrectomy

for duodenal ulcer should be avoided in thin or chronically malnourished patients.

MEDICAL MANAGEMENT OF DUODENAL ULCER Most patients with duodenal ulcer are treated medically as outpatients and never seen by a surgeon. Typically, the diagnosis is made with esophagogastroduodenoscopy (EGD). Biopsy of duodenal ulcer is unnecessary, but gastric biopsies should be taken to rule out H. pylori infection. Medical management includes acid suppression with a PPI, diagnosis and treatment of H. pylori infection (present in up to 90% of duodenal ulcer patients), elimination of NSAIDs, smoking cessation, and (in the appropriate clinical setting) evaluation for gastrinoma. Unless the patient has required hospitalization for an ulcer complication, long-term PPIs are not indicated. The obvious exceptions are duodenal ulcer patients who require long-term NSAIDs, aspirin, or anticoagulants, all of whom require PPI ulcer prophylaxis.

Perforated Duodenal Ulcer Duodenal ulcer perforation (Fig. 1), the most common indication for surgery, presents as an acute abdomen. The patient usually can pinpoint the onset of severe abdominal pain. There may or may not be a history suggestive of chronic duodenal ulcer. The longer surgery is delayed from the onset of perforation, the higher the mortality risk. On examination, the patient is very uncomfortable and loath to move. Tachycardia may be the only early vital sign abnormality. Fever and tachypnea then ensue, and hypotension is a late finding. The abdomen is rigid, and there is obvious peritonitis. Leukocytosis is common. Anemia suggests the possibility of a second, usually posterior, bleeding ulcer (“kissing ulcers”), which can be evaluated intraoperatively with direct inspection or EGD. An upright chest x-ray usually shows pneumoperitoneum (absent in 10% to 15% of cases). Computed tomography (CT) nearly always reveals extraluminal air in the upper abdomen, often with free peritoneal fluid. The mortality risk of perforated duodenal ulcer in the modern era is high, up to 30% in some series. Although this may be caused in part by the frailty of the patient population affected, there is no doubt that delayed treatment increases mortality risk. Prompt fluid

BOX 1  Helicobacter pylori Tests Tests for H. pylori (All Positive Patients Should Be Treated) • Fecal antigen test • Urea breath test • Esophagogastroduodenoscopy and biopsy • Rapid urease test • Histology • Culture • Molecular real-time polymerase chain reaction (RT-PCR) Some Common Helicobacter Treatment Regimens (10–14 Days) • Clarithromycin triple therapy (PPI, clarithromycin, amoxicillin, or metronidazole) • Bismuth quadruple therapy (PPI, bismuth, tetracycline, nitroimidazole) • Sequential therapy (PPI and amoxicillin for 5–7 days, and then a PPI, clarithromycin, and nitroimidazole for 5–7 days) • Hybrid therapy (a PPI and amoxicillin for 7 days, and then a PPI, amoxicillin, clarithromycin, and nitroimidazole for 7 days) PPI, Proton pump inhibitor.

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FIG. 1  Perforated duodenal ulcer.

resuscitation and intravenous (IV) antibiotics are important, but so is prompt surgery. Medical optimization, although necessary, should not be an excuse for prolonged delay in surgical treatment. In addition to routine empiric broad-spectrum perioperative antibiotics, selective antifungal treatment may be considered in frail, immunosuppressed, or hospitalized patients. Routine use of antifungal agents is not indicated. Rarely, a stable patient without peritonitis and with a radiologically documented sealed perforation may be cautiously managed nonoperatively. Laparotomy or laparoscopy with peritoneal washout (5 to 10 L) and omental patch closure of the perforation is the treatment of choice for most patients with a perforated duodenal ulcer. Peritoneal fluid should be sent for culture and sensitivity (including fungal studies). Routine ulcer biopsy is not necessary but should be performed if there is any suspicion of malignancy. At least one closed-suction peritoneal drain is placed. Leakage at the repair site is not uncommon.

Omental Patching Omental patching (Graham patching), a technique attributed to Dr. Roscoe Graham, is the most common method of perforated duodenal ulcer repair (Fig. 2). Typically, the hole in the duodenum is small (2 cm) merit special considerations. They are difficult to securely close with the Graham patch technique described earlier, but primary repair of a large perforated chronic

FIG. 2  Graham patch of perforated duodenal ulcer. (From Townsend C. Sabiston Textbook of Surgery, 21st ed. Philadelphia: Elsevier, 2021.)

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FIG. 3  This technique creates better apposition between the omentum and the duodenum. (From Yeo CJ. Shackleford’s Surgery of the Alimentary Tract. 8th ed. Philadelphia: Elsevier, 2019.)

duodenal ulcer is more prone to break down than primary repair of a similar-size acute duodenal laceration. And in the high-risk patient, an expeditious surgery is important. After peritoneal irrigation, the perforation is closed if possible with sutures or stapling, and the closure is buttressed with omentum or a falciform ligament. If it can be done safely, a Kocher maneuver facilitates primary closure. Multiple drains are placed. If the large perforation cannot be closed primarily, it can be plugged with omentum or falciform, which is pulled into the perforation using double-armed sutures placed first in the plug and then “inside out” into the duodenum surrounding the perforation (Fig. 4). Alternatively a loop of jejunum can be used as a serosal patch. Treatment of large perforations by direct intubation with or without an omental buttress is prone to ongoing leakage, but it can be used as a last resort or bailout procedure (Fig. 5). Multiple peritoneal drains are placed. In unstable patients, a damage control approach might be considered. The fact that large perforated duodenal ulcers are hard to fix is indicated by the wide variety of (sometimes anecdotal) repair techniques. One useful ancillary procedure that has been evaluated with a retrospective controlled study is the triple-tube technique, which

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Management of Duodenal Ulcers

and quick, and we have never regretted using it in the setting of highrisk duodenal perforation. We much prefer this to lateral duodenostomy or transpyloric intubation. For the most tenuous duodenal closures, we consider pyloric exclusion (pyloric closure with heavy absorbable suture and dependent loop gastrojejunostomy). One other option for repair of a large chronic duodenal perforation in a stable low-risk patient is a Roux-en Y duodenojejunostomy in which a tension-free two-layer anastomosis is created between the debrided duodenal opening and a Roux limb.

Definitive Ulcer Surgery

FIG. 4  Technique to “pull” an omental patch into a large perforated duodenal ulcer. (From Townsend C. Sabiston Textbook of Surgery. 21st ed. Philadelphia: Elsevier, 2021).

Definitive ulcer surgery can be considered in stable patients of low to medium risk (ASA 1 or 2) requiring emergency surgery for a perforated duodenal ulcer if there is a clinical history of duodenal ulcer, or if the perforation is large (>2 cm). Definitive surgery should not be performed if peritonitis is severe or well established (exudative). All of these contingencies (low-risk patient with a positive history or large perforation and without serious peritonitis) mean that the majority of patients with a perforated duodenal ulcer are not candidates for definitive ulcer surgery. Parietal cell vagotomy as a definitive ulcer surgery in this setting is largely of historical interest. Currently the two options for definitive surgery are (1) truncal vagotomy and gastrojejunostomy ([V/GJ] with or without temporary pyloric closure) after repair of perforation as described earlier; or (2) truncal V/A if the perforated duodenum can safely be resected with the antrum and a secure duodenal stump fashioned. If the ampulla is deemed to be at risk, a biliary Fogarty catheter can be advanced from above via the cystic duct or common bile duct. Resection should not be contemplated if a tenuous duodenal stump is likely or if injury to the ampulla or bile duct is an obvious possibility.

Minimally Invasive Surgery

DJ Gastrostomy 15 cm Retrograde duodenostomy 5 cm

Minimally invasive surgery for perforated duodenal ulcer is now commonplace, and some studies suggest that the laparoscopic approach is superior to open operation. Laparoscopy confirms the diagnosis, including the size and location of the perforation and the severity of peritonitis. Thorough irrigation of the peritoneal cavity can readily be accomplished laparoscopically. Laparoscopic omental patch closure of the perforation is usually straightforward for the typical small perforation. Even when conversion to open surgery is necessary, the laparotomy incision is smaller and optimally placed after laparoscopic evaluation. In the unlikely event that a definitive surgery is indicated, it can be performed either open or laparoscopically. Even a modest size perforation can be repaired laparoscopically, and vagotomy is straightforward for the minimally invasive surgeon with some foregut experience. A dependent loop gastrojejunostomy completes the ulcer surgery. Two types of vagotomy may be considered: (1) the more traditional bilateral truncal vagotomy or (2) a modified Taylor procedure. The latter consists of posterior truncal vagotomy and division of the segmental vagal branches to the anterior stomach with preservation of the anterior innervation to the antropyloric region. This technique may facilitate gastric emptying.

Postoperative Management Feeding jejunostomy

FIG. 5  Triple tube technique for high-risk perforated duodenal ulcer.

should be considered in high-risk perforations, whether repaired as described earlier or with one of the more complex surgeries described later. This involves placement of a gastrostomy, antegrade feeding jejunostomy, and a retrograde jejunostomy tube that is passed into the duodenum for decompression. This technique is safe

Postoperative management for many perforated ulcer patients starts in the ICU with continued optimization of critical organ function, fluid management, and treatment of sepsis. The decision to remove the NG tube and initiate oral liquids is made on clinical grounds. Postoperative contrast study (fluoroscopy or CT) is usually performed to rule out ongoing leak and to demonstrate gastric emptying. Antibiotics are discontinued on postoperative day 5 unless there is obvious ongoing infection. Peritoneal drains are removed 24 hours after the initiation of oral liquids if drainage is benign and the patient is doing well. Reoperation is sometimes required for persistent leakage from the perforation site or from abdominal wound dehiscence. Percutaneous drainage can be performed for localized infected fluid collections, but multiple fluid collections or extensive peritoneal fluid in the setting of sepsis may be a manifestation of uncontrolled

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leakage and is best treated with reoperation and washout. Some sort of abdominal reintervention is necessary in about 25% of patients after repair of a perforated duodenal ulcer. We think emergency surgery for duodenal ulcer is an indication for chronic PPI therapy and empiric treatment of H. pylori infection. Patients are strongly advised to avoid NSAIDs, aspirin, and smoking. Low-dose aspirin is permissible provided chronic PPI treatment is continued.

BLEEDING DUODENAL ULCER The most common reason for hospitalization and death in the duodenal ulcer patient is bleeding. However, bleeding has become an infrequent indication for surgery in duodenal ulcer largely because of the effectiveness of medical and endoscopic treatment. There also has been an increased appreciation of the risks associated with surgery for bleeding duodenal ulcer, including rebleeding, postoperative complications, and a postoperative in-hospital mortality rate as high as 40%. Endoscopic hemostatic therapy with cautery, topical agents, epinephrine injection, and/or clips has clearly decreased the need for surgery; selective angiography with embolization probably has too.

Risk Stratification Three-fourths of patients with bleeding duodenal ulcer (Fig. 6) will stop bleeding with only IV fluid and IV PPIs. These are administered to all patients admitted to the hospital with upper GI bleeding. The other 25% will continue to bleed or rebleed, and essentially all deaths related to bleeding duodenal ulcer occur in this group. Therefore it is important to identify patients in this group. Not surprising, these are the patients with the bigger bleeds. They are more likely to have hematemesis, hypotension, a multiunit transfusion requirement, and/or endoscopic stigmata (visible vessel and/or active bleeding). Two commonly used prognostic systems for risk-stratifying patients with upper GI bleeding are the Glasgow-Blatchford score (GBS) and the Rockall score (Box 2). The former is designed to identify lowrisk patients who do not require hospitalization (GBS 0–1) versus

BOX 2  Risk Stratification for Upper Gastrointestinal Bleeding Glasgow-Blatchford Score* • Elevated BUN • Low Hgb • Low BP • Elevated HR • Melena • Syncope • Liver disease • Heart failure

2–6 points 1–6 points 1–3 points 1 point 1 point 2 points 2 points 2 points

Rockall Score** • Age • Shock • Comorbidity • EGD stigmata • EGD diagnosis

0–2 points 0–2 points 0–3 points 0–2 points 0–2 points

*0 points = outpatient management.; 6+ points = 50% need endoscopic hemostatic Rx **0–1 points = 0% mortality; 5 points = 10% mortality; 8+ points = 40% mortality BP, Blood pressure; BUN, blood urea nitrogen; Hgb, hemoglobin; HR, heart rate.

high-risk patients who require treatment (usually endoscopic) to stop the bleeding (GBS ≥6 indicates a 50% likelihood of requiring treatment). The Rockall score predicts mortality risk. High-risk bleeding duodenal ulcer patients should be seen in consultation by an endoscopist and surgeon, and they should be watched carefully in the hospital, perhaps initially in the ICU. Endoscopic findings and the treatment plan should be understood by the surgeon if the surgeon is not the endoscopist. Deep posterior bleeding ulcers in the proximal duodenum are particularly worrisome because they may involve the gastroduodenal artery, which can cause exsanguinating hemorrhage. Hemostasis usually can be achieved with PPI infusion and endoscopic treatment. Rebleeding should prompt repeat endoscopic treatment and consideration of arteriography and possible angioembolization. Surgery should be considered for persistent or recurrent bleeding in patients with hemodynamic instability or a transfusion requirement in excess of 6 units of red blood cells, but recognizing (for example) that predicted postoperative mortality in an older adult patient with a bleeding duodenal ulcer, hypotension, chronic obstructive pulmonary disease (COPD), and a visible vessel on EGD is 40% by the Rockall score.

Surgery for Bleeding Duodenal Ulcer

FIG. 6  Bleeding duodenal ulcer. (Courtesy Dr. Gregory Ginsberg.)

There are three surgical options for bleeding duodenal ulcer: (1) oversewing alone, (2) oversewing with vagotomy and drainage, and (3) V/A. Clinical trials from a previous era suggest that the ultimate result (i.e., survival) is similar with either of the two latter surgical options, but reoperation for rebleeding is less common after V/A. However, resection for bleeding duodenal ulcer is rarely done nowadays because most surgical patients are at high risk. Furthermore, fashioning a secure duodenal stump can be difficult because the bleeding ulcer either must be resected, or, if not resected, it must be oversewn. Review of National Surgical Quality Improvement Program data suggests that vagotomy and drainage for a bleeding peptic ulcer may result in a significantly lower 30-day postoperative mortality rate (12%) than vagotomy and resection (23%) or oversewing alone (27%).

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Management of Duodenal Ulcers

Oversewing of a Bleeding Duodenal Ulcer Oversewing of a bleeding duodenal ulcer starts with exposure of the lesion, usually through a longitudinal duodenotomy or pyloroduodenotomy. The Kocher maneuver is done first because this not only decreases tension on the closure, but facilitates manual control of a bleeding gastroduodenal artery with the left hand of the surgeon standing on the patient’s left side (long fingers behind the head of the pancreas, thumb in front). Deep posterior ulcers usually require placement of two or three heavy suture ligatures placed in figure-of-8 or over-and-over fashion in the ulcer bed. The U-stitch has been well described. Surgeons with advanced hepato-pancreato-biliary experience might be tempted to ligate the gastroduodenal artery extralumenally above and below the duodenum, but this is usually hazardous and inadvisable, and it misses the pancreatic branch for which the U-stitch was conceived. Once hemostasis is achieved, the ulcer bed should be abraded with the sucker tip to ensure that rebleeding does not occur. The anterior incision can then be closed either longitudinally, or transversely as a pyloroplasty.

Definitive Ulcer Surgery Definitive ulcer surgery may be appropriate for some patients with a history of ulcer chronicity or for those with a large (>2 cm) deep posterior ulcer, but this is clearly contraindicated in ASA 4 and 5 patients and should be done quite selectively in ASA 3 patients. If the patient is stable and exposure straightforward, truncal vagotomy and drainage (pyloroplasty or gastrojejunostomy) is the preferred definitive surgery. In the setting of bleeding ulcer, parietal cell vagotomy, probably comparable to PPI therapy, is not indicated, and gastric resection is quite likely to be problematic, as discussed earlier.

Postoperative Management Postoperative management is similar to that after repair of a perforated duodenal ulcer. High-dose PPIs in the early postoperative period may decrease rebleeding risk. There is no evidence that transfusion triggers must be increased after surgery for a bleeding ulcer. Early rebleeding should be evaluated with upper endoscopy and arteriography (CT angiography or standard arteriography). Long-term smoking cessation is imperative. If NSAIDs are medically necessary, a selective COX-2 inhibitor should be considered, and long-term PPI therapy is necessary. Similarly, long-term PPIs are definitely prescribed if chronic aspirin or anticoagulants are necessary, and this treatment may not be unreasonable for all patients admitted for duodenal ulcer complications unless definitive surgery has been performed.

GASTRIC OUTLET OBSTRUCTION Chronic gastric outlet obstruction secondary to chronic inflammation and scarring is now the second most common indication for duodenal ulcer surgery in some hospitals. Patient history and endoscopic findings can usually differentiate between an acute potentially reversible obstruction and chronic obstruction. Patients usually experience nausea, nonbilious vomiting, epigastric distension, and weight loss. A succussion splash may be present on abdominal auscultation, and in the setting of high-grade obstruction and dehydration, hypokalemic hypochloremic metabolic alkalosis is often present. The differential diagnosis obviously includes cancer because most patients with these symptoms have malignant gastric outlet obstruction (pancreatic, duodenal, or gastric cancer). Evaluation includes EGD and biopsy, upper gastrointestinal fluoroscopy with oral barium, and CT. Endoscopic dilation and medical ulcer treatment may delay surgery for 1 to 2 years in one-half of patients with benign gastric outlet obstruction from duodenal ulcer, but most patients requiring hospitalization or dilation will ultimately undergo surgery.

Surgery for Obstructing Duodenal Ulcer Vagotomy and Antrectomy V/A is the gold standard surgery for obstructing duodenal ulcer, but V/GJ is a good alternative in some patients. The advantage of V/A is lower recurrence rate and reassurance that the cause of the obstruction is benign. The disadvantage is higher operative mortality risk (2%). The advantage of V/GJ is a lower operative mortality and the potential for reversal of the GJ in the unlikely event that dumping becomes intolerable. Another advantage is that V/ GJ is readily accomplished laparoscopically. A disadvantage of V/ GJ is that obstructing cancer may be missed, and marginal ulcer may occur. The remote possibility of pyloric channel or proximal duodenal cancer must be considered in the operative planning for obstructing ulcer because optimal surgical treatment may involve pancreaticoduodenectomy. V/A can be done through an upper midline or transverse incision. A mechanical retractor is helpful. Exploration of the gastroduodenal area for any evidence of malignancy is done. Truncal vagotomy is accomplished first. The peritoneum over the abdominal esophagus is incised, and the gastrohepatic ligament is opened above the hepatic vagal branches. Pulling down on these branches makes the anterior vagal trunk stand out, and it is clipped and severed easily; a short segment is sent to pathology. The phrenoesophageal ligament then is opened along the right crus, and the retroesophageal space is entered where the posterior vagus is reliably located, clipped, severed, and sent for biopsy. Unless it appears that duodenal stump closure would be difficult, we then proceed with antrectomy. The lesser curvature neurovascular bundle is divided at the angularis incisura, and the right gastroepiploic arcade is divided on the greater curvature at a point directly opposite. This is where the stomach is transected with a green handheld GIA or a purple or black laparoscopic GIA cartridge. The chronically obstructed stomach may be unusually thick walled, and it is important that adequately large staples be used lest the gastric closure dehisce. The gastrocolic ligament attached to the antrum (i.e., the specimen) is taken usually outside the gastroepiploic arcade, progressing distally to the right gastroepiploic pedicle, which is ligated and divided. The right gastric is also ligated and divided. The pylorus and duodenal bulb are carefully separated from the pancreas, and then the postpyloric duodenum is transected with a GIA or TA stapler. The outlet obstruction should be resected. If the obstruction is prepyloric, it is important that the surgeon ensure that the distal staple line is in fact distal to the pylorus to avoid retained antrum. Rarely, resection of the obstruction is difficult or hazardous because it is in the second portion of the duodenum. The surgeon should try hard to rule out cancer if the site of outlet obstruction is left behind, and intraoperative consultation with an hepato-pancreato-biliary colleague may be helpful. Antecolic isoperistaltic Billroth II gastrojejunostomy is performed on the greater curvature side of the gastric remnant, with the afferent loop on the greater curvature side and the efferent limb on the lesser curvature side. We avoid Roux-en Y reconstruction with a large gastric remnant because of the possibility of marginal ulceration and/or delayed gastric emptying. We usually do not oversew the duodenal staple line but after allowing some time to ensure complete hemostasis and no bile staining on the stump, just before abdominal closure we irrigate the staple line and cover it with well-vascularized omentum held in place by two or three strategically placed sutures. A closed-suction right upper quadrant drain is placed, although admittedly routine peritoneal drainage after gastrectomy is not supported by clinical evidence. V/GJ can be performed with an open or minimally invasive technique. After evaluation of the stomach and proximal duodenum, vagotomy is performed. Either a bilateral truncal or posterior truncal with anterior highly selective technique is acceptable. Loop gastrojejunostomy is then constructed to the dependent greater gastric

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curvature. We divide the little branches from the gastroepiploic to the stomach for a length of 6 to 8 cm, creating a target for the handsewn or stapled antecolic isoperistaltic gastrojejunostomy. Patients with obstructing chronic duodenal ulcer disease who are treated with V/GJ should be followed closely for 2 years to ensure that an obstructing cancer was not missed. If the patient is not doing well clinically, reevaluation and open exploration should be considered with conversion of the loop GJ to distal gastrectomy, which should include the area of obstruction.

INTRACTABLE DUODENAL ULCER The endoscopically documented persistence of a benign symptomatic duodenal ulcer despite adequate medical treatment should be a very unusual indication for surgery nowadays. The 50+-year-old literature describing the salutary effect of ulcer surgery for intractability is largely irrelevant to this situation nowadays. Assuming gastrinoma and cancer have been ruled out, a duodenal ulcer will heal if H. pylori infection has been cleared (best documented with a urea breath test, fecal antigen test, or endoscopic biopsy), the patient diligently takes PPIs as prescribed, diligently avoids NSAIDs and aspirin, and does not smoke. Surgery should not be considered for intractability unless the surgeon is certain that all of these conditions have been fulfilled. Though it may take a while, ulcer recurrence is almost inevitable after definitive ulcer surgery for intractability in patients who cannot give up NSAIDs or smoking. It is also important to keep in mind that if the patient has persistent peptic ulceration despite all the aforementioned conditions being fulfilled, perhaps the patient has some other unusual poorly understood factors predisposing to duodenal ulcer (e.g., stress or dysmotility). This may contribute to the high incidence of debilitating postoperative symptoms in patients undergoing vagotomy and drainage or V/A for intractable duodenal ulcer in the modern era.

MANAGEMENT OF THE DIFFICULT DUODENAL STUMP The routine closure of the proximal duodenum during Billroth II distal gastrectomy is accomplished most easily with a GIA- or TA-type stapler (blue cartridge). A two-layer suture closure is also straightforward in routine cases, but excessive suturing and imbrication should be avoided because it may predispose to stump leakage. Occasionally ulcer location or size or the extensiveness of the inflammation and/or scar may render secure duodenal closure difficult. In this situation, difficult duodenal stump closure is best avoided by not performing a distal gastrectomy because operative mortality skyrockets with postoperative duodenal leakage. However, a difficult duodenal stump is occasionally unavoidable. If the ulcer has destroyed the posterior duodenal wall, the anterior edge of the open duodenum can be sewn to the proximal or distal “lip” of the ulcer on the pancreas with interrupted suture. Secure hemostasis in the ulcer bed must be accomplished. The integrity of the closure is tested by placing the tip of the NG tube at the ligament of Treitz (through the gastrojejunostomy) and distending the duodenum with air. Additional sutures may be necessary to render the duodenal closure air tight. Then healthy omentum is sewn over the closure, and multiple closed-suction drains are placed. Duodenal decompression should be performed, ideally with a retrograde tube via the proximal jejunum; other options include lateral duodenostomy or NG decompression by threading the NG tube through the gastrojejunostomy into the afferent limb and duodenum. The latter option requires suturing or bridling the NG to the nose, and it soon becomes uncomfortable unless it can be converted to a percutaneous transgastric arrangement. As discussed earlier, placement of a large tube into the end of the duodenal stump inevitably leaks around the tube and should only be performed if no other primary duodenal closure options are available. Postoperative duodenal stump leakage is usually managed

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nonoperatively unless the patient develops diffuse peritonitis or worsening sepsis. At reoperation, wide drainage and source control are paramount. Suture closure of a leaking stump is destined for failure. Generally an appropriately sized tube is brought through the abdominal wall and placed into the leak, and the duodenum is gently snugged up around this tube, which is buttressed with omentum or falciform or peritoneum/skeletal muscle. Multiple closed-suction drains are placed. If a chronic fistula persists, a definitive repair can be attempted much later with Roux-en-Y duodenojejunostomy or resection.

CONCLUSION Duodenal ulcer is no longer considered a surgical disease. The effectiveness of modern medical management means that only a very small percentage of patients with this diagnosis will ever see a surgeon. However, general and acute care surgeons still have an important role in the management of hospitalized patients with duodenal ulcer. About 25% of this group have a perforated duodenal ulcer, and essentially all require emergency surgery. Prompt resuscitation and surgery in this group will save lives because even a delay of a few hours substantially increases mortality risk. The appropriate surgery for most of these patients is patch of the ulcer with peritoneal irrigation and drainage. About 75% of hospitalized duodenal ulcer patients experience bleeding, and only a small number require surgery, but the right surgery at the right time can rescue these patients. For the highest-risk patients (ASA 4 and ASA 5), probably the best surgery is secure oversewing of the bleeding ulcer and high-dose acid suppression. For patients with lower operative risk (ASA 1–3), probably the best surgery is secure oversewing of the ulcer, truncal vagotomy, and drainage. Duodenal ulcer patients requiring surgery for perforation or bleeding are a small, high-risk subgroup of hospitalized patients that largely accounts for the high postoperative mortality rate (up to 30%). Finally, most patients with ulcer-related chronic gastric outlet obstruction will be seen in the surgical clinic instead of the hospital, and the majority will eventually come to surgery. V/A remains the surgery of choice in this group. Other important but less common issues related to ulcer surgery are also discussed. suggested readings

Chey WD, Leontiadis GI, Howden CW, et  al. ACG Clinical Guideline: Treatment of Helicobacter pylori infection [published correction appears in Am J Gastroenterol. 2018;113(7):1102]. Am J Gastroenterol. 2017;112(2):212–239. Dempsey DT. The management of duodenal ulcers. In: Cameron J, Cameron A, eds. Current Surgical Therapy. 12th ed. Philadelphia: Elsevier; 2018. Kavitt RT, Lipowska AM, Anyane-Yeboa A, et al. Diagnosis and treatment of peptic ulcer disease. Am J Med. 2019;132(4):447–456. Lagoo J, Pappas TN, Perez A. A relic or still relevant—the narrowing role for vagotomy in the treatment of peptic ulcer disease. Am J Surg. 2014;207(1):120–126. Laine L, Barkun AN, Saltzman JR, et  al. ACG Clinical Guideline: Upper gastrointestinal and ulcer bleeding [published correction appears in Am J Gastroenterol. 2021;116(11):2309]. Am J Gastroenterol. 2021;116(5):899–917. Lal P, et  al. Controlled tube duodenostomy in the management of giant duodenal ulcer perforation: a new technique for a surgically challenging condition. Am J Surg. 2009;198(3):319–323. Lanas A, Chan FKL. Peptic ulcer disease. Lancet. 2017;390(10094):613–624. Søreide K, Thorsen K, Harrison EM, et  al. Perforated peptic ulcer. Lancet. 2015;386(10000):1288–1298. Sverdén E, Agréus L, Dunn JM, et al. Peptic ulcer disease. BMJ. 2019;367:I5495 Published 2019 Oct 2. Tarasconi A, Coccolini F, Biffl WL, et al. Perforated and bleeding peptic ulcer: WSES guidelines. World J Emerg Surg. 2020;15:3. Wang A, Yerxa J, Agarwal S, et al. Surgical management of peptic ulcer disease. Curr Probl Surg. 2020;57(2):100728. Wang YR, Richter JE, Dempsey DT. Trends and outcomes of hospitalizations for peptic ulcer disease in the United States, 1993 to 2006. Ann Surg. 2010;251(1):51–58.

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Management of Zollinger-Ellison Syndrome

Management of Zollinger-Ellison Syndrome David W. McFadden, MD, MBA, and Brian D. Shames, MD

Z

ollinger-Ellison syndrome (ZES) is a constellation of symptoms comprising severe peptic ulcer disease, chronic diarrhea, and gastroesophageal reflux disease (GERD). It is caused by gastrin-secreting tumors of the pancreas or duodenum that result in increased stimulation of the acid-secreting parietal cells of the stomach. Patients with ZES have two problems that must be addressed: control of the acid hypersecretion that causes refractory peptic disease (and its complications) and control of the gastrinoma, which is malignant in the majority of cases. The terms gastrinoma and ZES are often used synonymously. However, gastrinoma refers to the neuroendocrine tumor (NET) that secretes gastrin, and ZES refers to the clinical manifestations of the disease. Many tumors, including some non-NET neoplasms, synthesize gastrin, but in most it is not fully processed to biologically active gastrin. Consequently these tumors do not cause ZES as they do not secrete sufficient amounts of fully processed gastrin. Therefore, they are not referred to as gastrinomas by most clinicians and in the classification of pancreatic NETs (pNETs). The syndrome was first described in 1955 by Zollinger and Ellison, who reported two patients with severe ulcer diathesis associated with jejunal ulcerations who ultimately required total gastrectomy after undergoing several failed ulcer operations. In both of the initial patients, non–beta islet cell tumors were identified in the pancreas. Zollinger and Ellison postulated that these tumors were potentially secreting a hormone that caused acid secretion with resultant peptic ulcer disease. The paper was presented at the American Surgical Association in 1955, and in discussion, Dr. Lester Dragstedt, the father of vagotomy, opined that these tumor cells may be similar to the antral cells that produce gastrin. Interestingly, six additional cases were disclosed by discussants of the paper. The syndrome’s name was subsequently suggested by Dr. Ben Eiseman in 1956. In 1960, researchers using a tumor extract bioassay at the University of Liverpool discovered that tumors from ZES patients contained large amounts of a gastrin-like substance. Before the 1970s, ZES diagnosis required incisive clinical review and a high index of suspicion as there was an absence of blood or imaging tests to confirm the diagnosis. In 1966, a radioimmunoassay (RIA) for gastrin was described by James D. McGuigan and now serves as the linchpin of diagnosis. Before the development of gastrin RIA, patients usually underwent multiple gastric operations before diagnosis. Recommended treatment at that time became total gastrectomy as it reduced the mortality of the syndrome, which was generally related to ulcer diathesis complications, such as perforation or bleeding. Later advances in pharmacologic control of acid secretion with histamine-2 (H2) antagonists and proton pump inhibitors (PPIs) have essentially eliminated the need for total gastrectomy. Presently, it is recognized that ZES is caused by gastrin secretion from neuroendocrine tumors that arise from the pancreas, duodenum, or rarely ectopic sites. These tumors are called gastrinomas. In 20% to 25% of cases, ZES is associated with multiple endocrine neoplasia type 1 (MEN-1), an autosomal dominant disorder, whereas nearly 50% of patients with MEN-1 will have gastrinomas. An average of 8 years is reported from the start of symptoms to diagnosis secondary to the widespread use of PPIs. Current surgical treatment is predicated upon gastrinoma resection. It also relies on long-term pharmacologic suppression of acid secretion for control of the peptic ulcer disease and management of the hyperparathyroidism and other endocrine disorders associated with MEN-1.

CLINICAL PRESENTATION Behind insulinoma, gastrinoma is the second most common functional neuroendocrine tumor, with an annual incidence of 1 to 3 cases per 1 million people. Gastrinoma is the underlying cause of peptic ulcer disease in only 0.1% to 1% of patients and is one of the rarest of all causes of ulcer disease. ZES is usually diagnosed in the fifth decade of life, and it is diagnosed between 20 and 60 years of age in 90% of patients. It is more common in men. ZES most commonly occurs as a noninherited disease; however, it is associated with MEN-1 in 20% to 25% of cases. Gastrinoma is the most common functional neuroendocrine tumor in MEN-1, occurring in 50% of patients with the syndrome. Hence, MEN-1 must be excluded in the workup of patients with suspected gastrinoma, and patients with MEN-1 should also be screened for gastrinoma. Patients with MEN-1 have their disease onset almost a decade earlier; the average age of onset of ZES is 33.2 years for patients with MEN-1 compared with 43.5 years for sporadic gastrinoma patients. Gastrinoma is also seen in association with von Hippel-Lindau syndrome and von Recklinghausen’s disease. Gastric acid secretion is usually controlled by negative feedback mechanisms from the release of somatostatin by gastric D cells. This normally maintains gastric acid homeostasis and pH. Because of the unopposed gastrin release by the gastrinoma, severe peptic ulcer disease results from the excess gastric acid secretion via the trophic effect of gastrin on parietal cells. Significantly, ZES is not the initial diagnosis in 97% of affected patients. Presenting symptoms for this disease have altered little despite successful pharmacologic treatment of gastric hypersecretion and the pervasive use of these drugs for symptoms of dyspepsia and other digestive ailments. The clinical presentation of gastrinoma is often not specific. There is often overlap of the symptoms associated with this illness and other more common gastrointestinal conditions that result in a high frequency of misdiagnosis and diagnostic delays. In most series, abdominal pain and diarrhea were the most common symptoms, reported in more than 70%, followed by heartburn (44%), nausea (33%), vomiting (25%), and weight loss (17%). Despite an increased awareness of ZES, multiple experts have remarked that the diagnosis is more difficult today given the nearly ubiquitous use of PPIs. Diagnosis can normally be confirmed by measurement of fasting serum gastrin levels when the patient is off of PPIs, however the average time from symptom onset to diagnosis remains between 6 and 8 years. Another reason for the delay in diagnosis is that many patients with ulcer disease are symptomatically improved by H2 antagonists or PPIs without excluding the possibility of ZES. This treatment controls the acid secretion and related symptoms but may delay diagnosis if gastrinoma is not initially considered in the differential diagnosis.

CLINICAL PATHOLOGIC CORRELATION In nearly 70% of patients, gastrinomas are found in the pancreas or duodenum within the region known as the gastrinoma triangle. This devised triangle is bounded by the cystic duct, the second and third portion of the duodenum, and the neck and body of the pancreas. Rarely, gastrinomas may occur in ectopic locations, including the stomach, bile duct, periportal lymph nodes, lungs, heart, and ovaries. Most gastrinomas (50%–70%) are located in the duodenum rather than the pancreas. They are most common in the first portion of the duodenum with a diminishing incidence as one progresses distally. Duodenal gastrinomas may be very small and hence difficult to identify preoperatively and intraoperatively. Both pancreatic and duodenal gastrinomas occur in MEN-1 patients, however these patients are more likely to have multiple tumors in the pancreas or duodenum. Initially, it was thought that, similar to insulinomas,

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almost all sporadic gastrinomas occurred in the pancreas. However, it is now established that most (60%–95%) occur in the duodenum; in a recent series, they were 3- to 9-fold more frequent than pancreatic gastrinomas. Duodenal and pancreatic gastrinomas differ in their biologic behavior. Although both are associated with frequent lymph node metastases (30%–70%), pancreatic tumors have a much higher rate of liver metastases, which is the primary determinant of long-term survival. Hence, patients with pancreatic gastrinomas have a poorer prognosis. Sporadic gastrinomas are malignant in 60% to 90% of cases; approximately 13% to 53% (mean 34%) of patients have liver metastases at presentation, with most being diffuse liver involvement. Gastrinomas are generally well differentiated and slow growing. They have a low proliferative rate with a Ki-67 of 1% to 2%. The tumors are usually more indolent and slower growing than other gastrointestinal malignancies. Duodenal gastrinomas have a greater incidence of lymph node metastases than pancreatic gastrinomas, 70% versus 40%, respectively. Liver metastases occur in approximately 25% of patients and are more common with pancreatic primary tumors (50% vs. 10%), particularly those occurring to the left of the superior mesenteric vessels. Unlike lymph node metastases, liver metastases herald a poor prognosis, with the extent of liver involvement an important predictor of survival. In patients with diffuse liver metastases, the 10-year survival is 10% to 15% compared with 95% in the absence of liver metastasis. The prognosis is also more favorable in patients with single-lobe liver metastasis, with a 10-year survival of nearly 60%. Regardless of location, primary tumor size is predictive of distant metastasis (Table 1).

TABLE 1  Primary Tumor Size and Frequency of Distant Metastases Tumor Class

Diameter Range (cm)

T0 (no tumor)

Patients (No.)

Distant Metastases (%)

0

18

0

T1

0.4–1.0

21

10

T2

1.2–2.0

22

14

T3

2.2–2.6

16

12

T4

3.0–8.5

29

59

Modified from Ellison EC, Johnson JA. The Zollinger-Ellison syndrome: a comprehensive review of historical, scientific, and clinical considerations. Curr Probl Surg. 2009;46:13-106.

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DIAGNOSIS Although rare, a patient should be referred for prompt ZES workup in the presence of refractory peptic ulcer disease, long-standing diarrhea, ulcer disease in the absence of Helicobacter pylori infection, or failure to improve after treatment for established H. pylori and acid suppression therapy. In addition, the presence of hypercalcemia or nephrolithiasis should raise suspicion of possible MEN-1, and such patients should be screened for gastrinoma and MEN-1. The algorithm for the diagnosis of gastrinoma is shown in Figure 1. The diagnostic steps include measurement of gastric acid, baseline fasting gastrin levels, and secretin-stimulated serum gastrin levels as well as cross-sectional imaging. Fasting serum gastrin is the appropriate initial diagnostic test, but it is insufficient alone to prove the diagnosis. Several medical conditions may cause hypergastrinemia, including pernicious anemia and atrophic gastritis, which are the two most common causes of hypergastrinemia. In affected patients, it is common for the fasting gastrin level to exceed 1000 pg/mL. Therefore, a fasting serum gastrin level greater than 1000 pg/mL is not diagnostic for ZES unless it occurs in association with increased gastric acid secretion (gastric pH 110 pg/mL

5 to ≤10

High (55)

Insufficient data

High (85)

Insufficient data

>10

High (86)

High (86)

High (90)

High (71)

Data based on long-term follow-up of 1055 gastric, 629 small intestinal, 144 duodenal, and 111 rectal GISTs. GIST, Gastrointestinal stromal tumor; HPF, high-powered field. Modified from Miettinen M, Lasota J. Gastrointestinal stromal tumor: pathology and prognosis at different sites. Semin Diagn Pathol. 2006;23(2):70–83.

response (800 mg vs. 400 mg daily). PDGFRα-mutant tumors, representing 10% of GISTs, are almost always gastric and demonstrate comparably indolent biology. However, the most common PDGFRα mutation is exon 18 (D842V), which imparts imatinib resistance but does respond to avapritinib therapy, recently FDA-approved as first-line therapy for these patients. Thus, understanding the biology associated with a specific mutation and the expected response to imatinib can help plan treatment and follow-up.

SURGERY FOR PRIMARY DISEASE Indications Surgical resection remains the mainstay of treatment for most patients with GISTs. According to the National Comprehensive Cancer Network (NCCN), resection is indicated for all GISTs greater than 2 cm in size in patients who are otherwise acceptable candidates for surgery. Tumors less than 2 cm in size that

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Management of Gastrointestinal Stromal Tumors Points

0

Size (cm)

0

10

20

30

40

50

5

60

10

70 15

80 25

90 35

100 45

≥5/50 HPF Mitotic index 50%) but also develop in the small bowel, with 25% in the jejunum. Derived from the interstitial cells of Cajal, they comprise approximately 10% of small bowel tumors. About 20% to 30% of GISTs are malignant at presentation, more often malignant when involving the small bowel. On CT scan, they appear as smooth, well-defined masses arising from the small bowel wall demonstrating exophytic growth patterns and internal heterogeneity. They may have areas of central hemorrhage or necrosis (Fig. 6). GIST rarely metastasize to nodes or spread outside of the abdominal cavity but can be aggressive. Metastases to the liver can present with multiple serosal-based nodules. The primary lesions are known for causing ulceration through the mucosa, presenting with bleeding. GIST can be differentiated from other sarcomas of smooth muscle by immunostaining for c-KIT. Activating mutations of the KIT oncogene can be seen in over 80% of GISTs. CT-guided biopsy is usually not necessary as radiographic appearance is distinctive and resection is indicated. A laparoscopic approach for resection of GIST is often ideal. These tumors are exophytic, making them easier to locate than other small bowel tumors during laparoscopic exploration, and as they do not spread via lymphatics, lymphadenectomy is not required. A short segmental enterectomy with only 2 cm margins is recommended. If the tumor is bulky or adjacent organ involvement is

A

suspected, preoperative imatinib can aid in shrinking the mass to facilitate resection. Unfortunately, more than 50% of these masses recur within 5 years. To prolong disease-free survival, high-risk patients should be treated postoperatively with a minimum of 12 to 24 months of imatinib, and studies are ongoing regarding longer or even indefinite treatment to prevent recurrence. High-risk features include tumor size >2 cm, high mitotic index, poorly differentiated cell type, presence of metastasis, and positive margin.

Sarcoma Sarcoma, typically leiomyosarcoma, is rare, occurring most often in the ileum. Five-year survival is approximately 50%. Radical surgical excision is recommended if the primary disease is resectable. Similar to adenocarcinoma, if the disease is deemed unresectable, surgical bypass should be considered. Palliative radiation has a greater role in sarcoma management compared with other small bowel tumors.

Lymphoma The small bowel is the most frequently encountered extranodal site for lymphoma. This tumor is usually non–Hodgkin-type lymphoma and involves the small bowel mesentery more commonly than the luminal surface. It is most common in the ileum, the most lymphoid-rich region of the small bowel. Clinicians should maintain a high suspicion for other sites of involvement, as a solitary small

B

FIG. 5  Small bowel adenocarcinoma (A) intraoperative photo and (B) gross pathology. (B courtesy of Neil Neumann, MD, PhD, and Sarah Umetsi, MD, PhD).

A

B

FIG. 6  (A) Gross pathologic appearance high-grade GIST invading distal pancreas. (B) Gross pathologic appearance of intraluminal portion of GIST. (Images courtesy Neil Neumann, MD, PhD, and Sarah Umetsi, MD, PhD.)

S m al l B owe l



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may be necessary for obstruction, or the diagnosis of lymphoma may be made postoperatively after surgical intervention for small bowel obstruction (SBO) has already taken place. In patients without signs and symptoms of SBO, CT-guided or endoscopic biopsy is appropriate to guide therapy. Indeed, the main role of biopsy in small bowel tumors is to distinguish lymphoma, as most other small bowel masses require resection as the primary management.

Metastatic Disease Secondary involvement of the small bowel from other metastatic lesions presents as multifocal advanced cancer and not as an isolated small bowel lesion. Lung, melanoma, breast, colon, and cervical cancers can all spread to the small bowel. Sarcomas and adenocarcinomas can also impact the small bowel, either through direct erosion or carcinomatosis of overlying peritoneum. As an innocent bystander, the small bowel may need to be resected or bypassed depending on the type and stage of primary tumor.

SUMMARY

FIG. 7  Small bowel lymphoma.

intestinal lesion is a rare presentation for lymphoma. Patients with Celiac disease have a 20-fold higher risk of GI lymphoma, and patients with chronic immunosuppression including transplant recipients and those with HIV are also at an increased risk. On CT with IV contrast, the mass often appears well circumscribed and homogeneous (Fig. 7). A tissue diagnosis is required for lymphoma, and as there are a variety of non-Hodgkin subtypes, it is imperative that enough tissue is harvested to perform the full battery of cytopathology and flow cytometry. The subtype dictates the tumor behavior, treatment, and prognosis. Most small bowel lymphomas do not require resection and rather are best treated with multidrug chemotherapy. The 5-year survival is 50%, with poorer prognosis in males and the elderly. Surgery

Small Bowel Diverticulosis Jonathan B. Greer, MD

INTRODUCTION Although small bowel diverticulosis is a rare clinical entity, all general surgeons should be comfortable with its diagnosis and management. The true prevalence is unknown, but a busy practitioner will frequently encounter these in clinical practice. Less than 4% of all small bowel diverticula will become overtly symptomatic. The duodenum

Small bowel tumors are rare and present with a constellation of common symptoms. Late diagnosis makes the prognosis of small bowel malignancy particularly poor, and a thorough workup to rule out small bowel tumors should be undertaken in anyone with vague abdominal pain and paraneoplastic symptoms with no other apparent source. Aside from small bowel lymphoma, most other suspicious small bowel masses do not require biopsy and should be resected. Nuanced management of these malignant lesions has room for investigation, and surgeons should feel compelled to lead efforts to discover optimal treatment paradigms and create guidelines.

Suggested Readings Cross AJ, Leitzmann MF, Subar AF, et  al. A prospective study of meat and fat intake in relation to small intestinal cancer. Cancer Research. 2008;68:9274. Leoncini E, Carioloi G, La Vecchia C, et al. Risk factors for neuroendocrine neoplasms: a systematic review and meta-analysis. Annals of Oncology. 2016;27:68. Miettinen M & Lasota J. Gastrointestinal Stromal Tumors: Review on Morphology, Molecular Pathology, Prognosis and Differential Diagnosis. Archives of Pathology and Laboratory Medicine. 2006:1466–1478. Min KW, Leabu M. Interstitial cells of Cajal (ICC) and gastrointestinal stromal tumor (GIST): facts, speculations, and myths. Journal of Cellular and Molecular Medicine. 2006;10(4):995–1013.

is the most common site, while Meckel’s diverticula are the most wellknown. Small bowel diverticula can be congenital or acquired. These can be classified as either true or false, based on whether all three walls of the bowel are involved. Meckel’s diverticula are the most wellknown true diverticula of the small bowel. They are further classified by location (duodenal or jejunoileal), but they are best delineated by those that are asymptomatic and therefore incidentally detected versus those that present with clinical symptoms (usually bleeding or diverticulitis) and rarely as a cause of obstruction or perforation. Many manuscripts have been published on this topic, mostly single-center studies or case reports. There is a paucity of high-level evidence, however. Nonetheless, improvements in both axial imaging and advanced endoscopic techniques will likely lead to the increased detection of small bowel diverticulosis over time. This chapter will review the diagnosis and management of this clinical entity.

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Small Bowel Diverticulosis

DETECTION AND MANAGEMENT OF ASYMPTOMATIC (INCIDENTALLY DISCOVERED) SMALL BOWEL DIVERTICULOSIS The increasing frequency of high-quality cross-sectional imaging and endoscopic procedures has led to an increase in the detection of asymptomatic small bowel diverticulosis. However, this has not led to an increase in symptomatic cases. There are three principal groups of asymptomatic small bowel diverticula: duodenal, jejunoileal, and Meckel’s diverticula, a subset of jejunoileal diverticula that are always congenital and true diverticula.

Duodenal Diverticula The most common diverticula of the small bowel are duodenal diverticula, comprising 45% to 79% of cases. In terms of prevalence, a true number is difficult to ascertain, but these have been reported in 2% to 5% of upper gastrointestinal contrast studies, 7% of endoscopic retrograde cholangiopancreatography, and as high as 20% in one autopsy series. The only known risk factor is age. Duodenal diverticula are most commonly located in the second portion of the duodenum (60% to 95% of cases). They are much more commonly asymptomatic. These can be congenital or acquired, and extraluminal or intraluminal. The vast majority are acquired and extraluminal. The mechanism is thought to relate to weakness of the bowel wall where perforating vessels are found. There are rare congenital duodenal diverticula that are intraluminal, called windsock diverticula, and are lined with duodenal mucosa on the entirety of the diverticulum, both inside and outside, from a failure of canalization of the embryonal foregut. Diagnosis is made by the discovery of an outpouching of the duodenum on cross-sectional imaging, fluoroscopic contrast studies, endoscopy, or at the time of an abdominal operation. Though duodenal diverticula can be quite large, asymptomatic diverticula are, by definition, asymptomatic; therefore, no treatment is required. Particularly in cases that would require a pancreaticoduodenectomy, surgical resection is associated with significant morbidity and therefore is not recommended for an incidentally discovered diverticulum.

Jejunoileal Diverticula Jejunoileal diverticula are less common than duodenal diverticula, comprising less than 20% of small bowel diverticulosis in most series, although they are more likely to cause complications than their duodenal counterparts. The actual prevalence is unknown, but autopsy series have reported a prevalence as high as 7%. The vast majority are asymptomatic. These can be single or multiple, with 80% in the jejunum, 15% in the ileum, and 5% found in both. False diverticula are the most common. These are likely caused by the gradual weakening of the wall of the intestine from increased intraluminal pressure that can be generated by dysfunction of the migrating motor complexes. As such, age is the most widely reported risk factor. Other risk factors include intestinal dysmotility disorders. The most common location is the proximal jejunum, and these are frequently multiple. Jejunoileal diverticula can be discovered on laparotomy, although they are commonly also diagnosed on radiographic or endoscopic studies. Enteroclysis is the best radiographic study to evaluate jejunoileal diverticula, though CT and MR enterography are increasingly used as techniques improve. Capsule endoscopy may be useful as well. There is no role for the surgical management of incidentally discovered jejunoileal diverticula.

Meckel’s Diverticulum Meckel’s diverticula are the most common congenital diverticula of the small bowel and account for 25% of small bowel diverticula (Fig. 1). A prevalence estimate in an autopsy study was 1.23%.

FIG. 1  Common presentation of a Meckel’s diverticulum projecting from the antimesenteric border of the ileum. (From McKenzie S, Evers BM. Small intestine. In: Townsend CM Jr, ed. Sabiston Textbook of Surgery. 19th ed. Philadelphia: Elsevier; 2012.)

They are, by definition, true diverticula of the ileum and represent a remnant vitelline (omphalomesenteric) duct that connects the embryonic midgut to the yolk sac. This duct is normally obliterated during embryologic development. As a true diverticulum, it involves all three layers of the bowel wall and is always antimesenteric. The classic “rule of two” for Meckel’s diverticula is thus: They are located approximately 2 feet from the ileocecal valve, contain two types of heterotopic tissue (gastric or pancreatic), occur twice as commonly in males, in 2% of the population, are symptomatic in about 2% of cases, tend to be diagnosed within the first 2 years of life, and can extend over 2 inches in length. Additionally, there are two types of symptoms that can arise: bleeding and obstruction. Given their small size, most asymptomatic Meckel’s diverticula are discovered during surgery for another indication. They are less frequently found on axial imaging. Meckel’s diverticula have a low lifetime risk of complications related to the diverticula itself, and mortality is extremely rare. Therefore, in most cases, there is no compelling indication for surgical resection of an incidentally discovered Meckel’s diverticulum in an adult. Some authors advocate for prophylactic resection in children, and in adults in cases of palpable ectopic tissue, prior history of diverticulitis, hemorrhage, intussusception, or the presence of a mesodiverticular band. This is in contradistinction to the management of clinically significant Meckel’s diverticula, which will be discussed later in this chapter.

DETECTION AND MANAGEMENT OF SYMPTOMATIC SMALL BOWEL DIVERTICULOSIS The minority of small bowel diverticula present with clinical manifestations, which can be infection (diverticulitis), bleeding, or obstruction. Unlike the incidentally discovered and therefore asymptomatic versions, symptomatic small bowel diverticula require treatment.

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Duodenal Diverticula Only about 5% of patients with duodenal diverticula present with complications. The most commonly reported symptom is postprandial epigastric abdominal pain, which can be associated with nausea and vomiting. Obstruction from a duodenal diverticula is quite rare but can occur, particularly in cases in which the diverticula is large. This can result in extraluminal compression of the duodenum. There can also be extrinsic compression of the biliary tree or pancreatic duct, thus resulting in a rare cause of obstructive jaundice or recurrent pancreatitis. More commonly, infectious complications may develop, such as diverticulitis +/– abscess, perforation, and rarely, fistula. Bleeding may also occur secondary to diverticulitis as inflammatory erosion into a neighboring vessel may result in fairly significant bleeding, with hematemesis and melena as the presenting signs. After initial nasogastric tube decompression for duodenal obstruction, diagnosis of a duodenal diverticula as the underlying cause is usually one of exclusion, as a malignancy would be far more common. This diagnosis can be made by axial imaging, usually CT, although an upper gastrointestinal contrast study may also be helpful. These can be challenging in an obstructed patient. In conjunction with these radiographic studies, endoscopy is necessary to rule out mucosal-based lesions as the etiology. In cases of biliary tree or pancreatic duct obstruction from duodenal diverticula, axial imaging (CT or MRI) in concert with endoscopy, including ERCP, are essential to make the diagnosis. Duodenal diverticulitis will usually be diagnosed on CT with characteristic findings similar to the vastly more common colonic diverticulitis. CT angiography may be necessary to identify a bleeding vessel related to a duodenal diverticula, although endoscopy may also be helpful. The patient’s clinical condition should dictate whether purely diagnostic studies (e.g., CT angiography or endoscopy) can be safely done, rather than diagnostic and therapeutic modalities, such as mesenteric angiography in interventional radiology. Management of duodenal diverticulosis in the asymptomatic patient is straightforward (nothing to do) but can be more nuanced in symptomatic patients and varies greatly with the clinical scenario. The rare case of duodenal obstruction secondary to a duodenal diverticula may require surgical intervention. This may include resection of the diverticula alone with transverse closure of the duodenum, use of a serosal small bowel (Thal) patch, a Roux-en-Y duodenojejunostomy, or potentially a segmental duodenal resection. Assessment of the anatomic relationship between the ampulla of Vater and the line of transection is crucial for segmental resection of the duodenum. Involvement of the medial side of the duodenum that results in obstruction will require a pancreaticoduodenectomy. The more common case involving biliary or pancreatic obstruction should be temporized first via endoscopic means, usually with stenting. Surgical resection, which would be a pancreaticoduodenectomy, should be reserved for patients who fail endoscopic management. As with all complex hepatobiliary procedures, surgeon familiarity and comfort with these techniques along with well-delineated anatomic relationships between the duodenal diverticula and important neighboring structures is critical. Most cases of duodenal diverticulitis, even with contained perforation, can be managed conservatively with nil per os, placement of a nasogastric tube, antibiotics, and occasionally percutaneous drainage. Surgical management in the acute setting is almost never indicated and can be quite challenging. Bleeding duodenal diverticula are managed similar to other causes of upper gastrointestinal bleeding, either via endoscopy or interventional radiology. Surgical management is rarely indicated.

Jejunoileal Diverticula Symptomatic false jejunoileal diverticula are rare, but about 10% of all jejunoileal diverticula will become symptomatic. Patients can present with nonspecific symptoms such as abdominal pain, early satiety, bloating, and malabsorption (diarrhea and/or steatorrhea)

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secondary to small intestinal bacterial overgrowth (SIBO). The complications that can arise and therefore lead to detection are diverticulitis, bleeding, obstruction, or perforation. The clinical presentations associated with each of these complications are similar to their large bowel counterparts, although the pain is typically epigastric or periumbilical in location. Cross-sectional imaging is the most common means of detection as these patients will usually present with abdominal pain or melena. SIBO is treated with antibiotics. The treatment of jejunoileal diverticulitis is identical to that of colonic diverticulitis: bowel rest, intravenous fluids, and antibiotics. Surgical intervention is not always needed, particularly in isolated cases. Recurrent or complicated episodes may mandate segmental resection, although rare. Management of perforated jejunoileal diverticula depends greatly on the condition of the patient. Conservative management may be appropriate in cases in which the perforation has walled off and the patient is minimally symptomatic. Conversely, critically ill patients warrant urgent exploration and segmental resection. Enterocutaneous fistulae secondary to jejunoileal diverticulitis have been reported. A bleeding jejunoileal diverticulum can be found on push or double-balloon enteroscopy or on capsule endoscopy, and it should be considered in cases of gastrointestinal bleeding in which both esophagogastroduodenoscopy and colonoscopy are negative. Endoscopic management of bleeding can be difficult, and interventional radiology angioembolization is not typically attempted. After a trial of conservative management, surgical intervention is warranted. Small bowel obstructions secondary to jejunoileal diverticula are managed like adhesive small bowel obstructions. Resection of the diverticula would be warranted in cases of failure of conservative management. An uncommon clinical scenario is bowel obstruction secondary to an impacted fecalith. These can be treated surgical by enterotomy and stone extraction.

Meckel’s Diverticula The risk of a complication that leads to discovery of a Meckel’s diverticulum is estimated to be in the 2% to 6% range. The most common mechanism of a symptomatic Meckel’s diverticulum is thought to relate to acid production by heterotopic gastric mucosa within the diverticulum leading to ulceration. The symptoms/complications that can arise are bleeding, obstruction, or abdominal pain. These usually occur in the pediatric population. The relative proportion of each of these findings is not fixed, but one single-center series of known Meckel’s diverticula in pediatric patients had 19% discovered incidentally, whereas the remaining patients presented with the following: 35% gastrointestinal bleeding, 20% diverticulitis or perforation, 14% obstruction, and 12% intussusception. Gastrointestinal bleeding that is caused by a Meckel’s diverticulum may be acute or chronic. It is frequently associated with heterotopic gastric mucosa, much more so than an asymptomatic Meckel’s diverticulum. The suspicion of a bleeding Meckel’s diverticulum should be higher in young patients with no evidence of an inflammatory explanation for the bleeding, such as infectious illnesses or inflammatory bowel disease, or in adults 4 mg/dL

If any, then high probability (>50%)

Strong

Dilated CBD on US (>6 mm with gallbladder in situ) Bilirubin 1.8–4 mg/dL

If both, then high probability (>50%)

Moderate

Abnormal liver biochemical test other than bilirubin Age older than 55 years Dilated CBD on US/cross-sectional imaging

Intermediate to low (10%–50%)

TABLE 2 Tokyo 2018 Criteria for Diagnosing Acute Cholangitis Systemic inflammation

Tokyo 2018 Clinical Predictors

Diagnosis

A1) Fever (>100.4°F) and/or shaking chills

Definite diagnosis

A2) Laboratory evidence of inflammatory response

One item in A

WBC 10,000, increased CRP

One item in B

B1) Jaundice (T. bili ≥2 mg/dL)

Suspected diagnosis

B2) Laboratory evidence of cholestasis

One item in A

ALP >1.5 STD, GGT >1.5 STD, AST 1.5 STD

One item in either B or C

One item in C Cholestasis

Imaging

C1) Biliary dilatation C2) Evidence of etiology on imaging (i.e., stent, stricture, stone, etc.)

ERCP with biliary decompression is the procedure of choice for the treatment of acute cholangitis. A recent systematic review and meta-analysis by Iqbal et al. compared performance of ERCP 48 hours for cholangitis. ERCP with biliary decompression within 48 hours was associated a nearly twofold reduction in mortality. Khashab et al. demonstrated that a delay >72 hours was associated with an increased composite outcome of death, organ failure, or intensive care unit admission. The role and timing of ERCP in acute biliary pancreatitis remains controversial. The literature suggests there is no evidence that early routine ERCP significantly affects mortality and local or systemic complications of pancreatitis, regardless of predicted severity. Nevertheless, several studies have favored early ERCP in patients with acute biliary pancreatitis and cholangitis concurrently. Endoscopic sphincterotomy and stone extraction with extraction balloon catheters or wire baskets are successful in more than 90% of cases in achieving bile duct stone clearance. There are other techniques that can be used for stone extraction of difficult bile duct stones such as mechanical lithotripsy using a basket and the digital single operator cholangioscopy system with electrohydraulic lithotripsy or laser lithotripsy, the latter with more than 95% rate of stone clearance with low rate of adverse events. If stone removal is unsuccessful, which usually occurs if stones are large or numerous, then biliary decompression should be accomplished by placement of a biliary stent or nasobiliary drain. In most cases, endoscopic intervention should be followed by cholecystectomy. Biliary symptoms recur twice as commonly in patients whose gallbladder remains in situ with a 5-year risk of significant biliary adverse events leading to cholecystectomy as high as 15%.

Benign Biliary Strictures ERCP is indicated in the evaluation and treatment of benign biliary strictures, congenital bile duct abnormalities, and postoperative adverse events such as anastomotic strictures and biliary leaks. Biopsies and brushings can help define the etiology of benign biliary strictures and diagnostic yield may increase with cholangioscopy directed biopsies. Benign biliary strictures may be dilated with hydrostatic balloons (maximum biliary dilator diameter 10 mm) or graduated catheters passed over a guidewire. Benign biliary strictures amenable to endoscopic dilation include those secondary to chronic pancreatitis, dominant strictures in PSC, postoperative strictures, and strictures caused by stone disease. Single or multiple plastic stents may be used to maintain patency after initial dilation. Serial endoscopic dilation and maximal caliber stent placement can be used to achieve prolonged ductal patency in most benign postoperative strictures. Fully covered self-expandable metal stents (FCSEMS) are an alternative approach in benign biliary strictures. The cSEMS expand to lumen sizes larger than those of plastic stents, without the risk of tissue ingrowth and embedding such as in uncovered and partially covered metal stents, allowing an indwell time up to 12 months if necessary, and without compromising the ease of removal. Chronic pancreatitis accounts for 10% of all CBD strictures. Treatment is indicated for patients with jaundice and/or cholangitis, those with significant biliary dilation (12–15 mm) proximal to the stricture, and with abnormal liver function tests (AP >3 times the normal value for 6 months or longer). In patients with bile duct strictures resulting from chronic pancreatitis the use of multiple plastic

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Obstructive Jaundice: The Role of Endoscopic Intervention

stents over a long period (14 months) compared with a single stent increases the chance of long-term overall success to 65.2% with a high risk of restenosis (17%). The FCSEMS has been associated with high levels of success (97%–98%). In patients with PSC, MRCP is a noninvasive imaging test with comparable diagnostic accuracy to ERCP in the diagnosis of dominant strictures. A dominant stricture is defined as a lumen diameter of 1.5 mm or less in the CBD and 1 mm or less in the common hepatic duct and is seen in 45% to 58% of patients with PSC. In case of unclear results of an MRCP or clinical deterioration of a patient with prior diagnosis of PSC (worsening cholestasis, jaundice, or cholangitis), ERCP can aid in the diagnosis of a dominant stricture. Benign strictures in PSC patients respond well to endoscopic therapy with balloon dilation with or without stent placement. Limited data suggest that balloon dilation is often sufficient and that the use of stents may be associated with an increased risk of adverse events and cholangitis. Postsurgical strictures occur after orthotopic liver transplantation and laparoscopic cholecystectomy in 3% to 13% and 0.2% to 0.7%, respectively. Strictures recognized early in the postoperative/operative period are often associated with a bile leak caused by direct trauma, whereas delayed presentation is commonly associated with ischemic injury and resultant fibrosis. A commonly used classification for postoperative strictures is the Bismuth classification, based on location of the stricture within the bile tree seen in Table 3. Clinical presentation (elevation of liver function tests, pain, or jaundice) depends on the degree of bile duct obstruction. Endoscopic treatment usually involves serial placement of large bore plastic stents with exchange every 3 to 4 months. Balloon dilation is high risk in the first 4 weeks of surgery and is typically not performed. Success rates for this approach range from 74% to 90%

TABLE 3  Bismuth Classification for Benign Biliary Strictures Type

Criteria

I

Low common hepatic duct stricture with a length of common hepatic duct stump greater than 2 cm

II

Proximal common hepatic duct stricture with a common hepatic duct stump less than 2 cm

III

Hilar stricture, no residual common hepatic duct, but the hepatic ductal confluence is preserved

IV

Hilar stricture with involvement of hepatic ductal confluence and loss of communication between right and left hepatic duct

V

Involvement of an aberrant right sectorial duct alone or with concomitant stricture of the common hepatic duct

I

II

IIIa

IIIb

with recurrence rates as high as 30% within 2 years of stent removal. Distal postoperative biliary strictures (Bismuth I and II) are associated with better success rates compared with proximal hilar strictures (Bismuth III). cSEMS may have a potential benefit in the management of refractory benign biliary strictures due to their large caliber and longer duration of patency allowing them to be left in place longer, resulting in fewer procedures for serial dilations and placement of multiple plastic stents.

Malignant Biliary Strictures The most widely recognized cause of malignant distal biliary obstruction is pancreatic head cancer. Other causes of malignant obstructive jaundice are CCAs, gallbladder cancer, and metastatic tumors compressing the biliary system. ERCP can help identify distal biliary malignancies and enable diagnosis through either brush cytology samples or biopsies of directly visualized ampullary lesion. Only 25% to 30% of the liver volume is necessary to be drained for resolution of jaundice. The right hepatic duct drains 50% to 55%, the left hepatic duct drains 30% to 35%, and the caudate lobe drains 10% of the liver parenchyma. ERCP is the first-line method for biliary decompression. Only 20% of periampullary cancers are deemed resectable at the time of presentation. Several studies have shown evidence that argue against preoperative biliary drainage in patients with resectable disease. In patients with nonresectable malignant biliary obstruction, effective biliary decompression improves symptoms and enables patients to undergo palliative therapies. With the advent of neoadjuvant chemotherapy used to downstage potentially unresectable tumors in the hope of improving the outcome, preoperative biliary drainage has become even more clinically relevant. The most common method of achieving biliary drainage is by ERCP and stent placement (plastic or self-expandable metallic stent [SEMS]). In a comparison of stent types, plastic stents have a risk for bacterial biofilm formation increasing risk for cholangitis and stent occlusion. SEMS have a significantly wider diameter and higher patency rate in comparison to plastic stents. A retrospective study in patients of 272 patients who received preoperative drainage showed stent patency was significantly greater in the SEMS versus plastic stent group (125 days vs. 43 days, P < 0.001). Covered SEMS are designed to prevent tumor ingrowth into the stent through the stent interstices. They are also removable as the covering prevents embedding of the stent. A meta-analysis comparing cSEMS compared with uncovered SEMS involving eight studies concluded that the group of patients with cSEMS had lower incidence of adverse events, with no significant difference in dysfunction. Malignant hilar strictures are categorized according to the Bismuth-Corlette classification (Fig. 3). At the time of presentation, only a minority (48 hours is associated with a 25% mortality rate compared with 8% for SIRS that resolves within 48 hours. Other measures of severity have not been shown to be superior to SIRS; these include single serum markers such as C-reactive protein and procalcitonin as well as multifactorial scoring systems such as APACHEII, Ranson’s Criteria, Balthazar’s CT Severity Index, and the modified Glasgow score.

INITIAL MANAGEMENT Fluid Resuscitation Many patients with acute pancreatitis present in a hypovolemic state resulting from both their symptoms (i.e., anorexia, vomiting) and fluid sequestration/extravasation secondary to inflammation. Intravenous fluid resuscitation should be tailored to each patient, though most cases will require large-volume resuscitation (2500–4000 mL) within the first 24 hours. Traditional teaching suggested that patients should remain on rates of isotonic fluid as high as 20 mL/kg/hour with no enteral nutrition until their acute symptoms resolve; however, more recently these practices have been shown to increase the risk of morbidity and mortality. The most recent guidelines from the International Association of Pancreatology/American Pancreatic Association (IAP/APA) recommend goal-directed resuscitation with a starting rate of 5 to 10 mL/kg/hour. Metrics to guide resuscitation include noninvasive measurement of heart rate, mean arterial pressure, and urinary output. Invasive measurement of stroke volume or pulse pressure variation and central venous pressure can also be used as well as repeated hematocrit levels. Ringer’s lactate is the preferred fluid for initial resuscitation. Though challenging, every effort should be made to avoid both over-resuscitation and under-resuscitation. Over-resuscitation can lead to acute lung injury, abdominal compartment syndrome, and increased mortality, whereas inadequate resuscitation increases the risk of end organ damage and pancreatic necrosis from hypoperfusion. 539

540

Management of Acute Necrotizing Pancreatitis

BOX 1  Etiologies of Acute Pancreatitis Gallstones Alcohol use Instrumentation (i.e., ERCP) Hypertriglyceridemia Hypercalcemia Hereditary (e.g., PRSS1 mutation) Autoimmune Neoplasm Toxins Anatomic anomalies (e.g., pancreatic divisum) Infection Ischemia Idiopathic ERCP, Endoscopic retrograde cholangiopancreatography.

there is a 40% rate of occult infection, and fine-needle aspiration may aid in the decision to start antibiotics. Lastly, septic patients with no other likely sources of infection may benefit from empiric antibiotics as most of the pathogens responsible for the septic physiology of acute pancreatitis originate from among the gut microbiota. When antibiotics are prescribed for suspected or confirmed infected pancreatic necrosis, they should initially provide broad-spectrum coverage including antifungal coverage. The penetration of most antibiotics into necrotic pancreatic tissue is not fully understood, though there is evidence that carbapenems achieve high concentrations within pancreatic tissue after a single dose. In the absence of culture results, broad-spectrum coverage is essential because of the wide range of bacteria implicated in infected pancreatic necrosis. Infections are often polymicrobial, with enteric bacteria most often identified on culture; in a recent study of 137 intensive care patients with infected pancreatic necrosis, the most common bacterium on culture was Escherichia coli, though over 100 different species were identified.

Nutrition

Biliary Tract Management

Traditionally, patients with acute pancreatitis were kept nil per os until their symptoms resolved and lipase levels normalized. This strategy assumed that enteral nutrition would further stimulate the inflamed pancreas. Newer evidence shows significant benefits to early feeding, however, and current guidelines recommend oral feeding within 24 hours of admission, even if lipase levels have not normalized. Patients with mild to moderate acute pancreatitis who can tolerate a diet should be started on a low-fat or normal solid diet without a trial of a liquid or soft diet. In severe cases or in patients who do not tolerate an oral diet, nasogastric or nasojejunal feeds should be attempted once the patient is hemodynamically stable. Early feeding has been associated with decreased length of stay as well as decreased rates of infected pancreatic necrosis, multiple organ failure, and total necrotizing pancreatitis. This is likely caused, in part, by the fact that early feeding improves gut mucosal integrity and stabilizes the gut microbiome. Parenteral nutrition should be reserved for patients who do not tolerate oral or nasoenteric feeding within 5 to 7 days of admission; compared with enteral feeding, parenteral nutrition is associated with an increased risk of infected necrosis and multiorgan failure.

Routine ERCP is not indicated for all patients with gallstone pancreatitis. Most stones will pass through the ampulla into the duodenum without intervention. Retained gallstones in the common bile duct can lead to severe complications, however, and should be removed by ERCP. Patients with evidence of acute cholangitis should undergo ERCP as soon as possible to decompress their biliary system. If choledocholithiasis is suspected without cholangitis, it is reasonable to wait up to 24 to 48 hours to see if the biliary obstruction spontaneously resolves without ERCP. Patients with diagnosed or suspected mild biliary pancreatitis should undergo cholecystectomy during their index admission; cholecystectomy during the patient’s initial admission has been shown in a single randomized trial to decrease gallstone-related complications, readmission for recurrent pancreatitis, and mortality.

Antibiotics Prophylactic antibiotics are not indicated in acute pancreatitis without evidence of infection, even in severe cases or in the setting of sterile peripancreatic collections. Historically, pancreatitis patients were given prophylactic antibiotics because of concern that sterile collections could become contaminated and develop into infected pancreatic necrosis. Multiple randomized trials have now shown no benefit to prophylaxis with antibiotics from multiple classes. There are risks to indiscriminate antibiotic prophylaxis as well, including an increased risk of fungal infection and multi–drug-resistant organism development. Antibiotic administration should be limited to patients with either a diagnosed or suspected infection. The diagnosis of infected pancreatic necrosis can be difficult to make as patients with severe, noninfected pancreatitis and persistent SIRS can develop fever, hemodynamic instability, and leukocytosis, all of which raise concern for infection. If there is any suspicion for infected necrosis, a CT scan should be performed. Gas bubbles within a peripancreatic collection on CT are diagnostic for infected necrosis. Infected necrosis can also be diagnosed using percutaneous fine-needle aspiration of the necrotic collection; this was previously a widespread practice for all suspected cases of infected necrosis but is no longer routinely recommended because of a high false-negative rate (12%–25%) and the risk of contaminating sterile collections. In patients with persistent symptomatic illness without radiographic evidence of infection,

INTERVENTIONAL MANAGEMENT Pancreatic Fluid Collections Patients with acute pancreatitis are at risk for developing a variety of peripancreatic fluid collections, each with distinct characteristics. There are four main categories of pancreatic and peripancreatic fluid collections related to pancreatitis, which are defined broadly by their location, the timing of their formation, and whether they occur in the setting of interstitial edematous pancreatitis or necrotizing pancreatitis. Most patients with pancreatitis experience interstitial edematous pancreatitis, characterized by enlargement of the pancreas caused by edema with homogenous parenchymal enhancement on CT (Table 1). Fluid collections in the setting of interstitial edematous pancreatitis are defined as acute peripancreatic fluid collections (APFC) when they occur within 4 weeks after the onset of symptoms. APFCs are nonencapsulated and generally confined by normal tissue planes. Organized, encapsulated collections that persist past 4 weeks are termed pseudocysts. Both APFCs and pseudocysts are fluid-filled and extrapancreatic, though in many cases there is communication with the pancreatic ductal system. Necrotizing pancreatitis involves necrosis of either the pancreatic parenchyma, surrounding pancreatic tissues, or both. Necrosis occurs in 5% to 20% of pancreatitis cases and most commonly involves breakdown of both the pancreas and surrounding tissues. Nonencapsulated fluid collections within the first 4 weeks after diagnosis of necrotizing pancreatitis are defined as acute necrotic collections (ANCs). ANCs may appear homogenous early in their course, similar to APFCs, but over time they adopt a heterogeneous appearance on imaging with both fluid and solid components. Mature, encapsulated collections noted more than 4 weeks after the onset

Pa n c r e a s



541

TABLE 1  Classification of Pancreatic Fluid Collections Collection Type

Interstitial edematous pancreatitis

Acute necrotizing pancreatitis

Timing after Onset of Symptoms (wk)

Imaging Appearance (CT or MRI)

Acute peripancreatic fluid collection (APFC)

4 Weeks

transduodenal drainage may be necessary for select collections at the head of the pancreas without a clear transgastric window. Lumen-apposing metal stents (LAMS), a type of self-expanding metal stent, have grown increasingly popular as an alternative to double-pigtail stents. LAMS have a larger diameter and shorter length, hypothetically facilitating increased drainage. LAMS have been associated with decreased number of required procedures and decreased hospital stay, which is significant as a main detractor from endoscopic drainage has been the increased number of required procedures relative to a surgical approach. There are also safety concerns with LAMS as they have been associated with increased pseudoaneurysm bleeding and other stent-related complications. Given this concern for delayed adverse events with LAMS, a CT should be performed at three weeks after placement to assess whether the pancreatic collection has resolved. If the collection has resolved, the LAMS should be removed. For those that do not improve clinically after drainage with either pigtail stents or LAMS drainage, DEN can be performed via the created cystgastrostomy (Fig. 3). Eligible patients should likely undergo endoscopic drainage as their initial intervention based on multiple recent randomized controlled trials. The Dutch PENGUIN trial initially showed that endoscopic necrosectomy did not provoke as large of an inflammatory reaction as VARD (as judged by IL-6 levels); although this study involved a limited number of patients, the trial also showed decreased mortality and rates of major complications with an endoscopic necrosectomy. The TENSION trial from the same group more recently showed that patients randomized to an endoscopic step-up approach had similar morbidity/mortality but significantly lower rates of pancreatic fistula formation (5% vs. 32%). An endoscopic approach also avoids creation of problematic pancreatico-cutaneous fistulae. Results from the American MISER trial also supported an endoscopic step-up approach, showing similar mortality but significantly fewer major complications than a surgical step-up approach. This study reaffirmed that endoscopic management leads to decreased fistula formation (0% vs. 28%) and showed improved physical quality of life with lower total costs for an endoscopic approach. In this most recent trial, 67% of patients undergoing endoscopic drainage did not require necrosectomy, possibly caused in part by partial use of the LAMS that were not available in previous trials.

Percutaneous Drainage If endoscopic drainage is not feasible or is not likely to resolve infected pancreatic necrosis, then a surgical step-up approach should be pursued. The initial procedure in this approach is percutaneous drainage. Simple drainage alone will successfully resolve 25% to 55% of infected pancreatic collections, obviating the need for any necrosectomy procedures. In some patients, multiple drainage procedures are required to upsize or otherwise replace drains with diminishing

Transgastric or Transduodenal No Window For Drainage? Yes

No

Extension into Paracolic Gutters?

Yes

No Endoscopic Drainage

FIG. 2  Decision algorithm for initial intervention in infected pancreatic necrosis.

Percutaneous Drainage

Pa n c r e a s



Endoscopic Drainage

Lumen-Apposing Metal Stent (LAMS)

543

Percutaneous Drainage

Yes

Collection Resolved?

Double Pigtail Stents

Drain Removal

No Collection Resolved? Yes

No

Concern for Disconnected Pancreatic Duct Syndrome? Yes Consider Surgical Intervention

Retroperitoneal Drain Course? Yes

Endoscopic Necrosectomy

No

Video-Assisted Retroperitoneal Debridement (VARD)

Sinus Tract Endoscopic Debridement (STE)

No Stent Removal

Yes

Collection Resolved?

No

Consider DualModality Drainage

Yes

Fistula Formation?

FIG. 3  Endoscopic versus surgical step-up approaches.

output despite continued symptoms or a persistent collection on imaging.

incision, as well as a relatively high rate of external pancreatico-cutaneous fistulae compared with endoscopic procedures.

Video-Assisted Retroperitoneal Debridement

Sinus Tract Endoscopic Debridement

If percutaneous drainage is not sufficient, then the next procedure in the step-up approach is a minimally invasive necrosectomy (see Fig. 3). It is important to keep in mind that the route and location of the patient’s initial percutaneous drains may dictate further interventions, and a step-up strategy should be in place before initial drain placement. One technique for minimally invasive necrosectomy is VARD, which requires drain placement along a left retroperitoneal course. This initial drain will serve as a guide for the surgeon performing a VARD in the operating room. For this procedure, the patient is placed in a partial lateral decubitus position with the percutaneous drain prepped into the field. A 5-cm lateral flank incision is made over the percutaneous drain, and electrocautery is used to carry this incision through the retroperitoneum to the necrotic collection. Given the proximity of most collections to critical structures such as the spleen, kidney, and colon, the patient’s most recent CT should be carefully studied before dissection to avoid injuries. Once access to the necrotic collection has been established, suction and irrigation should be used to clear any liquid debris within the cavity. A ring forceps may be used to clear solid necrotic material in superficial collections. For deeper collections, a laparoscope and long, rigid retractors are used for visualization, and laparoscopic graspers can facilitate debridement (Fig. 4). Both free and lightly adherent necrotic material may be removed bluntly, however overly aggressive debridement of the necrosis increases the risk of bleeding. If densely adherent necrotic material is encountered, it can be left in place with a plan for postoperative lavage and potential repeat necrosectomy. Following debridement, drains are placed in the cavity and brought out through stab incisions adjacent to the initial incision. This allows for multilayer closure of the initial incision with decreased risk of wound complications. Complete debridement is often achievable after a single VARD procedure, and surgeons can use familiar equipment, which is an advantage over STE debridement. Disadvantages include an increased rate of wound complications given the larger initial

An alternative technique for minimally invasive debridement of infected pancreatic necrosis is STE debridement. Like VARD, this procedure follows percutaneous drainage and uses the drain tract as a guide for debridement. Unlike VARD, STE debridement is not limited to a retroperitoneal approach. Collections that require transperitoneal, intercostal, or other less common courses are accessible by STE debridement. This difference in approaches emphasizes the importance of discussing drain placement in detail with the interventional radiologist and developing a strategy for eventual debridement at the time of initial drainage. If possible, the drain should also access the collection at one end; this will facilitate the debridement described in the following sections using a rigid nephroscope. For STE debridement, the patient may be placed in either a supine or lateral decubitus position depending on the drain location. As with VARD, the drain is prepped into the field. Under fluoroscopic guidance, a guidewire is placed through the drain and into the necrotic collection. After the drain is removed, a nephrostomy balloon dilator catheter is placed over the wire and inflated with contrast to a pressure of 20 psi for 1 minute. After tract dilation, a rigid nephroscope is advanced into the cavity through a 30-Fr working sheath with continuous irrigation to assist with visualization. Graspers are then introduced through the nephroscope to begin debridement. As necrotic material is removed, a working space develops, and the sheath may be advanced. After debridement, a large-bore drainage catheter is placed over the wire and into the cavity. STE debridement with a flexible endoscope has been described as well, though it does not allow for as rapid debridement as a rigid nephroscope. If flexible endoscopy is planned either for debridement or to assess residual necrosis in the cavity, the tract will require additional dilation. Debridement should be continued until all loose or nonadherent necrosis has been removed. Even more so than in VARD, overly aggressive debridement should be avoided in STE debridement given the difficulty of stopping bleeding during this procedure. If bleeding does occur, direct pressure with gauze packing should be attempted. Alternatively, the working sheath may be advanced past the point of

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Management of Acute Necrotizing Pancreatitis

A

B

C

D

E

bleeding to “jail” the bleed while the debridement continues distally. The best strategy, however, is to err on the side of caution and avoid bleeding by leaving densely adherent necrosis in place with a plan for repeat debridement after a period of irrigation. If the patient requires irrigation, then a smaller catheter should be placed next to the above-mentioned drainage catheter at the end of the procedure to allow for lavage. This can be accomplished by suturing the drains together and advancing them simultaneously over the guidewire.

FIG. 4  Operative steps for video-assisted retroperitoneal debridement.

Dual-Modality Drainage DMD is a combination of percutaneous drainage and transgastric endoscopic drainage. This approach combines the advantages of both approaches. Namely, it reduces the formation of external pancreatic fistulae seen in percutaneous drainage while also facilitating drainage of larger collections that cannot be resolved easily by endoscopic drainage alone. With a purely endoscopic approach, multiple necrosectomies are often required for complete resolution; if patients

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are slow to resolve, then additional drainage with a percutaneous catheter may shorten their duration of treatment. Similarly, if a patient develops external fistulae after percutaneous drainage, then additional transgastric endoscopic drainage can be used to relieve pressure on the tract.

Surgical Transgastric Necrosectomy Laparoscopic or open transgastric necrosectomy is an option for surgical drainage of collections limited to the lesser sac. This approach provides the benefit of durable internal drainage while avoiding the risk of external fistula formation. It also allows for complete debridement in one procedure, an advantage over endoscopic procedures that create a similar cystgastrostomy. This operation can be performed through a small upper midline incision or laparoscopically with a 12-mm port at the umbilicus and additional ports in each upper quadrant. A second 12-mm port is generally placed in the right upper quadrant to facilitate use of both a laparoscopic stapler and ultrasound. An anterior gastrotomy is created, and the collection is identified using ultrasonography. A posterior gastrotomy is created, allowing for drainage and debridement with laparoscopic graspers. After adequate debridement, the cystgastrostomy is created between the posterior gastric wall and the cyst capsule using either monofilament nonabsorbable suture or a laparoscopic stapler. Nasocystic catheters for irrigation can be placed under direct visualization as well as postpyloric feeding tubes. At the end of the procedure, the anterior gastrotomy is closed either with a stapler or a two-layered suture closure.

Open Transperitoneal Necrosectomy Despite the paradigm shift to a step-up approach to infected pancreatic necrosis, there remains a role for open necrosectomy in select patients. Open transperitoneal necrosectomy was first described in 1988 by Beger and is performed via laparotomy through bilateral subcostal incisions. The lesser sac is opened, and necrotic material is removed bluntly. At the end of the procedure, two large bore drains are left in place for postoperative irrigation and drainage. When counseling patients on this operation, it is useful to keep in mind that often-quoted high mortality rates are generally from studies in which open necrosectomy was performed as the initial intervention instead of the final intervention in a step-up approach. A more recent series of 68 well-selected patients undergoing open necrosectomy at a high-volume center showed a more favorable in-hospital mortality rate of 8.8%.

Postprocedural Irrigation Following both endoscopic and minimally invasive necrosectomy procedures, catheters may be left within the necrotic cavity to facilitate irrigation. This is particularly useful if the surgeon or endoscopist anticipates the need for a second necrosectomy procedure. Successful irrigation requires separate catheters for inflow and outflow. Following endoscopic procedures, this involves a nasocystic catheter for inflow with double-pigtail stents or a LAMS for outflow. Following surgical drainage, irrigation is performed through percutaneous catheters. Irrigation protocols vary by institution. Irrigation may be either continuous or intermittent every 4 to 6 hours. Normal saline is used as the irrigant, and volumes in described protocols range from 1 L total per day to 200 mL/hour (4.8 L/day).

KEY PANCREATITIS-RELATED COMPLICATIONS Chronic Pancreatitis and Pancreatic Insufficiency Many patients who survive episodes of necrotizing pancreatitis develop chronic pancreatitis with repeated pain episodes and

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potential exocrine and endocrine pancreatic insufficiency. A recent review of patients with necrotizing pancreatitis estimated that 16% to 45% will be diagnosed with either chronic pancreatitis, insufficiency, or both on long-term follow-up. Endocrine and exocrine insufficiency can be either coincident or diagnosed individually, and both may be diagnosed up to several years after the index episode of pancreatitis. Exocrine insufficiency may be treated with enzyme replacement therapy, while endocrine insufficiency requires insulin supplementation.

Splanchnic Vein Thrombosis Thrombosis of the portal, splenic, and superior mesenteric veins is common in acute necrotizing pancreatitis, occurring in 16% to 36% of patients. These thromboses form as a result of inflammation surrounding the splanchnic vasculature, compression from pancreatic fluid collections, and likely altered coagulation during acute pancreatitis. Symptoms range broadly from asymptomatic thromboses to more severe complications such as bowel ischemia, chronic portal hypertension, gastric variceal bleeding, symptomatic splenomegaly, and hepatic failure. Treatment typically involves anticoagulation, though there are little data on the ideal length and timing of anticoagulation. Limited retrospective data suggest that there may be a benefit to prophylactic anticoagulation in acute necrotizing pancreatitis to prevent splanchnic thromboses, however this is not currently recommended in any guidelines because of the risk of hemorrhage.

Disconnected Pancreatic Duct Syndrome Disconnected pancreatic duct syndrome (DPDS) may also be noted either early or intermediately in pancreatitis patients. DPDS results from necrosis of a central portion of the pancreas, disconnecting a functional pancreatic tail from the main duct leading to the ampulla. If DPDS is identified before any intervention, then the patient’s initial intervention should include endoscopic drainage with a soft pigtail stent that can be left in place indefinitely. Use of a LAMS should be avoided. If percutaneous drainage is used, the continuous reaccumulation of pancreatic secretions from the viable tail segment will place the patient at high risk of prolonged drainage and external fistula formation. In select patients, endoscopic stenting may be feasible to reconnect the tail to the ampulla. Up to 80% of patients with diagnosed DPDS will eventually require operative intervention, with the two most common procedures being cystojejunostomy for internal drainage or distal pancreatectomy. The two operations have comparable success rates, though distal pancreatectomy has a higher rate of endocrine insufficiency and usually requires splenectomy.

Pseudoaneurysm A less common but potentially life-threatening complication from necrotizing pancreatitis is pseudoaneurysm-related bleeding. Pseudoaneurysms form as pancreatic and visceral arteries are bathed in enzyme-rich pancreatic fluid, weakening the vessel walls. Estimates of the incidence of pseudoaneurysm formation in necrotizing pancreatitis range from 1% to 10%, with the splenic and gastroduodenal arteries most commonly involved. Pseudoaneurysms are usually asymptomatic and diagnosed incidentally on imaging. Any pseudoaneurysm occurring in the setting of pancreatitis should be angioembolized as soon as possible to prevent massive hemorrhage from rupture. Patients with undiagnosed pseudoaneurysms may present with a small volume “sentinel” bleed from initial rupture. Sentinel bleeds precede a short window of hemodynamic stability in which angioembolization can be performed before life-threatening hemorrhage occurs from complete rupture of the pseudoaneurysm. In patients with external drains, any new-onset bloody output should be treated as a potential pseudoaneurysm until proven otherwise. In this scenario, either CT angiography or formal angiography in the interventional suite should be performed based on the patient’s

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Gallstone Pancreatitis

hemodynamic stability. Given the difficulty of surgically controlling pseudoaneurysm-related bleeding in the setting of pancreatic necrosis, operative intervention should only be pursued when angiography has failed or is not immediately available for hemodynamically unstable patients.

RECURRENCE PREVENTION Strategies to prevent recurrent episodes of pancreatitis are dependent on their etiology. All patients who present with gallstone pancreatitis should undergo cholecystectomy. Ideally this should occur during the patient’s index admission, though timing may be variable based on the presence of peripancreatic collections. If any collections are present, current recommendations are to delay cholecystectomy until the collections resolve or until 6 weeks after the initial onset of symptoms. This strategy is based on retrospective data that show an increased risk of infected pancreatic necrosis with early cholecystectomy in the setting of peripancreatic collections. If patients eventually undergo open or laparoscopic necrosectomy, then cholecystectomy can be performed simultaneously. Patients presenting with alcoholic pancreatitis should be enrolled in programs to encourage alcohol abstinence. Given the fact that alcoholic pancreatitis generally occurs after prolonged alcohol abuse, long-term behavioral therapy and counseling may be required. Those with hyperlipidemia-induced pancreatitis benefit from fibrate therapy as well as diet modification. Hypercalcemia causing pancreatitis may be from multiple etiologies, though the most common is hyperparathyroidism, and patients should undergo evaluation for a parathyroidectomy.

Gallstone Pancreatitis Katherine A. Morgan, MD, and William P. Lancaster, MD

A

cute pancreatitis (AP) is the most common gastrointestinal diagnosis for hospital admission and a leading source of healthcare costs in the United States; the most common cause of AP is gallstones. The prevalence of gallstones in the United States is approximately 30%. A much smaller proportion of patients with gallstones will develop symptoms or a complication, but this still represents a substantial proportion of the population. The treatment for gallstone pancreatitis (GSP) includes managing the acute episode and preventing another event with cholecystectomy. The timing of cholecystectomy is dictated by the severity of pancreatitis. In patients with mild disease, cholecystectomy should be performed promptly, ideally during the same admission, to prevent recurrent disease. Twenty percent of patients, however, will develop severe acute pancreatitis (SAP), which often requires more extensive intervention. In this group of patients with severe disease, marked by local complications (e.g., peripancreatic fluid, parenchymal edema, and necrosis) and systemic inflammatory response including other organ compromise, cholecystectomy should be deferred. In the setting of SAP, delaying cholecystectomy until resolution of the acute inflammatory response and the resultant peripancreatic complications is associated with improved morbidity and mortality.

S uggested R eadings Bakker OJ, van Santvoort HC, van Brunschot S, et al. Endoscopic transgastric vs surgical necrosectomy for infected necrotizing pancreatitis: a randomized trial. JAMA. 2012;307:1053–1061. Bang JY, Arnoletti JP, Holt BA, et al. An endoscopic transluminal approach, compared with minimally invasive surgery, reduces complications and costs for patients with necrotizing pancreatitis. Gastroenterology. 2019;156 1027.e3–1040.e3. Banks PA, Bollen TL, Dervenis C, et  al. Classification of acute pancreatitis—2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013;62:102–111. Fagenholz PJ, Thabet A, Mueller PR, Forcione DG. Combined endoscopic trangastric drainage and video assisted retroperitoneal pancreatic debridement—The best of both worlds for extensive pancreatic necrosis with enteric fistulae. Pancreatology. 2016;16:788–790. Fong ZV, Fagenholz PJ. Minimally invasive debridement for infected pancreatic necrosis. J Gastrointest Surg. 2019;23:185–191. van Brunschot S, van Grinsven J, van Santvoort HC, et al. Endoscopic or surgical step-up approach for infected necrotising pancreatitis: a multicentre randomised trial. Lancet. 2018;391:51–58. van Santvoort HC, Besselink MG, Bakker OJ, et  al. A step-up approach or open necrosectomy for necrotizing pancreatitis. N Engl J Med. 2010;362:1491–1502. Working Group IAP/APA Acute Pancreatitis Guidelines. IAP/APA evidence-based guidelines for the management of acute pancreatitis. Pancreatology. 2013;13(4 Suppl 2):e1–e15. Zyromski NJ, Nakeeb A, House MG, Jester AL. Transgastric pancreatic necrosectomy: How I do it. J Gastrointest Surg. 2016;20:445–449.

department visits and contributes to 5400 deaths per year in the United States. More than $2.5 billion are spent annually on the treatment of AP. According to the Atlanta classification (Table 1), 80% of patients with pancreatitis have mild AP. GSP is the most common type of AP, accounting for 40% to 70% of cases. Risk factors for GSP include increased age, female gender, multiple small stones, and a large cystic duct diameter.

PATHOPHYSIOLOGY The pathophysiology of GSP includes intrapancreatic activation of pancreatic enzymes leading to autodigestive destruction of pancreatic and retroperitoneal soft tissue as well as a robust systemic inflammatory response due to the production of circulating inflammatory mediators. Local effects include abdominal pain and gastrointestinal tract dysfunction (obstruction, bleeding, perforation), and systemic

TABLE 1 Atlanta Classification for Acute Pancreatitis Severity

Characteristics

Mild

No organ failure No local or systemic complications

Moderate

Transient organ failure (7 mm

Lateral pancreaticojejunostomy

Familial

Total pancreatectomy with islet autotransplantation

Nondilated duct with recurrent acute pancreatitis

Endoscopic minor papillotomy

Nondilated duct endotherapy failure

Operative sphincteroplasty

Nondilated duct endotherapy failure with moderate to severe chronic pancreatitis in the head

Pancreatoduodenectomy

Operative sphincteroplasty failure

Pancreatoduodenectomy

Pancreatoduodenectomy failure

Total pancreatectomy with islet autotransplantation

WHIPPLE PROCEDURE Pancreatoduodenectomy may be indicated in patients with pancreas divisum who have failed minor duct sphincteroplasty when changes of chronic pancreatitis develop in the head of the pancreas. The operative technique is not different from that described elsewhere in this book. When a resection of the head is indicated in pancreas divisum, the divided neck of the pancreas is usually soft with a nondilated pancreatic duct, one at risk for anastomotic leak. Therefore, internal and external anastomotic stenting and postoperative octreotide infusion may diminish the risk of postoperative pancreatic fistulas. If head resection in pancreas divisum fails and patients become candidates for TPIAT, islet yields may be uncompromised. Islet volume is greater in the tail and body than in the head of the pancreas, and islet loss is limited in a head resection for pancreas divisum. When anastomotic obstruction occurs after a Whipple procedure, acinar cells atrophy before destruction of the islets. The resultant islet-rich, acinar-poor atrophied pancreas may be favorable isolation for islet autotransplantation. The issue of whether patients with pancreas divisum with chronic pancreatitis should undergo a speculative Whipple procedure or a TPIAT is unanswered.

HYBRID PROCEDURES Variations of the Whipple procedure and the Puestow procedure have been used in chronic pancreatitis associated with pancreas divisum in a fashion similar to their use in chronic pancreatitis not associated with pancreas divisum. Although typically the Beger and Frey procedures are selected for patients with an inflammatory mass in the head of the pancreas, they have been used in pancreas divisum not associated with enlargement of the head of the pancreas. The Frey procedure was developed because of the ascribed failure of the LPJ to drain the head and uncinate process of the pancreas. In pancreas divisum, the head should be drained effectively with a longitudinal ductotomy. The use of multiple resection and drainage techniques is an indication of the difficulty in patient selection and management in chronic pancreatitis associated with pancreas divisum.

TOTAL PANCREATECTOMY WITH ISLET AUTOTRANSPLANTATION TPIAT is indicated in patients with chronic pancreatitis with intractable pain who have failed medical, endoscopic, and surgical management. Pancreas divisum is a risk factor for chronic pancreatitis in about 15% of the cohort in the reports of TPIAT in the management of chronic pancreatitis. Typical patients with pancreas divisum who are selected to TPIAT have undergone endoscopic sphincterotomy, operative sphincteroplasty, and pancreatic head resection in

succession over many years. The unanswered question is whether TPIAT should be undertaken sooner rather than later if endoscopic treatment fails. That discussion is beyond the scope of this chapter.

CONCLUSION Given the paucity of comparative effectiveness studies evaluating the impact of endoscopic or surgical minor papillotomy on nonobstructive recurrent acute and chronic pancreatitis, the management of pancreas divisum is primarily based on experience. Although the divisum anatomic variant is common, its association with chronic pancreatitis is by no means a sine qua non. When pancreas divisum is associated with intractable pain associated with chronic pancreatitis or with recurrent pancreatitis, the approach should mimic that for patients with standard duct anatomy: (1) alcohol and tobacco cessation is necessary; (2) a trial of pancreatic enzyme replacement therapy may be considered, especially if exocrine pancreas insufficiency is documented; and (3) genetic mutations and polymorphisms should be investigated, knowing that the odds identifying highrisk mutations are higher in the setting of divisum. A management strategy based on a regional experience extending with the surgical management of pancreas divisum is suggested in Table 2. The pathway outlined in Table 2 differs from much of the experience in the current literature and underscores the influence of regional population differences and their attendant practices. As the pathogenesis of pancreatitis is better understood, treatment strategies will become less intuitive and experience-based and more effective. To seek and to find evidence on which to base the management of pancreas divisum is to repeat Samuel Johnson’s experience described in the preface to his 1755 A Dictionary of the English Language: “I saw that one inquiry only gave occasion to another, that book referred to book, that to search was not always to find, and to find was not always to be informed; and that thus to pursue perfection, was, like the first inhabitants of Arcadia, to chase the sun, which, when they had reached the hill where he seemed to rest, was still beheld at the same distance from them.”

S uggested R eadings Bertin C, Pelletier AL, Vullierme MP, et al. Pancreas divisum is not a cause of pancreatitis by itself but acts as a partner of genetic mutations. Am J Gastroenterol. 2012;107:311–317. Borak GD, Romagnuolo J, Alsolaiman M, et al. Long-term clinical outcomes after endoscopic minor papilla therapy in symptomatic patients with pancreas divisum. Pancreas. 2009;38:903–906. Chacko LN, Chen YK, Shah RJ. Clinical outcomes and nonendoscopic interventions after minor papilla endotherapy in patients with symptomatic pancreas divisum. Gastrointest Endosc. 2008;68:667–673.

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Coté GA, Durkalski-Mauldin VL, Serrano J, et  al; SHARP Consortium. SpHincterotomy for Acute Recurrent Pancreatitis randomized trial: rationale, methodology, and potential implications. Pancreas. 2019;48(8):1061– 1067. Cotton PB. Congenital anomaly of pancreas divisum as cause of obstructive pain and pancreatitis. Gut. 1980;21:105–114. Lans JI, Geenen JE, Johanson JF, et  al. Endoscopic therapy in patients with pancreas divisum and acute pancreatitis: a prospective, randomized, controlled clinical trial. Gastrointest Endosc. 1992;38:430–434. Morgan KA, Romagnuolo J, Adams DB. Transduodenal sphincteroplasty in the management of sphincter of Oddi dysfunction and pancreas divisum in the modern era. J Am Coll Surg. 2008;206:908–914. Pappas SG, Pilgrim CHC, Kelm R, et al. The Frey procedure for chronic pancreatitis secondary to pancreas divisum. JAMA Surg. 2013;148:1057–1062.

Schlosser W, Rau BM, Poch B, et al. Surgical treatment of pancreas divisum causing chronic pancreatitis: the outcome benefits of duodenum-preserving pancreatic head resection. J Gastrointest Surg. 2005;9:710–715. Schnelldorfer T, Adams DB. Outcome after lateral pancreaticojejunostomy in patients with chronic pancreatitis associated with pancreas divisum. Am Surg. 2003;69:1041–1044. Warshaw AL, Simeone JF, Schapiro RH, et  al. Evaluation and treatment of the dominant dorsal duct syndrome (pancreas divisum redefined). Am J Surg. 1990;159:59–64.

Diagnosis and Management of Autoimmune Pancreatitis

manifest before, during, or after the onset of AIP. Conversely, type II AIP, classified as idiopathic duct-centric pancreatitis, has no predilection toward any age group and often has normal serum IgG4 levels. Its clinical profile is distinctively different from the systemic manifestations of type I AIP, resembling more of a localized, pancreas-specific process associated with inflammatory bowel disease as its only extrapancreatic site (see Table 1). The common presenting symptoms of AIP include weight loss, abdominal pain, and endocrine as well as exocrine insufficiency. It can also present with painless jaundice caused by a distal common bile duct stricture, masquerading as pancreatic ductal adenocarcinoma. Many surgical series report a 2% to 3% AIP resection rate for presumed pancreatic cancer. However, there is no evidence of increased risk of pancreatic cancer in patients with AIP, making it all the more important for providers to be aware of and avoid the pitfalls of operating on AIP. Awareness of AIP and its medical treatment may help differentiate it from other pathologies that require operations and also indicate when an operation is required.

Zhi Ven Fong, MD, MPH, and Andrew L. Warshaw, MD

INTRODUCTION Autoimmune pancreatitis (AIP) is inflammation of the pancreas characterized histologically by lymphoplasmacytic infiltration and fibrosis that may or may not be associated with a pancreatic mass, and therapeutically by its dramatic response to corticosteroid administration. There are two subtypes of AIP with different clinical profiles, two different diseases with similar histology (Table 1). Type I AIP is classified as lymphoplasmacytic sclerosing pancreatitis. It is more common in older men and is associated with elevated serum immunoglobulin G4 (IgG4) levels and extrapancreatic autoimmune diseases such as Sjogren syndrome, rheumatoid arthritis, primary sclerosing cholangitis, orbital pseudotumor, retroperitoneal fibrosis, and inflammatory bowel disease. Extrapancreatic involvement can

DIAGNOSIS AND EVALUATION The diagnostic approach to AIP can be based on the following five cardinal findings: 1. Cross-sectional (CT/MRI) and ductal imaging (ERCP) of the pancreas

TABLE 1  Clinical Profiles of Type I and Type II Autoimmune Pancreatitis Clinical Feature

Type I AIP

Type II AIP

Age at presentation

>50 years of age

30 to 50 years of age

Sex

M>F

M = F

Serum IgG4 elevation

Yes

No

Histopathology

Lymphoplasmacytic infiltration with storiform fibrosis Obliterative phlebitis High levels of IgG4 staining

Lymphoplasmacytic infiltration with storiform fibrosis Granulocytic epithelial lesions

Other organ involvement

Yes

No

Association with inflammatory bowel disease

Low

High

Response to corticosteroids

Good

Good

Relapse after corticosteroid treatment

High

Low

AIP, Autoimmune pancreatitis; F, female; IgG4, immunoglobulin G4; M, male.

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FIG. 1  Radiographic finding of a lobulated, hypodense pancreatic head mass in a patient with autoimmune pancreatitis. (Modified from Gill M, Brar K, Godara R, et al. Autoimmune pancreatitis masquerading as carcinoma head of pancreas: A case report and review of literature. Ann Med Surg [Lond]. 2019;45:82–85.)

A

B

FIG. 2  Radiographic and pathologic features of autoimmune pancreatitis. (A) CT scan demonstrating a pancreatic duct stricture that tapers at the body region with no upstream dilation. (B) Correlating pathologic specimen demonstrating periductal fibrosis that correlates with the ductal strictures appreciated on CT.

2. Serum IgG4 levels 3. Other organ involvement 4. Histopathology 5. Response to corticosteroid therapy

Cross-Sectional and Ductal Imaging of the Pancreas The classic radiographic appearance of AIP on cross-sectional imaging (either CT or MRI) is of a diffusely enlarged, sausage-shaped pancreas with homogenous attenuation and little to no visible pancreatic duct. It can sometimes be associated with a rimlike enhancement, termed a halo. It can also present as a focal mass in the pancreatic head mimicking pancreatic ductal adenocarcinoma (Fig. 1). In this case, clarification of the diagnosis requires histopathologic examination of a core biopsy of the resected specimen. This is especially common in type II AIP wherein a focal masslike lesion occurs in up to 35% of cases. Cross-sectional imaging and ERCP in AIP also commonly demonstrate long-segment or multiple pancreatic duct strictures but without upstream dilation, which is characteristic of pancreatic ductal adenocarcinoma (Fig. 2).

Serum IgG4 Levels Serum IgG4 is the single best diagnostic tool for AIP. The sensitivity of an elevated serum IgG4 is as high as 80% to 99% in patients with type I AIP, but only 17% in those with type II AIP. Given the variability in the upper limits of normal IgG4 levels between laboratories and the potential for false positives, only a 2-fold elevation in IgG4 levels should be considered suggestive of the diagnosis of AIP. Although patients with pancreatic cancer can also present with elevated serum IgG4 levels, fewer than 1% have levels twice that of the upper limit of normal. Therefore, elevation in serologic markers should be corroborated with associated clinical, pathologic, or radiographic findings.

Histopathology The histology of the pancreas can be examined as part of a pancreas-directed core biopsy or as a resected pathologic specimen. The findings differ between type I and type II AIP (Tables 2 and 3). For type 1 AIP, the finding of any of the three following features

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TABLE 2  International Consensus Diagnostic Criteria for Type I Autoimmune Pancreatitis Diagnosis

Primary Basis for Diagnosis

Imaging Evidence

Collateral Evidence

Definitive type I AIP

Histology

Typical/indeterminate

At least three of the following on core biopsy or resection: 1. Periductal lymphoplasmacytic infiltrate without granulocytic infiltration 2. Obliterative phlebitis 3. Storiform fibrosis 4. Abundant (910 cells/HPF) IgG4-positive cells

Imaging

Typical

Any one of the following: 1. Elevated IgG4 levels 2. At least two of the classic histopathology findings 3. Other organ involvement proven histologically or classic radiographic appearance 4. Response to corticosteroids

Indeterminate

At least two of the following: 1. Diffuse enlargement of pancreatic parenchyma with delayed enhancement on imaging 2. Pancreatic duct strictures without marked upstream dilation 3. Elevated IgG4 levels 4. Other organ involvement proven histologically or ­classic radiographic appearance 5. At least three of the classic histopathology findings 6. Response to corticosteroids

Indeterminate

Elevated IgG4 levels/other organ involvement proven ­histologically or classic radiographic appearance + Response to corticosteroids OR Pancreatic duct strictures without marked upstream dilation + Elevated IgG4 levels/other organ involvement proven ­histologically or classic radiographic appearance/at least two of the classic histopathology findings + Response to corticosteroids.

Indeterminate

Elevated IgG4 levels/other organ involvement proven ­histologically or classic radiographic appearance/at least two of the classic histopathology findings + Response to corticosteroids

Response to steroids

Probable type I AIP

AIP, Autoimmune pancreatitis; HPF, high-power field; IgG4, immunoglobulin G4.

can be diagnostic: periductal lymphoplasmacytic infiltrate without granulocytic infiltration, obliterative phlebitis, storiform fibrosis, or abundant (>10 cells/high-power field [HPF]) IgG4-positive cells. The diagnosis of type II AIP requires both granulocytic infiltration of the duct wall with or without granulocytic acinar inflammation and absent or scant (0–10 cells/HPF) IgG4-positive cells.

Other Organ Involvement The involvement of extrapancreatic organs is more characteristic of type I AIP and not type II. As previously mentioned, these include Sjogren syndrome, rheumatoid arthritis, primary sclerosing cholangitis, orbital pseudotumor, retroperitoneal fibrosis, and/or inflammatory bowel disease. The histologic criteria of any three of the

following in the extrapancreatic organs are considered diagnostic: marked lymphoplasmacytic infiltration with fibrosis and without granulocytic infiltration, storiform fibrosis, obliterative phlebitis, or abundant (>10 cells/HPF) IgG4-positive cells.

Response to Corticosteroid Therapy In patients with either form of AIP, corticosteroid administration should result in marked radiographic improvement of pancreatitis and normalization of IgG4 levels within 2 to 4 weeks. However, response to corticosteroid therapy alone is not diagnostic of AIP. Patients with pancreatic ductal adenocarcinoma can also demonstrate subjective symptomatic improvement and a sense of well-being when given corticosteroid therapy. A persistently elevated or rising

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TABLE 3  International Consensus Diagnostic Criteria for Type II Autoimmune Pancreatitis Diagnosis

Imaging Evidence

Collateral Evidence

Definitive type II AIP

Typical/indeterminate

Histologic findings of both granulocytic infiltration of duct wall with or without granulocytic acinar inflammation and absent or scant IgG4-positive cells OR Clinical inflammatory bowel disease + Both granulocytic and lymphoplasmacytic acinar infiltrate and absent or scant IgG4-positive cells + Response to corticosteroids

Probable type II AIP

Typical/indeterminate

Both granulocytic and lymphoplasmacytic acinar infiltrate and absent or scant IgG4positive cells/clinical inflammatory bowel disease + Response to corticosteroids

AIP, Autoimmune pancreatitis; IgG4, immunoglobulin G4.

serum carbohydrate antigen 19-9 (CA 19-9) should alert the provider to the likelihood of cancer.

INTERNATIONAL CONSENSUS DIAGNOSTIC CRITERIA Given the unreliability of any single aforementioned “cardinal” findings by themselves, a combination of the features is required to reliably make a diagnosis of AIP. For type I AIP, a combination of features is often adequate without the need for histology. However, given the absence of a reliable serum biomarker and extrapancreatic involvement, the diagnosis of type II AIP requires a tissue biopsy for histologic diagnosis. In 2011, the International Association of Pancreatology reviewed the literature and offered an international consensus for the diagnosis of AIP. Tables 2 and 3 detail the criteria for type I and type II AIP, respectively. Although complex, these diagnostic criteria have been demonstrated to be highly reliable, with validation studies reporting sensitivity and specificity rates of 95% and 100%, respectively.

FINDINGS NOT TYPICAL OF AIP Just as important as recognizing AIP’s cardinal features, providers should be aware of symptoms that are typically not associated with AIP to avoid misdiagnosis. Although AIP can present as abdominal pain, it typically does not present as painful pancreatitis requiring narcotics. It also does not present as marked cachexia with inability to eat, which is more suggestive of pancreatic cancer. Radiographically, it is also typically not associated with pseudocysts and calculi seen with alcohol-induced pancreatitis or with ductal dilation upstream to the point of stricture, which occur with pancreatic neoplasms.

TREATMENT Medical Treatment AIP generally responds very well to corticosteroid administration, with symptoms such as jaundice, endocrine insufficiency, and exocrine insufficiency resolving within 2 to 4 weeks of treatment initiation (Fig. 3). For patients with mild jaundice and no signs of infection, endoscopic biliary stenting is rarely indicated, and they should be treated with corticosteroids alone. Endoscopic stenting

should actually be avoided if possible, given the elevated risk of infection in patients with AIP who will typically be treated with longterm corticosteroids. Non-response to corticosteroid administration should cue the provider to consider an alternate diagnosis such as cancer. The International Consensus Diagnostic Criteria for Autoimmune Pancreatitis recommends 0.6 to 1 mg/kg per day of prednisone for 2 weeks, followed by interval imaging and CA 19-9 levels. If the patient is responding to therapy, the prednisone can be tapered by 5 to 10 mg per day every 1 to 2 weeks until a daily dose of 20 mg, then decreased by 5 mg every 2 weeks. Patients with imaging features of sausage-like swelling and peripancreatic halo have been found to have a favorable response to corticosteroids, likely reflecting an early inflammatory phase. Conversely, patients with ductal strictures or focal swelling are likely to have a poorer response to corticosteroids, perhaps as a result of greater fibrosis. In patients who do not respond to corticosteroids, treatment with immunomodulatory drugs such as rituximab and azathioprine can be considered, although more studies are required before they can be routinely recommended. AIP recurrence or relapse is common, with a reported occurrence ranging from 31% to 60% during the tapering or after discontinuation of corticosteroids. The Japanese Consensus Guidelines for AIP proposed maintenance therapy with 5 mg per day of prednisone for 3 years to mitigate disease relapse or recurrence. However, it is still unclear if maintenance therapy improves long-term outcomes enough to warrant the side effects of being on long-term steroids. Some studies have demonstrated that patients who have elevated pretreatment IgE levels or proximal bile duct stricture or IgG4-sclerosing cholangitis are at a higher risk of relapse and should be considered for maintenance corticosteroid therapy. In patients whose diagnosis cannot be confirmed despite undergoing biopsy of the pancreas more than once, surgical resection of the involved segment can be considered in lieu of unresolved concerns for potential malignancy.

Surgical Treatment The two main indications for surgical resection are as follows: 1. Diagnostic uncertainty and concern for cancer 2. Unresponsiveness to corticosteroid therapy or immunomodulators and continuing symptoms

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Diagnosis and Management of Autoimmune Pancreatitis

A

B

A1

B1

FIG. 3  Treatment effect of corticosteroids on autoimmune pancreatitis. (A) CT scan demonstrating enlargement with a patchy hypoenhancement rind surrounding the pancreatic head along with common bile duct wall thickening. (A1) Endoscopic retrograde cholangiopancreatography demonstrating a strictured common bile duct (arrow). (B) Posttreatment CT demonstrating resolution of pancreatic head hypoenhancement after 3 weeks of 40 mg/day of prednisone. (B1) ERCP cholangiogram showing interval improvement of the common bile duct stricture (arrow).

It is important to note that despite all of the aforementioned cardinal features of AIP, diagnostic uncertainty may still remain. Surgical resection should be considered when there is sufficient suspicion for malignancy. Resection should be tailored toward the predominant area of inflammation: pancreatoduodenectomy for a mass in the head of the pancreas and distal pancreatectomy for masses in the body and/or tail of the pancreas. The peripancreatic inflammation induced by AIP creates a fibrotic reaction that distorts normal anatomic planes and can tether peripancreatic vessels, making the portal vein and superior mesenteric vein dissection more difficult. In one surgical series, the Johns Hopkins group compared pancreatectomy outcomes for 37 patients with AIP versus those with other diagnoses and reported a higher incidence of “difficult superior mesenteric vein dissection” of 71% versus 44% in the non-AIP group (P < 0.05). They also reported greater operative blood loss (mean 1290 cc vs. 832 cc in the nonAIP group, P < 0.05), albeit with similar transfusion requirements, postoperative length of hospital stay, and overall complication rates. Notably, 68% of patients who underwent resection for AIP reported improved quality of life, while 18% and 14% reported no change or diminished quality of life, respectively. In the largest surgical series to date (n = 74) reported from the Massachusetts General Hospital and the Mayo Clinic, 51% of patients underwent classic pancreatoduodenectomy, 24% underwent pylorus-preserving pancreatoduodenectomy, 14% underwent distal pancreatectomy with splenectomy, 7% underwent distal pancreatectomy without splenectomy, and only 4% required total pancreatectomy. The reported median estimated blood loss was 600 cc, the major morbidity (Clavien Dindo Grade III or greater) was 14%, and the perioperative

mortality rate was 1%. Because of difficult dissection or inability to clear the superior mesenteric vein without injury, 20% of patients required vein resection and reconstruction. The incidence of postoperative pancreatic fistula was only 7%, possibly because these patients characteristically had a firm, fibrotic pancreatic gland. Nonetheless, recurrent AIP developed subsequently in the pancreatic remnant in 17% of patients, underscoring the importance of continued follow-up, even after surgical resection. It is also worth mentioning that all 17% of recurrences were treated medically and did not require reoperation. Total pancreatectomy has been reported only as single cases. It may be reasonably indicated in type I AIP involving the entire pancreas in a patient with persistent pain after failed corticosteroid treatment. Added to the immediate morbidity and mortality of a total pancreatectomy are the lifelong burdens of endocrine and exocrine insufficiency. Because the islets tend to be spared in AIP, concurrent islet cell transplantation can be considered.

FOLLOW-UP AND SURVEILLANCE As noted, the recurrence and relapse rate of AIP is significant after either medical or surgical treatment. Given the limited long-term data on AIP, there has been no formal recommendation for the follow-up of patients with treated AIP. Perhaps most commonly used is the Mayo Clinic protocol, which is based on organ system involvement. For patients with biliary strictures, serologic testing (liver function test, IgG4, and CA 19-9 levels) every 12 weeks for the first 1 to 2 years is prescribed. In patients without biliary involvement, no surveillance is required unless patients present

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with recurring symptoms, which warrant cross-sectional imaging with either CT or magnetic resonance cholangiopancreatography (MRCP). Even though IgG4 is recommended in the Mayo follow-up protocol, studies have demonstrated that it has little value in predicting or diagnosing clinical recurrence after initial treatment. Patients frequently present with elevated levels without any associated clinical symptoms or manifestations. CA 19-9 levels are similarly nonspecific as elevated levels can be seen in both benign and malignant conditions, but measurement of both in combination may be more discriminating.

SUMMARY AIP is a rare form of mass-forming pancreatic inflammation that can masquerade as pancreatic cancer and can lead to unnecessary operations. Accurate recognition of the cardinal features of AIP, a medically treated condition, must be balanced against missing the chance to resect a lethal malignancy. A better understanding and heightened awareness of AIP has led to a decreasing number of unnecessary operations performed in AIP.

Management of Pancreatic Necrosis Linda Ye, MD, and O. Joe Hines, MD

DEFINITIONS AND DIAGNOSIS Acute pancreatitis is a common indication for inpatient hospitalization in the United States. Patients may present with epigastric abdominal pain radiating to the back, nausea, vomiting, abdominal distention, or signs of dehydration. Acute pancreatitis is diagnosed based on two of the following three criteria: (1) abdominal pain consistent with acute pancreatitis, (2) serum lipase or amylase activity >3 times greater than the upper limit of normal, and (3) findings of pancreatic inflammation on imaging. The etiology of acute pancreatitis varies widely, with the more common causes including gallstones, alcohol, idiopathic/autoimmune, metabolic (e.g., hypertriglyceridemia, hypercalcemia), iatrogenic (e.g., postendoscopic retrograde cholangiopancreatography), trauma, medications, or anatomic abnormalities (e.g., pancreas divisum).

Severity Classification of Acute Pancreatitis The severity of acute pancreatitis is most commonly defined based on the 2012 Atlanta classification (Table 1), which includes three grades: mild, moderately severe, and severe. Mild acute pancreatitis is not associated with local or systemic complications or organ failure, and mortality is very rare (48 hours, and can involve single or multiple organs. Mortality risk significantly increases with severe acute pancreatitis up to 36% to 50%, with extremely high risk of mortality with infected pancreatic necrosis. A limitation of

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S uggested R eadings Clark CJ, Morales-Oyarvide V, Zaydfudim V, et al. Short-term and long-term outcomes for patients with autoimmune pancreatitis after pancreatectomy: a multi-institutional study. J Gastrointest Surg. 2013;17(5):899–906. Hardacre JM, Iacobuzio-Donahue CA, Sohn TA, et  al. Results of pancreaticoduodenectomy for lymphoplasmacytic sclerosing pancreatitis. Ann Surg. 2003;237(6):853–858; discussion 858–859. Maruyama M, Watanabe T, Kanai K, et al. International Consensus Diagnostic Criteria for Autoimmune Pancreatitis and its Japanese amendment have improved diagnostic ability over existing criteria. Gastroenterol Res Pract. 2013;2013:456965. Milosavljevic T, Kostic-Milosavljevic M, Jovanovic I, Krstic M. Extraintestinal manifestations of autoimmune pancreatitis. Dig Dis. 2012;30(2):220–223. Sahani DV, Sainani NI, Deshpande V, et al. Autoimmune pancreatitis: disease evolution, staging, response assessment, and CT features that predict response to corticosteroid therapy. Radiology. 2009;250(1):118–129. Shimosegawa T, Chari ST, Frulloni L, et  al.; International Association of Pancreatology. International consensus diagnostic criteria for autoimmune pancreatitis: guidelines of the International Association of Pancreatology. Pancreas. 2011;40(3):352–358. Zaheer A, Singh VK, Akshintala VS, et al. Differentiating autoimmune pancreatitis from pancreatic adenocarcinoma using dual-phase computed tomography. J Comput Assist Tomogr. 2014;38(1):146–152.

the Atlanta classification is that it does not account for real-time measurements of disease activity in a dynamic disease, such as acute pancreatitis. Final severity grades evolve over the disease course and require continued clinical and radiologic follow-up. Other grading systems have been validated to predict severity of acute pancreatitis, including Pancreatitis Activity Scoring System (PASS), which uses an additive, continuous monitoring system to provide dynamic measures of disease activity during the entire course of illness. Clinically important parameters include organ failure, systemic inflammatory response, pain, pain medication, and intolerance to solid diet. Other scoring systems include Ranson’s criteria, the Acute Physiology and Chronic Health Examination (APACHE) II score, bedside index of severity in acute pancreatitis (BISAP) score, and CT severity index. The CT severity score is based on the degree of necrosis, inflammation, and presence of fluid collections on imaging.

Local Complications of Acute Pancreatitis By definition, local complications are associated with moderately severe and severe acute pancreatitis and should be suspected in patients with a protracted clinical course. Symptomatically, patients may experience persistent or worsening abdominal pain, poor appetite or tolerance of diet, fever, organ failure, and sepsis. Table 2 defines the local complications of acute pancreatitis, CT findings, and typical timing of diagnosis. Local complications of acute pancreatitis can be classified in two broad categories. Interstitial edematous pancreatitis is an acute inflammation and diffuse enlargement of the pancreas without necrosis. Two types of local collections may develop in these severe cases of pancreatitis not associated with necrosis: acute peripancreatic fluid collection (APFC) and pancreatic pseudocyst. APFCs are homogenous, nonencapsulated fluid collections adjacent to the pancreas without necrosis, typically diagnosed within 4 weeks of symptom onset. Pancreatic pseudocysts are encapsulated fluid collections with a well-defined inflammatory wall without significant necrosis seen after 4 weeks of disease onset. Most APFCs and pseudocysts resolve spontaneously.

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Management of Pancreatic Necrosis

TABLE 1  Grades of Severity of Acute Pancreatitis (2012 Revised Atlanta Classification) Grade

Organ Failure

Local or Systemic Complications

Risk of Mortality

Mild

Absent

Absent

Very rare (14 days, >POD 14

Days of oral intolerance

7

14

21

Vomiting and gastric distention

+/–

+

+

Use of prokinetics

+/–

+

+

Biochemical leak

Persistent drainage >3 weeks, clinically relevant change in management, percutaneous/endoscopic drainage, angiographic procedures, infection without organ failure

Reoperation, organ failure, death

Onset (early (24 hours, late >24 hours)/severity

Early/mild

Early/severe or late/mild

Late/severe

Location

Intraluminal/extraluminal

Intraluminal/extraluminal

Intraluminal/extraluminal

Clinical condition

Good

Good to moderately impaired

Severely impaired, life-threatening

DELAYED GASTRIC EMPTYING*

POSTOPERATIVE PANCREATIC FISTULA†

POSTOPERATIVE PANCREATIC HEMORRHAGE‡

*Functional gastroparesis after surgery without mechanical obstruction as determined by upper gastrointestinal contrast series or endoscopic evaluation. † Amylase >3 times upper limit institutional normal serum amylase value. ‡ All postoperative episodes of hemorrhage after pancreatic resection including gastrointestinal or intraabdominal hemorrhage, and early or delayed postoperative bleeding.

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developed to predict postoperative risk of pancreatic fistula and to guide the management of perianastomotic drains. Pancreatic fistulas are generally detected by the presence of amylase-rich fluid from the surgical drains or the presence of a peripancreatic fluid collection on CT imaging. Pancreatic fistula can be associated with signs of infection (leukocytosis, fever) and can cause delayed gastric emptying or postpancreatectomy hemorrhage. If a deep space infection is present, it is important to obtain adequate drainage not only for source control, but also to prevent the fluid from necessitating out the surgical site, leading to fascial dehiscence. ISGPS grade B fistulas can usually be managed with drainage, antibiotics, and the use of somatostatin analogues. On rare occasions, patients with severe disruption of the pancreaticojejunostomy may require surgical reexploration for definitive management.

Delayed Gastric Emptying Delayed gastric emptying remains a troublesome complication after pancreaticoduodenectomy, the pathophysiology of which is not fully understood and is likely multifactorial. Differences in surgical technique have been analyzed. The incidence of delayed gastric emptying appears to be lower with antecolic as compared with retrocolic gastrojejunostomy. Rates of delayed gastric emptying do not appear to be different when comparing standard pancreaticoduodenectomy to pylorus-preserving pancreaticoduodenectomy. However, it is possible that surgical technique may affect delayed gastric emptying. A recent review of robotic pancreaticoduodenectomies identified an acute angle (3 times upper limit institutional normal serum amylase value ↓ Biochemical leak ↓ Persistent drainage >3 weeks* Clinically relevant change in management of postoperative pancreatic fistula Percutaneous or endoscopic drainage* Angiographic procedures for bleeding* Signs of infection without organ failure* ↓ Grade B pancreatic fistula ↓ Reoperation* Organ failure* Death* ↓ Grade C pancreatic fistula *Treatment/event postoperative pancreatic fistula related. Modified from Bassi, C, Marchegiani G, Dervenis C, et al. The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 years after. Surgery. 2017;161:584–591.

irregularities, thrombosis, active bleeding, or pseudo-aneurysm development. In such circumstances, conservative, noninvasive management is always advocated as the first approach. Adequate nutritional support has been considered a key element of fistula management because patients are in a hypercatabolic state with electrolyte depletion being accentuated by high-output fistulae. Notably, as suggested by an ISGPS consensus statement, there appears to be no benefit from avoiding oral intake for those who can tolerate it. In fact, recent randomized controlled trials indicate equivalent fistula closure rates with oral feeding when compared with artificial nutrition, with no significant increase in fluid output. A standard diet, rather than low-fat meals, is now allowed by most experts in such circumstances. However, when oral intake is not feasible, enteral nutrition through either a nasojejunal tube or a feeding jejunostomy should be preferred over parenteral nutrition to prevent enteric bacterial overgrowth and infectious complications associated with long-term fasting. Conversely, there is no concrete evidence supporting the efficacy of somatostatin-analogue administration in reducing fistula output and promoting fistula closure. Therefore such drugs should not be employed as standard treatment. Finally, there is no standardization of drain management in CR-POPF patients. With the purpose of intraabdominal drainage being to evacuate infected or amylase-rich fluids, drains can be safely removed as soon as fluid volume falls below 50 mL per day. The characteristics are serosanguinous with no purulent, biliary, or enteric components, and the amylase value has relatively normalized. However, even in such cases, late fistulas presenting after drain removal or hospital discharge are possible and should not be dismissed. Fever, abdominal tenderness and pain, impaired bowel function, leukocytosis, and elevated C-reactive protein are usually present in the case of infected collections associated with POPF. CT scans often show gas bubbles within peripancreatic collections, which indicate internal bacterial growth or communication with the GI tract. In such circumstances, rapid deterioration toward sepsis and severe hemorrhage should be foreseen. Therefore most experienced

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Management of Complications after the Whipple Procedure

pancreatic surgeons prefer to transfer the patient to an intermediate or intensive care unit. A step-up approach comprising noninvasive treatment as the first tactic is now unanimously recommended, leaving surgical exploration as a final option in the case of failure of nonoperative interventions. Fluids should be adequately administered to prevent hypotension, dehydration, and electrolyte imbalances. If no preoperative or intraoperative cultures are available, broad-spectrum antibiotics should be chosen empirically considering institution-specific epidemiologic data. Gram-positive, enteric gram-negative, and anaerobe bacteria must be routinely covered, along with fungi when parenteral nutrition has been initiated. Subsequently, antibiotic treatment may be targeted according to drain effluent cultures, if necessary. The goal of interventional procedures is to obtain source control by removing intraabdominal infection to minimize the septic insult to the patient and favor tissue healing. Percutaneous drain placement represents the intervention of choice when peripancreatic fluid collections are present, and its superiority compared with relaparotomy as initial treatment has been repeatedly demonstrated. Although ultrasound-guided catheter placement may be possible in the case of large, superficial collections, CT-guided procedures performed by dedicated interventional radiologists are preferred to prevent vascular and intestinal injuries. Endoscopic ultrasound-guided drainage procedures are also gaining consensus in such circumstances, in line with consolidated results obtained with the treatment of pancreatic pseudocysts. In this respect, it is noteworthy to emphasize the need for dedicated support systems with unrestricted availability of interventional radiology, endoscopy, infectious disease, and critical care services at institutions where pancreatic surgery is performed. Most patients are successfully managed with such a nonoperative approach. It should also be noted that in certain circumstances, fluid collections may not be either mature enough or safely accessible for drainage techniques. In such circumstances, antibiotic administration alone may suffice, but this is predicated on the degree of the patient’s illness being relatively low in concert with active surveillance/anticipation for progressive clinical downturn paired with swift clinical reaction. The major retrospective study conducted thus far comparing primary nonoperative and surgical management for CR-POPF indicates that up to 77% of patients treated with primary catheter drainage display CR-POPF resolution without the need for surgery, with a significant advantage compared with those undergoing primary surgery in terms of mortality (14% vs. 36%), multiorgan failure (16% vs. 39%), new-onset diabetes (12% vs. 44%), need for additional relaparotomies (22% vs. 45%), intensive care unit admission (37% vs. 87%), and length of stay (median: 29 vs. 55 days). However, relaparotomy must be considered in the case of no clinical improvement with maximal supporting care, collections inaccessible to percutaneous/endoscopic drainage, evidence of bowel perforation or necrosis, as well as suspicion of peripancreatic bleeding not suitable for endovascular treatment. No consensus regarding appropriate timing and optimal operative conduct is available because these constitute rare and daunting circumstances, even for seasoned pancreatic surgeons. Given the presence of inflammatory necrotic tissue and adhesions, the more time passes from index surgery, the more challenging and riskier the reintervention becomes. Among the multiple surgical options proposed, extensive debridement of peripancreatic necrotic tissue with wide drainage is a baseline mandate. Wide drainage only (a so-called less is more approach) and salvage completion pancreatectomy (albeit with a mortality rate as high as 50%) are both endorsed by expert surgeons in the case of evident anastomotic disruption, while any attempt to reconstruct the pancreatic anastomosis or convert to a different anastomosis (e.g., from pancreatico-jejunostomy to gastro-jejunostomy) is commonly discouraged. Other salvage approaches to consider are directly intubating and externalizing the duct, or a “bridge-stenting” to the disconnected jejunal loop, with

the aim of diverting most of the pancreatic juice either externally or internally. However, it should be said that such procedures are almost anecdotal, even for long-time, experienced pancreatic surgeons, and this scenario is among the most challenging they may ever face in their career. Decision making is largely dependent on intraoperative findings and anatomy, the patient’s hemodynamic stability, and the surgeon’s skills. In fact, massive pancreatic necrosis consequent to pancreatic fistula is frequently accompanied by the failure of hepaticojejunostomy or gastrojejunostomy and diffuse peritonitis. Therefore whichever approach is employed, laparotomy with subsequent second-look operations are sometimes necessary, and mortality surpasses 50%.

POST-PANCREATECTOMY ACUTE PANCREATITIS (PPAP) In 2021, the ISGPS consortium proposed definition criteria of post-pancreatectomy acute pancreatitis (PPAP) as a distinct complication from pancreatic fistula. From the biologic standpoint, PPAP describes an acute pancreatic inflammatory process occurring in the (early) postoperative period — probably as a consequence of manipulation, trauma, ischemia/hypoperfusion of the pancreatic parenchyma, or stasis of pancreatic juice associated to the surgical procedure. If on the one side such a notion is not novel (in fact, debate on its existence, definition, and impact has ignited a years’long scientific querelle), qualifying PPAP as an independent, noteworthy event to be reported and addressed represents a cultural step forward in the pancreatic surgery community. As per the ISGPS criteria, sustained hyperamylasemia (namely, an increase of serum amylase activity greater than institutional upper limit persisting in the first 48 hours postoperatively) is the backbone of PPAP diagnosis, along with cross-sectional imaging confirmation of intra- and peri-pancreatic edema, fluid collections, or necrosis. Notably, the threshold in serum amylase measurement chosen for PPAP diagnosis is lower than the one traditionally employed for diagnosis of acute pancreatitis (namely, 3 the upper normal limit), since even a moderate, but persistent, amylase increase has been correlated with overall and severe morbidity after surgery. Furthermore, keeping with the logic employed for the grading of POPF, clinically relevant PPAP is defined by the need of either noninvasive (e.g., pharmacologic, endoscopic, or interventional radiologic treatment — grade B PPAP) or invasive approaches (e.g., reintervention, treatment of single or multiorgan failure for at least 48 hours — grade C POPF). As of this writing (summer 2022), the only study utilizing the ISGPS nomenclature reported a 21% rate of PPAP following pancreatoduodenectomy. Interestingly, in such series CR-POPF incidence was 4× as high among patients with PPAP (41 vs.12%), and half the patients who developed CR-POPF were also diagnosed with PPAP. At first, as one of the strongest independent predictors of POPF, it might seem that PPAP simply precedes or accompanies fistula development by impairing the healing of the pancreatic anastomosis. However, debate is still ongoing on whether PPAP constitutes a precursor (namely, a proper causal event) or a phenomenon (namely, a biochemical marker) of ongoing pancreatic fistula. More likely, POPF and PPAP constitute elements of the same biologic process involving the dehiscence of pancreatico-enteric anastomosis. Interestingly, recent studies have also demonstrated the association between PPAP and abdominal and systemic complications in patients without CR-POPF, such as organ space infections, collections, hemorrhage, and sepsis, thus justifying the introduction of PPAP as an independent clinical entity. Given its recent appearance in the surgical vocabulary, no study has yet defined any specific treatment/mitigation approach for PPAP after the Whipple procedure nor, in general, pancreatectomies. Hopefully, a consensus definition and grading system for PPAP will serve as a foundation to identify diagnostic and

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603

TABLE 3  International Study Group of Pancreatic Surgery Consensus Definitions of Postpancreatectomy Hemorrhage DEFINITIONS Time of Onset Early hemorrhage (≤24 hours after the end of the index operation) Late hemorrhage (>24 hours after the end of the index operation) Location Intraluminal (anastomotic suture lines, cut surface of the pancreas, stress ulceration, pseudoaneurysm) Extraluminal (arterial or venous vessels, diffuse bleeding from resection area, anastomotic suture lines, pseudoaneurysm) Severity of Hemorrhage Mild Decrease in hemoglobin concentration 3 units packed cells Need for invasive treatment (interventional angiographic embolization or relaparotomy) GRADING SCALE Grade

Onset, Severity, and Location

Clinical Condition

A B C

Early, mild intraluminal or extraluminal bleeding Early, severe intraluminal or extraluminal bleeding Late, mild intraluminal or extraluminal bleeding Late, severe intraluminal or extraluminal bleeding

Good Good to moderately impaired Severely impaired, life-threatening

Modified from Wente MN, Veit JA, Bassi C, et al. Postpancreatectomy hemorrhage (PPH): an International Study Group of Pancreatic Surgery (ISGPS) definition. Surgery. 2007;142:20–25.

prognostic criteria in order to recognize risk factors of PPAP, as well as prevent, mitigate, and, eventually, treat its sequelae.

POSTPANCREATECTOMY HEMORRHAGE With a reported incidence around 10%, PPH can represent a life-threatening complication and often requires emergent invasive procedures. This broad-ranging concept is classified according to its time of onset (early vs. late), site of bleeding (intraluminal vs. extraluminal) and severity (mild vs. severe) per the ISGPS terminology (Table 3). Although a decrease in hemoglobin levels is commonly observed because of the equilibrium of intraoperative blood loss combined with fluid administration in the early postoperative period, early bleeding (≤24 hours) is usually attributable to technical failure in obtaining hemostasis or, alternatively, underlying coagulopathy. Common sites of bleeding are the hepatic and superior mesenteric arteries, the gastroduodenal artery stump, the pancreatic stump, and the pancreatico-duodenal vessels in the retroperitoneum. In this particular circumstance of major bleeding with hemodynamic instability, immediate surgical reexploration is recommended because the source of bleeding is often easily identified and controlled, with the subsequent postoperative course being likely uneventful. Conversely, delayed PPH can occur up to several days or weeks after index surgery, and it is usually associated with, and often caused by, coexistent complications such as POPF, bile leaks, intraabdominal collections, or bowel perforation. In fact, vessel erosion by

enzyme-rich or infected fluid derived from anastomotic leaks, in association with vascular wall lesions caused inadvertently during skeletonization or reconstruction, can lead to pseudoaneurysm formation and bleeding. Therefore PPH always should be considered when other intraabdominal complications occur, and postoperative contrast-enhanced imaging evaluation must also include a thorough assessment of major peripancreatic vessel integrity to identify wall irregularities, pseudoaneurysms, and subtle bleeding. Notably, a self-limiting small amount of blood emanating from drains, often referred to as a sentinel bleed, precedes a major hemorrhage in up to one-third of cases, thus imposing rapid assessment of hemodynamic and laboratory parameters to prevent a fatality. As soon as a late hemorrhage is suspected, contrast-enhanced CT is requisite (Fig. 1A) Proper fluid resuscitation should be implemented immediately, with red blood cell and fresh plasma transfusions being considered to facilitate the patient’s coagulative capacity and maintain adequate peripheral oxygenation. In the case of hematemesis, a nasogastric tube must be rapidly inserted: notably, this can result not only from intraluminal upper GI bleeding, but also from intraperitoneal hemorrhage with the blood entering the GI tract through a dehiscent anastomosis. Even for the hemodynamically stable patient, intensive care unit transfer is advisable for adequate monitoring and support because initially mild hemorrhage can rapidly evolve into overwhelming bleeding and shock. Subsequently, once the patient is hemodynamically stable, either interventional angiography or endoscopy should be considered depending on the suspected site of bleeding. Multiple approaches are available to achieve hemostasis depending on the site and the

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Management of Complications after the Whipple Procedure

FIG. 1  (A) Contrast-enhanced CT scan of a patient with CR-POPF developing hypotension, tachycardia, and oliguria. The common hepatic artery (arrow) is surrounded by fluid with internal air bubbles. Vessel profile irregularity is evident, with high suspicion for pseudoaneurysm development. (B) A selective celiac trunk arteriography confirms common hepatic artery irregularity with a 6-mm pseudoaneurysm (arrow) proximal to the gastroduodenal artery stump. The proper hepatic artery, left hepatic artery, and splenic artery appear normal. (C) A cover metal stent is placed from the common to the proper hepatic artery to exclude both the pseudoaneurysm and the gastroduodenal artery stump from blood flow. Control angiogram shows no active bleeding.

caliber of the damaged vessel. Vessel embolization with coils or glue or covered stenting is employed in the case of endovascular procedures (Fig. 1B, C), whereas argon-plasma coagulation or clipping are available during endoscopic approaches. Interventional procedures are now considered as the first approach for late PPH, with relaparotomy being reserved for deteriorating, hemodynamically instable patients or those not responsive to noninvasive approaches. In fact, especially when POPF and peritonitis are present, surgical access to the bleeding vessel is made harder because of hematomas, peripancreatic abscesses, dehiscent anastomoses, and adhesions, and once at the epicenter, vascular integrity is fragile, making control and definitive resolution dubious. As is the case with CR-POPF (see earlier), re-laparotomies are associated with high mortality rates and the need for second looks to obtain definitive hemostasis and abdominal wall closure.

DELAYED GASTRIC EMPTYING Frequently associated with CR-POPF, intraabdominal collections, and tissue inflammation, delayed gastric emptying is described as another common complication following the Whipple procedure,

with historically reported occurrence varying from 30% to 40%. Fortunately, despite such considerable incidence, DGE management is mostly supportive and rarely requires interventional procedures. Improvements in POPF prevention/management as well as the common adoption of an antecolic placement of the gastroenteric anastomosis have likely hastened progress over time, to the point where the incidence of this should now be considered in the 10% range. As with its presumed pathophysiology (pyloric spasm and/or gastroparesis caused by enteric neuropeptide dysregulation, stomach denervation, devascularization, peripancreatic inflammation, and possibly fluid overload), the definitions of DGE employed in the literature over the years were nebulous, thus hampering their applicability. According to the 2007 ISGPS consensus definition (Table 4), maintenance of a nasogastric tube for more than 3 days (or need for reinsertion following postoperative day 3) and the inability to tolerate solid food by postoperative day 7 should be considered DGE. Notably, unlike CR-POPF, there are neither quantitative nor biochemical diagnostic criteria, thus leading to imprecise estimation of the real incidence DGE according to various practice habits employed at different institutions. DGE should be suspected whenever a patient has trouble resuming oral feeding after surgery,

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TABLE 4  International Study Group of Pancreatic Surgery Consensus Definition of Delayed Gastric Emptying Nasogastric Tube Grade Requirement

Days of Oral Vomiting Intolerance and Gastric (POD) Distension

Use of Prokinetics

A

4 to 7 days or reinsertion >POD 3

7

±

±

B

8 to 14 days or reinsertion >POD 7

14

+

+

C

>14 days or reinsertion >POD 14

21

+

+

Definition: Functional gastroparesis after surgery without mechanical obstruction as determined by upper gastrointestinal contrast series or endoscopic evaluation. POD, Postoperative day. Modified from Wente MN, et al. Delayed gastric emptying (DGE) after pancreatic surgery: a suggested definition by the International Study Group of Pancreatic Surgery (ISGPS). Surgery. 2007;142:761–768.

with early typical complaints presenting as abdominal distension, discomfort, bloating, and nausea. Most manifest with vomiting after initial tolerance of oral intake, thus requiring discontinuation and resumed nasogastric decompression. Notably, these attributes are also common with generalized ileus, so teasing the two entities apart is challenging. Accordingly, three severity grades are established by the ISGPS consensus based on the delay of oral intake resumption and the therapeutic approaches employed by the surgeon to treat such a condition (see Table 4). By definition, DGE is a functional condition, therefore the diagnosis of such implies that causes of upper gastrointestinal mechanical obstruction (such as gastrojejunal anastomosis stricture, perianastomotic ulcer, or abscess) are excluded. CT scans and upper GI endoscopy are usually necessary to rule out the presence of such mechanical factors, while a Gastrografin swallow usually confirms gastric distension and a slower passage of contrast into the jejunal loop. Prolonged nasogastric tube decompression and antiemetic/prokinetic drug administration are almost always necessary, resulting in prolonged fasting and delayed discharge. Subsequently, resumption of oral intake should be undertaken gradually. In the authors’ experiences, chewing gum, carbonated drinks, and cold food (such as ice cream) may be helpful in stimulating peristalsis and promoting feeding resumption. For those unable to tolerate food for several days, artificial nutrition must be considered, but this is necessary in only a fraction of all DGE circumstances. Despite not being demonstrated as superior in terms of DGE resolution, enteral nutrition should be preferred over total parenteral nutrition. The vast majority of DGE cases are self-limiting and generally have minor effects on postoperative recovery. In fact, prolonged enteral

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feeding (weeks) through jejunostomy or percutaneous endoscopic gastrostomy is exceedingly rare. However, the psychological burden of DGE on patients (as well as costs associated with longer hospital stays, medication employed, and delays to adjuvant therapies) should not be underestimated.

CHYLE LEAK Among the pancreatectomy-specific complications coded by the ISGPS, chyle leak has been recently described, perhaps because of its relatively rare occurrence. It results from the accidental damage or disruption of the cisterna chyli or its major tributaries during the operation because they are located behind the pancreatic head and body, lateral to the aorta, or adjacent to the superior mesenteric artery and vein within the mesenteric pedicle. Diagnosis can be suspected whenever milky drain fluid appearance is evident after resumption of oral feeding, especially if an extended peripancreatic lymphadenectomy or periadventitial aortic/proximal superior mesenteric artery dissection had been performed. Per the ISGPS consensus, chyle leak is defined when the drain fluid triglyceride content is ≥110 mg/dL/1.2 mmol/L on or after postoperative day 3. Often though, this is rather self-evident by its white, opaque characteristic alone. Similar to the CR-POPF definition, no fluid volume threshold is required for the diagnosis. As chyle leak is confirmed, surgeons usually employ a prudent step-up approach encompassing dietary restrictions, such as a no/low-fat diet, enteral nutrition with middle-chain triglyceride (MCT) implementation, or even total parenteral nutrition. Specifically, because MCTs are directly emitted into the venous blood rather than gut lymphatic after absorption, MCT-enriched preparation should be preferred in chile leak patients without reducing the caloric intake. At the authors’ institutions, a 72  hour nil-per-os challenge is started as soon as chyle leak is suspected, with most patients recovering without the need for further intervention. Percutaneous drainage of intraabdominal chyle ascites may be necessary for patients with related symptoms, whereas additional procedures such as lymphatic duct embolization or relaparotomy for direct suture are thankfully anecdotal.

S uggested R eadings Bassi C, Marchegiani G, Dervenis C, et  al. The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 years after. Surgery. 2017;161:584–591. Casciani F, Bassi C, Vollmer CM Jr. Decision points in pancreatoduodenectomy: Insights from the contemporary experts on prevention, mitigation, and management of postoperative pancreatic fistula. Surgery. 2021;170(3):889–909. Smits J, van Santvoort H, Besselink M, et al. Management of severe pancreatic fistula after pancreatoduodenectomy. JAMA Surg. 2017;152(6):540–548. Vollmer C, Lewis R, Hall B, et al. Establishing a quantitative benchmark for morbidity in pancreatoduodenectomy using ACS-NSQIP, the Accordion Severity Grading System, and the Postoperative Morbidity Index. Ann Surg. 2015;261(3):527–536. Wente MN, Bassi C, Dervenis C, et al. Delayed gastric emptying (DGE) after pancreatic surgery: a suggested definition by the International Study Group of Pancreatic Surgery (ISGPS). Surgery. 2007;142:761–768. Wente MN, Veit JA, Bassi C, et al. Postpancreatectomy hemorrhage (PPH): an International Study Group of Pancreatic Surgery (ISGPS) definition. Surgery. 2007;142:20–25.

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Vascular Reconstruction During the Whipple Operation

Vascular Reconstruction During the Whipple Operation Benedict Kinny-Köster, MD, and Jin He, MD, PhD

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ascular resection and reconstruction are often encountered during pancreatoduodenectomy (Whipple operation) for pancreatic malignancies. Venous and arterial reconstructions allow for margin-free resection of tumors that demonstrate vascular involvement. Because tumors that are attached to the mesoportal venous, hepatic arterial, or superior mesenteric arterial system are usually located in the pancreatic head or uncinate process, strategies of reconstruction are particularly (but not exclusively) relevant during pancreatoduodenectomy. A radical tumor resection in combination with chemotherapy is considered the only curative-intent treatment approach in pancreatic ductal adenocarcinoma (PDAC) without evidence for distant spread. This treatment paradigm became increasingly promising with the improved efficacy of the FOLFIRINOX combination chemotherapy (folinic acid/leucovorin, fluorouracil/5FU, irinotecan, oxaliplatin). In addition to elective oncologic indications, the principles of vascular reconstruction apply for situations when surgeons are confronted with the intraoperative injury of essential vessels. Here, knowledge about the individual patient’s anatomy, such as aberrant hepatic arteries, may influence surgical strategies. Besides primary tangential or end-to-end repair, patches and conduits can be utilized to bridge long tangential or segmental vascular defects. Furthermore, the postoperative management of complications is critical for the clinical success as vascular reconstructions are associated with increased perioperative morbidity. Potential complications include postpancreatectomy hemorrhage, postoperative thrombosis, liver or bowel ischemia, portal hypertension, ascites, infection, and diarrhea. Herein, we summarize technical considerations including options of conduit materials and implications on postoperative management based on the current literature and cumulative experiences from a high-volume center.

PATIENT SELECTION FOR ELECTIVE VASCULAR PANCREATIC SURGERY Currently, a pancreatic mass without distant metastases that is attached to surrounding vasculature is being categorized into resectable, borderline resectable, or locally advanced according to the extent of circumferential vessel involvement on radiographic imaging (National Comprehensive Cancer Network guidelines for PDAC, last update 2021). Preoperative chemotherapy is often considered if the serum tumor marker CA19-9 is high, indicating an increased risk of systemic (micrometastatic) spread. Because imaging scans have limited specificity to differentiate vital tumor from scar tissue after FOLRININOX chemotherapy, we recommend that every patient without distant metastatic spread after preoperative chemotherapy undergoes surgical exploration. We also reported that discriminating different depths of invasion for major arteries with regard to their distinct histologic layers (tunica adventitia with overlying nerval plexus vs. tunica media) has direct surgical implications. Overall, surgical exploration with possible pancreatoduodenectomy and vascular resection/reconstruction is associated with improved survival in patients with favorable clinical predictors (e.g., normalized CA 19-9 during chemotherapy or long progression-free interval) and especially relevant for young patients with great performance status.

VENOUS RECONSTRUCTION When performing pancreatoduodenectomy for patients with venous involvement, venous resection should be performed en bloc with the tumor specimen to achieve a negative margin. The surrounding mesoportal venous drainage of the intestines can be involved by tumor between the distal superior mesenteric vein (SMV) in the area of the jejunal and ileal tributaries and the proximal portal vein (PV) toward the liver hilum. If the primary tumor can be resected with tangential venous resection, primary tangential repair should be attempted either transversely or longitudinally if subsequent narrowing of the vein diameter is not exceeding 50%. Otherwise, a vascular patch may be utilized (bovine pericardium, autologous peritoneum, or falciform ligament). For segmental resections, a primary end-to-end reconstruction should be carried out if a tension-free anastomosis can be performed. This is often feasible for vascular defects less than 3 cm in length. Mobilization of the liver through dissection of the surrounding ligaments may support this approach. For a long segmental resection, conduits with a sufficient size match are important tools for reconstruction (Fig. 1). For this purpose, we preferably utilize the left renal vein, greater saphenous vein, or occasionally left internal jugular vein as autologous interposition grafts. Although robust evidence about patency and postoperative outcomes is lacking, we have experienced favorable results over synthetic PTFE (polytetrafluoroethylene) conduits or cryopreserved allogenous vein grafts that constitute alternatives if autologous veins are not accessible. Nevertheless, synthetic PTFE conduits with ring enforcement are a quickly accessible option, especially when facing unexpected intraoperative venous injuries. When using cryopreserved vein grafts, we match them with the patient’s blood group. When the tumor causes occlusion of the SMV through external compression, cavernous collateralization around the pancreatic head is often evident and can provoke massive intraoperative blood loss during the resection phase. For improved control, the distal SMV or even a prominent jejunal/ileal tributary can be bypassed to the PV with a synthetic PTFE conduit (“venous bypass graft first”) or to the inferior vena cava (mesocaval shunt) before resection of the Whipple specimen to temporarily divert the intestinal drainage. After resection, the bypassed venous flow should be reevaluated and optimized (e.g., primary reconstruction or autologous vein graft). A permanent mesocaval shunt with a primary anastomosis (end-toside) or a conduit (distal end-to-end, proximal end-to-side anastomoses) may be an option in patients with particularly caudal tumor involvement after mesoportal reconstruction of the main intestinal drainage, if an additional jejunal or ileal tributary remains with considerable backflow. Preservation of venous collaterals, if feasible, may also facilitate decreased postoperative intestinal congestion and mitigate risks associated with potential postoperative thrombosis of the reconstructed segment. When performing a venous resection of the confluence, the splenic drainage must be considered to prevent varices of the short gastric veins. If the splenic vein cannot be reinserted, a spleno-renal shunt with a primary anastomosis or a conduit (splenic vein to left renal vein), or a spleno-caval shunt (e.g., if the left renal vein was resected for an interposition graft) prevents sinistral portal hypertension. Importantly, similar considerations apply for the venous drainage of the stomach. Particularly after splenectomy with subsequently interrupted venous flow through the short gastric veins, the coronary vein plays a critical role to prevent upstream congestion and ischemia. If not preserved (e.g., during a total pancreatectomy), insertion into the mesoportal venous axis or inferior vena cava should be attempted. When performing a venous resection, tangential venous control or distal and proximal venous control is achieved with vascular clamps. For segmental reconstructions, we communicate with the anesthesiologist to administer an intravenous injection of heparin

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FIG. 1  Reconstruction of the mesoportal venous flow with an interposition graft. (A) Cavernous transformation of the PV/SMV illustrated at a three-dimensionally rendered CT scan. Preoperatively planned, feasible locations of distal and proximal anastomoses (red arrows) of a potential conduit (in blue) are shown. (B) Mesoportal conduit (cryopreserved saphenous vein) tunneled below the CHA. CHA, Common hepatic artery; PV, portal vein; SMA, superior mesenteric artery; SMV, superior mesenteric vein. (From Kinny-Köster B, van Oosten F, Habib JR, et al. Mesoportal bypass, interposition graft, and mesocaval shunt: Surgical strategies to overcome superior mesenteric vein involvement in pancreatic cancer. Surgery. 2020;168[6]:1048–1055.)

(5000 units or 70 units per kg body weight) immediately before clamping. Tangential or segmental reconstruction can be performed with both interrupted or running Prolene sutures (5-0 or 6-0 USP). Just before finishing segmental reconstruction, the distal clamp is reopened before the proximal clamp to release air and potential minor clots. We do not compromise inflow of the SMA during mesoportal venous reconstruction. After reestablished perfusion, flow can be evaluated by intraoperative Duplex ultrasound or transit time flow measurement (TTFM) distally and proximally. Sufficient drainage should be confirmed by resolving intestinal and splenic congestion before performing the pancreatico-jejunostomy.

ARTERIAL RECONSTRUCTION Arterial reconstructions during the Whipple procedure affect the hepatic arteries and SMA. Reconstruction of the hepatic arterial inflow may involve the common hepatic artery, the proper hepatic artery, or the right and left hepatic arteries individually, especially in patients with an aberrant anatomy (e.g., Michels type 3 anatomy, replaced right hepatic artery originating from the SMA). To understand the implications for reconstruction of a specific artery, it is crucial to review the preoperative arterial phase CT imaging. In addition to the identification of an aberrant liver arterial blood supply, the origin of the celiac trunk (ruling out a median arcuate ligament) and SMA should carefully be evaluated as potential collaterals between the two major branches surrounding the pancreatic head (gastroduodenal artery and its arcades) will be divided and limit compensatory flow in case of occlusion. To clarify on the extent of SMA involvement early intraoperatively, we recommend an “artery-first” approach that aims to confirm feasibility of reconstruction before committing to a point-of-no-return during resection. Tangential resections of the full vessel wall should not be performed because of the high risk for tears of the tunica intima, which may provoke intimal dissection and intraluminal blockage. For short segmental resections, an end-to-end anastomosis can be attempted. However, we have experienced that the extent to mobilize arterial cuffs toward each other is often limited. Thereby, reconstruction with conduits may be necessary. To perform a precise and controlled anastomosis, it is paramount to consider different sites for the

proximal anastomosis. Although in most cases the site of transection represents a feasible option for an end-to-end anastomosis, the side wall of the supraceliac aorta, suprarenal aorta, infrarenal aorta, right renal artery, and right iliac artery can be valuable alternatives for a side-to-end anastomosis to a conduit that connects the liver or superior mesenteric territory. As for venous reconstructions, we prefer autologous venous grafts that must be reversed when implanted to overcome venous valves. In particular situations when long conduits are necessary or when facing unexpected intraoperative arterial injuries, synthetic PTFE grafts are again a valuable choice. In rare instances, the transposition of an artery in close proximity to the resected segment with a matching diameter may be an alternative (e.g., transposition of the splenic artery with splenectomy or left gastric artery). However, although these reconstructions only require one vascular anastomosis, we have experienced a tendency for increased turbulent flow that compromised perfusion. If the middle colic or right colic arteries are involved by the tumor in the mesentery, transection may necessitate a partial colectomy of ischemic segments (multivisceral resection). If the intestines appear edematous after resection of the specimen because of an extensive procedure with prolonged clamping of the superior mesenteric artery (SMA), the bile duct and pancreatic duct may temporarily be drained externally. Reconstruction of intestinal continuity can be performed secondarily within 24 to 48 hours. In patients with arterial reconstruction and a high-risk for fistula from pancreatico-jejunostomy (soft gland texture or duct ≤3 mm), we tend to perform a total pancreatectomy. When performing an arterial anastomosis, the technical steps are identical to venous reconstruction. Before proceeding with the pancreatico-jejunostomy, sufficient perfusion should be confirmed by Duplex ultrasound or TTFE.

PERIADVENTITIAL DISSECTION OF ARTERIES Recently, a novel concept coined periadventitial dissection (also referred to as arterial divestment) was developed. It is indicated and a valuable option, especially for patients with borderline resectable or locally advanced PDAC after preoperative chemotherapy.

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Intraoperative exploration revealed that, although abutting or encasing the SMA on CT, the arterial tunica media often is not invaded (Fig. 2). This allows for resection of the tumor with the tunica adventitia and the attached neural plexus on top of the SMA (PLsma) through dissection within the arterial periadventitial plane. We recommend performing periadventitial dissection hemicircumferentially (to the right side of the SMA, if tumor involvement was less than 180 degrees) to decrease the risk of prolonged postoperative diarrhea. Periadventitial dissection should be performed en bloc through entering of the plane at an area without tumor contact to avoid transection through tumor tissue (no-touch principle). The same principle is applicable to the celiac trunk and common hepatic artery. With this technique, arterial resection and reconstruction can be prevented while still achieving a macroscopically margin-free resection (commonly R0, sometimes R1 with tumor cells apparent within a 1-mm margin). Although oncologic outcome data are still limited, clinical trials are underway to study its efficiency in reducing local recurrences, even in patients without arterial involvement.

ROBOTIC VASCULAR PANCREATIC SURGERY Robotic pancreatoduodenectomy with short tangential venous reconstructions can be safely performed by experienced robotic pancreatic surgeons after passing a learning curve. However, we typically perform an open procedure whenever a segmental resection of veins or arteries may be required from the assessment of preoperative CT imaging. The concept of periadventitial dissection together with retropancreatic nerve plexus resection (level 1, 2, or 3 according to Inoue, 2016) should be considered and implemented during robotic pancreatoduodenectomy. Here, the TRIANGLE area (retropancreatic triangular-shaped space enclosed by the common hepatic artery, SMA, and superior mesenteric vein/portal vein) describes the anatomic correlate to achieve a radical dorsal and medial margin during both open and robotic pancreatoduodenectomy. If surgeons face

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uncontrolled venous or arterial bleeding during robotic resection, careful and blunt compression should be attempted to reach temporary control. Through a hand-assisted port, control may be facilitated with closure of the lumen by a finger. Care should be taken to not enlarge injuries, a scenario that veins are particularly prone to. However, conversion to laparotomy with the opportunity of an improved overview is a critical bailout option (e.g., to access and cross-clamp the supraceliac aorta for arterial bleeding).

POSTOPERATIVE MANAGEMENT AND COMPLICATIONS Evidence to promote postoperative patency of vascular reconstructions and to balance risks of thrombosis versus postoperative hemorrhage are lacking. In our practice, we administer lifelong aspirin for segmental reconstructions (primary end-to-end or with conduits) in the venous or arterial system, and for tangential reconstructions with patches in the venous system. For tangential reconstructions with primary repair, we do not regularly prescribe an antiplatelet regimen (only considered for long reconstructions with considerable narrowing). Therapeutic anticoagulation with low-molecular-weight heparin is rarely administered. Although this describes our standard protocol, adjustments are considered on an individualized basis in certain high-risk situations. It is important to monitor hepatic ischemia postoperatively (AST, ALT, lactate) and to rule out intestinal ischemia (lactate). We perform duplex ultrasound to evaluate vascular patency routinely on postoperative day 1 and continue with serial examinations in patients with ascites or abnormal liver function. If acute arterial occlusion is suspected with clinical and laboratory signs of ischemia, a dual-phase CT scan is performed. After identification of the exact localization, the extent of occlusion, and potential collaterals, the patient is taken back to the operating room to revise the arterial reconstruction. Although removal of emboli with a Fogarty catheter should be attempted, the reconstruction often must be taken down and recreated. Of note, in patients in whom the CT scan demonstrates partial occlusion or a pseudoaneurysm of the hepatic

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FIG. 2  Illustration of periadventitial dissection and its underlying principle. (A) Hemicircumferential periadventitial dissection of the SMA during a robotic pancreatoduodenectomy with a retropancreatic level 3 dissection. # depicts the arterial tunica media with the overlying lamina elastica externa; * marks the neural plexus SMA. (B) Schematic cross-section of the performed periadventitial dissection with the anatomic layers of the arterial wall and the applied transection line. IPDA, Inferior pancreaticoduodenal artery; PLph II, plexus pancreatic head II; SMA, superior mesenteric artery; SMV, superior mesenteric vein. (Figure 2B made in ©BioRender, biorender.com.)

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artery, interventional angioplasty with stent placement or coil embolization, respectively, is primarily indicated as opposed to relaparotomy. If acute (early postoperatively), complete venous occlusion occurs in the portal vein (i.e., distally to the confluens) after venous reconstruction, surgical exploration and removal of thrombotic material should be performed in both proximal and distal directions with a Fogarty maneuver, especially if the liver serum transaminases are rapidly increasing.. If optimization seems feasible from a surgical-technical perspective, the venous reconstruction should be revised to decrease the risk of recurrent thrombosis. For acute occlusion in the superior mesenteric vein, therapeutic anticoagulation should be administered. However, therapy must be balanced with risk of bleeding on an individualized basis. Medical management of ascites with furosemide and spironolactone may be helpful under monitoring of serum electrolytes. For increased losses of fluid through the intraoperatively placed drainages, careful resuscitation with crystalloids should be considered. Chronic thrombosis in the venous system often does not provoke initial clinical symptoms and does not indicate anticoagulation therapy. However, because of portal hypertension and subsequent collateralization, the development of varices, especially in the esophagus and gastric fundus, require surveillance. In addition to the medical team, the patient should be aware that an event of hematemesis represents an emergency that would demand rapid diagnosis and treatment (esophagogastroscopy). Postpancreatectomy hemorrhage (PPH) is a major complication after vessel reconstruction. The International Study Group of Pancreatic Surgery differentiates between early versus late (cutoff 24 hours), extraluminal versus intraluminal, and mild versus severe appearance. Early-extraluminal-severe PPH as diagnosed by increased sanguineous drainage output should be attacked primarily with surgical reexploration without prior imaging, especially in unstable patients. If late PPH is suspected (mild/severe and extraluminal/intraluminal), a CT angiogram and subsequent interventional angioplasty are indicated to locate and treat the hemorrhage, which is often caused by an arterial pseudoaneurysm. If unsuccessful, immediate laparotomy is critical to prevent hemorrhagic shock. After resection or periadventitial dissection of the SMA, (neurogenic) diarrhea, sometimes persisting for 4 to 12 weeks postoperatively, is a complication that burdens patients. When bacterial enteritis is ruled out, oral antidiarrheal drugs may be utilized to mitigate the impaired bowel motility. It is important that fluid and nutrient supply are monitored and replaced appropriately to avoid severe weight loss and a decrease in performance status. In addition, oral supplementation of pancreatic enzymes should be considered to support exocrine pancreatic dysfunction. Sometimes, parenteral nutrition is necessary to bridge limited intestinal absorption. We have experienced that, although prolonged diarrhea is challenging for patients to manage, affected patients will regain bowel function eventually.

Palliative Interventions for Patients with Operable and Advanced Pancreatic and Periampullary Cancer Ashley Krepline, MD, Susan Tsai, MD, MHS, and Douglas B. Evans, MD

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he treatment of patients with pancreatic cancer (PC) is complicated by disease-associated symptoms that can often prevent the

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SUMMARY Herein, we describe the technical considerations to perform venous and arterial reconstructions during pancreatoduodenectomy for pancreatic malignancies. These considerations can also be applied to other pancreatic diseases such as advanced neuroendocrine tumors or chronic pancreatitis. Furthermore, we recommend periadventitial dissection, which is an evolving technique that often allows for macroscopically margin-free tumor resections while avoiding arterial resection. These tools allow for oncologic resections with acceptable safety. In addition, these techniques can be utilized for accidental vascular injuries that may appear during pancreatoduodenectomy. Because of the postoperative morbidity and mortality after vascular reconstructions, timely management of complications is of the essence to minimize events of failure to rescue. Elective vascular reconstructions should be performed in high-volume centers where interdisciplinary expertise and resources are readily available (surgeons, interventional radiologists, anesthesiologists). Patients with an indication for vascular reconstruction and periadventitial dissection must be carefully selected based on performance status and indicators of tumor biology to balance the potential harm with promising benefits.

Acknowledgment We express our gratitude to Christopher L. Wolfgang for contributing the images of Figure 1.

S uggested R eadings Habib JR, Kinny-Köster B, van Oosten F, et  al. Periadventitial dissection of the superior mesenteric artery for locally advanced pancreatic cancer: Surgical planning with the “halo sign” and “string sign. Surgery. 2021;169(5):1026–1031. Kinny-Köster B, Habib JR, Javed AA, et  al. Technical progress in robotic pancreatoduodenectomy: TRIANGLE and periadventitial dissection for retropancreatic nerve plexus resection. Langenbecks Arch Surg. 2021;406(7):2527–2534. Kinny-Köster B, Jabib JR, van Oosten F, et al. Conduits in vascular pancreatic surgery: analysis of clinical outcomes, operative techniques, and graft performance. Ann Surg. 2022 Jul 15 [online ahead of print]. Kinny-Köster B, van Oosten F, Habib JR, et  al. Mesoportal bypass, interposition graft, and mesocaval shunt: Surgical strategies to overcome superior mesenteric vein involvement in pancreatic cancer. Surgery. 2020;168(6):1048–1055. Schneider M, Hackert T, Strobel O, Büchler MW. Technical advances in surgery for pancreatic cancer. Br J Surg. 2021;108(7):777–785.

successful delivery of systemic therapy. Now that systemic therapy is associated with improved response rates, it is even more important that we have effective strategies for biliary and gastric outlet/ duodenal decompression as well as reliable techniques for tumor biopsy given the emerging field of molecular oncology, which relies on somatic mutation testing of tumor samples. Importantly, the definition of palliative care, palliative surgery, or any palliative intervention is the relief of disease-associated symptoms. The treatment of patients with incurable cancer, where the treatment is being applied to maximize length and quality of life, is often (inappropriately) referred to as palliative therapy. If the treatment is not being applied to relieve a symptom, it is not palliative therapy. For patients with PC, systemic therapy is not possible in the absence of durable biliary decompression and a mechanism to deliver reliable nutrition—usually via an enteral route. Furthermore, systemic therapy will rarely be associated with a response in the

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absence of a reasonably good performance status. As physicians have become increasingly specialized, the patient with PC can often be an orphan without a home—the medical oncologist cannot treat the patient with, for example, an elevated bilirubin; the gastroenterologist has placed a stent that may or may not be associated with a decline in liver function tests; the surgeon feels as though there is little role for their involvement as the patient has locally advanced or metastatic disease; and the patient is caught in the middle. Perhaps it would help to provide some guiding principles that we have adopted at the LaBahn Pancreatic Cancer Program: ■ The patient with PC needs a home; a team or service responsible

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for the infrastructure needed to maximize performance status and optimize the patient’s chances for receiving active anticancer therapy. Within our program, this is the surgery service, but it can be any subspecialty service. In the absence of a defined team of physicians/physician extenders who will own the challenges that accompany this diagnosis, patients will fail to receive potentially life-extending therapy and often die of biliary sepsis, nutritional depletion, or hypoglycemia. Many phase III trials (of all stages of PC) have demonstrated huge numbers of patients who fail to receive all intended therapy due to the inability to optimally manage bile duct and duodenal obstruction, pain, and other disease-associated symptoms—there is no other solid tumor where such challenges exist. The interventional gastroenterologist should never come first. Any patient with bile duct obstruction should receive a good quality CT/MRI before an endoscopic retrograde cholangiopancreatography (ERCP) or endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA). The most unfortunate (and preventable) situation involves the patient with a complication of an endoscopic procedure in whom the stage of disease cannot be determined due to the absence of high-quality imaging before procedure-associated pancreatitis or intestinal perforation. The management of biliary decompression needs to be tailored to the overall goals of care. For the patient with operable PC for whom neoadjuvant therapy is planned, high-risk procedures should be avoided. If endoscopic stent placement is unsuccessful, the “plan B” options include either a transhepatic catheter or a surgery-first approach. Higher risk endoscopic procedures should be reserved for patients with locally advanced and metastatic disease where a complication of the procedure will not risk a potentially curative treatment approach. Duodenal stents should, in general, be avoided in patients with operable disease in the absence of multidisciplinary review. In our experience, an uncovered metal stent in the duodenum does make the operation of pancreaticoduodenectomy more difficult. In such patients, we prefer a minimally invasive (laparoscopic/ robotic) gastrojejunostomy. Not every patient is treatable, but every patient should receive a thoughtful review of the individual factors that affect this decision: medical comorbidities and whether they can be optimized, success in biliary and gastric outlet decompression if present, and the social determinants of health. By addressing these critically important variables individually, one can make an accurate determination of what is and is not possible. This will also prevent the inappropriate application of surgery in patients where there is too small a chance for complete recovery.

INITIAL EVALUATION OF THE PATIENT WITH PANCREATIC/PERIAMPULLARY CANCER We have a simple approach—high-quality, triple-phase CT and a careful physical examination followed by EUS-guided FNA/ core biopsy (or US-guided core biopsy of extrapancreatic sites if metastatic) and ERCP with metal stent placement when biliary

obstruction is present. The EUS and ERCP are typically performed at the same anesthesia induction (monitored anesthesia care). If the diagnosis is established on endoscopic biopsy, a metal stent is placed in the bile duct; if the diagnosis is unclear at the time of endoscopy, a plastic stent is preferred. The patient can then be accurately staged and evaluated for treatment to include assessment of eligibility for a clinical trial. At the time of initial evaluation, the patient and their support system are also seen by genetic counseling, nutritional support, diabetes management, and our psychology services. The programmatic infrastructure needed for such patients is significant and one reason why some feel that all newly diagnosed patients should be managed at a larger referral center for diagnosis, staging, and an opinion regarding treatment sequencing. Patients with advanced PC face difficult treatment decisions, and open communication about goals of care will help patients to make sound, informed decisions. Understanding personal goals and preferences will help shape conversations concerning treatment recommendations and engage patients in shared decision making. It is also important to elicit patient preferences for how information is communicated and what level of detail is suitable. Along with a foundational understanding, treatment goals should be revisited as necessary at future encounters. Patients with advanced PC are frequently monitored with imaging and basic laboratory tests to assess treatment response; they should also be closely examined for impending complications. These may manifest as signs of current or impending biliary obstruction, bowel obstruction, ascites, tumor infiltration into the abdominal neural plexus (celiac axis), or significant portal venous narrowing/ obstruction. In addition, routine assessment of pain, nausea, vomiting, abdominal distension, and cachexia can be helpful. Involvement of palliative care services can often facilitate addressing multiple challenging symptoms.

BILE DUCT OBSTRUCTION Over 70% of patients with PC will present with biliary obstruction leading to jaundice and malabsorption. The response of the patient to hyperbilirubinemia can be quite variable. Some patients have profound pruritus, fatigue, anorexia, and occasionally nausea and vomiting; others are less affected. We do not have an explanation for the variable patient response to biliary obstruction. Durable relief of biliary obstruction is necessary to allow for the delivery of optimal anticancer therapy, and in those with symptomatic pruritis, to relieve this often-disabling symptom. Multiagent system therapy cannot be delivered in the presence of hyperbilirubinemia. In the setting of normal underlying liver function, it normally takes 1 to 3 weeks for the bilirubin to normalize following stent placement. This assumes a bilirubin in the 10 to 20 mg/dL range; higher bilirubin levels may take longer to normalize. Rarely, patients may have profound cholestasis in the absence of a history of liver disease. We see this once or twice per year, and it is manifested by an elevated bilirubin that does not decline despite perfect stent placement. Such patients may take 6 to 10 weeks for the bilirubin to normalize. Waiting this long to begin systemic therapy is rather unappealing, and proceeding to surgery incurs unnecessary risk. If the patient has an operable tumor, we would typically proceed with 5-fluorouracil (5FU)-based chemoradiation directed at the primary tumor and regional lymph nodes; infusional 5FU can be safely delivered in the setting of hyperbilirubinemia. We would then plan to use postoperative adjuvant systemic therapy based on the molecular profiling of the primary tumor. An immediate surgical approach to the patient who fails to experience a decline in bilirubin following stent placement is usually ill-advised and reflects a combination of surgeon inexperience and impatience of the multidisciplinary team. With regard to biliary stents, several series have demonstrated that ERCP can be safely and effectively performed in the vast majority of patients with malignant obstructive jaundice. Early



complications after ERCP occur in 5% of patients when performed by experienced subspecialty gastroenterologists and most commonly include ERCP-induced pancreatitis, bleeding or, rarely, duodenal perforation; hence the importance of high-quality cross-sectional imaging before ERCP. Self-expanding metal stents (SEMS) are clearly superior to plastic stents with respect to stent patency and stent-related complications. Because of the smaller lumen, plastic biliary stents are more likely to occlude from biliary sludge or bacterial overgrowth and often require more frequent stent exchange, whereas SEMS are susceptible to tumor in-growth within the interstices of the stent in some patients. Covered SEMS avoid the complication of tumor in-growth but are prone to stent migration and can cause cystic duct obstruction. In the patient who still has a gallbladder in place, we favor an uncovered metal stent as a covered stent is more likely to be associated with stent-associated cholecystitis due to obstruction of the cystic duct.

Our Guiding Principles for the Management of Bile Duct Obstruction 1. High-quality cross-sectional imaging should always be performed before ERCP or EUS. 2. On-site cytopathology should be performed at the time of EUSFNA; if the diagnosis of adenocarcinoma is established on immediate slide review, a SEMS (usually uncovered) can be placed while the patient remains sedated. If the diagnosis is unclear (pending review of the cell block made from the sample placed in formalin), then a plastic stent or occasionally a covered SEMS (if the gallbladder is no longer present) is placed. 3. If the ERCP is unsuccessful, there are three options: a surgery-first approach, a rendezvous procedure (placement of a transhepatic wire through the ampulla to guide endoscopic stent placement by the gastroenterologist), or placement of a percutaneous transhepatic catheter (PTC) by Interventional Radiology. We consider a surgery-first approach in patients with localized periampullary (duodenal or ampullary in origin) and a bilirubin level less than 15 to 16 mg/dL. We prefer a rendezvous procedure in all patients with operable PC where neoadjuvant therapy is favored. Transhepatic catheters are reasonable in patients with locally advanced or metastatic disease where cure is not possible. This is because the bile is contaminated with tumor cells in at least one-third of patients with malignant bile duct obstruction, and tumor recurrence can occur at the skin/dermis where the PTC enters the patient to traverse the liver. 4. If a SEMS is placed and the bilirubin fails to decline, we usually repeat the CT scan and the ERCP once to ensure optimal stent placement. If the patient has an operable tumor, we transition to 5FU-based chemoradiation by week 3 or 4 if the bilirubin has not made a significant downward trend. As a general rule, we make our decision with regard to treatment sequencing once staging is complete, and we assume the bilirubin (if elevated) will decline over 2 weeks following stent placement. We typically have initiated systemic therapy within 3 weeks of initial presentation in most all patients with newly diagnosed PC. If by week 3, after stent placement, there is no significant downward trend in bilirubin, and we are sure that the stent is in optimal position and fully expanded, then we will proceed (by week 4) with 5FU-based chemoradiation in those patients with operable tumors. If the patient has advanced disease and the bilirubin is slow to decline, options are limited; 5FU alone may have little benefit over best supportive care. Ursodiol and other supportive measures are initiated as soon as it is apparent that we are dealing with a cholestatic liver. 5. If the patient develops stent-associated cholecystitis, optimal treatment is a percutaneous transhepatic cholecystostomy tube (see selected reference); this will not delay ongoing systemic therapy or chemoradiation—or at least cause a minimal delay—and is favored over laparoscopic or open cholecystectomy.

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Operative biliary bypass is an alternative strategy to allow for drainage of an obstructed biliary tree. In patients with locally advanced and metastatic pancreatic or periampullary cancer, they are now, in some cases, outliving the patency of even SEMS—due to the improved response rates seen with available systemic therapies. In such patients, there are two options when metal stents become occluded: an operative bypass or placement of a PTC. For patients of reasonable performance status where ongoing systemic therapy is planned, we would normally proceed with an operative biliary bypass if technically feasible. For those in whom a strategy of best supportive care is planned, a PTC may be the best option. It is usually a mistake to persist with endoscopic attempts at clearing a SEMS once repetitive occlusions have begun to occur. There are several techniques that may be utilized for a biliary bypass. The most common, and durable, technique is a retrocolic choledocho/ hepatico-jejunostomy with a Roux-en-Y reconstruction. If a patient has not had a prior cholecystectomy, a cholecystectomy should be performed in addition to the biliary drainage procedure, even in the absence of cholelithiasis or symptoms. Rarely, tumors of the uncinate process may grow into the root of the small bowel mesentery and result in mesenteric foreshortening, making creation of a Roux limb impossible. Importantly, the increased durability of a hepaticojejunostomy must be weighed against the potential for perioperative morbidity, especially in patients with advanced cancer. Operative palliative procedures in patients with advanced cancer must be done with limited morbidity and zero mortality; this is not the time to take unnecessary risk.

GASTRIC OUTLET (DUODENAL) OBSTRUCTION Nausea and vomiting in patients with advanced PC can be due to mechanical and/or nonmechanical problems. An initial evaluation should include a thorough history and physical followed by radiographic studies to identify obstruction related either to the primary tumor (duodenal obstruction) or a metastatic deposit (malignant small or large bowel obstruction). In the absence of a mechanical etiology, the symptoms may be related to malignant gastroparesis or chemotherapy-associated nausea and are best treated with pharmacologic agents. Suspicion for a mechanical obstruction can be supported by the presence of a dilated stomach on CT scan, and may be confirmed by an upper gastrointestinal fluoroscopy or endoscopy when necessary. Obstruction of the duodenum due to a malignant tumor of pancreatic, periampullary, or duodenal origin can be treated with either an endoscopic stent or an operative bypass. Duodenal stenting has become a well-established technique to treat malignant gastric outlet obstruction. A SEMS can be endoscopically placed across a malignant stricture or area of narrowing. When successfully placed, approximately 90% of patients can tolerate a soft or somewhat regular diet and adequately hydrate and aliment themselves. Reintervention for tumor infiltration into the uncovered stent can often be managed with the placement of an additional covered SEMS within the existing uncovered stent. If there is associated jaundice, biliary stenting should be performed before duodenal stent placement, as placement of a biliary stent after placement of a duodenal stent is technically difficult. The decision to perform duodenal stenting or surgical gastrojejunostomy depends on the expected survival of the patients as well as the plans for eventual surgery as the presence of a duodenal stent makes the operation of pancreaticoduodenectomy more difficult. Gastrojejunostomy can be performed via an open or laparoscopic approach. Classically, a retrocolic gastrojejunostomy was performed by sewing the posterior wall of the distal stomach to a loop of proximal jejunum in a stapled or hand-sewn, side-to-side fashion. Studies comparing the efficacy of laparoscopic compared with open gastrojejunostomy are limited; however, a laparoscopic approach allows for the more rapid administration of anticancer therapy.

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Our Guiding Principles for the Management of Duodenal Obstruction with and without Bile Duct Obstruction 1. If the patient has an operable pancreatic, periampullary, or duodenal tumor and neoadjuvant therapy is planned, we favor a laparoscopic/robotic gastrojejunostomy. 2. If the patient has advanced disease, a duodenal SEMS can be placed as an outpatient procedure or with a brief hospital admission and may be the preferred approach. 3. In the setting of combined duodenal and distal bile duct obstruction, we would, in general, favor placement of a PTC for relief of biliary obstruction followed by a laparoscopic gastrojejunostomy. We accept the risk for tumor implantation, at the site of the PTC, in this complicated situation. Placement of a duodenal stent or simply a venting gastrostomy tube may be most appropriate in patients with advanced disease. In rare patients with an isolated duodenal or periampullary cancer strategically located in D2, and associated with biliary and duodenal obstruction, there may be a role for a surgery-first approach. 4. In patients with operable disease where neoadjuvant therapy is preferred, the goal of palliative biliary and gastric decompression is to normalize the bilirubin to allow for systemic therapy and provide a durable means of enteral nutrition—so that systemic therapy or chemoradiation can be initiated as soon as possible. As mentioned, placement of a duodenal stent will make a subsequent operation more difficult; therefore, we prefer a PTC and a laparoscopic gastrojejunostomy. As neoadjuvant therapy has become more common for patients with pancreatic and periampullary cancer, accurate staging has taken a back seat to the initiation of systemic therapy, as virtually all stages of disease are now receiving systemic therapy first. This is both good news and bad: good, in that patients with PC are receiving systemic therapy without delay; and bad, in that accurate staging is often not performed other than differentiating localized from metastatic disease. Patients who have either a bile duct or duodenal obstruction often are endoscopically stented—usually a routine procedure for those with bile duct obstruction, but sometimes a mistake in patients with isolated duodenal obstruction who may be candidates for a pancreaticoduodenectomy in the future. For patients with combined bile duct and duodenal obstruction, they are often managed with an attempt at both biliary and duodenal SEMS. In our opinion, this is a mistake for those with potentially operable disease. The involvement of the surgical oncologist in the initial care of the patient with newly diagnosed pancreatic, periampullary, or duodenal cancer cannot be overemphasized. Patients with duodenal obstruction and those with combined bile duct and duodenal obstruction are among the most complicated patients who require multidisciplinary review to select the best form of palliation, which will greatly affect the ability of the patient to receive optimal treatment sequencing (chemotherapy, radiation, and surgery).

OPEN PROPHYLACTIC BILIARY AND GASTRIC BYPASS As previously mentioned, palliative therapy implies that the patient is suffering from active symptoms. However, at times, palliative care decisions are made to prevent future complications in asymptomatic patients. The classic example of this is when patients, thought to have operable periampullary cancer, are discovered at the time of laparotomy to have unresectable or metastatic disease. This should be a very uncommon event as diagnostic laparoscopy is performed at the time of planned pancreaticoduodenectomy in virtually all patients taken to surgery in an effort to find radiographically occult extrapancreatic metastatic disease and thereby avoid laparotomy. Similarly, in 2022, the preoperative radiographic assessment of local tumor resectability is highly accurate; therefore, unresectability for local tumor-vessel

reasons should be a very rare event. That said, if one is found with an open abdomen at the time of laparotomy for planned pancreaticoduodenectomy, and the patient has either very low volume metastatic or locally unresectable disease, we would proceed with an operative biliary bypass for those patients with a bile duct stent in place. There is nothing worse than having to deal with recurrent biliary stent occlusion in a patient who has had a laparotomy for PC but did not receive a biliary bypass; this is an avoidable situation. The decision to also perform a gastrojejunostomy is made based on the extent of duodenal involvement and the presence or absence of liver or peritoneal disease. Peritoneal carcinomatosis is a particularly challenging pattern of failure and often the least responsive to systemic therapy. We, therefore, would consider a gastrojejunostomy in this setting only if the patient was symptomatic or there was clear anatomic evidence of impending duodenal obstruction. Before the advent of accurate preoperative cross-sectional imaging and routine diagnostic laparoscopy, the finding of advanced local or distant disease was a somewhat common event in patients with PC resulting in a significant body of literature on this topic. In frequently quoted randomized trials, patients with PC who underwent laparotomy for intended resection and were found to be unresectable at the time of operation were randomized to receive prophylactic hepaticojejunostomy or prophylactic hepaticojejunostomy with gastrojejunostomy. In those who received both a hepaticojejunostomy and a prophylactic gastrojejunostomy, no patient developed subsequent symptoms of gastric outlet obstruction before death. In contrast, of the patients who did not receive a gastrojejunostomy, symptoms of gastric outlet obstruction requiring intervention developed in 19% to 41%. Neither study identified increased morbidity, mortality, or differences in overall survival between the two surgical intervention arms. This early experience supported the routine use of double bypass at the time of a nontherapeutic laparotomy for patients with PC. Although concomitant prophylactic gastric and biliary bypass at the time of nontherapeutic laparotomy has been the standard practice for many years, unresectability at the time of laparotomy is now a rare event. Therefore, many residents and even surgical oncology/HPB fellows have little experience with open operative double bypass. Our preferred approach is a retrocolic hepaticojejunostomy created with a Roux-en-Y limb. We usually create a defect in the transverse mesocolon to the patient’s right of the middle colic artery; if this space cannot be easily developed, we make the defect to the left of the middle colic vessels. We remove the gallbladder if it is in place and divide the hepatic duct at the superior border of the indwelling metal stent. Usually, the metal stent cannot be removed. We close the distal bile duct, always culture the bile (as the bacteria contained herein are usually the same ones responsible for any subsequent infections), and create an end-to-side hepaticojejunostomy with interrupted monofilament absorbable suture. We typically have the knots on the inside for the back row and the knots on the outside for the anterior row. Intestinal continuity is restored approximately 40 to 50 cm downstream (caudal to the transverse mesocolon) with creation of a jejunojejunostomy. If a gastrojejunostomy is also performed, we use the proximal jejunum, just distal to the ligament of Treitz, and proximal to the jejunojejunostomy. We typically create the Roux limb for the biliary anastomosis a generous distance (60–70 cm) from the ligament of Treitz. This form of double bypass has the advantage of diverting the bile from the stomach, thereby avoiding the complication of alkaline reflux gastritis. For the gastrojejunostomy, we create a separate defect in the transverse colon mesentery to the left of the middle colic artery. If there was inadequate room for the Roux limb to the right of the middle colic vessels, both the biliary limb and the proximal jejunum for the gastrojejunostomy can go through the same large defect in the transverse mesocolon to the left of the middle colic vessels. We favor a hand-sewn two-layer gastrojejunostomy fashioned to the posterior aspect of the distal stomach. The only risk of a gastrojejunostomy performed in this fashion is what we refer to as “cycling”; namely, the gastric contents can exit the stomach into the

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duodenum (in the absence of tumor-associated obstruction at that time), then reenter the stomach at the site of the gastrojejunostomy, and continue in this circle, not exiting the gastrojejunostomy. This is a very rare complication and more common in patients where there is no significant narrowing of the duodenum.

Our Guiding Principles for the Management of Biliary and Duodenal Obstruction at the Time of Open Laparotomy 1. We virtually always perform a Roux-en-Y hepaticojejunostomy if we have an open abdomen and an unresectable situation due to locally advanced or distant metastatic disease. 2. We have a very low threshold to also perform a prophylactic gastrojejunostomy at the time of biliary bypass. We favor a retrocolic gastrojejunostomy performed proximal to the jejunojejunostomy.

PALLIATIVE PANCREATICODUODENECTOMY A small volume of literature exists describing the benefits of palliative resection for patients with PC and much of this is confusing due to the incorrect use of the term “palliative”. As previously mentioned, “palliative” refers to the relief of symptoms. It is incorrect to refer to an intervention (surgery or any other interventional procedure) as palliative simply because the entire tumor was not resected. For example, an incomplete resection at the time of pancreaticoduodenectomy (R1 or R2 resection) is often referred to as a palliative resection—this is an incorrect use of the term. We have performed just a handful of what we would consider to be a palliative pancreaticoduodenectomy. In such situations, we have typically had a patient with locally advanced or low volume metastatic disease who either experiences an endoscopic complication (perforation) or experiences uncontrolled hemorrhage due to tumor-induced ingrowth into the duodenum. These are often sudden, unexpected events and occur at the most inopportune times. Options may be very limited, and in the absence of best supportive care and pain control (end of life support), surgery may be the only option. We have encountered such situations approximately once every 5 years or so. In such situations, we have removed the duodenum and simply closed the pancreas, combined with a biliary and gastric anastomosis; an unattractive operation but one that allows time to discuss treatment and end of life goals with the patient and family.

MALIGNANT BOWEL OBSTRUCTION Malignant bowel obstruction due to peritoneal carcinomatosis is an ominous complication in patients with PC and one without a good solution. These patients often suffer from severe, debilitating malnutrition and cancer cachexia that can be further exacerbated by malignant ascites. Malignant ascites essentially eliminates surgery as an option for almost any reason, as postoperative ascites usually becomes much worse than before the operation, and wound dehiscence is of significant risk. Relief of nausea and vomiting may require gastric decompression with a nasogastric tube in the acute setting and a venting gastrostomy tube for home management. In very select patients who have no ascites and very low volume disease, an operative exploration and surgical bypass may be considered. We have performed fewer than five or six such operations over the past decade, and they are rarely successful when the underlying cause is carcinomatosis due to PC. Adequate pain control with opioids is critically important, either by the intravenous or subcutaneous route, and can be transitioned to equivalent transdermal doses when the patient has a stable opioid requirement. Antisecretory agents may reduce splanchnic blood flow, intestinal secretions, and cramping abdominal pain; the somatostatin analogue octreotide has been effective for palliation in prospective trials. In addition, haloperidol is effective in relieving nausea and vomiting in patients with malignant bowel obstruction. In the authors’ opinion, it is imperative

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to engage a palliative care specialist for these patients to aid in the transition to comfort care.

MALIGNANT ASCITES Malignant ascites can lead to debilitating abdominal distension and early satiety. Ascites in the patient with PC is usually due to carcinomatosis; cytology may or may not be positive. In patients who have undergone a prior pancreaticoduodenectomy, occlusion of the superior mesenteric or portal vein may result in venous hypertension in the midgut and also cause intractable ascites. This cause of ascites is very rare in the absence of a prior operation. When occlusion of the superior mesenteric vein (SMV) or portal vein occurs over a long period of time, as is the case with locally advanced tumors of the pancreatic head or uncinate process, collaterals develop around the pancreatic head, thereby preventing mesenteric venous hypertension in almost all patients. When the pancreatic head has been removed (pancreaticoduodenectomy), such collaterals cannot develop; therefore, an occasional patient has developed either ascites or gastrointestinal hemorrhage due to mesenteric venous hypertension in the mid-gut. Extrahepatic portal hypertension of this etiology can be treated with a mesocaval bypass, and we have performed this operation in selected situations (see Suggested Readings). For patients with malignant ascites, therapeutic paracentesis relieves symptoms, but continued fluid loss will, in general, hasten the demise of the patient. Plasma expanders, such as albumin, have been effective in preventing circulatory collapse and should be used with high volume paracenteses. In patients with an anticipated survival of less than 3 or 4 months, the placement of an indwelling pigtail or tunneled catheter to control ascites, with drainage at home, can be useful. In selected patients, we have also used a peritoneal-venous (Denver) shunt that diverts the ascites into the right internal jugular vein and the systemic venous system. This can be quite effective in some patients; however, catheter occlusion due to build-up of proteinaceous debris is somewhat common.

VASCULAR THROMBOSIS The incidence of thromboembolic disease in patients with PC is higher than other metastatic cancers and ranges from 10% to 20% in clinical trials and as high as 50% in autopsy series. Thrombosis can occur in the mesenteric veins due to tumor compression or in the peripheral veins due to the overall hypercoagulable state. Narrowing or thrombus within the SMV or portal vein should be treated with anticoagulation therapy whenever possible to prevent propagation of the thrombus to complete occlusion; this is especially important in patients who are receiving neoadjuvant therapy and have an option for surgical resection with vascular reconstruction. An acute thrombus in the mesenteric venous system, splenic vein, or other extraabdominal sites is typically treated with enoxaparin at therapeutic doses. In patients with tumors in the pancreatic head or uncinate process where there is any degree of narrowing of the SMV or portal vein, we prefer at least half-dose therapy, usually with a direct oral anticoagulant (rivoraxaban if there is a biliary stent in place and apixaban if there is no risk for hyperbilirubinemia and liver dysfunction). If mesenteric venous thrombosis occurs during neoadjuvant therapy, it can convert an operable situation into an inoperable one. This is a rare complication, but when it occurs, it is devastating for the patient and their family. Overall, we feel that anticoagulation of some kind is underutilized in patients with PC who are receiving active anticancer therapies.

TUMOR-ASSOCIATED PAIN MANAGEMENT Patients with unresectable PC often suffer from tumor-associated abdominal and back pain due to direct tumor infiltration of the celiac ganglion. Effective pain management often requires opioid analgesia,

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which can have debilitating side effects, including dizziness and sedation. More recently, the trend in pain management has been to optimize pain control with the lowest dose of opioids in combination with other adjunct analgesics to provide effective and consistent pain control. Celiac plexus block has become increasingly utilized in the treatment of PC-related pain symptoms. A celiac plexus block involves injecting a 50% alcohol solution or other neurolytic agent into the celiac ganglion or splanchnic nerves under CT, EUS, or fluoroscopic guidance. In the event a patient undergoes a nontherapeutic laparotomy, a celiac plexus block may also be performed at that time. Over 80% of patients experience improvement in pain control after a celiac plexus block in blinded or sham studies, as measured by reduction of opioid requirements. Studies have demonstrated improved pain scores at 4 and 8 weeks with a celiac plexus block compared with narcotic therapy alone; a meta-analysis of patients who received a celiac plexus block demonstrated pain relief in 90% at 3 months, and relief persisted long-term in 70% to 90% of patients. Short-term effects related to celiac plexus block include diarrhea, hypotension, and pain related to the procedure, which typically resolve with time. In fact, the presence of diarrhea associated with the performance of the block is one way to be sure that the block was placed in the correct location. For patients with potentially operable PC, we avoid celiac blocks for two reasons: first, the improvement/resolution of a patient’s pain is a useful clinical parameter for assessment of response to chemotherapy; and second, dissection of the celiac and SMA origins can be more difficult after a celiac block. For patients with more advanced disease, celiac plexus block should be considered in the initial pain management plan and may be repeated in patients who demonstrated a prior benefit from neurolysis.

DEPRESSION The rates of depression and suicide among patients with PC are the highest in any cancer population. Elevated levels of circulating cytokines such as interleukin-6 and tumor necrosis factor-α are thought to alter neurohormonal pathways in the brain causing depressive symptoms even before the diagnosis of cancer. Studies report that depression occurs in one- to two-thirds of patients and has a significant impact on quality of life. Many symptoms of depression mimic symptoms associated with PC itself (fatigue, anorexia, weight loss), complicating the diagnosis of depression. However, asking a patient whether they have “felt depressed most of the time” is a validated tool with good sensitivity and specificity for identifying depression even among patients who are terminally ill. Antidepressants are effective in patients with advanced cancers, and supportive counseling may help patients to strengthen coping strategies. An early referral to a psychologist or palliative care specialist can be beneficial to all patients regardless of stage of disease; we have incorporated a fulltime psychologist within our multidisciplinary PC program.

CONCLUSION The initial management of bile duct and duodenal obstruction can often facilitate or completely unravel the initial management of the

patient with PC. In this chapter, we have tried to clarify our approach to the palliation of biliary and gastric outlet obstruction based on the stage of disease and goals of therapy. The patient with PC presents a series of complex clinical challenges, which often result in frustration and disappointment on the part of the patient and their family; it is critically important that the same emotions are not present in the treatment team. The multidisciplinary team of physicians, advanced practice providers, and all members of the program need to embrace the complexity of patient management and develop consistent strategies for optimizing patient performance status, liver function, and nutritional support as only then can potentially effective anticancer therapy be considered. As neoadjuvant therapy for operable disease has become more commonly applied to patients with localized PC, especially in the clinical trial setting, the importance of managing bile duct and duodenal obstruction has been brought forward with a clarity not previously appreciated. Healthcare delivery in the United States continues to move in the direction of large integrated systems, involving many hospitals and points of care, providing an opportunity to streamline the initial diagnosis and management of the patient with PC.

S uggested R eadings Chavez MI, Tsai S, Clarke CN, et al. Distal splenorenal and mesocaval shunting at the time of pancreatectomy. Surgery. 2019;165(2):298–306. Jariwalla NR, Khan AH, Dua K, et  al. Management of Acute Cholecystitis during Neoadjuvant Therapy in Patients with Pancreatic Adenocarcinoma. Ann Surg Oncol. 2019;26(13):4515–4521. Kneuertz PJ, Cunningham SC, Cameron JL, et  al. Palliative surgical management of patients with unresectable pancreatic adenocarcinoma: trends and lessons learned from a large, single institution experience. J Gastrointest Surg. 2011;15:1917–1927. Krepline AN, Christians KK, George B, et al. Venous thromboembolism prophylaxis during neoadjuvant therapy for resectable and borderline resectable pancreatic cancer-Is it indicated? J Surg Oncol. 2016;114(5):581–586. Mora J, Krepline AN, Aldakkak M, et al. Adjuvant therapy rates and overall survival in patients with localized pancreatic cancer from high Area Deprivation Index neighborhoods. Am J Surg. 2020;222(1):10–17. Rajamanickam ES, Christians KK, Aldakkak M, et al. Poor Glycemic Control Is Associated with Failure to Complete Neoadjuvant Therapy and Surgery in Patients with Localized Pancreatic Cancer. J Gastrointest Surg. 2016;21(3):496–505. Tsai S, Christians KK, George B, et  al. A Phase II Clinical Trial of Molecular Profiled Neoadjuvant Therapy for Localized Pancreatic Ductal Adenocarcinoma. Ann Surg. 2018;268(4):610–619. Tsai S, Evans DB, eds, Current Management of Pancreatic Cancer. Pawlik, TM ed. Surgical Oncology Clinics of North America 2021; 30; No. 4 Elsevier, Philadelphia Tsai S, Ritch PS, Erickson BA, Evans DB, eds. Management of Localized Pancreatic Cancer: Current Treatment and Challenges. Switzerland: Springer; 2019. Ward EP, Evans DB, Tsai S. Ten-year experience in optimizing neoadjuvant therapy for localized pancreatic cancer-Medical college of Wisconsin perspective. J Surg Oncol. 2021;123(6):1405–1413. Wolff RA, Crane CH, Li D, Evans DB, Maitra A, Tsai S. Neoplasms of the exocrine pancreas. In: Bast RC, Croce CM, Hawk E, Khuri FR, Pollock RE, Tsimberidou AM, Willett C, Willman C, eds. Holland-Frei Cancer Medicine. Tenth Edition Hoboken, NJ: Wiley Blackwell; 2022: in press.

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Neoadjuvant and Adjuvant Therapy for Pancreatic Cancer Lawrence W. Wu, MD, and Daniel A. Laheru, MD

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ancreatic ductal adenocarcinoma is an aggressive malignancy with high mortality. The only possibility of long-term cure involves a complete, microscopically negative (R0) resection. However, there is still high mortality after R0 resection due to recurrence from the presence of radiographically occult micrometastatic disease. As such, chemotherapy is used for all stages of disease, including resectable, borderline resectable, and locally advanced disease. In this chapter, we delineate the most updated stage-specific recommendations.

DEFINING THE CLINICAL STAGE OF DISEASE The American Joint Commission on Cancer staging of pancreatic adenocarcinoma follows the Tumor, Node, Metastasis framework. This staging system can provide valuable prognostic information. However, it is limited in the preoperative setting because it does not indicate whether a tumor is resectable. The National Comprehensive Cancer Network (NCCN) defines resectability as resectable, borderline resectable, locally advanced, and metastatic (Table 1). These criteria are based on the tumor relationship to vascular anatomy and presence of extrapancreatic disease. Pancreatic protocol computed tomography (CT) scan of the abdomen/pelvis is used to assess the tumor, its relationships to critical vasculature, and presence of intraabdominal metastases. Resectable pancreatic cancer (Fig. 1A) is defined by a primary tumor that does not contact any arterial vessel (celiac artery [CA], superior mesenteric artery [SMA], or common hepatic artery [CHA]) and does not contact the superior mesenteric vein (SMV) or portal vein (PV), or contacts the SMV/PV less than 180 degrees without vein contour irregularity. Borderline resectable disease (Fig. 1B) is defined by limited tumor contact less than 180 degrees with the SMA or CA and without involvement of aorta or uninvolved gastroduodenal artery, contact with CHA without extension to CA or hepatic artery bifurcation or contact with the SMV/PV more than 180 degrees, contact less than 180 degrees with contour irregularity of vein, tumor contact with inferior vena cava, or short segment SMV/PV thrombosis amenable to resection and vein reconstruction. Locally advanced disease (Fig. 1C) includes more than 180-degree involvement of the SMA or CA, or extensive involvement of the SMV/PV without proximal and distal targets for vascular reconstruction. Extensive SMA involvement is considered unresectable because of the poor survival and higher morbidity and mortality expected following SMA resection. Unfortunately, the potential presence of radiographically undetectable micrometastases limits this framework. Nonetheless, this staging system is key for determining the next steps of clinical management.

RESECTABLE PANCREATIC CANCER For resectable pancreatic cancer, surgery followed by adjuvant therapy has traditionally been the preferred modality of treatment. A complete surgical excision of the pancreatic cancer is the only opportunity for cure, and an upfront surgery captures the disease at a timepoint when it is in a resectable state. Adjuvant chemotherapy should occur within 8 weeks of surgical resection, assuming

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TABLE 1  Definition of Resectability Status Used by the National Comprehensive Cancer Network (NCCN) RESECTABLE Tumor-artery relationship

No radiographic evidence of arterial contact [celiac artery (CA), superior mesenteric artery (SMA), or common hepatic artery (CHA)].

Tumor-vein relationship

No tumor contact with the superior mesenteric vein (SMV) or portal vein (PV) or ≤180 degrees contact without vein contour irregularity

BORDERLINE RESECTABLE Tumor-artery relationship

Tumor contact ≤180 degrees of SMA or CA. Tumor contact >180 degrees of the CA without involvement of aorta and uninvolved gastroduodenal artery. Tumor contact with CHA without extension to CA or hepatic artery bifurcation. Tumor contact with variant arterial anatomy (e.g., accessory right hepatic artery).

Tumor-vein relationship

Tumor contact of SMV or PV >180 degrees, tumor contact ≤180 degrees with contour irregularity of vein, tumor contact with inferior vena cava, or short segment SMV/PV thrombosis amenable to resection and vein reconstruction.

LOCALLY ADVANCED Tumor-artery relationship

Tumor contact (>180 degrees) of SMA or celiac artery, or contact with CA and aortic involvement.

Tumor-vein relationship

Occlusion of SMV, PV, or SMV-PV without suitable vessels above and below the tumor to allow for reconstruction (no distal or proximal target for vascular reconstruction).

adequate recovery from the procedure. Before adjuvant therapy, a formal restaging CT scan and serum CA 19-9 should be performed. Per NCCN, the preferred adjuvant therapies are modified FOLFIRINOX (oxaliplatin, irinotecan, leucovorin and short-term fluorouracil) or gemcitabine plus capecitabine. Modified FOLFIRINOX should be limited to those with ECOG 0-1, and thus gemcitabine plus capecitabine may be more suitable for patients with lower performance status. In the PRODIGE-24/CCTG PA-6 trial, patients who underwent R0 or R1 resection and with ECOG performance status 0 or 1 had improved survival with adjuvant modified FOLFIRINOX over adjuvant gemcitabine alone (21.6 months vs. 12.8 months, hazard ratio 0.58, 95% CI 0.46–0.73). In the ESPAC-4 trial, patients who underwent R0 or R1 resection had improved survival with adjuvant gemcitabine plus capecitabine over adjuvant gemcitabine alone (28.0 months vs. 25.5 months, hazard ratio 0.82, 95% CI 0.68–0.98). There

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are no trials directly comparing modified FOLFIRINOX or FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin) versus gemcitabine plus capecitabine. In the 5-year update for the APACT trial, patients who underwent R0 or R1 resection with ECOG performance status 0 or 1 had improved survival with adjuvant gemcitabine plus nanoparticle albumin-bound (nab)-paclitaxel over adjuvant gemcitabine alone (41.8 months vs. 37.7 months, hazard ratio 0.80, 95% CI 0.68–0.95). The full trial results have not been published yet and are not reflected in any of the major treatment guidelines. Gemcitabine alone may be considered for patients with poorer performance status who may not tolerate multiagent therapy, but this comes at increased risk for recurrence. The role for adjuvant radiation is controversial. In the ESPAC-1 trial, patients who underwent R0 resection were randomized to observation, chemotherapy with fluorouracil and leucovorin, chemoradiotherapy with 20-Gy in 10 daily fractions and fluorouracil, or chemoradiotherapy followed by chemotherapy. There was worse survival in patients treated with any chemoradiotherapy compared with those not treated with any chemoradiotherapy (15.9 months vs. 17.9 months, hazard ratio 1.28, 95% CI 0.99–1.66). The EORTC 4001322012/FFCD-9203/ GERCOR Phase II study found chemoradiation (gemcitabine + 50.4 Gy in 28 fractions for 5–6 weeks) decreased local recurrence (11% vs. 24%) compared with chemotherapy with gemcitabine alone. However, disease-free survival and overall survival were not statistically different. The role of neoadjuvant chemotherapy as an alternative to immediate surgery followed by adjuvant chemotherapy is controversial. Delaying immediate surgery during a resectable phase of the disease creates a risk of progression where the tumor becomes inoperable. The neoadjuvant chemotherapy treatment route requires tissue biopsy, which is another procedure that may result in morbidity. Biliary stenting is another procedure that may occur in the interim

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FIG. 1  Clinical staging is based on tumor-vessel contact. Contrastenhanced, axial CT images showing tumor (yellow arrow), superior mesenteric vein (blue arrowhead), and superior mesenteric artery (red arrow). (A) Resectable pancreatic cancer (PC). Hypodense tumor is present in the pancreatic head with preservation of the fat plane between the pancreas and the superior mesenteric vein (SMV) and without tumor abutment of the superior mesenteric artery (SMA). (B) Borderline resectable PC. Note the hypodense tumor that abuts both the SMV and the SMA. (C), Locally advanced PC. The hypodense tumor encases (>180 degrees) the SMA.

period between neoadjuvant therapy and surgery that results in additional morbidity. The benefits of neoadjuvant chemotherapy are likely highest in high-risk, potentially resectable tumors (i.e., highly elevated CA 19-9 >200, large primary tumors, large regional lymph nodes). The benefits of neoadjuvant therapy include (1) the early treatment of micrometastatic disease, which is common and can lead to early postoperative recurrences; (2) enhanced patient selection (patients who do not tolerate neoadjuvant therapy would not benefit from a major resection; disease progression on neoadjuvant therapy indicates more aggressive disease characteristics); (3) improved delivery and completion rates; (4) decreased rate of pancreatic fistula formation; and (5) enhanced efficacy of chemoradiotherapy (given the well-oxygenated environment), with corresponding higher negative margin resection and lymph node-negative rates (Box 1). The PREOPANC trial randomized patients with borderline resectable or potentially resectable pancreatic cancer (approximately 50% each) to neoadjuvant chemoradiotherapy with gemcitabine or to immediate surgery followed by adjuvant gemcitabine. R0 resection rate was significantly higher with neoadjuvant therapy (71% vs. 40%). There was increased but not statistically significant improvement in median survival with neoadjuvant therapy versus immediate surgery (16 months vs. 14.3 months, hazard ratio 0.78, 95% CI 0.58–1.05). Neoadjuvant therapy was associated with higher rates of serious (grade 3 or higher) adverse events compared with immediate surgery (52% vs. 41%). The phase II PACT-15 trial randomized patients with resectable pancreatic cancer to immediate surgery followed by 6 months of adjuvant gemcitabine; immediate surgery followed by 6 months of adjuvant cisplatin, epirubicin, gemcitabine, and capecitabine (PEGX); or three cycles of neoadjuvant PEGX before surgery and three cycles of adjuvant PEGX. The median overall survival was 38.2 months for the neoadjuvant PEGX group compared with 20.4

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BOX 1  Potential Advantages and Disadvantages of Neoadjuvant Therapy Advantages • Ability to deliver systemic therapy to all patients • Identification of patients with aggressive tumor biology (manifested as disease progression) at the time of posttreatment and preoperative restaging who thereby avoid the toxicity of surgery • Increased efficacy of radiation therapy; free radical production in a well-oxygenated environment • Decreased radiation-induced toxicity to adjacent normal tissue because the radiated field is resected at the time of pancreatectomy • Decreased rate of positive resection margins; superior mesenteric artery margin in particular • Decreased rate of pancreatic fistula formation • Potential for the tumor size to decrease, especially in borderline resectable tumors, which may facilitate surgical resection Disadvantages • Potential for complications from pretreatment endoscopic procedures (endoscopic ultrasound scan and fine-needle aspiration, and endoscopic retrograde cholangiopancreatography) • Biliary stent–related morbidity; stent occlusion during neoadjuvant therapy • Disease progression obviating resectability; loss of a window of resectability may occur (rarely) in the borderline resectable patient • Coordination of multiple physicians during the preoperative phase; discrete handoff from surgeon to medical oncologist to radiation oncologist (as occurs with adjuvant therapy) is not possible in the neoadjuvant setting

months with adjuvant gemcitabine or 26.4 months with adjuvant PEGX. A phase III trial was not pursued, because the standard of care for adjuvant therapy had changed. The preferred neoadjuvant chemotherapy is modified FOLFIRINOX followed by chemoradiotherapy, which is based on evidence primarily from the borderline resectable pancreatic cancer patient population. All patients with resectable pancreatic cancer should receive chemotherapy. The current evidence supports immediate surgery followed by adjuvant chemotherapy for a total of 6 months. However, if there are high-risk tumor features, it is reasonable to consider neoadjuvant therapy as the patient may have borderline resectable pancreatic cancer.

BORDERLINE RESECTABLE PANCREATIC CANCER The goal of surgery in pancreatic cancer is to have a R0 resection, which is the only outcome that has a possibility of long-term cure. Patients with borderline resectable disease are at higher risk for incomplete resection, which portends a similar survival rate to those who did not undergo any surgery. Neoadjuvant chemotherapy should be utilized in most cases to improve the chance of an R0 resection. The preferred regimens are FOLFIRINOX, modified FOLFIRINOX followed by chemoradiation if ECOG 0-1, or gemcitabine plus nab-paclitaxel followed by chemoradiation. For patients with known germline or tumor BRCA1/2 or PALB2 mutations, then the preferred regimens are FOLFIRINOX, modified FOLFIRINOX followed by chemoradiation if ECOG 0-1, or gemcitabine and cisplatin followed by chemoradiation. The rationale behind the different chemotherapy is due to increased evidence of increased sensitivity

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to platinum agents as these mutations are in genes necessary for homologous recombination repair (HRR), which repairs DNA damage. Other related HRR genes include ATM, BAP1, BARD1, BLM, BRIP1, CHEK2, FAM175A, FANCA, FANCC, NBN, RAD50, RAD51, RAD51C, and RTEL1. The rationale behind these chemotherapy regimens in the borderline resectable and locally advanced setting stems from survival benefit shown in large phase III studies for metastatic pancreatic cancer. The MPACT trial randomized patients with metastatic pancreatic cancer to gemcitabine and nab-paclitaxel versus gemcitabine alone. There was improved survival in the gemcitabine and nab-paclitaxel group (8.5 months vs. 6.7 months, hazard ratio 0.72, 95% CI 0.62–0.83). This survival benefit comes with increased neutropenia (38% vs. 27%) and peripheral neuropathy (17% vs. 1%). The PRODIGE4/ACCORD11 trial randomized patients with metastatic pancreatic cancer to FOLFIRINOX versus gemcitabine. There was improved survival in the FOLFIRINOX group (11.1 months vs. 6.8 months, hazard ratio 0.57, 95% CI 0.45–0.73). This survival benefit comes with increased neutropenia (45.7% vs. 21%) and peripheral neuropathy (9% vs. 0%). The PREOPANC trial as mentioned previously found significantly higher R0 resection with neoadjuvant chemoradiotherapy therapy compared with immediate surgery (71% vs. 40%). However, survival benefit was not statistically significant (16 months vs. 14.3 months, hazard ratio 0.78, 95% CI 0.58–1.05). The ESPAC-5F trial randomized for patients with borderline resectable cancer to immediate surgery, neoadjuvant gemcitabine plus capecitabine, neoadjuvant FOLFIRINOX, or chemoradiotherapy with capecitabine. The preliminary report found 1-year survival rate higher in neoadjuvant therapy compared with immediate surgery (77% vs. 42%). The R0 resection rate was 23% vs. 15% for neoadjuvant therapy compared with immediate surgery. The data with regard to adding radiotherapy to neoadjuvant chemotherapy is mixed. The Phase II Study of Preoperative FOLFIRINOX Followed by Accelerated Short Course Radiation Therapy for Borderline-Resectable Pancreatic Cancer selected patients with borderline resectable cancer and ECOG 0-1 to be treated with eight cycles of neoadjuvant FOLFIRINOX. After restaging imaging, patients with resolution of vascular involvement were treated with short-course chemoradiotherapy with capecitabine, and those with persistent vascular involvement were treated with long-course chemoradiotherapy with fluorouracil or capecitabine. Ultimately, 27 patients (56%) had short-course chemoradiotherapy and 17 patients (35%) had long-course radiotherapy. R0 resection was obtained in 31 study patients (65%) and obtained in 97% of the patients who underwent resection. The median overall survival of all patients was 37.7 months. The Alliance A021501 trial randomized patients with borderline resectable cancer and ECOG 0-1 to neoadjuvant modified FOLFIRINOX with radiotherapy or to neoadjuvant modified FOLFIRINOX alone. Preliminary results from the trial found the R0 resection rate was greater in the neoadjuvant chemotherapy alone group compared with neoadjuvant chemoradiation (42% vs. 25%). The median overall survival was also greater in the neoadjuvant chemotherapy alone group compared with neoadjuvant chemoradiation (31 months vs. 17.1 months). Neoadjuvant chemotherapy remains the best option to improve the likelihood of a R0 resection. FOLFIRINOX or modified FOLFIRINOX are the most promising chemotherapy options for those who can tolerate it. The exact timing and duration of neoadjuvant chemotherapy and the benefit of radiotherapy are being studied in several ongoing trials and will help optimize treatment for this stage of pancreatic cancer.

LOCALLY ADVANCED PANCREATIC CANCER Locally advanced pancreatic cancer is nonmetastatic but unresectable due to the tumor’s location relative to critical local vasculature.

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The goal is to potentially obtain a R0 resection given its curative potential. Several studies have shown that intensive chemotherapies may result in downstaging of the tumor for resection in a small proportion of patients. The preferred chemotherapy regimens are the same as in borderline resectable pancreatic cancer, which are FOLFIRINOX, modified FOLFIRINOX if ECOG 0-1, or gemcitabine plus nab-paclitaxel. For patients with known germline or tumor BRCA1/2 or PALB2 mutations, then the preferred regimens are FOLFIRINOX, modified FOLFIRINOX if ECOG 0-1, or gemcitabine plus cisplatin. The NEOLAP trial randomized patients with localized pancreatic cancer to induction gemcitabine plus nab-paclitaxel followed by gemcitabine plus nab-paclitaxel versus induction gemcitabine plus nab-paclitaxel followed by FOLFIRINOX. Median overall survival was statistically unchanged (18.5 months vs. 20.7 months), and R0 resection rate was not statistically different. However, the overall conversion rate to surgical resection was 32%. This was the first clinical trial that required explorative laparotomy in all patients without radiographic evidence of disease progression, which may have also contributed to high surgical conversion rates. The LAPACT trial was a single-arm trial with patients with locally advanced pancreatic cancer who were treated with induction chemotherapy gemcitabine plus nab-paclitaxel followed by investigator’s choice of continued chemotherapy, chemoradiation, or surgery. Of the patients in the study, 15% underwent surgical resection (7% R0, 8% R1 resection) demonstrating some feasibility of downstaging. For patients with poor performance status with ECOG ≥2, single-agent gemcitabine is a reasonable alternative. The role of radiotherapy is controversial, and clinical trials have found no survival benefit to initial neoadjuvant chemoradiotherapy versus initial neoadjuvant chemotherapy alone. There may be a role for chemoradiotherapy after initial chemotherapy. Several single center institutional retrospective studies have found improved resection rates and modest survival benefits, but this has not borne out in randomized trials yet. The LAP07 trial randomized patients with locally advanced pancreatic cancer at two different points. First, the patients were randomized to neoadjuvant gemcitabine versus neoadjuvant gemcitabine and erlotinib. The patients were randomized again to the same chemotherapy or chemoradiotherapy if they had 4 months of progression-free survival. Chemoradiotherapy was associated with decreased locoregional tumor progression (32% vs. 46%). However,

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there was no statistically different survival between chemotherapy versus chemoradiotherapy (16.5 months vs. 15.2 months, hazard ratio 1.03, 95% CI 0.79–1.34). If a patient has good performance status with a significant radiographic response and stable or decreasing CA19-9, then surgery should be strongly considered if the patient meets resectability criteria.

CONCLUSION AND FUTURE DIRECTIONS The paradigm of treatment for pancreatic cancer has evolved significantly. One integrated approach based on the most recent evidence and guidelines is summarized in Figure 2 and Table 2. There are several ongoing clinical trials aimed at addressing several of the questions posed earlier in the chapter. These include neoadjuvant chemotherapy for resectable pancreatic cancer, the optimal adjuvant and neoadjuvant therapies, and the role of radiation therapy. The only possibility of a long-term cure for pancreatic adenocarcinoma involves an R0 resection. Even with an R0 resection, the overall survival rates are quite poor given relatively high risk of recurrence and presence of micrometastatic disease. There is ongoing development of novel therapeutics for systemic disease, which has resulted in significant research in systemic therapies targeting multiple mechanisms including angiogenesis, receptor tyrosine kinases, and insulin-growth-factor-1. However, these therapies have largely been unsuccessful. Besides the FOLFIRINOX and gemcitabine regimens mentioned previously, there have been a few other promising regimens in a limited set of circumstances. Immunotherapy with pembrolizumab should be considered if the patient’s tumor is microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR). Poly(ADP-ribose) polymerase (PARP) inhibitors such as olaparib should be considered in patients with germline BRCA1/2 or PALB2 mutations. Neurotrophic tyrosine receptor kinase (NTRK) inhibitors such as larotrectinib or entrectinib should be considered if the tumor is positive for NTRK gene fusion. Unfortunately, these promising therapies apply to a very small minority of pancreatic cancer patients. Overall, there have been tremendous advances in chemotherapy regimens and timing, standardized staging systems, and imaging

Surgery

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Consider if high-risk features3

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Aer restaging imaging, selecve explorave laparotomy and curaveintent resecon

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FIG. 2  Integrated approach to pancreatic cancer based on resectability. In all cases, consider enrollment in clinical trial. 1 Modified FOLFIRINOX or gemcitabine plus capecitabine if good performance status. 2 FOLFIRINOX or modified FOLFIRINOX, or gemcitabine plus nab-paclitaxel if good performance status. 3 Highly elevated CA19-9>200, large primary tumors, large regional lymph nodes.

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TABLE 2  Key Clinical Trials in Pancreatic Cancer Study (Year)

Patient Number

Resectability

Intervention

Key Outcomes

ESPAC-1 (2004)

289

Resectable

1. Observation 2. Chemotherapy with fluorouracil + leucovorin 3. Chemoradiation with 20-Gy in 10 daily fractions and fluorouracil 4. Chemoradiation followed by chemotherapy

Worse survival in patients treated with any chemoradiotherapy compared with no chemoradiotherapy (15.9 months vs. 17.9 months)

ESPAC-4 (2017)

732

Resectable

1. Adjuvant gemcitabine and capecitabine 2. Adjuvant capecitabine

Improved survival 28.0 months vs. 25.5 months

PRODIGE-24/CCTG PA-6 (2018)

493

Resectable

1. Adjuvant modified FOLFIRINOX 2. Adjuvant gemcitabine

Improved survival 21.6 months vs. 12.8 months

EORTC 40013-22012/ FFCD-9203/ GERCOR (2010)

90

Resectable

1. Chemoradiation with gemcitabine 2. Adjuvant gemcitabine alone

Decreased local recurrence (11% vs. 24%) Disease-free survival and overall survival were not statistically different

APACT (preliminary results) (2021)

866

Resectable

1. Adjuvant gemcitabine plus nab-paclitaxel 2. Adjuvant gemcitabine

Improved survival 41.8 months vs. 37.7 months

Alliance A021501 (preliminary results) (2021)

126

Borderline resectable

1. Neoadjuvant chemotherapy with modified FOLFIRINOX 2. Neoadjuvant chemoradiotherapy with modified FOLFIRINOX

R0 resection rate higher in neoadjuvant chemotherapy alone (42% vs. 25%) Overall survival improved with neoadjuvant chemotherapy alone (31 months vs. 17.1 months)

PREOPANC (2020)

246

Resectable and borderline resectable

1. Neoadjuvant chemoradiotherapy with gemcitabine 2. Immediate resection followed by adjuvant gemcitabine

R0 resection rate was significantly higher with neoadjuvant therapy (71% vs. 40%) No statistically significant improvement in median survival

LAP07 (2016)

449

Locally advanced

1. Neoadjuvant gemcitabine with chemoradiation 2. Neoadjuvant gemcitabine with additional chemotherapy

No statistically significant survival difference

NEOLAP (2021)

165

Locally advanced

1. Gemcitabine and nab-paclitaxel followed by gemcitabine and nab-paclitaxel 2. Gemcitabine and nab-paclitaxel followed by FOLFIRINOX

High overall R0 resection rate (32%)

MPACT (2013)

861

Metastatic

1. Gemcitabine + nab-paclitaxel 2. Gemcitabine

Overall survival improved (8.5 months vs. 6.7 months)

PRODIGE 4/ACCORD 11 (2011)

342

Metastatic

1. FOLFIRINOX 2. Gemcitabine

Overall survival improved (11.1 months vs. 6.8 months)

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modalities. These advances will serve as the backbone for ongoing research and further development of therapeutics in this field.

S uggested R eadings Conroy T, Hammel P, Hebbar M, et  al. FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer. N Engl J Med. 2018;379(25):2395– 2406. Conroy T, Desseigne F, Ychou M, et  al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817–1825.

Rare and Unusual Pancreatic Tumors Jon M. Harrison, MD, and Carlos Fernandez-del Castillo, MD

INTRODUCTION Although pancreatic ductal adenocarcinoma (PDAC), intraductal papillary mucinous neoplasm (IPMN), and pancreatic neuroendocrine tumor (PNET) are the most common indications for pancreatectomy, rarer pancreatic neoplasms and masses may warrant resection. These include cystic, epithelial, and mesenchymal tumors as well as inflammatory processes and other malignancies, all of which can masquerade as a more sinister pathology. As such, recognizing these less common pancreatic lesions is important for proper clinical management. In this chapter, the relevant clinical, histopathologic, and management options for several rare and unusual pancreatic lesions will be discussed (Box 1).

BOX 1  Rare and Unusual Pancreatic Tumors Cystic Lesions Benign • Serous cystadenoma (SCA) • Lymphoepithelial cyst (LEC) Neoplastic • Mucinous cystic neoplasm (MCN) • Solid-pseudopapillary neoplasm (SPN) Epithelial Cell Tumors • Acinar cell carcinoma (ACC) • Pancreatoblastoma (PBA) Mesenchymal Cell Tumors • Perivascular epithelioid cell tumor (PEComa) • Solitary fibrous tumor (SFT) Inflammatory Masses and Additional Malignancies Inflammatory masses • Groove pancreatitis • Autoimmune pancreatitis Additional malignancies • Pancreatic lymphoma (PL) • Metastases

Neoptolemos JP, Palmer DH, Ghaneh P, et al. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial. Lancet. 2017;389(10073):1011–1024. Philip PA, Lacy J, Portales F, et al. Nab-paclitaxel plus gemcitabine in patients with locally advanced pancreatic cancer (LAPACT): a multicentre, open-label phase 2 study. Lancet Gastroenterol Hepatol. 2020;5(3):285– 294. Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369(18):1691– 1703.

BENIGN PANCREATIC CYSTS Serous Cystadenoma Serous cystadenoma (SCA) is a benign, nonmucinous lesion that accounts for 33% of pancreatic cysts. They are distributed throughout the pancreas and generally occur in postmenopausal females. The more common microcystic variant has a distinctive honeycomb appearance (Fig. 1) or central, calcified scar, which can be appreciated on axial imaging. A less common macrocystic variant lacks this characteristic appearance. The epithelial lining of either type, however, is composed of cuboidal, glycogen-rich cells that are thought to arise from the centroacinar cells of the pancreatic ductal system (see Fig. 1). Although most SCAs are sporadic, the lifetime risk for development in patients with von Hippel-Lindau syndrome approaches 40%. The majority of SCAs are discovered incidentally, but some patients may present with nonspecific abdominal pain, a palpable mass, or obstructive symptoms. In instances of the macrocystic variant, a more extensive workup with endoscopic ultrasound (EUS), fine-needle aspiration (FNA), and cyst fluid sampling may be necessary to rule out similar-appearing pathologies such as IPMN, mucinous cystic neoplasm (MCN), or cystic PNET. In general, SCA fluid has low carcinoembryonic antigen (CEA) and amylase levels; however, cytologic atypia is a common finding that may confound the diagnosis. In terms of management, SCAs should be considered for resection in patients with pain or obstructive symptoms. A Whipple procedure is required for proximal lesions, whereas a middle or distal pancreatectomy without splenectomy can be considered for body and tail SCAs. Although an exceedingly rare invasive form of SCA (serous cystadenocarcinoma) has been historically described, updated series question the authenticity of this tumor. As a result, formal lymphadenectomy is not necessary for complete resection.

Lymphoepithelial Cyst First described in 1985, the lymphoepithelial cyst (LEC) is a much rarer (0.5%) and often incidentally discovered benign cystic lesion. Unlike SCAs and other pancreatic cysts, LECs are more common in middle-aged males, and its histologic hallmarks include a keratinized stratified squamous epithelium, which produces caseous cyst contents, and a subepithelial germinal center full of monomorphic lymphocytes (Fig. 2). This latter feature suggests that LECs may arise from tertiary lymphoid structures; however, other etiologies including cystic degeneration, pancreatic duct metaplasia, or a teratoma-like origin have also been purported. On imaging, an LEC appears as a well-circumscribed, unilocular or multilocular lesion but can occasionally become secondarily infected or rupture (see Fig. 2). Some LECs may also have elevated tumor markers or be mistaken for MCNs given their similar imaging characteristics. Management of LECs consists of segmental resection or enucleation

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FIG. 1  Serous cystadenoma (SCA). (A) T2 MRI reveals an 8.5-cm multilobulated pancreatic head cyst. (B) SCA gross pathology demonstrates many small cysts in a honeycombing pattern. (C) Large, multicystic spaces lined by bland cuboidal cells on SCA histopathology.

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FIG. 2  Lymphoepithelial cyst (LEC). (A) CT shows a 6.6-cm multilobulated pancreatic tail cyst with foci of intralesional air and pericystic inflammation, (B) Gross pathology shows caseous material extruding from the cyst core formed from a keratinized epithelial lining. (C) Prominent germinal centers (arrows) characteristic of LEC histology. (D) Magnified view reveals a subepithelial layer (arrows) composed of monomorphic lymphocytes.

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depending on anatomic location. Internal drainage may also be considered for poor surgical candidates.

cystadenocarcinoma include a solid component, mural nodule, or calcifications. Because of the lifetime risk of malignancy, all MCNs should be considered for formal resection, and only in rare instances of invasive carcinoma is surgery noncurative. Because this neoplasm does not metastasize through the lymphatic system, formal lymphadenectomy and splenectomy are not necessary. Care, however, must be taken not to violate the capsule and spill cyst contents intraoperatively.

NEOPLASTIC PANCREATIC CYSTS Mucinous Cystic Neoplasm MCNs represent 25% of pancreatic cysts and 2% of all pancreatic neoplasms. They are commonly found in the pancreatic body and tail and occur almost exclusively in perimenopausal females. This gender predisposition is related to the pathophysiology of MCNs as this neoplasm is thought to arise from the gonadal tissue that abuts the fetal pancreas before descending into the pelvis. These tumors are hormonally sensitive, and histologically, a classic subepithelial layer of ovarian-type stroma differentiates MCNs from IPMNs and other pancreatic cysts (Fig. 3). Although KRAS or RNF43 mutations can be found on MCN fluid or tissue biopsy, the GNAS mutation found in IPMNs is not seen in MCNs. Patients with MCNs often present with nonspecific abdominal pain and undergo axial imaging with either CT or MRI. Radiographically, they appear as well-encapsulated, unilocular or multilocular cystic lesions (see Fig. 3). In equivocal cases, EUS with FNA can be performed to sample cyst fluid, which usually reveals an elevated CEA level. Because MCNs do not communicate with the pancreatic ductal system, amylase levels are often low; however, cases of elevated levels have been reported. Adequate sample cytology may also reveal atypia or dysplasia, and roughly 5% to 15% of MCNs harbor malignancy (see Fig. 3). Additional concerning features for mucinous

Solid Pseudopapillary Neoplasm The solid pseudopapillary neoplasm (SPN) is another neoplastic lesion that represents about 5% of resected pancreatic cysts and 1% of pancreatic tumors. Before its current designation by the World Health Organization (WHO) in 1996, historic names for SPN included Frantz tumor, Hamoudi tumor, and papillary cystic neoplasm. SPNs are characteristically well-circumscribed lesions found in the pancreatic body and tail of young females (Fig. 4), and although they are grouped with other pancreatic cysts, SPNs are in fact a cavitary lesion that forms as the tumor grows and necroses. Histologically, the epithelial lining of SPNs is composed of foamy histiocytes as well as polygonal cells that organize into stalks and pseudopapillae (see Fig. 4). Curiously, the origin cell type for this tumor remains unknown, and no pathologic equivalent has been described in other organ systems. On molecular analyses, 90% of SPNs harbor WNT/B-catenin pathway mutations, and these tumors stain positive for neuron-specific enolase (NSE), vimentin (VIM), alpha-1 antitrypsin (A1AT), and the membrane metallopeptidase, CD10.

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FIG. 3  Mucinous cystic neoplasm (MCN). (A) T2 MRI reveals an 8.4-cm pancreatic tail cyst with thin, peripheral septations. (B) Gross pathology shows bivalved MCN with a smooth epithelial lining. (C) Foveolar-type mucinous epithelium and prominent subepithelial ovarian-type stroma (arrows) characteristic of MCN. (D) Tubulopapillary projections and nuclear pleomorphism consistent with mucinous cyst adenocarcinoma in situ.

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FIG. 4  Solid pseudopapillary neoplasm (SPN). (A) CT demonstrates a 2.6-cm hypoenhancing pancreatic body cyst abutting the posterior wall of the stomach. (B) A well-circumscribed tan-colored pancreatic mass consistent with SPN. (C) Fibrovascular cores engulfed in poorly cohesive sheets of neoplastic cells. (D) Monomorphic tumor cells organized in a pseudopapillary pattern around intervening capillaries.

Like MCNs, SPNs usually present with nonspecific abdominal pain or are found incidentally during workup for another pathology. Given its unique clinical features, EUS and FNA are usually not necessary for diagnosis. Patients should undergo formal oncologic resection, and a minimally invasive or robotic approach can be considered if technically feasible. Although a complete resection is generally curative, the recurrence rate for SPN is approximately 4.4%, and instances of distant metastatic spread have been reported. Surveillance is therefore an important component of the management for patients with SPN. For recurrent disease, attempts at surgical management should be pursued.

EPITHELIAL CELL TUMORS Acinar Cell Carcinoma Acinar cell carcinoma (ACC) represents 1% to 2% of pancreatic tumors and is more common in males. The pancreatic acinar cells, which comprise >90% of the pancreatic parenchyma, normally synthesize and secrete digestive enzymes such as lipase, trypsin, and chymotrypsin. As neoplastic ACC cells proliferate, a paraneoplastic syndrome caused by lipase hypersecretion may manifest as extremity erythema nodosum, polyarthralgia, and eosinophilia. Together, these symptoms constitute Schmid’s triad, which is seen in roughly 10% to 15% of ACC patients. As such, lipase levels can be followed as part of disease surveillance, while other markers alpha fetoprotein (AFP) serum levels can also be followed. Histologically, tumor cells are organized into one of two patterns. In the acinar pattern, cancer cells organize to form small lumina, whereas in the absence of luminal

structures, sheets of neoplastic cells coalesce to form a solid pattern. Both patterns, however, are commonly mixed within an individual tumor. A cystic variant, which can be mistaken for other pancreatic cystic lesions, can be appreciated on imaging or histology, and importantly, other nonductal epithelial components found within the ACC tumor mass can be mistaken for pancreatoblastoma (PBA) or PNET. All patients with ACC should undergo formal oncologic resection for definitive management, though many ACC tumors present large and exophytic masses with locoregional disease. In such instances, neoadjuvant FOLFIRINOX-based chemoradiotherapy can effectively downstage the tumor and increase resectability. In terms of outcomes, overall survival for resected ACC is better compared with PDAC: 92% and 53% at 1 and 5 years, respectively. Because of its metastatic potential, however, postoperative surveillance should be continued in a similar manner to PDAC. Adjuvant chemoradiation is also recommended for all patients who did not receive up-front therapy as well as for recurrent or metastatic disease. In very select instances of isolated ACC metastases, metastectomy can also be considered.

Pancreatoblastoma PBA is another rare pancreatic exocrine malignancy that accounts for 25% of pediatric pancreatic tumors and can be associated with other syndromes such as Beckwith-Wiedemann syndrome and familial adenomatous polyposis. Albeit uncommon, these tumors can also occur in young and middle-aged adults, and the prognosis is often poorer in these cases.

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D

FIG. 5  Perivascular epithelioid cell tumor (PEComa). (A) MRI shows a 3.2-cm hypoenhancing mass (arrow) in the pancreatic tail with distal atrophy. (B) Gross pathology shows a well-circumscribed mass with a fibrotic capsule and yellowish central nodules consistent with PEComa. (C) Large epithelioid cells with prominent nucleoli (arrows) and clear cytoplasm among small blood vessels. (D) HMB45 staining (brown) characteristically seen in PEComa.

PBAs arise from primordial epithelial cell nests that form cores of keratinized spindle cells called squamoid corpuscles. For diagnostic and surveillance purposes, AFP is the most reliable biomarker for PBA and is seen in up to 70% of cases; however, other markers including alpha-1 antitrypsin (A1AT) and lactate dehydrogenase (LDH) may also be elevated. Infrequently, PBAs secrete adrenocorticotropic hormone (ACTH), resulting in a Cushing-like paraneoplastic syndrome. Regarding presentation, PBAs are usually found in the pancreatic head and cause persistent abdominal pain or obstructive symptoms. In children, an abdominal mass may be palpated on physical examination, and calcifications are a common finding on axial imaging. Overall survival rates for PBA mirror ACC; however, recurrence is more common. For unresectable or recurrent disease, patients treated with cisplatin and doxorubicin-based chemotherapeutic regimens can achieve long-term survival.

MESENCHYMAL PANCREATIC TUMORS PEComa First described in 1996, the perivascular epithelioid cell tumor (PEComa) is a rare pancreatic mesenchymal tumor that is thought to originate from the pericyte or myofibroblast cells enveloping capillaries and small blood vessels. These tumors can arise in any organ system and are related to the clear cell or sugar tumors found in tuberous sclerosis patients. The link between pancreatic PEComa and tuberous sclerosis, however, remains unclear. On imaging, PEComas are well-circumscribed and hypoenhancing (Fig. 5). Histologically, these tumors are notable for large epithelioid cells suspended among a trabecula of fine vessels (see Fig. 5).

Necrosis and hyalinization are other common histologic features, and spindle-shaped cells can also be seen. Positive staining for melanin 45 (HMB45), alpha smooth muscle actin (ACTA2), and desmin (DES) are additional histologic features found in PEComas (see Fig. 5). Although very rare, these tumors have malignant potential, and metastases have been reported in larger (>5 cm) and highly mitotic (>1/50 high-power fields [HPF] or Ki-67 index >5%) gynecologic PEComas. Pancreatic PEComas, although potentially benign, should be formally resected given their unclear natural history or in instances of diagnostic uncertainty.

Solitary Fibrous Tumor The solitary fibrous tumor (SFT) is another mesenchymal tumor composed of spindle-shaped cells. This tumor can arise from the pancreas or metastasize from primary lesions in the pleura, extremities, or head and neck region. These tumors can arise throughout the pancreas and have a characteristic fleshy texture on gross pathology (Fig. 6). Common histologic markers for SFT include transmembrane protein CD34, transcription factor STAT6, and survival protein BCL2. Although malignancy has been described in large (>10 cm) and highly mitotic (>4 mitoses/10 HPF) forms of metastatic SFT, no cases of malignant pancreatic SFT have been reported. Even in cases of SFT metastases to the pancreas, long-term survival is possible after partial pancreatectomy or tumor enucleation.

Schwannoma and Paraganglioma Found adjacent to or within the pancreatic parenchyma, schwannomas are benign and well-circumscribed masses arising from the

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A

625

B

FIG. 6  Solitary fibrous tumor (SFT). (A) Fleshy pancreatic tail mass consistent with SFT. (B) Densely packed spindle cells amidst staghorn-like blood vessels. Notable perivascular hyalinization is also seen (arrow).

PHA CHA PV

A

GDA CBD

Sch

Antoni A

Antoni B

C

B

FIG. 7  Peripancreatic schwannoma. (A) CT demonstrates a 3.2-cm homogenous mass abutting the common hepatic artery, portal vein, and pancreatic neck. (B) Intraoperative image of solid peripancreatic mass (forceps tips) posterior to common hepatic artery trifurcation. (C) Antoni A area composed of spindle cell fascicles, and Antoni B area characterized by scattered cells within a loose matrix. CBD, Common bile duct; CHA, common hepatic artery; GDA, gastroduodenal artery; PHA, proper hepatic artery; PV, portal vein; Sch, schwannoma.

sheath of peripheral nerves (Fig. 7). Although an association between von Recklinghausen’s disease and pancreatic schwannomas has been reported, most cases are sporadic. Histologically, these lesions can be solid, cystic, or contain focal areas of hemorrhage, calcifications, or

xanthomatous debris. Staining for S100 proteins, NCAM1 (CD56), and transcription factor SOX10 are common, and either tumor enucleation or formal resection is appropriate, especially for larger lesions (>6 cm), which may have an increased risk of malignancy.

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Rare and Unusual Pancreatic Tumors

Although similar to schwannomas, paragangliomas arise from rests of extraadrenal chromaffin cells, and patients must undergo hormonal testing to identify features of catecholamine excess before resection. Paragangliomas appear to be a nonneoplastic entity and tend to occur in the pancreatic body and tail. Importantly, histologic markers for paragangliomas such as synaptophysin (SYP), chromogranin (CHGA), and anti-insulinoma protein 1 (INSM1) may be mistaken for a neuroendocrine tumor. Tumor enucleation or simple excision through a laparoscopic or robotic approach are adequate forms of treatment.

INFLAMMATORY MASSES AND SECONDARY MALIGNANCIES Groove (Paraduodenal) and Autoimmune Pancreatitis Various forms of pancreatic inflammation such as groove and autoimmune pancreatitis can present as a pancreatic mass. In groove, or paraduodenal, pancreatitis, chronic inflammation occurs at the interface of the duodenum and the pancreatic head between the major and minor pancreatic papillae (Fig. 8A). As in other forms of pancreatitis, groove pancreatitis is more common in males and in patients with a history of alcohol or tobacco abuse. Presenting symptoms may include obstructive jaundice or gastric outlet obstruction, which prompt further workup. Although tumor markers are often negative, axial imaging may reveal a hypodense mass in the pancreatic head or ampulla. A subtle but classic radiographic finding for groove pancreatitis is the presence of a curvilinear collection or

lesion; however, a segmental form of the disease that infiltrates the pancreatic head is indistinguishable from more sinister pathologies. Although treatment is supportive in cases of biopsy-proven groove pancreatitis, cytology may be misleading and lead to pancreatoduodenectomy to rule out cancer. Autoimmune pancreatitis (AIP) is another inflammatory condition that presents as a pancreatic mass. Two forms of this disease have been described, and a careful history and physical examination may reveal xerostomia, obstructive uropathy, biliary cirrhosis, or other stigmata of the systemic form (AIP I). This form tends to occur in older male patients and is mediated by IgG4, which is elevated in up to 70% of patients. Histologically, infiltrative IgG4-positive plasma cells engulf the pancreatic acini and cause the lymphoplasmacytic sclerosing pattern of inflammation characteristic of this form of AIP. On axial imaging, the pancreas may appear congested or “sausage-like”; however, a hypoenhancing mass may be seen and mistaken for pancreatic cancer (Fig. 8B). Main pancreatic duct structuring or common bile duct dilation can also be seen in AIP I and raise further concerns for a neoplastic process. By contrast, AIP II is more common in younger patients and commonly associated with inflammatory bowel disease. IgG4 levels are usually normal, and on histology, the lymphoplasmacytic infiltrate targets pancreatic ducts rather than acini and forms hallmark granulocyte epithelial lesions (GELs). Workup with EUS and FNA may be necessary for patients with a pancreatic mass who lack features of AIP however, resection for diagnostic purposes is not uncommon. For confirmed cases, treatment includes high-dose (0.6–1 mg/kg) corticosteroids. Importantly, relapses occur in 60% of AIP1 cases compared with 10% in AIP2,

A

B

C

D

FIG. 8  CT shows inflammatory processes and additional malignancies. (A) Groove pancreatitis: diffuse stranding and inflammatory changes surrounding the first portion of duodenum and pancreatic head in addition to a 2.9-cm hypodense fluid collection (arrow), (B) Autoimmune pancreatitis type I: 2-cm infiltrative pancreatic tail mass with associated narrowing of the splenic vein. (C) Pancreatic lymphoma: a bulky 2.9-cm mass arising along the porta hepatis and extending into the pancreatic head causing intrahepatic biliary ductal dilatation (arrow). (D) Metachronous renal metastasis: 1.1-cm hyperenhancing pancreatic head mass in a patient with history of renal cell carcinoma.

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and azathioprine can be incorporated into the treatment of refractory cases.

ADDITIONAL MALIGNANCIES Primary Pancreatic Lymphoma Primary pancreatic lymphoma (PPL) is a duplicitous mimicker of PDAC, yet this rare pathology represents only 20

Classification/Grade

Well-differentiated panNEN: panNET

HPF, High-power field; PanNEC, pancreatic neuroendocrine carcinoma; PanNEN, pancreatic neuroendocrine neoplasm; PanNET, pancreatic neuroendocrine tumor.

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disease and symptoms including weight loss, abdominal distention, and abdominal pain. In very rare instances, fulminant liver failure is the first presentation in poorly differentiated PNETs resulting from replacement of liver parenchyma with disease. F-PNETs present with specific symptoms related to the type of hormone that is being overproduced (Table 2). Hormone-producing tumors include insulinomas, gastrinomas, vasoactive intestinal peptide (VIP)-secreting tumors, glucagonomas, somatostatinomas, PNETs resulting in carcinoid syndrome caused by production of serotonin, and even less common tumors that make hormones like adrenocorticotrophic hormone (ACTH), calcitonin, growth hormone–releasing factor, and parathyroid hormone–related peptide (PTHrP). Because of the hormone-related syndromes, F-PNETs are usually detected earlier. Once identified, the diagnostic workup is similar for both F-PNETs and NF-PNETs. Diagnostic workup should focus on determining if the tumor is functional, complete staging, and evaluation for associated familial syndromes, which may lead to screening for other associated cancer and potentially change the timing of operative management for the PNET.

DIAGNOSTIC EVALUATION The diagnosis of PNETs is multifaceted. Patients most often present to surgeons with cross-sectional imaging already done, with a tumor that has specific characteristics consistent with a PNET. The surgeon should complete a thorough history and physical examination focusing on clinical signs and symptoms that accompany F-PNETs and NF-PNETs. Physicians should assess general symptoms associated with pancreatic neoplasms, including jaundice, dark urine, acholic stool, weight loss, abdominal pain, and back pain. Furthermore, they should inquire about symptoms associated with hormone-related syndromes with PNETs. These include hypoglycemic episodes, tremors, palpitations, anxiety, hunger, confusion, seizures, diarrhea, refractory peptic ulcer disease, gastroesophageal reflux, rashes, new-onset diabetes, gallstones, venous thrombosis, wheezing, flushing, weight loss, or weight gain. They should also look for physical examination findings such as migratory erythema, central obesity, jaundice, hirsutism, facial fullness, cardiac murmurs, and wheezing. If a patient is referred for hormonal syndromes classic for F-PNETs without cross-sectional imaging, triple-phase CTMRI with and without contrast should be obtained. Once the diagnosis of PNET is suspected, the patient must be completely staged. Cross-sectional imaging of the chest and abdomen allows for evaluation of the relationship to major vascular structures and assessment of the liver, lungs, and intraabdominal lymph nodes for obvious metastatic disease. Recently, functional imaging has been more commonly used in the diagnostic and staging evaluation. It is also useful in the setting of occult PNETs that present with hormonal syndromes but no identified tumor on cross-sectional imaging. Biochemical markers are used to confirm the diagnosis and evaluate for functional symptoms. Endoscopic ultrasound with fine needle aspiration (EUS/FNA) is the most common modality used to establish a tissue diagnosis when necessary. Often, the characteristic imaging findings are enough to proceed to surgical management without a tissue diagnosis and EUS/ FNA is reserved for instances in which the diagnosis is in question, resection is not possible, or the tumor pathology (grade) will change management, as in the setting of metastatic disease. Figure 1 provides an algorithm for evaluation, staging, and management of PNETs.

Cross-Sectional Imaging Cross-sectional imaging with multiphase CT of the abdomen and pelvis or MRI with and without contrast play a vital role in the diagnosis, staging, and assessment of resectability in patients with PNETs. CT and MRI are helpful in evaluation of vascular involvement, which would preclude resection of the primary tumor. When water is used as oral contrast, pancreatic protocol CTs can also identify small

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Pancreatic Neuroendocrine Tumors of the Pancreas Excluding Gastrinoma

TABLE 2  Clinical Presentation of Pancreatic Neuroendocrine Tumor Subtypes Tumor

Hormone

Symptoms

Nonfunctional PNET

Varies (pancreatic polypeptide, chromogranin A, others in small quantities)

Asymptomatic, abdominal/back pain, nausea/vomiting, pancreatitis, obstructive jaundice

Insulinoma

Insulin

Hypoglycemic symptoms (tremor, palpitations, anxiety, hunger, cognitive impairment, seizure, coma), fasting hypoglycemia, rapid correction with glucose (Whipple triad)

Gastrinoma

Gastrin

Severe, medically refractory peptic ulcer disease, gastroesophageal reflux, diarrhea (Zollinger-Ellison syndrome)

VIPoma

Vasoactive intestinal peptide (VIP)

Watery diarrhea, hypokalemia, achlorhydria (WDHA syndrome, pancreatic cholera or Verner Morrison syndrome)

Glucagonoma

Glucagon

Necrolytic migratory erythema, weight loss, diabetes mellitus, diarrhea, venous thrombosis

Somatostatinoma

Somatostatin

Diabetes, gallstones, steatorrhea, weight loss

Pancreatic carcinoid

Serotonin, tachykinins

Flushing, diarrhea, bronchospasm, valvular heart disease (carcinoid syndrome)

ACTHoma

Adrenocorticotropic hormone (ACTH)

Obesity, facial plethora, round face (moon facies), hirsutism, hypertension, bruising, fatigue, depression, dorsal fat pad, glucose intolerance, stria, proximal weakness, menstrual irregularities, decreased fertility (Cushing syndrome)

GRFoma

Growth hormone–releasing factor (GRF or GHRF)

Coarse facial features, enlarged hands and feet, macroglossia, deepening of voice, skin thickening, sleep apnea, arthritis, cardiovascular disease, insulin resistance, fatigue, weakness (acromegaly)

PTHrPoma

Parathyroid hormone–related protein (PTHrP)

Nephrolithiasis, weakness, bone pain, nausea, constipation, polyuria, depression (hypercalcemia)

Suspected PNET on cross-sectional imaging 1) History and physical exam; 2) Biochemical testing CgA, NSE, PP (other hormones as indicated based on symptoms); 3) Dedicated imaging of pancreas with triphasic CT/MRI; 4) CT Chest or Dotatate/PET CT Imaging atypical for PNET Confirm diagnosis on EUS/FNA

Imaging typical for PNET

Non metastatic

Metastatic

Non functional

Functional Unresectable

Resectable primary and metastases

>2 cm

Resectable primary tumor and metastases

1) Check WHO grade; consider debulking if low grade; 2) Somatostatin receptor antagonists; 3) Peptide receptor radionuclide therapy; 4) Liver directed local therapy

1-2 cm

20%. (A) The mass appears hyperenhancing in the arterial phase (arrow) (B) The same mass is shown in the venous phase (arrow) with washout of contrast.

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Pancreatic Neuroendocrine Tumors of the Pancreas Excluding Gastrinoma

Biochemical Markers We do not recommend sending a wide panel of biochemical markers on all patients with PNETs, but rather sending biochemical tests based on symptoms. Such markers are confirmatory but often do not aid in the diagnosis given the distinct radiographic characteristics of these tumors. Chromogranin A (CgA) is considered one of most understood general clinical biomarkers of neuroendocrine tumors. It has a sensitivity of 66% and specificity of 95% and overall accuracy of 71% in PNETs. Serum chromogranin A is recommended both as a marker for diagnosis and for clinical follow-up in NF-PNETs after surgical resection. After surgical resection, return of chromogranin A to normal confirms complete resection, and chromogranin A has an established role in detecting recurrent or metastatic disease and serves as an independent marker for progression-free survival (PFS) and overall survival (OS). Chromogranin A can be falsely elevated in patients with inflammatory bowel disease, renal failure, liver failure, and chronic use of proton-pump inhibitors. Neuron-specific enolase (NSE) is a glycolytic enzyme produced in the neurons of neuroendocrine cells. Elevated NSE levels are associated with poor differentiation and shorter PFS. In conjunction with chromogranin A levels, NSE levels may be used to predict outcomes when response occurs after treatment. Pancreatic polypeptide (PP) is produced by pancreatic islet cells in the head and uncinated process of the pancreas. The combination of PP with chromogranin A improves the sensitivity for detection of PNETs from 25% to a total of 93% in patients with nonfunctioning PNETs. Its diagnostic sensitivity ranges from 41% to 68% in patients with PNETs. We recommend sending chromogranin A, NSE, and PP for all suspected NF-PNETs and sending specific hormone levels based on symptoms only as described later (see Fig. 1). In patients with insulinomas, insulin levels are found to be elevated inappropriately in the setting of low serum glucose levels. Insulin is secreted by the beta cells of the pancreas. Patients with insulinomas develop Whipple triad, which includes (1) fasting hypoglycemia, (2) associated hypoglycemic symptoms including tremors, palpitations, anxiety, hunger, weight gain, confusion, seizures, and coma, and (3) resolution with glucose administration. In the patient with symptoms consistent with insulinoma syndrome, a 72-hour monitored fast documenting low serum glucose and high serum insulin levels at the time of hypoglycemic symptoms confirms the diagnosis. Patients with suspected insulinoma should also be screened for serum C-peptide levels and urine sulfonylurea levels. The absence of C-peptide at the time of hypoglycemia with inappropriately high insulin levels implies exogenous insulin administration. High urine sulfonylurea levels imply the use of inappropriate oral antihyperglycemic agents. Most insulinomas are benign and rarely metastasize. Glucagon is secreted by the alpha cells of the pancreas. It plays a counterregulatory role to insulin, and a level greater than 500 pg/ mL is usually detected in patients with glucagonomas. Glucagonoma is rare; patients may present with necrolytic migratory erythema caused by amino acid deficiency, weight loss, diabetes mellitus, and poor glucose tolerance. Glucagonomas have high malignant potential and may be part of MEN-1. Glucagon levels should be sent in the setting of the classic necrolytic migratory erythema rash and/or new-onset diabetes mellitus in the presence of a NET. VIP is a hormone that plays an important role in gastrointestinal contraction and pancreatic exocrine function. It has a classic clinical presentation of watery diarrhea, hypokalemia, and achlorhydria (Verner-Morrison syndrome). VIPomas are usually malignant and often present with synchronous metastasis to the liver and regional lymph nodes. Elevated VIP levels are highly specific to VIPomas when present in patients with PNETs. This syndrome is profound, and it is unlikely that a tumor without profound diarrhea is secreting VIP, and it should not be seen in patients without such symptoms. Somatostatin is a hormone that inhibits the endocrine secretion and motility of the stomach and gallbladder. Patients may be symptomatic or may present with an often subtle triad of hyperglycemia,

FIG. 5  Glucagonoma staining (brown) seen microscopically at 20× magnification in a patient who did not have classic syndromic symptoms. The diagnosis of functional pancreatic neuroendocrine tumor is confirmed by histopathologic staining for various hormones.

cholelithiasis, and indigestion. Somatostatinomas are a rare form of PNETs that are usually difficult to diagnose in the preoperative setting. Gastrin is usually present in patients with gastrinomas. This topic will be covered extensively in a separate section of this book. PNETs can also secrete rare hormones, including serotonin, parathyroid hormone–related protein (PTH-rp), ACTH, and growth hormone– releasing factors. These instances are incredibly rare. In many cases, the functional syndromes are clinically obvious, but in some cases hormone secretion is found only on histopathologic staining (Fig. 5).

EUS/FNA Definitive tissue diagnosis of a PNET can be established through pathologic examination of tissue obtained through needle biopsy. This is most useful in cases in which the preoperative imaging is not classic and the diagnosis remains in question. This may be the case in cystic neuroendocrine tumors, which differ in radiographic appearance. The use of EUS/FNA is not necessary in all patients with PNETs. Because of their typical appearance on cross-sectional imaging and the presence of functional imaging, EUS/FNA should be utilized only when the diagnosis of PNET is not certain or there is a high suspicion for mixed tumors. It is also used when the grade of tumor would affect clinical management, such as in the setting of metastatic disease. In this case, establishment of high-grade, poorly differentiated tumors would represent a contraindication to resection or debulking, while low-grade, well-differentiated tumors mandate an aggressive approach with resection of the primary and complete resection or debulking of metastatic disease. However, EUS/FNA has limitations. On EUS/FNA, there is poor correlation of the FNA-determined grade with final pathology because of significant tumor heterogeneity. In 50% of patients with grade 2/grade 3 tumors, the final pathologic grade differs from the FNA biopsy. EUS/FNA biopsy is also utilized in the setting of clinical trials when tissue diagnosis is necessary for enrollment. EUS can also be utilized to help in sampling regional lymph nodes and detecting vascular invasion, but this adds little over modern cross-sectional imaging. EUS is also important in patients with MEN-1, as is dotatate PET/CT, where it aids in detecting multifocal disease. The use of EUS/FNA should be used judicially as it carries the risks of gastrointestinal tract perforation, pancreatitis, and bleeding.

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MANAGEMENT OF PNETS The management of PNETs depends on many factors including: (1) tumor functional status, (2) tumor location in the head, body, or tail of the pancreas, (3) tumor size, (4) tumor grade and differentiation, and (5) presence of regional lymph node metastasis or distant metastasis (see Fig. 1). Assessing the tumor grade and risk of lymph node metastasis is of paramount importance when making management decisions, especially in the setting of metastatic disease.

Functional PNETs With the exception of insulinomas, F-PNETs are usually malignant. In addition, they secrete hormones that cause symptoms. As such, surgical resection is the standard of care for all nonmetastatic, functional, sporadic PNETs. Surgical resection improves patient survival and allows for control of the endocrine syndromes associated with the specific PNET. Surgical resection provides curative intent therapy and decreases the risk of future problems. The development of metastatic disease is least common in insulinomas (approximately 15%) ranging to up to 90% in gastrinomas, glucagonomas, and VIPomas. Cure rates vary with surgical resection and range from 90% for insulinomas to around 40% with gastrinomas. Surgical planning in the setting of F-PNETs should consider the presence of metastasis to regional lymph nodes. Formal oncologic resection with local lymphadenectomy through either a pancreaticoduodenectomy or distal pancreatectomy with splenectomy is usually utilized based on the location of the tumor. Regional lymphadenectomy increases the chances of biochemical cure and improves OS. However, because insulinomas have low malignant potential, as do small incidentally found NF-PNETs, enucleation may be considered in these cases. For enucleation to be considered, the PNET must be at least 2 to 3 mm from the main pancreatic duct.

Nonfunctional PNETs Surgical management of NF-PNETs depends on multiple factors including size, location, presenting symptoms, proximity to the pancreatic duct, presence of regional lymphadenopathy, presence of metastatic disease, and the grade and degree of differentiation of the tumor. All NF-PNETs greater than 2 cm in size should undergo formal oncologic resection with regional lymphadenectomy because 50% of NF-PNETs greater than 2 cm will have nodal metastasis. PNETs have a more favorable prognosis than tumors of the exocrine pancreas, even in the setting of node-positive disease. Multiple meta-analyses have shown survival benefit in surgically resected patients, even in the setting of node-positive disease. The management of NF-PNETs less than 2 cm remains controversial. Sharpe and colleagues reviewed the national cancer data base (NCDB) and found that OS was improved with resection of patients of PNETs of all sizes. Surgical resection provided improved OS at 3 and 5 years in patients with NF-PNETs less than 2 cm in size who underwent surgical resection. However, many other studies have shown that small, asymptomatic tumors can be safely observed. For tumors this size, tumor grade and differentiation play a big role in decision making as the risk of malignant behavior is presumably higher in high-grade tumors. The current literature divides small NF-PNETs into those less than 1 cm and those with size between 1 and 2 cm. PNETs that are less than 1 cm in size are usually benign and have an indolent course. In these instances, surveillance without surgical resection is indicated. However, there are no clear-cut guidelines regarding the frequency of surveillance. We usually perform cross-sectional imaging with multiphase CT or MRI every 6 months for the first 2 years and then annually thereafter. It is unclear when or if such imaging should be stopped in the setting of a stable NF-PNET over a significant period. In patients undergoing surveillance, indications for resection would include increase in size, development of regional lymph node enlargement, or, in rare instances, patient anxiety.

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The management of PNETs that are 1 to 2 cm in diameter carries even more controversy. Toste et al. reported a 7% incidence of metastasis to regional lymph nodes in patients with PNETs less than 2 cm. In a recent study from 16 European centers, 210 patients underwent surgical resection of NF-PNETs less than 2 cm in diameter. The incidence of lymph node metastasis was 10.6%. Only 3% of patients had lymph node metastasis in grade 1 tumors; this number increased to 16% in grade 2 tumors and 100% in grade 3 tumors. Therefore, in the setting of 1- to 2-cm PNETs, biopsy with determination of grade may help guide management, with the caveat mentioned regarding the limitation of FNA for determining tumor grade because of tumor heterogeneity. For PNETs less than 2 cm, the presence of biliary obstruction or pancreatic duct obstruction warrants resection. Also, in young patients who have a potential long period for observation, resection should be considered. Enucleation can be considered in low-grade tumors without proximity to the main pancreatic duct. In higher-grade tumors, larger tumors, and those close to the pancreatic duct, formal resection is achieved with pancreaticoduodenectomy or distal pancreatectomy with or without splenectomy.

Metastatic Disease The liver is the most common site of metastasis of PNETs, with 65% of patients with metastasis having disease in the liver. The 5-year OS for PNETs is 75% to 90% in the setting of localized disease and is decreased to 13% to 50% in patients with metastatic disease to the liver. This wide range of survival reflects the heterogeneity in presentation. In the setting of metastatic disease, determining tumor grade and differentiation is critically important in management decisions. Complete resection or debulking of liver metastasis should be considered in patients with symptomatic disease and low-grade, well-differentiated histology. The goal is to achieve complete resection while keeping an adequate functional liver remnant. R0/R1 resection is preferred over R2 resection (debulking) and is associated with higher 5-year survival. Debulking of liver disease up to 80% is an acceptable treatment strategy for well-differentiated, low-grade disease. However, debulking is not indicated in the setting of highgrade, poorly differentiated disease. The use of microwave ablation, radiofrequency ablation, and enucleation are strategies employed to provide a liver parenchyma–sparing approach in the setting of unresectable liver metastases. In addition to resecting metastatic disease, primary tumor resection in this setting shows improved survival and should be considered. This is usually done at the same time.

SURGICAL APPROACHES Minimally Invasive Approaches PNETs are often small without vascular involvement and ideal for minimally invasive approaches. Minimally invasive approaches have been proven to be safe and effective in management of all pancreatic tumors with oncologic outcomes on par with open approaches. In fact, minimally invasive distal pancreatectomy has become the standard of care for management of disease in the body and tail of the pancreas and provides several advantages over the open approach. The LEOPARD trial supported these findings clearly in patients with left-sided pancreatic tumor. This is not as clear with respect to right-sided tumors. Zeureikat et al. reported on 1028 patients who underwent either robotic or open pancreaticoduodenectomy. They concluded that in the hands of experienced robotic surgeons, the robotic approach was associated with longer operative times, but also a reduction in blood loss and in major complications. There was no difference in 90-day mortality, wound infection, clinically relevant postoperative pancreatic fistulas, or readmission rates.

Enucleation Enucleation carries the theoretical advantage of improved endocrine and exocrine postoperative function. It can be used in patients with

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Intraoperative Radiation for Pancreatic Cancer

benign tumors with smaller size and small insulinomas. The proximity to the pancreatic duct or involvement of it precludes enucleation. A 2- to 3-mm distance from the pancreatic duct is needed to avoid injury and pancreatic leak. Although enucleation has been proven to have similar outcomes to formal resection with respect to mortality, morbidity, and return to work in carefully selected patients, it is associated with increased risk of postoperative pancreatic fistula. Resection margins for both formal resection and enucleation have not been clearly defined in the literature, but current teaching suggests that any negative margin is acceptable.

MANAGEMENT OF UNRESECTABLE PNETS Use of long-acting somatostatin analogues is warranted in the setting of symptomatic disease in patients who show positive expression of somatostatin receptors. Somatostatin receptor antagonists show an antiproliferative effect and are associated with prolonged PFS. Two somatostatin receptor antagonists are most commonly used: lanreotide and octreotide long-acting release (LAR). The use of octreotide LAR has been associated with longer times to tumor progression compared with placebo. In the CLARINET trial, treatment with lanreotide was associated with prolonged PFS in patients with advanced PNETs. Somatostatin receptor antagonists are also the treatment of choice for patients with excessive hormone secretion before surgery or if surgical resection cannot be performed, and they can significantly improve symptoms related to hormonal syndromes. Targeted therapies have been employed for management of locally advanced, metastatic unresectable PNETs. Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, and sunitinib, a tyrosine kinase inhibitor, are generally recommended as second-line therapies after somatostatin receptor antagonists in patient with positive expression of somatostatin receptors. They are used as first-line therapies if there is no expression of somatostatin receptors. Everolimus and sunitinib have been shown to improve PFS to 11 months on average compared with placebo. Other agents being investigated include cabozantinib, sulfatinib, and lenvatinib. Chemotherapy may be used in patients with poorly differentiated PNETs, high tumor burden, and/or elevated Ki-67 index. Temozolomide and streptozocin are used for well-differentiated tumors, whereas platinum-based regimens are used in the setting of poorly differentiated disease. They can help in decreasing tumor burden to allow surgical resection when indicated.

Intraoperative Radiation for Pancreatic Cancer Amol Kumar Narang, MD, Joseph M. Herman, MD, MSc, MSHCM, and Abhinav V. Reddy, MD

INTRODUCTION Although intraoperative radiation therapy (IORT) for pancreatic cancer has a long history of inquiry, improvements in systemic control with multiagent chemotherapy have increased the enthusiasm for aggressive local therapy, including more frequent exploration and attempts at radiation dose escalation. As such, there has been renewed enthusiasm surrounding the potential use of IORT. Indeed,

Recently, peptide receptor radionuclide therapy (PRRT) has shown great promise in patients with metastatic disease. Peptide receptor radionuclide therapy is applied in patients with advanced neuroendocrine tumors. It usually incorporates a radioisotope like Yttrium-90 or Lutetium-177 and a somatostatin receptor antagonist. This allows for delivering targeted radiation to the tumor. Several studies have demonstrated the role of PRRT in patients with advanced PNETs with an overall response rate ranging between 16% and 61%. The phase 3 Lu-DOTATATE PRRT trial showed an overall response rate of 39% in all NETs of the midgut. PNETs showed the highest response rates in other studies involving patients with a NET. For this reason, PRRT may be attempted in patients with high expression of somatostatin receptors.

CONCLUSION PNETs are a heterogeneous group of tumors that present treatment challenges. Treatment of patients with PNETs should be tailored based on size, location, tumor grade and differentiation, presence of symptoms, and distant metastasis. It should be approached in a multidisciplinary fashion with the goal to control symptoms and provide long term OS. Cure should be considered feasible in patients with low-grade tumor, even in the setting of metastatic disease to the liver. Further work is needed to better understand this disease entity.

S uggested R eadings Fang JM, Shi J. A Clinicopathologic and molecular update of pancreatic neuroendocrine neoplasms with a focus on the New World Health Organization Classification. Arch Pathol Lab Med. 2019;143(11):1317–1326. Gharios J, Hain E, Dohan A, et al. Pre- and intraoperative diagnostic requirements, benefits and risks of minimally invasive and robotic surgery for neuroendocrine tumors of the pancreas. Best Pract Res Clin Endocrinol Metab. 2019;33(5):101294. Guilmette JM, Nosé V. Neoplasms of the neuroendocrine pancreas: an update in the classification, definition, and molecular genetic advances. Adv Anat Pathol. 2019;26(1):13–30. Howe JR, Merchant NB, Conrad C, et al. The North American Neuroendocrine Tumor Society Consensus Paper on the Surgical Management of Pancreatic Neuroendocrine Tumors. Pancreas. 2020;49(1):1–33. Ma ZY, Gong YF, Zhuang HK, et  al. Pancreatic neuroendocrine tumors: A review of serum biomarkers, staging, and management. World J Gastroenterol. 2020;26(19):2305–2322. Scott AT, Howe JR. Evaluation and management of neuroendocrine tumors of the pancreas. Surg Clin North Am. 2019;99(4):793–814.

IORT provides an opportunity for the focused delivery of high doses of radiation while shielding radiosensitive structures that often limit the dose of external beam radiation therapy (EBRT). Nevertheless, considerable challenges exist surrounding the development of a successful IORT program. Beyond the need for a shielded operating room and delivery system, successful administration of IORT requires a coordinated effort between the radiation oncology and surgery teams. As such, it is critical that surgeons interested in administering IORT have an in-depth understanding of both the scientific and technical underpinnings of this treatment modality.

REVIEW OF EXISTING LITERATURE Early exploration of IORT for pancreatic cancer came from Japanese investigators. In the 1970s, Kyoto University investigators described their experience with IORT for locally advanced disease, in which doses of 20 to 40 Gy resulted in improvements in tumor-related pain. These findings subsequently prompted investigators at the

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Massachusetts General Hospital (MGH) and the Mayo Clinic to further study IORT for pancreatic cancer in both the unresectable and resectable setting. In 1984, MGH reported outcomes among unresectable patients treated with IORT and EBRT, noting high rates of pain improvement and a median survival of 16.5 months. Three years later, Mayo investigators retrospectively reported outcomes among resected patients who received either postoperative EBRT alone or IORT followed by postoperative EBRT, noting higher rates of 1- and 2-year local control in patients who received both modalities. Since then, encouraging data have been reported in both the unresectable and resectable settings, as outlined in the following sections.

IORT for Unresectable Disease Multiple subsequent series, including reports from Mayo and Japan, further explored IORT in the locally advanced setting, suggesting improvements in local control with the use of both IORT plus EBRT compared with EBRT alone. These findings prompted a multi-­ institutional US study through the Radiation Therapy Oncology Group, namely Report 8505, in which locally advanced pancreatic cancer patients were treated with IORT to 20 Gy followed by 50.4 Gy of EBRT. Unfortunately, median survival in this cohort was only 9 months, which dampened enthusiasm for the role of IORT. Since then, however, other institutions have published positive long-term results with the use of IORT, with MGH reporting the most robust experience. An analysis of long-term outcomes among 194 locally advanced patients who were treated at MGH with IORT between 1978 and 2010 showed decent outcomes, particularly among well-selected patients with smaller tumors, with a 2-year overall survival of 16% and with a small fraction of patients (3%) experiencing long-term survival more than 5 years. These findings have renewed interest in IORT as a component of therapy for locally advanced pancreatic cancer, particularly with more patients with more advanced disease now undergoing attempted exploration in an era of better systemic control with multiagent chemotherapy. The most modern experience is from MGH, where patients were treated with multiagent FOLFIRINOX and chemoradiation followed by surgical exploration and IORT. The majority of patients (86/132, 65%) underwent resection and IORT, while 46 (35%) underwent IORT alone. Among the 46 patients who underwent IORT alone, 1-year, 2-year, and 5-year overall survival rates were promising at 98%, 49%, and 9%, respectively, which are much more favorable than those from the initial MGH report.

IORT for Resected Disease Following the results of the Mayo study of resected patients, the National Cancer Institute conducted a small, randomized trial of 24 patients comparing resection alone to resection with IORT. Patients in the IORT arm experienced improvements in local control and survival. Since then, subsequent institutional reports (see the Suggested Readings) have also suggested improvements in local control with the administration of IORT. A recent study from MGH reported on outcomes among patients with borderline resectable disease or locally advanced patients who were managed with a modern regimen of up-front multiagent systemic therapy (primarily FOLFIRINOX or gemcitabine/Abraxane), chemoradiation to a median dose of 50.4 Gy, and surgical exploration with or without IORT. The report analyzed 68 patients who made it through the neoadjuvant regimen without progression, of whom 41 successfully (60%) underwent resection, 18 (27%) had unresectable disease, and 9 (13%) had metastatic disease. Among the 41 patients who underwent resection, 22 were treated with IORT to a dose of 10 Gy. Patients treated with IORT experienced improved survival without additional toxicity or complications. Furthermore, unresectable patients who were treated with IORT to a dose of 15 Gy experienced an encouraging median survival of 24.8 months. The most modern experience with

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IORT in the postoperative setting also comes from MGH, where patients with borderline or locally advanced pancreatic cancer were treated with FOLFIRINOX and chemoradiation (median dose of 50.4 Gy) followed by surgical resection with or without IORT. In the no-IORT group, R1 resection was associated with poorer overall and disease-free survival. However, in the IORT group, there was no difference in overall and disease-free survival between patients who underwent R0 versus R1 resection, suggesting that IORT may mitigate the negative effects of R1 resection.

PATIENT SELECTION As reflected in the literature, well-established guidelines for the use of IORT for pancreatic cancer are lacking. Nonetheless, institutional data support consideration of IORT in instances (1) when close or positive margins are expected at the time of resection or (2) when disease may be unresectable, both of which are frequent scenarios with pancreatic cancer. Certainly, the decision to consider IORT should be discussed in a multidisciplinary setting, and its potential use should be defined ideally from the outset of therapy. Importantly, it is unlikely that intraoperative radiation alone is sufficient to achieve tumoricidal doses for either gross or microscopic disease, and as such, IORT should be used in combination with either preoperative or postoperative radiation therapy. Although postoperative radiation can be considered with the use of surgical clips for guidance of radiation fields, preoperative radiation is often preferred for a number of reasons, including the following. 1. Better definition of the intact tumor target in the preoperative setting as compared with the often-ill-defined surgical bed in the postoperative setting. 2. Displacement of bowel by the intact tumor in the preoperative setting compared with filling of the surgical bed by bowel in the postoperative setting. 3. Improved oxygenation of target tissue in the preoperative setting, rendering the target potentially more radiosensitive compared with the postoperative setting. 4. Removal of irradiated tissue with the preoperative approach.

EQUIPMENT IORT can be administered using multiple devices, including LINAC-based electron beam radiation therapy (intraoperative electron radiation therapy [IOERT]), low-energy photon therapy, low-doserate brachytherapy, or high-dose-rate (HDR) brachytherapy. Each of these modalities are viable strategies with their own relative merits. HDR-based IORT delivers a more concentrated dose at the surface of the target with sharp fall-off, which may be optimal for a surgical cavity/margin, whereas IOERT delivers a more homogenous dose of radiation to a greater depth. A significant advantage of an HDRbased technique lies in its method of delivery through the use of customized applicators that can allow delivery of radiotherapy to irregular surfaces compared with the rigid cone applicators that are required for IOERT or IORT with low-dose photons. At our institution, we have primarily used an HDR technique to take advantage of the flexible applicators; therefore, the technique described in this chapter will primarily focus on the administration of HDR-based IORT. Newer applicators that allow the delivery of low-dose-rate brachytherapy such as the CivaSheet are also under investigation. As noted, HDR-based IORT requires the use of a flexible flap applicator along with an HDR-based after-loader system. The Freiburg flap is the applicator used at our institution and consists of silicone balls that are 1 cm in diameter and are connected to form a flexible planar sheet through which 6Fr catheters can be inserted. The size and shape of the Freiburg flap can be customized at 1-cm intervals based on the dimensions of the target site. The after-loader system used at our institution is the Nucletron system by Elekta ; however, other applicators and after-loader systems are available.

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Intraoperative Radiation for Pancreatic Cancer

TECHNIQUE The first step of HDR-based IORT is for the surgeon to try to retract as much radiosensitive normal tissue such as bowel (see Normal Tissue Toxicity later in this chapter) out of the field and protect these structures by placing lead shields in front of them. Subsequently, the surgeon and radiation oncologist should jointly identify the highrisk surgical bed and/or gross disease. The target area is measured to inform the size of the applicator. The target area can also be marked with a marking pen to aid in accurate positioning of the applicator. Once the dimensions of the applicator have been finalized and the prescription dose and depth have been selected, the radiation oncologist’s physics team can subsequently begin developing the radiation plan, which primarily consists of determining the amount of time that the radioactive source will spend in each silicone ball. While the radiation plan is being developed, the radiation oncologist can preselect an applicator that is closest to the desired size. If an exact match is not available, the applicator can be cut to the appropriate size. Before proceeding further, it is a good idea to place the applicator in the surgical field to ensure that the chosen dimensions are optimal and that the applicator fits well into the surgical field. Additionally, the entrance route of the catheters from the after-loader into the surgical cavity and subsequently into the applicator should also be considered to ensure that the catheters will not be kinked as a result of sharp angling. Thereafter, 6Fr catheters are thread through the applicator and secured on either side of the applicator. The catheters are subsequently labeled in numeric order. It is helpful to place labels on the catheters both at a point near the applicator (at our institution, we use the labels as one of the mechanisms of securing the catheters to the applicator) as well as at a point a distance away from the applicator. These labels are critical because they allow accurate identification of the catheters, even after the applicator can no longer be visualized once packing has been placed. At this point, the applicator and catheters can be positioned into the surgical field in the location that had been previously defined (Fig. 1). Wet lap sponges can be packed on top of the applicator to help ensure its stability (Fig. 2). If need be, sutures can also be considered to further secure the applicator in place. Additional lead shields can be placed to minimize radiation dose to surrounding structures, with 3 mm of lead roughly reducing the dose by 70%. Of note, it is important to remember to cover lead shields with wet gauze to minimize the backscatter dose. Distance from the applicator also helps reduce the radiation dose, with the prescribed dose dropping to 70%, 50%, and 35% at 1, 2, and 3 cm, respectively. Thereafter, the catheters are connected to the

FIG. 2  Packing over the Freiburg flap to ensure stability.

after-loader, and a dry run is performed without a radiation source to ensure that there are no kinks or other obstacles to successful delivery. The room is evacuated, and appropriate video surveillance of the patient is confirmed. Radiation delivery can subsequently commence. Total treatment time is dictated by the prescription dose, the size of treatment area, and the activity of the source. At our institution, we use an 192Ir source, which has a half-life of 73 days.

TARGET VOLUME DELINEATION There is no consensus on optimal field design in the setting of IORT. Currently, IORT is most commonly targeted to the vascular margin at risk for microscopic residual disease in the setting of gross total resection or residual gross tumor in the setting of unresectable disease. Whether “elective” irradiation of larger volumes of tissue at risk for microscopic, subclinical residual disease in peripancreatic perineural tracts or lymph node basins should be pursued, particularly in the setting of gross total resection, is an open question.

DOSING Given that IORT consists of high doses of radiation administered at one time, the biological effective dose of a given IORT prescription dose is significantly higher than an equal EBRT dose administered in a fractionated manner. Conversion factors between IORT and fractionated EBRT doses are primarily derived from in vitro data and animal studies and therefore must be interpreted with some caution. Nevertheless, Table 1 provides helpful estimates for IORT dose conversions. In general, multiplication of an IORT dose by 2.2 to 2.5 yields a rough estimate for an equivalent fractionated EBRT dose to tumor, whereas multiplication of an IORT dose by 3 yields a rough estimate for an equivalent fractionated EBRT dose to normal tissue.

TABLE 1  Conversion Estimates Between IORT and EBRT Doses

FIG. 1  Freiburg flap in the surgical bed connected with catheters to an after-loader (not shown).

IORT Dose

EBRT Tumor Dose

EBRT Normal Tissue Dose (Acute)

EBRT Normal Tissue Dose (Late)

10 Gy

17 Gy

20 Gy

30 Gy

15 Gy

31 Gy

37 Gy

65 Gy

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NORMAL TISSUE TOXICITY Data describing normal tissue toxicity from IORT come primarily from canine models. In general, EBRT for pancreatic cancer will approach the radiation tolerance of bowel, so great effort should be made to limit any further bowel exposure from IORT to minimize the risk of late bowel toxicity such as obstruction, ulceration, perforation, or fistula. Sites used for anastomotic creation should be avoided in particular. As opposed to HDR brachytherapy, IOERT may allow for minimization of dose to anastomotic sites. Dose to the ureter, although usually less relevant to the treatment of pancreatic cancer, should also be minimized because excessive dose to the ureter can result in ureteral stenosis. In canine models, IORT doses above 18 Gy in combination with EBRT doses of 50 Gy led to significant risk of ureteral stenosis. Although typical IORT prescription doses tend to be below 18 Gy, effort should still be made to shield the ureter. Vascular structures have a higher radiation tolerance compared with bowel and ureter. Nonetheless, at high IORT and EBRT doses, clinically significant intimal hyperplasia and medial wall fibrosis have been described, with the potential for subsequent complications including arterial thrombus. Although these risks tend to be less apparent at the IORT and EBRT doses used in the abdomen, caution should nonetheless be taken, particularly if the patient has received prior courses of radiation. Last, patients should be counseled on the risk of neuropathy, which tends to occur with IORT doses in excess of 15 Gy. For pancreatic IORT, the effect on wound healing should be less relevant compared with IORT in more superficial sites, with modern series from MGH showing no increase in wound complications in patients receiving IORT.

CONCLUSION IORT represents a potential treatment option for decreasing local recurrence in pancreatic cancer patients with resected or unresectable disease, particularly when administered as a boost in combination with either preoperative or postoperative EBRT. Successful delivery of IORT requires a joint effort between the surgical oncologist and radiation oncologist to ensure appropriate targeting and

Transplantation of the Pancreas Niraj M. Desai, MD, and James F. Markmann, MD, PhD

INTRODUCTION Type 1 diabetes mellitus, formerly known as juvenile diabetes, is characterized by hyperglycemia resulting from destruction of the insulin-producing beta cells of the pancreatic islets of Langerhans. This loss of beta cells is caused by T-lymphocyte–mediated autoimmune destruction that typically occurs during childhood or early adolescence. Insulin replacement can lead to acceptable control of blood glucose levels; however, affected individuals are subject to the development of various secondary complications, including cardiac disease, stroke, retinopathy and blindness, nephropathy and renal failure, peripheral and autonomic neuropathy, and peripheral vascular disease. Although careful blood glucose control has been demonstrated to decrease the number of diabetes-related secondary

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minimization of radiation exposure to surrounding structures. In the era of contemporary multiagent systemic therapy leading to better systemic control, IORT can serve as a tool to provide more durable local control for this disease.

S uggested R eadings Abe M, Takhashi M. Intraoperative radiotherapy: the Japanese experience. Int J Radiat Oncol Biol Phys. 1981;7:863–868. Cai S, Hong TS, Goldberg SI, et al. Updated long-term outcomes and prognostic factors for patients with unresectable locally advanced pancreatic cancer treated with intraoperative radiotherapy at the Massachusetts General Hospital, 1978 to 2010. Cancer. 2013;119:4196–4204. Hackert T, Strobel O, Michalski CW, et al. The TRIANGLE operation—radical surgery after neoadjuvant treatment for advanced pancreatic cancer: a single arm observational study. HPB (Oxford). 2017;19:1001–1007. Harrison JM, Wo JY, Ferrone CR, et  al. Intraoperative radiation therapy (IORT) for borderline resectable and locally advanced pancreatic ductal adenocarcinoma (BR/LA PDAC) in the era of modern neoadjuvant treatment: short-term and long-term outcomes. Ann Surg Oncol. 2020;27:1400–1406. Keane FK, Wo JY, Ferrone CR, et al. Intraoperative radiotherapy in the era of intensive neoadjuvant chemotherapy and chemoradiotherapy for pancreatic adenocarcinoma. Am J Clin Oncol. 2018;41:607–612. Nishimura A, Nakano M, Otsu H, et  al. Intraoperative radiotherapy for advanced carcinoma of the pancreas. Cancer. 1984;54:2375–2384. Roldan GE, Gunderson LL, Nagorney DM, et al. External beam versus intraoperative and external beam irradiation for locally advanced pancreatic cancer. Cancer. 1988;61:1110. Sekigami Y, Michelakos T, Fernandez-Del Castillo C, et  al. Intraoperative radiation mitigates the effect of microscopically positive tumor margins on survival among pancreatic adenocarcinoma patients treated with neoadjuvant FOLFIRINOX and chemoradiation. Ann Surg Oncol. 2021;28:4592–4601. Shipley WU, Wood WC, Tepper JE, et al. Intraoperative electron beam irradiation for patients with unresectable pancreatic carcinoma. Ann Surg. 1984;14:200–289. Sindelar WF, Kinsella TJ. Studies of intraoperative radiotherapy in carcinoma of the pancreas. Ann Oncol. 1999;10(suppl 4):226. Tepper JE, Noyes D, Krall JM, et al. Intraoperative radiation therapy of pancreatic carcinoma: a report of RTOG-8505. Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys. 1991;21:1145.

complications, it has also been shown to lead to an increased number of dangerous hypoglycemic episodes. Technologic advances (insulin pumps and continuous glucose sensors) may help reduce the incidence of secondary complications and the number of hypoglycemic episodes. Transplantation therapy for type 1 diabetes was developed as an alternative to insulin administration, with the goal of reducing or eliminating the development of secondary complications of the disease by perfecting glycemic control. The pancreas—both the whole organ and isolated pancreatic islets—is being transplanted into individuals with type 1 diabetes. Clinical islet transplantation has been an experimental therapy available at only a few academic centers for the past 20 years. However, in 2021, the US Food and Drug Administration granted regulatory approval to CellTrans as the first entity approved to supply pancreatic islets as a commercial product for transplantation into highly select diabetic individuals with severe hypoglycemia unawareness. In contrast, whole-organ pancreas transplantation is an established and widely available therapy for the treatment of individuals with type 1 diabetes and also a highly select group of individuals with type 2 diabetes. Whole-organ pancreas transplantation is the main focus of this chapter.

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Transplantation of the Pancreas

WHOLE-ORGAN PANCREAS TRANSPLANTATION History and Early Results On December 20, 1893, Dr. P. Watson Williams grafted pieces of a sheep pancreas into the subcutaneous tissues of a diabetic child who died 3 days later of unrelenting diabetic ketoacidosis. This first attempt to treat diabetes with transplantation, although unsuccessful, preceded decades of animal experimentation in which investigators developed the methods necessary to perform a vascularized pancreas transplant. The first vascularized pancreas transplant in a patient was performed on December 17, 1966, by Drs. William Kelly and Richard Lillehei at the University of Minnesota. The patient achieved temporary insulin independence but eventually required graft removal and ultimately died of postoperative complications. The subsequent early experience with pancreas transplantation was characterized by some technical success, but no graft functioned beyond 1 year. Most pancreas grafts that were successful from a technical perspective were lost as a result of rejection. The initial enthusiasm for this procedure dwindled so much that it was nearly abandoned by the mid-1970s. However, further technical refinements and the introduction of more potent immunosuppressive medications (first cyclosporine and then tacrolimus) allowed for more favorable outcomes after pancreas transplantation. Throughout the 1980s and early 1990s, the number of pancreas transplants performed in the United States increased dramatically, peaking at nearly 1500 transplants during 2004. However, this number has declined since, with fewer than 1000 pancreas transplants performed in the United States during 2021.

Indications and Patient Selection The majority of patients undergoing pancreas transplantation have type 1 diabetes mellitus and end-stage renal disease. In these individuals, pancreas transplantation is performed with simultaneous kidney transplantation (simultaneous pancreas and kidney [SPK] transplantation) or after successful kidney transplantation (pancreas after kidney [PAK] transplantation). The normal blood glucose control achieved by the transplanted pancreas should protect the transplanted kidney from recurrent diabetic nephropathy and is beneficial from an overall quality-of-life perspective. In a small proportion of patients with difficult-to-control diabetes but with preserved renal function, pancreas transplantation alone (PTA) is performed. In the United States for the 3-year period ending in 2021, 85% of pancreas transplantations were SPK, 6% PAK, and 9% PTA. SPK and PAK recipients require immunosuppressive therapy to protect both the kidney and pancreas from rejection, whereas in the case of PTA recipients, the need for immunosuppression is solely for the pancreas itself. For this reason, careful individual risk-to-benefit consideration is essential in selecting PTA recipients. Potential pancreas recipients are carefully screened for contraindications to transplantation, such as an ongoing infectious process or malignancy. These candidates almost always have medical comorbid conditions resulting from secondary complications from diabetes; therefore, a thorough assessment of a candidate’s cardiovascular status is essential. Cardiac contraindications to pancreas transplantation include the presence of noncorrectable coronary artery disease, ejection fraction of less than 40%, or myocardial infarction within the previous 6 months. Recipient age is also important, although there is no consensus as to what an upper age limit should be for undergoing pancreas transplantation. National data indicate that almost all pancreas transplants in the United States are performed in recipients younger than 65 years of age.

The Donor Operation Selection of an appropriate deceased donor for pancreas procurement includes standard donor selection criteria. In addition, there is a bias toward using organs from younger, leaner, and hemodynamically stable deceased donors. Donor organs that require high doses of vasopressor are considered higher risk for complications in the recipient. In addition, pancreata with significant infiltration of fat in the parenchyma are usually avoided because they are associated with a greater likelihood of postoperative complications such as pancreatitis, peripancreatic fat necrosis, and infection. On the basis of these relatively stringent selection criteria, only a fraction of deceased donors are deemed suitable for whole-organ pancreas donation. In the United States, there were 13,863 deceased donors during 2021; however, only 976 pancreata were transplanted from 7% of all deceased donors, in comparison with 8666 livers (63%) and 19,843 kidneys (72% of all deceased donors). Pancreas procurement from a deceased donor is performed in careful conjunction with liver procurement. The blood supply to the liver is identified to ensure that both organs can be removed and transplanted. In most cases, aberrant blood supply should not preclude the transplantation of both organs. Initial dissection involves division of the gastrocolic ligament to expose the anterior surface of the pancreas. Visual inspection is considered an important element in pancreas procurement because this is an opportunity to assess the organ for the presence of infiltrating fat, fibrosis, or hematoma that might preclude transplantation. The portal triad is carefully dissected, with division of the common bile duct and the gastroduodenal artery. In addition, the common hepatic, the proximal left gastric, and the proximal splenic arteries are all dissected free from surrounding lymphatic tissues. Further dissection of the pancreas includes performing Kocher’s maneuver to mobilize the pancreatic head and dividing the lienophrenic and lienocolic ligaments to mobilize the pancreatic body and tail. Of note, the spleen is left in continuity with the pancreas to minimize manipulation of the gland, and it is removed later during backbench preparation. The duodenum is decontaminated by flushing of a solution containing povidone-iodine, an antibiotic, and an antifungal through a nasoduodenal tube. After the donor has been prepared with heparin, the abdominal aorta is ligated at the iliac bifurcation, and a cannula is placed in a retrograde direction for perfusion. The liver surgery team may also place a cannula into a portal vein tributary, such as the inferior mesenteric vein, for portal perfusion. The supraceliac aorta is cross-clamped, the vena cava is vented, and the abdominal organs are flushed in situ with preservation solution (Belzer UW Cold Storage Solution) at 4°C. In addition, topical cooling of the organs is performed. Once the organs have been adequately flushed, the liver and pancreas are removed either en bloc and divided on the back table or removed separately from the donor. In the latter situation, the liver is removed first, by division of the portal vein 1 cm cephalad to the superior margin of the pancreatic head (at the level of the coronary vein) and division of the splenic artery 5 mm beyond its origin, which thus preserves the entire celiac axis with the liver. Next, removal of the pancreas proceeds. The proximal duodenum (just beyond the pylorus) and the distal duodenum (near the ligament of Treitz) are divided with a GIA stapler. The small bowel mesentery and transverse colon mesentery that lie inferior to the pancreas are divided. The superior mesenteric artery is divided just above its origin from the aorta. Long segments of iliac arteries and veins are removed for vascular reconstruction on the back table.

Backbench Preparation of the Pancreas In relation to other solid organs, the pancreas requires more preparation before transplantation into the recipient. This back table preparation is performed in ice-cold preservation solution to minimize further ischemic injury to the organ. The duodenum is often shortened with a GIA stapler, with care to exclude any gastric

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tissue and also not to compromise the opening of the ampulla of Vater. The small bowel mesentery is divided by firing a stapler across this mesentery and then reinforcing it with running Prolene suture. The transverse colon mesentery is divided in a similar manner. The spleen is removed by dividing the vessels in the splenic hilum, being careful not to injure the tail of the pancreas. Finally, the arterial inflow to the graft is reconstructed because the organ has two major sources of blood supply that are not in continuity: the splenic artery, which supplies the pancreatic body and tail, and the superior mesenteric artery, which supplies the pancreatic head. In most instances, arterial reconstruction can be performed with a donor iliac artery as a Y-graft. The internal iliac artery is joined to the splenic artery, and the external iliac artery is joined to the superior mesenteric artery. Both anastomoses are performed in an endto-end manner with fine Prolene (6-0) sutures. The common iliac artery of the Y-graft can then be anastomosed to the recipient artery to provide the arterial inflow to the pancreas. In rare instances, it is necessary to create a portal vein extension graft on the backbench with donor iliac vein; however, this technique is avoided when possible because it may increase the risk of venous thrombosis of the pancreas graft.

The Recipient Operation Unlike the techniques for most solid-organ transplantations, those for transplanting the pancreas have evolved significantly. Partial segmental grafts containing only the pancreatic body and tail were once common; however, this technique is rarely used now. Exocrine secretions were previously managed by pancreatic duct ligation or by injection of a polymer that would cause duct obliteration; today the exocrine secretions are handled by internal drainage. The two significant areas in pancreas transplantation in which current techniques differ are the drainage of exocrine secretions and the venous drainage of the graft. Exocrine drainage is performed either via the intestinal tract or via the bladder. Throughout most of the 1980s and 1990s, drainage of the pancreatic secretions into the recipient bladder was the most common form of exocrine drainage. This technique is convenient for monitoring organ function by measurement of amylase levels in the urine. However, problems with hematuria, cystitis, bicarbonate loss, and dehydration are all associated with bladder drainage. These complications necessitate surgical revision to enteric drainage in 20% of bladder-drained pancreas recipients. Because of these issues and the lower rejection rates observed with newer immunosuppressive medications, the vast majority of transplant centers now perform enteric drainage of exocrine secretions. This enteric drainage is either directly into a loop of jejunum in a side-to-side manner or into a Roux limb of jejunum. The venous drainage of the graft is either to the systemic circulation (via an iliac vein or the inferior vena cava) or to the portal circulation. Portal venous drainage has the advantage of delivering insulin in a more physiologic manner inasmuch as insulin undergoes a “first pass” through the liver, and the hyperinsulinemia that results from systemic drainage is avoided. An immunologic advantage of portal drainage has also been observed in several experimental studies in which the delivery of foreign antigen via the portal system results in diminished immune responses. Despite these theoretical advantages, there has been no demonstrable difference in outcomes between portal and systemic venous drained pancreatic transplants in humans, and systemic venous drainage is how the preponderance of pancreas transplants are performed. There are two common locations in the abdomen where a pancreas transplant is placed, on the basis of the type of venous drainage planned: either in the pelvis (most commonly the right side) for systemic venous drainage or in the midabdomen for portal venous drainage. When the graft is placed in the pelvis, the donor portal vein is anastomosed to the external iliac vein, the common iliac vein, or the inferior vena cava. In this pelvic position, the graft is oriented with the duodenum inferiorly if bladder drainage is planned

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(Fig. 1A) or with the duodenum in either the superior (Fig. 1B) or inferior direction if enteric drainage is planned. Alternatively, for portal venous drainage, the pancreas is placed in the midabdomen below the transverse colon with the duodenum oriented superiorly. The portal vein of the pancreas is anastomosed to the major branch of the superior mesenteric vein found in the small intestine mesentery in an end-to-side manner (Fig. 2). Enteric drainage for exocrine secretions must be used with portal venous drainage. With either technique, the arterial Y-graft of the pancreas is anastomosed in an end-to-side manner with either the recipient’s iliac artery (common or external) or distal aorta.

COMPLICATIONS The major complications after pancreas transplantation are often technical in nature. Thrombosis (arterial or venous) is more frequent in pancreatic grafts than in other solid-organ transplants, and the reported incidence is approximately 5% to 10%. Thrombosis often occurs within the first week after transplantation and is characterized by a sudden increase in serum glucose levels. In most instances of thrombosis, graft removal is necessary. Early pancreatitis occurs in 10% to 20% of cases and is largely a reflection of ischemic damage to the gland during preservation and subsequent reperfusion injury. Elevated serum amylase levels and graft edema are characteristic, and graft pancreatitis is usually treated with octreotide. Leakage at the site of pancreatic exocrine drainage is another early complication, with management often dictated by the method of drainage. Bladder-drained transplants with a small leak at the duodenocystostomy can often be managed by Foley catheter drainage of the bladder, which allows the site of leakage to heal over time. Leaks at the duodenojejunostomy in transplants with enteric drainage usually result in peritonitis, and operative intervention is necessary to control the leak. Rejection after pancreas transplantation was once very common. The diagnosis of pancreas rejection is often difficult, and a variety of indicators are used to help establish the diagnosis. These include increased serum amylase levels, decreased urinary amylase excretion (if bladder drainage is used), biopsy of the pancreas, and the presence of hyperglycemia. Hyperglycemia is a late indicator of rejection, however, and the pancreas is often difficult to salvage once hyperglycemia has occurred. If SPK transplantation is performed, then renal allograft dysfunction can often assist with the diagnosis of pancreatic rejection because the rejection process is usually occurring in both organs. As a result of the high incidence of rejection and the difficulty in establishing the diagnosis, pancreas transplant recipients usually receive potent induction immunosuppression with a T-cell–depleting agent and maintenance therapy with tacrolimus, mycophenolate mofetil, and corticosteroids. The total amount of immunosuppression that pancreas transplant recipients receive is among the highest for any solid-organ transplant. As a result, they are more susceptible to the complications of immunosuppressive therapy. These complications include infection with opportunistic bacteria, viruses, and fungi; malignancy; and gastrointestinal complications. The high incidence of these complications highlights the importance of effective prophylaxis strategies.

RESULTS Patient and graft survival after pancreas transplantation have improved significantly since the 1990s. The rates of patient survival are approximately 98% at 1 year and 92% at 5 years after SPK transplantation. Similar patient survival rates are reported for PAK and PTA recipients. Graft survival is variable, depending on the type of pancreas transplant performed (Fig. 3), and the reliability of the data is variable because of the lack of a widely accepted definition of pancreas graft failure. Nonetheless the reported 1- and 3-year pancreas graft survival rates for SPK recipients are 89% and 80%, respectively.

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Transplantation of the Pancreas

A

B

FIG. 1  Whole-organ pancreas transplantation with systemic venous drainage. The pancreas is placed on the right side of the pelvis with anastomosis of the donor portal vein to the recipient iliac vein for venous drainage. The donor iliac artery Y-graft is sewn to the recipient iliac artery for arterial inflow to the graft. Kidney transplantation can be performed simultaneously with the left-sided iliac vessels. (A) The donor duodenum is oriented inferiorly to allow anastomosis to the recipient bladder (shown) or to the recipient small intestine (not shown) for pancreatic exocrine drainage. (B) Alternatively, the donor duodenum is oriented superiorly to allow anastomosis to the recipient small intestine for pancreatic exocrine drainage.

For PAK and PTA recipients, 1- and 3-year pancreas graft survival rates are 84% and 66%, respectively. The effect of a successful pancreas transplant on the complications associated with diabetes mellitus is debated. Because the successful transplant restores euglycemia and normal hemoglobin A1c levels, most proponents argue that diabetic complications should cease and the damage perhaps be reversed. Neuropathy appears to stabilize and often improve after pancreas transplantation, whereas retinopathy progression is slowed after several years of graft function. The

Pancreas graft survival (%)

100

SPK PTA PAK

90 80 70 60 50 40 30 20 10

FIG. 2  Whole-organ pancreas transplantation with portal venous drainage. The pancreas is placed in the midabdomen with anastomosis of the donor portal vein to the major branch of the recipient superior mesenteric vein for venous drainage. The donor iliac artery Y-graft is sewn to the recipient iliac artery for arterial inflow to the graft. The donor duodenum is oriented in the superior direction for anastomosis to the recipient small intestine. Kidney transplantation can be performed simultaneously with either the left (shown) or right (not shown) iliac vessels.

0

1 year

3 years

5 years

Time after transplant FIG. 3  Pancreas graft survival rates at 1, 3, and 5 years after whole-organ transplantation by transplantation category. PAK, Pancreas-after-kidney (transplantation); PTA, pancreas transplantation alone; SPK, simultaneous pancreas and kidney transplantation.

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development of diabetic nephropathy in the transplanted kidneys of SPK and early PAK recipients appears to be prevented by successful pancreas transplantation. In PTA recipients, diabetic nephropathy appears to stabilize after the transplant; however, the renal benefit is probably outweighed by the detriment to renal function caused by the maintenance immunosuppressive agents, specifically tacrolimus or cyclosporine.

RISK-TO-BENEFIT CONSIDERATIONS Considerable evidence suggests that a pancreas transplant can stabilize the secondary complications of diabetes and, in some cases, reverse the damage. Despite this evidence, the procedure is considered appropriate for only a subset of patients with type 1 diabetes because of its highly invasive nature in comparison with insulin therapy and because of the potential for significant surgical complications. Therefore, risk-to-benefit considerations are of utmost importance in pancreas transplantation and play an essential role in the recipient selection process. In several important studies, researchers have evaluated the survival benefit of pancreas transplantation by examining large data sets to compare the survival of pancreas recipients with that of patients who were on a waiting list for transplantation but did not receive a pancreas. In this study design, the two patient groups were as similar as possible. Because the indications, risks, and benefits differ depending on whether a patient has underlying renal failure, these analyses were stratified according to whether a patient remained waitlisted or underwent an SPK, PAK, or PTA procedure. All studies revealed a marked survival benefit for patients who received SPK transplants, with a greater than 50% reduction in mortality at 4 years in comparison with similar patients who remained on the waiting list. In contrast with the clear survival benefit of SPK transplantation, the data for PAK and PTA recipients are less clear. In one study, the mortality rate among both PAK and PTA recipients was increased 4 years after transplantation; compared with the patients who remained on the waiting list, PAK recipients exhibited a 42% increase in mortality, and PTA recipients exhibited a 57% increase in mortality. However, another study demonstrated no difference in mortality rates among PAK and PTA recipients, with a trend toward improved survival in the PAK and PTA recipients in comparison with patients who remained on the waiting list. There are two important caveats to these risk-to-benefit studies. The first is that the effect of pancreas transplantation on quality of life was not evaluated in these nonrandomized retrospective analyses and would probably heavily favor the PAK and PTA recipients. Whether this factor would outweigh any survival disadvantage in the short term and the significant cost of these complex procedures has not been evaluated. A second critical outcome measure that is lacking from these studies is the long-term effect of successful pancreas transplantation on the secondary complications of diabetes. There is considerable evidence that diabetic nephropathy, neuropathy, and retinopathy may be positively affected by the long-term normoglycemia conferred by transplantation. These results substantiate the marked clinical benefit observed in the care of patients who receive SPK transplants. The relative

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contributions of the transplanted kidney and of the transplanted pancreas to the overall survival benefit have not been differentiated. This issue is significant because of the marked survival benefit that has been documented in the setting of kidney transplantation alone in diabetic recipients. Although the survival benefit for SPK recipients is clear, the data demonstrating a lack of survival benefit for PAK and PTA recipients remain controversial. At a minimum, the studies available to date suggest a narrow therapeutic margin for PAK and PTA recipients. Perhaps the most meaningful conclusions that can be drawn at present are that recipients should be selected with the utmost care, donor organs should be optimal, and the surgery should be performed at transplantation centers with favorable outcomes. The field is dynamic as a result of both improvements in surgical techniques and in perioperative management.

FUTURE DIRECTIONS Continued advancements in the care of individuals with type 1 diabetes may eventually render pancreas transplantation obsolete. Ongoing improvements in glucose sensing with continuous glucose monitoring (CGM) and insulin delivery via insulin pumps have improved the lives of countless individuals by making insulin delivery constant, thereby allowing more precise glycemic control. Improvements in software algorithms combined with wireless connectivity now allow closed-loop systems to automatically adjust the amount of insulin being delivered via a pump based on glucose readings obtained from a CGM, thus creating an “artificial pancreas.” Cellular therapy with embryonic stem cell–derived pancreatic beta cells has moved from the laboratory to early clinical trials. At least two products are undergoing testing in phase 1/2 clinical trials, with some early success being observed. A stem cell–derived product offers the hope of a limitless source of pancreatic beta cells that would be available to all individuals with type 1 diabetes seeking an alternative treatment option to exogenous insulin. In addition, a stem cell–derived product has the potential for genetic manipulation before differentiation using advanced techniques such as CRISPR. Genetic manipulations could be used for a variety of reasons, including enhancement of cellular function and reduction or elimination of immunogenicity. Although still several years from becoming an available treatment, stem cell–based therapy appears to be the ultimate transplant option for individuals with type 1 diabetes.

S uggested R eadings Gruessner RW, Sutherland DE, eds. Transplantation of the Pancreas. New York: Springer; 2004. Gruessner RW, Sutherland DE, Gruessner AC. Mortality assessment for pancreas transplants. Am J Transplant. 2004;4(12):2018–2026. Kandaswamy R, Stock PG, Miller J, et  al. OPTN/SRTR 2019 Annual data report: pancreas. Am J Transplant. 2021;21(Suppl 2):138–207. Venstrom JM, McBride MA, Rother KI, et al. Survival after pancreas transplantation in patients with diabetes and preserved kidney function. JAMA. 2003;290:2817–2823.

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Total Pancreatectomy and Islet Autotransplantation for Chronic Pancreatitis

Total Pancreatectomy and Islet Autotransplantation for Chronic Pancreatitis

age. Missing one dose of insulin in a patient with brittle diabetes can result in death. The physiologic disabilities created by the procedure are often permanent and should be taken very seriously.

Isabel S. Dennahy, MD, Christi Walsh, MSN, CRNP, and Martin A. Makary, MD, MPH

Pain Control

INTRODUCTION Proper patient selection is a critical part of surgical therapy with any operation, but patient selection is especially challenging in the case of total pancreatectomy with islet autotransplantation (TPIAT). All of us who have performed this procedure for many years have regrets about offering the procedure to patients who technically met the criteria but ended up having a poor outcome because of poor social support, opioid addiction, or underestimation of a patient’s ability to manage severe diabetes later in life when it occurs. TPIAT is an option for a very small subset of patients being considered for surgical therapy for chronic pancreatitis (CP). We find that the Frey procedure is the procedure of choice for most patients with chronic pain and a dilated pancreatic duct, unless they have a precancerous gene mutation as the etiology. As a result, genetic testing has become a standard of care in these patients. We do not perform TPIAT procedures for patients with alcoholic pancreatitis (AP) or patients with mild symptoms. Instead, we reserve this highly morbid procedure for patients with debilitating pain and a genetic mutation or idiopathic cause for pancreatitis. The procedure is intended to achieve the desired outcome of pain improvement and prevent or temper the effects of endocrine insufficiency. It has now been adopted at numerous centers worldwide, with the number of procedures being performed annually across the United States more than tripling in the past 20 years.

PATIENT SELECTION Over the past several years, we have narrowed our criteria for performing a TPIAT procedure. In addition to setting a high bar with patient selection, we work hard to ensure that patients understand what it is like to have severe brittle diabetes that may result from the procedure and what it is like to take pancreatic enzymes with each meal. Even though insulin-dependent diabetes can be averted for several years after the procedure, we tell all patients that they will develop diabetes as a result of the procedure. For those who already have diabetes, we tell them that it may result in brittle diabetes because the autotransplanted islets do not have good longevity in many patients. In short, we only offer the procedure to those who understand what it means to have brittle diabetes in the short term and in the future when they may be older and frail. Some surgeons even inform all TPIAT patients that they will develop diabetes; it’s just a matter of how long after the procedure. As a starting point, no patient should undergo TPIAT unless they are able and motivated to regularly check their blood glucose levels, inject themselves with insulin three times a day, and take oral pancreatic enzymes with each meal. Surgeons should not only consider if a patient can be compliant with this regimen in their current state of health and age, but also if they will still be able to do so in 20 or 30 years. For example, if a 50-year-old patient has some cognitive slowing, it should be anticipated that they will not be able to comply with an insulin regimen in 20 years’ time, when they are 70 years of

EVIDENCE Before considering patient selection, it is important to have an understanding of the potential outcomes of the procedure and the factors that may affect this.

Review of data from the past 50 years has demonstrated favorable results in terms of pain control following TPIAT for CP. Significant improvements in pain can be achieved in the form of reduction in opiate requirements or freedom from opiate use in most patients. Studies describe improvements in pain scores in approximately 70% of patients, with the largest study from the University of Minnesota demonstrating pain improvements in 85% to 92% of patients. There is limited data on long-term pain outcomes; however, two studies looking at the longer-term durability of this operation suggest up to 82% of patients freedom from persistent pain at 5 or 10 years post-TPIAT. Given these results, we inform all patients that there is a 20% chance that they may have the operation (possibly with a complication such as brittle diabetes) and have zero pain relief after the operation. In other words, patients should understand that there is a roughly 20% risk that they will be in the exact same pain that they started with. Proper informed consent for this procedure requires several clinic visits over time.

Endocrine Function TPIAT is associated with postoperative lifelong insulin requirements in two-thirds of patients. This is typically from a baseline of no diabetes or non–insulin-dependent diabetes, which can represent a significant change for patients and must be weighed against the potential for pain relief during preoperative counseling. However, in the natural course of CP without surgery, 83% of patients will develop some degree of diabetes within 25 years of diagnosis regardless, albeit usually mild. The prospect of post-TPIAT insulin dependence lies in stark contrast with the type IIIc (brittle) diabetes that would result from total pancreatectomy (TP) alone. TP alone is associated with “difficult-to-control” brittle diabetes in over 75% of patients, and the removal of glucagon-containing α-cells can result in unpredictable responses to exogenous insulin and episodes of dangerous hypoglycemia. Glucagon-containing α-cells are important in insulin regulation. Without them, swings in blood glucose levels are magnified and more difficult to control. Several large-scale studies have documented C-peptide levels as a measure of graft (islet) function as well as different classes of insulin dependence after autologous islet transplantation. Approximately 90% of patients have evidence of islet function following transplantation. This translates into varying degrees of glucose tolerance or insulin dependence, with patients falling approximately into a rule of thirds: one-third of patients (30%) are insulin independent at 3 years post-TPIAT; one-third (33%) require supplementation with once-daily or intermittent insulin doses; and one-third (37%) require a more intensive basal-bolus–style regimen of insulin. Limited data looking at hypoglycemic events after TPIAT have shown that patients may have difficulties with glucose homeostasis postoperatively, even if they retain insulin independence. In a study of 14 patients, 11 reported frequent hypoglycemic events, with 50% of these having daily episodes of hypoglycemia. Patients also tend to suffer from muted or absent symptom responses during these episodes. It is hypothesized that because of hepatic gluconeogenesis and

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glycogenolysis, local hyperglycemia impairs the detection of systemic hypoglycemia by the islets. Several studies have suggested, however, that this may be ameliorated by additional non-hepatic sites of islet transplantation. Some element of exhaustion of transplanted islets occurs over time, with notable increases in patients’ insulin requirements over the years following TPIAT. Initial small-scale studies looking at long-term graft function demonstrated that all patients maintain evidence of C-peptide production at 10 years posttransplant. However, recent long-term data from the University of Minnesota found that of 140 patients with data at 10 years posttransplant, only 20% maintained insulin independence. In this study, the proportion of patients requiring basal-bolus insulin increased from 23% to 52% after 10 years.

Overall Quality of Life Importantly, the improvements in pain scores and opiate requirements are translated into noticeable improvements in quality of life (QoL) for these patients. After TPIAT, 84% of patients report improvement in QoL, with further increases after the first year postoperatively. These improvements are sustained at 5 and 10 years on long-term follow-up. QoL has also been shown to improve even if patients are still requiring some opiates and, significantly, QoL improvements are maintained regardless of postoperative insulin requirements. However, the highest percentage of improvement is understandably seen in patients who achieve both pain control and insulin independence.

Factors Predictive of Outcome Unfortunately, despite success in the majority of patients, 10% to 20% of patients will see no improvement in pain or QoL. Furthermore, if these patients fall on the worse end of the spectrum of postoperative glycemic control or suffer complications of the operation, it may worsen their QoL in a significant way. As a result, many groups have attempted to tease out which patients derive success from the operation and which do not. A landmark study from the University of Alabama at Birmingham in 2013 assessed outcomes according to underlying etiology of the disease. This study found that patients with AP showed no meaningful improvement in pain scores or QoL following surgery, and they were also more likely to have a low islet yield and higher insulin requirements at follow-up. Factors that influence islet yield include low body weight (BMI 30); personal or family history of diabetes; longer duration of disease (>5 years); more progressive disease as evidenced either by atrophy, calcifications, or ductal dilation on imaging or by endocrine or exocrine insufficiency; and previous pancreatic resection. The greatest predictor of postoperative endocrine function across a number of studies has been transplanted islet mass, with a 28-fold increased risk of graft failure among patients with 5000 IE/kg transplanted. Unfortunately, islet yield cannot yet be accurately predicted preoperatively.

PREOPERATIVE EVALUATION Any personal history of genetic risk factors for recurrent AP or CP (e.g., CFTR, SPINK1, or PRSS1) is important to note as the lifetime risk of pancreatitis and pancreatic cancer may warrant stronger consideration of TPIAT. Marked portal hypertension is a contraindication to islet infusion because of intraoperative increases in portal pressure.

Investigations Preoperative laboratory testing should include further assessment of endocrine function. This typically includes glucose tolerance testing,

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HbA1c measurement, and C-peptide measurements. Exocrine function is sometimes assessed via fecal elastase testing and fat-soluble vitamin levels, but these tests are not essential. Imaging should be obtained to confirm features of CP, assess the extent of fibrosis, and establish the vascular anatomy in the area. The location of disease in the pancreas should also be evaluated for consideration of localized resection. It is also important to rule out any evidence of pancreatic neoplasm, as this is a direct contraindication to IAT. Further imaging assessment of any pancreatic lesions noted during workup should be performed using endoscopic ultrasound. Significant ductal dilation (>5 mm) seen in patients without a precancerous genetic mutation to provide strong indication for prophylactic resection may warrant consideration of a decompressive operation in place of TPIAT.

SURGICAL PLANNING Our practice is to offer TPIAT to patients with debilitating chronic pain of pancreatic origin who either have a genetic mutation or are not a candidate for a hybrid resection/drainage operation.

Timing of Surgical Intervention Our practice is to have found the following triggers to be milestones to discuss surgery for eligible patients with CP with debilitating pain or multiple episodes of acute pancreatitis each year for multiple years: 1. Development of prediabetes or any evidence of exocrine insufficiency 2. Identification of a genetic cause of recurrent acute pancreatitis 3. A person’s inability to be in school or work as a result of recurrent attacks of acute pancreatitis

COUNSELING AND DECISION MAKING Patients should be adequately counseled on the statistical outcomes in terms of both pain control and postoperative endocrine function. They should also be counseled on the potential complications of the operation and postoperative care, including diabetic and nutritional monitoring as well as lifelong pancreatic enzyme replacement. Given the considerable risks behind TPIAT, especially the risks of nonimprovement in pain and loss of glycemic control, patients are generally recommended to undergo evaluation by a multidisciplinary team including a gastroenterologist, a hepatopancreaticobiliary surgeon, an endocrinologist, an anesthesia pain specialist, and/or a neuropsychologist as part of their preoperative assessment. As part of guidance from PancreasFest 2012 on TPIAT in CP, review by this team is intended to “review alternative interventions, assess the likelihood of success in reducing pain and preventing or minimizing diabetes, follow the patient through the procedure and provide guidance for long-term care.” At our institution, we schedule multiple clinic visits before scheduling surgery to ensure that patients are comfortable with the decision. We have multiple discussions to prepare the patient for the possibility of failed pain control as well as the development of diabetes. We generally discuss with patients that diabetes is inevitable, regardless of initial postoperative function, and that islet autotransplantation is intended to delay this. Transplanted islets rarely maintain enough insulin production to keep a patient insulin-free beyond 10 years.

OPERATIVE TECHNIQUE TPIAT involves performance of TP followed by isolation and processing of islets before islet infusion. At our institution, minimally invasive TP is the procedure of choice when appropriate. This may either be laparoscopic or robotic, depending on surgeon experience. Our conversion rate is approximately 10%, usually resulting from

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Total Pancreatectomy and Islet Autotransplantation for Chronic Pancreatitis

extensive scarring from recurrent episodes of pancreatitis. Approximately 30% of our cases are planned open because of surgical history or other factors. The operative approach for TP varies among centers. Duodenal-sparing TP was previously performed but has been largely abandoned. Our preference is to perform a traditional pre-pyloric resection. We sometimes perform a splenectomy to be able to perfuse the tail of the pancreas after it is removed. In contrast with TP performed for pancreatic cancer, the surgical resection during a TPIAT is modified to minimize warm ischemic time. As a result, full mobilization of the pancreas should be achieved before vascular ligation, with the exception of the gastroduodenal artery (GDA), which has good backflow. To achieve this, we generally perform a Whipple procedure if allowed by scarring and process the pancreatic head while then dissecting out the body and tail of the pancreas. The body and tail are subsequently processed after vessel ligation as a final step.

■ Dissection of the hepatoduodenal ligament to isolate the

Preparation

■ ■ ■ ■ ■ ■

Islet isolation techniques vary among centers. These variations include same-day intraoperative isolation and transplant versus laboratory isolation with next-day transplant in interventional radiology. Intraoperative islet isolation allows for immediate processing of the pancreas and a patient-centered approach. It also minimizes cold ischemia time and maximizes efficiency of the operation as well as islet yield.

■ ■ ■ ■ ■

■ ■ ■ ■ ■

portal structures and the GDA, and clipped transection of the GDA Creation of a tunnel underneath the neck of the pancreas from the superior mesenteric vein cephalad Performance of a cholecystectomy Transection of the common hepatic duct Transection of the neck of the pancreas Mobilization of the first portion of the jejunum through the defect in the ligament of Treitz and stapled transection of the jejunum Dissection of the head of the pancreas off of the SMA Delivery of the Whipple specimen and processing by the transplant team Medial-to-lateral mobilization of the body and tail of the pancreas Stapled transection of the splenic artery and vein Delivery of the distal pancreatectomy specimen and processing by the transplant team Mobilization and resection of the spleen End-to-side hepaticojejunostomy Antecolic side-to-side gastrojejunostomy Intraportal infusion of islets via angiocatheter Closure of venotomy Surgical drain placement and abdominal closure

Islet Processing and Infusion

After entry to the abdomen has been achieved (whether laparoscopic or open), the following steps are performed (Fig. 1):

As described, the separate Whipple and distal pancreatectomy specimens are delivered to the transplant team and processed in parallel to completion of surgical resection. Steps for processing each of the specimens are as follows (Fig. 2):

■ Mobilization of the right colon and hepatic flexure and takedown

■ Flushing of the arterial system (the Whipple specimen via the

FIG. 1  Representative image of separate Whipple and distal pancreas specimens with cannulation of the pancreatic duct of the distal pancreatectomy specimen.

FIG. 2  Laparoscopic infusion of islet isolate into the portal vein.

Total Pancreatectomy

of the greater omentum from the greater curvature of the stomach ■ Release of the lesser curve of the stomach from the lesser omentum and stapled transection of the stomach just proximal to the pylorus ■ Performance of an extended Kocher maneuver to mobilize the pancreatic head and expose it to the superior mesenteric artery (SMA)

GDA and the distal pancreatectomy via the splenic artery) with cold preservation solution ■ Removal of peripancreatic tissues from the specimen ■ Cannulation of the pancreatic duct with an angiocatheter (if not permitted by scarring, enzyme solution may be injected directly into the parenchyma at multiple sites) ■ Distension of the duct with combined solution of collagenase and thermolysin

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■ Sectioning of the pancreas into pieces less than 1 cm3 in size ■ Placement of sections into a Ricordi digestion chamber with addi-

tional enzyme solution (pulmozyme)

■ Collection of isolate and measurement of the final islet count

Portal pressure is measured via the angiocatheter during infusion with the aim of maintaining this below 15 to 20 mm Hg. If portal pressures remain persistently elevated above this level or the volume of isolate exceeds 20 mL, remaining tissue can be injected into the peritoneal cavity, mesentery, or stomach wall.

INTRAOPERATIVE CARE Blood glucose levels should be closely monitored throughout the case, with maintenance of serum glucose of 100 to 120 mg/dL. Multiple animal studies have demonstrated that hyperglycemia is detrimental to transplanted islet engraftment; therefore, euglycemia may be important for initial graft survival.

POSTOPERATIVE CARE At our institution, patients are typically transferred to the surgical intensive care unit postoperatively. The patient is also kept on an insulin drip overnight for tight control. Following this, endocrinology is consulted to provide recommendations on further glycemic control and assist with the transition to subcutaneous insulin injection. Daily C-peptides are measured at this point to monitor graft function. Patients are then generally maintained on intravenous insulin for the first 1 to 3 months postoperatively (goal glucose in the range of 100–120) as strict normoglycemia is thought to reduce stress on the transplanted islets and allow for maximal engraftment. We generally consult the acute pain service postoperatively also in patients with high preoperative opiate requirements. They will see the patient and provide recommendations throughout their recovery. A nasogastric tube is placed in the operating room and maintained for at least the first night following surgery. Thereafter, when the patient is demonstrating evidence of bowel function, we advance the diet until tolerating a regular diet. Creon is added when tolerating semisolid food. If there are no other issues, a surgical drain is monitored postoperatively and removed when drainage is consistently 50,000 mm3 usually have mild bleeding, and levels < 10,000 mm3 put patients at the greatest risk for major internal bleeding. Interestingly, children often present at around the 5 years of age with sudden onset of petechiae or purpura several days or weeks after an infectious illness. In contrast, adults seem to experience a more insidious and chronic form. Notably, splenomegaly is generally regarded as uncommon in ITP for both children and adults. Its presence warrants alternative diagnoses to be explored. The medical workup for ITP and symptomatic thrombocytopenia is quite extensive and should include the exclusion of other common disease processes such as systemic lupus erythematosus (SLE), antiphospholipid syndrome, human immunodeficiency virus (HIV), and hepatitis C (Hep C), to name a few. Although the first-line therapy for ITP is oral prednisone, there still remains no good consensus on the duration of therapy. However, on average most responders, which account for 50% to 75% of patients, will see dramatic improvements within 3 weeks. For severe cases with confirmed or presumed internal bleeding, intravenous immunoglobulin is indicated. Splenectomy is indicated in failure of medical management including prolonged steroid use with undesired effects, relapse after treatment to maintain platelet count levels >30,000 mm3, and in rare cases for life-threatening acute bleeding. Splenectomy in children with ITP remains controversial as their clinical courses are usually self-limited, and complete remission is seen in more than 70% of children regardless of medical therapy selected.

Thrombotic Thrombocytopenic Purpura Thrombotic thrombocytopenic purpura (TTP) is a serious medical condition characterized by thrombocytopenia, microangiopathic hemolytic anemia, and neurologic, renal, or cardiac complications. Its incidence is reported to be approximately 4 individuals per 1 million. Abnormal clotting of platelets occurs in arterioles and capillary beds, predisposing the patient to microvascular thrombotic events. The reduction in lumen size caused by clumping of platelets also leads to deformation of red blood cells, which are then subjected to hemolysis by the spleen. Clinical manifestations of TTP are hallmarked by petechial hemorrhages in the lower extremities, fever, neurologic symptoms (from generalized headaches to altered mental status or seizures), renal failure, and infrequently heart failure or cardiac arrythmia. Patients may also demonstrate flulike symptoms, malaise, or fatigue, making its differential diagnosis often broad. The diagnosis is confirmed by peripheral blood smear, which shows classic schistocytes, nucleated red blood cells, and basophilic stippling. In conjunction with thrombocytopenia and a negative Coombs test, the diagnosis of TTP is however often easy to make. Although plasma exchange is the first-line therapy for TTP, splenectomy should be considered in patients who experience a relapse or who require multiple plasma exchange therapies to control severe symptoms.

Sp l e e n

MALIGNANT CONDITIONS White Cell Disorders Chronic Lymphocytic Leukemia Chronic lymphocytic leukemia (CLL) is considered a subtype of NHL highlighted by progressive accumulation of old and nonfunctioning lymphocytes. Although the most common presentation of CLL includes lymphadenopathy, clinical presentations of CLL can be nonspecific and include weakness, fatigue, fever, and night sweats, along with frequent bacterial and viral infections. Splenomegaly may be present, and if massive, splenectomy may be indicated to also help improve cytopenias and facilitate chemotherapy in patients whose cell counts are prohibitively low.

Hairy Cell Leukemia Hairy cell leukemia (HCL) is an uncommon white cell disorder representing only 2% of all adult leukemias. HCL is characterized by pancytopenia, a large number of abnormal lymphocytes in the bone marrow, and splenomegaly. These lymphocytes contain irregular hairlike cytoplasmic projections, as the name implies. Splenectomy for HCL was historically performed as a palliative procedure (especially in pregnancy), alleviating symptoms of splenomegaly and normalizing peripheral blood counts, but it may not lead to morphologic bone marrow remissions. Asymptomatic patients with HCL require no specific therapy.

Hodgkin’s Lymphoma Hodgkin’s lymphoma (HL) is a disorder of the lymphoid system characterized by the presence of Reed-Sternberg cells. More than 90% of patients with HL present with lymphadenopathy above the diaphragm. Massive lymphadenopathy within the mediastinum can lead to shortness of breath, cough, and pneumonia. Lymphadenopathy below the diaphragm is uncommon but often suggests advanced disease. Although the spleen is often an occult site, massive splenomegaly with HL is uncommon, and therefore the role of splenectomy may be limited.

Non-Hodgkin’s Lymphoma Non-Hodgkin’s lymphoma (NHL) encompasses all malignancies derived from the lymphoid system except classic HL. A proliferation of any one of the three predominant lymph cell types (natural killer cells, T cells, or B cells) may be included in the category of NHL. Because of the varied cell types, the clinical subtypes also vary, including but not limited to nodal versus extranodal, indolent versus aggressive, and very aggressive types. Clinical presentations may include mild lymphadenopathy or no symptoms to more aggressive symptoms such as pain, fever, and night sweats. Splenomegaly also exists in some, but not all forms of NHL. Although splenectomy does not alter the natural history of disease in NHL, it is indicated in cases in which a diagnosis cannot be established in peripheral tissue or for the management of an enlarged spleen.

MYELOPROLIFERATIVE DISORDERS Acute Myeloid Leukemia Acute myeloid leukemia (AML) involves abnormal growth of stem cells in the bone marrow with a rapid and dramatic presentation. The incidence of AML in the United States is approximately 10,000 new cases each year and accounts for just over 1% of all cancer deaths. Death from AML may be seen within weeks to months if untreated. Presenting symptoms are nonspecific and include viral-like illness with fever, malaise, and bone pain caused by expansion into the medullary space. Standard treatment includes systemic therapy and stem cell transplantation. Because of concerns of post-splenectomy infection in neutropenic patients on chemotherapy, splenectomy may be considered in AML only when massive splenomegaly leads

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to left upper quadrant abdominal pain and/or early satiety from mass effect.

Chronic Myelogenous Leukemia Chronic myelogenous leukemia (CML) involves abnormal growth of the primitive pluripotent stem cells in the bone marrow that result in significant increases in erythroid, megakaryotic, and pluripotent progenitors on peripheral blood smear. It has a much more indolent course compared with AML and is hallmarked by transposition between the BCR gene on chromosome 9 and the ABL gene on chromosome 22. CML accounts for roughly 15% of all leukemias, with an incidence in the United States of 1.5 per 100,000. Although often asymptomatic, CML can cause fatigue, anorexia, left upper quadrant pain, and early satiety. Roughly one-half of patients will have splenomegaly, with splenectomy indicated to relieve symptoms associated with mass effect. Notably, splenectomy has no impact on blast crises and does not alter disease progression.

Chronic Myelomonocytic Leukemia Chronic myelomonocytic leukemia (CMML), like AML and CML, is characterized by proliferation of hematopoietic elements in the bone marrow and blood. CMML differs histologically from CML as it is hallmarked by monocytosis in the peripheral smear and in the bone marrow. Like CML, roughly 50% of patients will present with splenomegaly, for which splenectomy may be indicated to relieve symptoms associated with mass effect.

Essential Thrombocythemia Essential thrombocythemia (ET) occurs from abnormal growth of the megakaryocytic cell line, resulting in increased levels of platelets in the bloodstream, as the name implies. Diagnosis is made by first excluding other conditions that can cause thrombocytosis (such as CML and polycythemia vera). Clinical manifestations of ET include vasomotor symptoms as well as thrombohemorrhagic events including recurrent fetal loss in women of childbearing age. Although hydroxyurea can be used to reduce thrombotic events, it unfortunately does not reduce the risk of myelofibrosis or conversion to AML. Although splenomegaly may occur in one-third to one-half of patients, it is not believed to be helpful in the early stages of ET and is only reserved for the later stages of disease, when myeloid metaplasia may have developed.

Myelofibrosis (Agnongenic Myeloid Metaplasia) Agnongenic myeloid metaplasia (AMM) can be referred to as myelosclerosis, idiopathic myeloid metaplasia, or osteosclerosis. It may be associated with a number of benign or malignant disorders and present with or without splenomegaly. Histologically, nucleated red blood cells and immature myeloid elements in the blood are present in nearly 100% of cases and strongly suggest the diagnosis of AMM. Teardrop poikilocytosis may also be present. AMM must be differentiated from primary neoplasms such as lymphoma; adenocarcinoma of the GI tract, lung, prostate, and breast; and conditions such as tuberculosis in which myelofibrosis may occur secondarily. Treatment depends on symptoms, with splenomegaly symptoms being treated with splenectomy.

Polycythemia Vera Polycythemia vera (PV) is a progressive myeloproliferative disorder characterized by an increase in all cell lines to include red blood cells, white blood cells, and platelets. PV is rare, with an annual incidence of 5 to 17 per 1 million individuals. Physical examination findings are hallmarked by hypertension, conjunctival plethora, ruddy cyanosis, and hepatosplenomegaly. Treatment will depend on

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Splenectomy for Hematologic Disorders

disease characteristics and may include simple phlebotomy, aspirin, or chemotherapy for more severe disease. As with ET, splenectomy may not be helpful in early disease and is best reserved for patients with later-stage disease.

PRIMARY TUMORS OF THE SPLEEN AND METASTASIS The most common primary tumors of the spleen are sarcomas, many of which are linked to environmental and occupational exposures (such as vinyl chloride or thorium dioxide). Lung carcinoma is the tumor that most commonly metastasizes to the spleen, although melanoma and colorectal and ovarian carcinoma can spread to the spleen as well. Splenectomy can be considered in isolated splenic metastasis.

MISCELLANEOUS CONDITIONS Amyloidosis Amyloidosis is a disorder of abnormal extracellular protein deposition. Like NP, there are multiple forms of amyloidosis, each with its own clinical presentation from mild asymptomatic to those that lead to multiorgan system failure. Only 5% of patients with amyloidosis will experience splenomegaly, and a smaller percentage of patients with secondary amyloidosis may even present with splenic rupture. Splenectomy may be indicated in symptomatic patients.

Gaucher’s Disease Gaucher’s disease is a lipid-storage disorder characterized by the deposition of glucocerebroside in the cells of the macrophage-monocyte system. The underlying abnormality is a deficiency in the activity of lysosomal hydrolase in which abnormal glycolipids storage results in organomegaly such as hepatosplenomegaly. Thus symptoms including abdominal pain and early satiety may be seen in addition to normocytic anemia, thrombocytopenia, leukopenia, bone pain, pathologic fractures, and jaundice. Hematologic findings occur as a result of sequestration of formed blood elements in the spleen for which splenectomy may be indicated, although it may not correct the underlying disease process.

Niemann-Pick Disease Niemann-Pick (NP) disease is another inherited disorder that includes four subtypes (A, B, C, and D), each with its own unique clinical presentation. NP results from abnormal lysosomal storage of sphingomyelin and cholesterol in cells of the macrophage-monocyte system. Splenomegaly is common, and splenectomy is indicated for symptomatic patients.

Sarcoidosis Sarcoidosis is an inflammatory disease characterized by noncaseating granulomas. Signs and symptoms of sarcoidosis range in severity and are typically nonspecific including fatigue and malaise. Although the most common organ involved are the lungs, the spleen is the second most common and occurs in approximately 25% of patients. Massive splenomegaly, however, is rare, with a reported incidence around 3%. Splenectomy effectively relieves symptoms of splenomegaly and may correct hematologic manifestations such as anemia and thrombocytopenia often seen in sarcoidosis.

PERIOPERATIVE CONSIDERATIONS Vaccination Vaccinations directed at encapsulated pathogens are the mainstay of preventive therapy for the asplenic patient. Although rare,

overwhelming post-splenectomy sepsis (OPSI) remains the most dreaded and extreme infectious complication of splenectomized patients. OPSI is seen more commonly in the pediatric population, therefore strong risk-benefit analysis must be undertaken when considering total splenectomy in children and adolescents. Although the risk of OPSI is seen more frequently within 2 years of splenectomy, asplenic patients remain at risk for OPSI lifelong. Recommended vaccinations include an annual influenza vaccine but also must include therapy against the encapsulated bacteria: Streptococcus pneumoniae (which is responsible for >50% of OPSIs), Haemophilus  influenzae type B, and Neisseria meningitidis. Ideally, patients will receive their vaccines 2 weeks before elective splenectomy. If splenectomy is performed emergently, although vaccinations can be administered immediately postoperatively (especially in a poorly compliant trauma patient!), strong consideration should be given to delayed administration for 2 weeks to avoid the transient immunosuppression seen with surgery, which has been shown to reduce vaccine efficacy.

Deep Vein Thrombosis Prophylaxis Deep vein thrombosis (DVT) can be seen after splenectomy, especially in myeloproliferative disorders requiring splenectomy, with portal vein thrombosis arising in as many as 50% of these patients. Therefore all patients undergoing splenectomy should be given sequential compression devices (SCDs) and considered for subcutaneous heparin preoperatively. For patients at the highest risk, such as obese patients, smokers, or patients with cancer, postoperative DVT prophylactic therapy with low-molecular-weight heparin should be strongly considered on discharge.

SPLENECTOMY TECHNIQUES Open During open splenectomy, the patient is positioned on the operating table in the supine position. Although an upper midline incision may be more commonly selected in the case of traumatic spleen rupture or when massive splenomegaly is anticipated to make the exposure attained by a subcostal incision suboptimal, our preference is to use a left subcostal incision for the vast majority of elective splenectomies. This incision is made paralleling the left costal margin and two fingerbreadths below. Once entered into the peritoneal cavity, our preference is to use a Bookwalter retractor for exposure. The first steps of the procedure involve dividing the ligamentous attachments. In patients with significant splenomegaly, once lesser sac access has been achieved by either the gastrosplenic or gastrohepatic attachments, early ligation of the splenic artery found along the superior border of the pancreas may be preferable before full mobilization of the spleen is attempted (as in the case of traumatic spleen rupture in which timely control of the arterial blood supply may be needed). In other more elective cases, we typically begin our dissection by dividing the splenocolic ligament. Further medial mobilization of the spleen can then be achieved by incising its lateral peritoneal attachments, notably the splenophrenic ligament, and gently retracting the spleen into the midline. The short gastrics then may be taken individually with an energy device such as a LigaSure, or by individual clamps and silk ties, with care to avoid retraction of a vessel and bleeding as well as avoiding injury to greater curve of the stomach. When possible, during the dissection of the splenic hilum, we recommend individual identification and ligation of the splenic artery and then vein (in that order) and conscious awareness of the tail of the spleen to avoid injury. Once the spleen is passed off the field as the specimen, meticulous hemostasis should be confirmed with irrigation and suction. Faint retroperitoneal ooze can be touched up with electrocautery and gentle packing as needed. A nasogastric tube to decompress the stomach overnight may be considered.

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Laparoscopic Laparoscopic splenectomy remains the gold standard for elective splenectomy procedures for patients with normal-size spleens. In experienced hands, these procedures are associated with decreased blood loss, shorter hospital stay, and overall lower morbidity compared with open splenectomy. Although initially performed via an anterior approach with the patient supine (Fig. 1), the lateral approach with patients in the right lateral decubitus position was popularized for adult and pediatric patients by Skinner et al. in the early 1990s. The lateral approach routinely involves the use of four trocars including the use of two working ports for the operating surgeon, a 10- to 12-mm camera port, and an assistant port (Fig. 2). As with open splenectomy, the splenocolic ligament and

12-mm camera port 10-12-mm camera port 5-mm camera port 5-mm optional port

FIG. 1  Laparoscopic anterior approach.

12-mm camera port 10-12-mm camera port 5-mm camera port 5-mm optional port

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lateral peritoneal attachments are divided with resultant medial mobilization of the spleen. Next, the short gastric vessels are usually taken with a bipolar energy device such as a LigaSure. With gentle retraction of the spleen, the splenic hilum is then accessed for application of clips or stapler to both the splenic artery and then the vein individually when possible. Using this approach, the operating surgeon can easily visualize the tail of the pancreas and avoid injury. The spleen may then be removed in an endoscopic retrieval bag and meticulous hemostasis ensured before desufflation and port removal.

Robotic Robotic splenectomy procedures were first cleared by the US Food and Drug Administration (FDA) in 2002, for which the daVinci surgical system (Intuitive Surgical, Sunnyvale, CA) remains one of few robotic platforms that can be used for splenectomy procedures. Generally speaking, these procedures are most commonly performed in the right lateral decubitus position with trocar placements similar to their laparoscopic counterparts (described earlier). The reported advantages of robotic surgery have inspired many surgeons to explore these procedures. Although notably, the patient experiences seen with laparoscopic and robotic procedures have largely been comparable as the procedural steps, number of incisions, and anticipated postoperative recovery are similar. Strong proponents of robotic surgery argue that ergonomic benefits for the surgeon and technologic advances seen with surgical robotics (e.g., motion-scaling, tremor reduction, and improved optics including surgeon control of the camera) make robotic procedures preferable when choosing between straight-stick laparoscopy and robotic platforms. However, these potential benefits to the surgeon remain difficult to objectively quantify and generally have been poorly supported (or studied) in the literature to date to offset the significantly higher costs seen with robotic splenectomy. The entry into the market for competing devices with newer and potentially better technology as well as potential cost improvements, which may be seen with increased competition entering the market, may alter these considerations in the future.

CONCLUSIONS Splenectomy for hematologic disorders remains an important procedure in the armamentarium of the foregut surgeon and is indicated to treat a broad range of clinical conditions, as discussed in this chapter. As with all surgical procedures, careful risk-benefit analysis, preoperative planning, and patient education are the hallmark of ensuring favorable outcomes for our patients.

S uggested R eadings

FIG. 2  Laparoscopic lateral approach.

Fitzgerald PG, Langer JC, Cameron BH, et al. Pediatric laparoscopic splenectomy using the lateral approach. Surg Endosc. 1996;10(8):859–861. Park A, Gagner M, Pomp A. The lateral approach to laparoscopic splenectomy. Am J Surg. 1997;173(2):126–130. Park AE, Weltz AS, Targarona EM. Chapter 34: Spleen. In: Brunicardi CF, ed. Schwartz’s Principles of Surgery. 11th ed.: McGraw-Hill; 2019.

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Management of Cysts, Tumors, and Abscesses of the Spleen

Management of Cysts, Tumors, and Abscesses of the Spleen P. Marco Fisichella, MD, Nicola Tamburini, MD, and Ciro Andolfi, MD

SURGICAL ANATOMY OF THE SPLEEN The operative surgeon must have a full knowledge of spleen anatomy. The spleen is positioned in the upper left quadrant of the abdomen and is protected by ribs 9 to 12. In a healthy, normal person, it is 10 to 12 cm in length and weighs approximately 100 g. The anatomy of the splenic vasculature differs among patients. The splenic artery usually arises from the celiac axis; however, in rare instances it may originate from the aorta, the superior mesenteric artery, the middle colic artery, the left gastric artery, the left hepatic artery, or the accessory right hepatic artery. The splenic artery’s branching pattern is likewise varied and has traditionally been classified into two types: distributed and magistral. The less frequent magistral type is composed of a long splenic trunk that separates closer to the hilum into three or four bigger branches that enter the hilum in a more compact bundle, making dissection of the individual vessels more difficult. The splenic trunk also gives rise to the left gastroepiploic artery, which runs along the stomach’s greater curvature and should be preserved throughout the procedure. The inferior polar arteries, which come from the left gastroepiploic artery, are, nevertheless, ligated during the initial phases of a splenectomy. The short gastric vessels arise from the stomach fundus and connect to the superior polar artery of the spleen. During the procedure, these vessels are taken in order to expose the splenic hilum. In addition to its variable vascularity, the spleen’s complex architecture is supported by many ligaments that sustain it. A detailed knowledge of these ligaments aids in the laparoscopic execution of the surgery, and their anatomy should be routinely reviewed by the staff before to each operation. Anteriorly, the gastrosplenic ligament includes the short gastric and gastroepiploic vessels. The splenic vessels and pancreatic tail can be located posteriorly within the splenorenal ligament. Laterally, the spleen is connected to the diaphragm superiorly by the phrenicosplenic ligament, which is part of the phrenicocolic ligament, and to

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the splenic flexure of the colon inferiorly by the splenocolic ligament. The phrenicocolic and splenocolic ligaments are typically avascular structures that may be safely separated during surgery.

SPLENIC CYSTS Splenic cysts are uncommon and frequently discovered by chance; however, because of the widespread use of abdominal imaging nowadays, the prevalence of splenic cysts is estimated to be as high as 1%. Several classification systems for splenic cysts have been proposed. Martin classified splenic cysts into type 1 (or true cysts), which are cysts with an epithelial lining, and type 2 cysts (or false cysts), which are cysts that lack an epithelial lining. Pseudocysts are usually posttraumatic and originate in an organized subcapsular hematoma that failed to reabsorb. Rarely, splenic pseudocysts are secondary to a prolonged splenic abscess or an infarct. Other classification systems are based on pathogenesis or the etiology of splenic lesions. Fowler classified splenic cysts as parasitic cysts and nonparasitic cysts (Fig. 3). Parasitic cysts are caused mainly by Echinococcus granulosus and usually are seen in endemic areas. Calcification in the cyst wall or daughter cysts might be used to make a radiologic diagnosis. Serologic tests can help in diagnosis. For parasitic splenic cysts, the management is typically surgical. If the patient’s risk factors make surgery unreasonably risky and the cyst is smaller than 5 cm in diameter, a method known as PAIR (puncture of cyst; aspiration of cyst contents; injection with 3% hypertonic saline, alcohol, or 0.5% silver nitrate to sterilize the cyst; and reaspiration, in conjunction with anthelminthics) has been described. Typically, parasitic cysts should not be drained percutaneously because of the risk of seeding or anaphylaxis. Spleen preserving surgery can be done if there is a small solitary cyst on the periphery; however, because of the invasive nature of the infection, care must be given to ensure that there are 1-centimeter margins from the cyst. If preserving the spleen does not appear to be an option, a splenectomy should be performed. Extreme caution should be used to avoid rupture or spilling of the cyst contents into the abdominal cavity; in fact, anaphylactic shock and death have been reported as a result of cyst contents spilling and spread. Primary splenic true cysts account for 10% of all nonparasitic cysts; they are lined with squamous epithelium and are considered to be congenital. They are identified in children and teenagers accidentally and are typically asymptomatic. They are benign in nature and have elevated cancer antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA). The majority of other nonparasitic cysts

B FIG. 3  (A) Patient with a symptomatic splenic cyst found on computed tomography. (B) The spleen was removed with the cyst intact.

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are pseudocysts caused by trauma. Other extremely rare primary nonparasitic cysts are of mesothelial and dermoid origin. The clinical importance of splenic cysts is mostly caused by the mass effect (i.e., affecting surrounding organs) and their ability to rupture and bleed profusely. Small, asymptomatic, nonparasitic splenic cysts or pseudocysts can be monitored, whereas symptomatic cysts would typically enlarge, necessitating surgery. When operative, simple cysts can be managed in a variety of ways, from total splenectomy to simple deroofing of the cyst. The trend is moving toward spleen preservation whenever possible, with partial splenectomy, decapsulation, cyst fenestration, or deroofing. There is also the option for percutaneous drainage. This topic is controversial, and some recommend it, while others have found that it should not be attempted because of high recurrence rates. The technique for decapsulation involves suctioning out the cyst, opening the anterior cyst wall, and then circumferentially excising the cyst wall using an energy device. This is preferred over simple unroofing, which has a higher recurrence rate. In patients with recurrent splenic cysts or initial splenic cysts, partial splenectomy is recommended because the recurrence rate is lower than after decapsulation.

SPLENIC PELIOSIS Splenic peliosis is a benign disease that has been observed in the liver. Sinusoidal dilation leads to the appearance of multiple bloodfilled “cystic” cavities scattered within the splenic parenchyma in the parafollicular red pulp. The rupture of these cavities might result in hemorrhagic shock and death. HIV, systemic steroid use, oral contraceptives, and persistent hematologic diseases such as Hodgkin’s lymphoma and multiple myeloma are also risk factors for peliosis. Both the liver and spleen are involved in the majority of these cases. The occurrence of isolated splenic involvement is exceedingly unusual, and it usually manifests as hemoperitoneum. Even when peliosis is discovered accidentally, complete splenectomy should be performed to eliminate the risk of bleeding.

SPLENIC TUMORS Primary splenic neoplasms are uncommon tumors that are classified according to their origin tissue (Box 1). Lymphoid neoplasms arise from the white pulp, whereas vascular neoplasms arise from the red pulp. In addition to this classification, primary neoplasms can be classified into benign and malignant tumors. Benign tumors include hemangioma, lymphangioma, hamartoma, and littoral cell angioma. Malignant tumors include lymphoma and angiosarcoma. Other tumors such as lipoma and inflammatory pseudotumors have been described but are exceedingly rare, with very few reports in the literature. Secondary neoplasms also occur within the spleen, with melanoma, breast, lung, ovary, colon, stomach, and pancreatic neoplasms all being reported as metastasizing to the spleen.

BOX 1  Splenic Neoplasms Benign tumors • Hemangioma • Lymphangioma • Hamartoma • Littoral cell angioma Malignant tumors • Lymphoma • Angiosarcoma Nonvascular, nonhematopoietic tumors • Inflammatory pseudotumor • Mesenchymal tumors Metastatic tumors

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Benign Tumors Hemangioma Hemangiomas originate from the vascular endothelium and are the most common benign primary tumors of the spleen. Most patients are asymptomatic and identified incidentally on radiographic imaging for other indications. The majority are solitary and less than 2 cm in diameter; however, hemangiomatosis and generalized angiomatosis syndromes can occasionally show numerous and widespread disease lesions. Splenic hemangiomas are classified as either capillary or cavernous, with the latter being more frequent. These two patterns have slightly different appearances on imaging. On CT, cavernous hemangiomas appear larger in size and have a cystic appearance with intermittent areas of hypodensity, which enhance peripherally with contrast administration. The capillary subtype demonstrates smaller hypodense or isodense masses on CT with homogeneous enhancement with contrast administration. Hemangiomas larger than 2 cm have an associated risk of bleeding and may be considered for complete or partial splenectomy.

Lymphangioma Lymphangiomas are less frequent and are believed to be congenital lymphatic abnormalities. These abnormalities can fill with eosinophilic proteinaceous material, causing increased weight of the spleen, and they become symptomatic as a result of the mass effect. The absence of the cystic look associated with hemangiomas distinguishes them from the latter. These lesions, like hemangiomas, can be unifocal or part of a systemic lymphangiomatosis syndrome that affects several organs. They can be multiloculated, lobulated, and cystlike, unlike hemangiomas. Lymphangiomas detected in adulthood are typically incidental on imaging, and patients remain asymptomatic. Three histologic subtypes are capillary, cavernous, and cystic. On ultrasound, multiple hypoechoic cysts are separated by hyperechoic septate, and calcifications can be seen. They are more common in a subcapsular location and may have enhancing septa and peripheral rim calcification (Fig. 4). Although splenectomy has traditionally been the gold standard of treatment for suspected splenic lymphangiomas, partial splenectomy is becoming increasingly common.

Hamartoma Splenic hamartomas are uncommon benign tumors characterized by red pulp malformation without organized lymphoid follicles. They are generally tiny and found by chance on imaging, although they can occasionally appear as a big mass or diffuse splenomegaly. Although most patients are asymptomatic, this entity has been associated to spontaneous splenic rupture, especially in larger masses. Ultrasonography shows a well-circumscribed homogeneous solid mass, whereas CT shows early enhancement with intravenous contrast and uniform delayed enhancement of an isodense mass. Because of stagnation inside the red pulp sinusoids, larger hamartomas may show more heterogeneous contrast uptake and longer contrast retention. Although imaging is helpful in determining a diagnosis, it is not always accurate, and percutaneous biopsy is recommended when possible. If biopsy is not possible, splenectomy is indicated for definitive diagnosis and management.

Littoral Cell Angioma Littoral cells, the cells that line the red pulp, can cause littoral cell angioma, a benign vascular tumor of the spleen. The spleen is involved in a diffuse nodular pattern in this condition. As a result, patients may have splenomegaly and hypersplenism symptoms such as anemia, tiredness, and bleeding. Hemoperitoneum and splenic rupture have also been reported. Multiple isodense masses of various sizes can be seen on noncontrast CT. Following contrast administration, the masses appear hypodense on the early portal phase, returning to an isodense appearance on the delayed phase. When littoral cell angiomas are found, splenectomy is recommended because of

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FIG. 4  (A) Large (>5 cm) calcified splenic lesion was identified on computed tomography. (B) The thin calcified wall is noted on the surgical specimen after splenectomy.

the danger of splenomegaly and hypersplenism. Pathologic specimens reveals small vascular channels connecting cystic areas with papillary projections on histology, confirming the diagnosis.

Malignant Tumors Lymphoma The most common primary malignant tumor of the spleen is lymphoma. Primary splenic lymphoma is rare, occurs in approximately 1% to 2% of all lymphomas, and is most commonly diffuse large B-cell lymphoma. Diagnosis of primary splenic lymphoma relies on imaging techniques. A primary splenic lymphoma will appear as a single large mass or multiple focal splenic masses. The masses are generally well defined and hypoechoic. Primary splenic lymphoma patients typically present with nonspecific symptoms, including fever, night sweats, and weight loss, and sometimes specific symptoms, such as splenomegaly and left upper quadrant pain. Secondary lymphoma of the spleen is considerably more frequent than primary lymphoma of the spleen. The most prevalent feature on examination for primary splenic lymphomas is splenomegaly, which occurs in more than two-thirds of patients. Disease confined to the spleen and hilar nodes with no recurrence following splenectomy has traditionally been used as a diagnostic criterion. Fine-needle aspiration and core needle biopsy were formerly avoided because of fears that puncturing the hypervascular, fragile spleen may result in hemorrhagic consequences. Most subsequent research studies have disproved this, and it is now considered a safe practice. Splenic marginal zone lymphoma, in particular, is a slow-growing subtype that nearly invariably manifests as splenomegaly. Hepatitis C virus infection is linked to it. Splenectomy has been the standard treatment for this subtype of primary splenic lymphoma, but more recently, rituximab monotherapy has been proven to be effective as a first treatment for this subtype of primary splenic lymphoma. With appropriate treatment, the prognosis is favorable, with an estimated 5-year overall survival rate of 80% to 95%.

Angiosarcoma The rare angiosarcoma is the most frequent primary nonhematopoietic malignant tumor of the spleen. These tumors, also known as hemangiosarcomas, are very aggressive and have a poor prognosis. Splenomegaly and evidence of metastasis, most often to the liver,

regional nodes, bone marrow, and lungs, are common in patients with advanced disease. Because of the aggressive nature of the cancer, these patients may develop cachexia in addition to the clinical manifestations associated with splenomegaly. Less common findings include ascites and pleural effusion. Spontaneous rupture can be the first symptom, and it is a terrifying, although extremely rare, and potentially fatal consequence. On imaging, there are several complicated heterogeneous and hypervascular masses. Calcifications are uncommonly observed. Biopsy, like lymphoma, has been avoided in the past because of concerns about bleeding, but it is now regarded safe if precautions are taken. When possible, splenectomy is used to treat the condition.

Other Nonvascular, Nonhematopoietic Splenic Tumors An inflammatory pseudotumor is a rare benign splenic tumor. The cause is unknown, although it is thought to be linked to an inflammatory reparative response following traumatic or viral damage. Patients are generally asymptomatic but may present with symptoms from mass effect, which is usually an incidental finding on imaging. These pseudotumors show as a hypodense mass with delayed contrast enhancement and central scarring on CT. Splenectomy should be performed if the patient is symptomatic or if the diagnosis is in doubt. The presence of spindle cell growth and plasma cells in the pathology report will confirm the diagnosis. Mesenchymal tumors such as fibroma, fibrosarcoma, lipoma, angiomyolipoma, leiomyosarcoma, and malignant fibrous histiocytoma have been described in the literature and are very rare. Apart from the characteristic presence of fat in lipoma, there are no specific pathognomonic features on imaging with these neoplasms. Patients are frequently asymptomatic, and the diagnosis is made after splenectomy.

Metastatic Tumors In metastatic disease, splenic involvement is uncommon. Splenic metastases are seen in less than 10% of all cancers that go untreated. There are several theories as to why the spleen appears to be immune to metastases. There are no afferent lymphatics, the splenic arteries have a sharp angle, and the splenic lymphoid tissue itself has anticancer activity. Hematogenous spread is the most likely route when

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splenic metastases do occur. The most common primary malignancies to metastasize to the spleen are melanoma and breast, lung, and ovarian cancers. Rarely, metastases from colon, stomach, and pancreas primary tumors are also found. Though infrequent, these latter tumors may spread via direct invasion into the spleen. Diffuse infiltration is rare. More commonly, metastatic disease is seen as solitary or multiple masses. Radiologic findings vary with the primary neoplasm. Cystic and necrotic degeneration can occur, particularly with melanoma. Calcifications may be noted with mucinous adenocarcinomas. Carcinomatosis and pseudomyxoma peritonei may manifest as serosal implants on the splenic surface, also visualized as splenic margin scalloping.

SPLENIC ABSCESS Splenic abscess is uncommon, yet it can be deadly if left untreated. According to a large series of Western autopsies, the incidence of this disease ranges from 0.14 % to 0.7%. They are most commonly spread hematogenously in the presence of bacteremia or fungemia, although they can also spread contiguously. Splenic abscess has traditionally been associated to endocarditis, although it has also been linked to urinary tract infections and gastrointestinal infections. As a result of changing lifestyle trends, the prevalence of diabetes mellitus, HIV/ AIDS, and liver illness is increasing, predisposing individuals to splenic abscesses. Ultrasonography or CT are the best ways to make a diagnosis. Antibiotic treatment should be designed to cover the organisms that are most often cultivated. The most common isolates are gram-positive cocci, such as Staphylococcus and Streptococcus species, and gram-negative enteric organisms, such as Salmonella species. Coverage for Mycobacterium and Candida species should be considered in immunocompromised patients, especially those who may present in septic shock. In most recent studies, definitive treatment of splenic abscesses with percutaneous draining has had satisfactory results. Patients with unilocular abscesses are the most likely to achieve complete resolution with percutaneous or imageguided drainage. Splenectomy is recommended for individuals who do not improve clinically, have multiloculated abscesses, or have partial resolution after first drainage.

SURGERY Splenectomy is one of the most common procedures performed by general surgeons, and it is used to treat trauma and hematologic disorders. Because of its position in the abdomen, the spleen is highly susceptible to damage caused by trauma because it lacks a protective anatomic cage. The most frequent indications for splenectomy are grade 4-5 spleen injury, symptoms of massive splenomegaly, cysts, abscesses and tumors of the spleen, and diagnosis and treatment of hematologic diseases. Splenectomy can be done by an open or laparoscopic procedure. The surgical team’s experience and the patient’s history of previous abdominal operations are two criteria that influence the decision. Laparoscopic splenectomy remains the gold standard of surgical treatment for elective patients. When compared with open splenectomy, laparoscopic splenectomy has the advantages of a shorter hospital stay, less postoperative discomfort, and lower morbidity. We describe laparoscopic splenectomy, as it is the most common surgery performed today for splenic lesions.

Preoperative Considerations Preoperative evaluation includes a detailed history and physical examination with focus on abdominal symptoms, a complete blood count, and a CT scan of the abdomen. Preoperative imaging is critical for surgical planning. For measuring the size of the spleen, CT and ultrasonography are also viable options. The former is likely to be preferred because it provides a better view of anatomic connections and anatomy (e.g., auxiliary spleens) and lymphadenopathy, and

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it provides a clear interpretation of the vascular anatomy. Medical comorbidities, splenic size, blood counts, concurrent coagulopathy, previous splenic irradiation, and percutaneous manipulation are all factors to consider before undergoing surgery. In particular, planning includes correction of any coagulopathy to the degree possible. Steroids and intravenous immunoglobulin are used to increase platelet counts preoperatively for patients with idiopathic thrombocytopenic purpura (ITP). Nevertheless, laparoscopic splenectomy can be performed safely and effectively in patients with ITP who have platelet counts as low as 20,000/μL. In fact, recent studies support the notion that laparoscopic splenectomy is feasible with platelet counts below 20,000/μL without transfusion. Before performing a skin incision, appropriate pretreatment antibiotics are administered. Despite the risk of bleeding, there is also a chance of splanchnic thrombosis following splenic artery manipulation; therefore it is advisable to administer low-molecular-weight heparin before induction of anesthesia and maintain it for up to 1 month postoperatively as prophylaxis. When the short gastric arteries are dissected along the larger curvature, gastric decompression via an orogastric or nasogastric tube can minimize gastric distention and enhance visibility. Intraoperative blood products should be available, especially in patients with severe thrombocytopenia. After ligation of the splenic artery, platelets are transfused only as needed and are rarely required. To reduce the risk of overwhelming post-splenectomy sepsis, patients are immunized against encapsulated organisms (Haemophilus influenzae B, polyvalent pneumococcus, and meningococcus vaccines) 2 weeks before splenectomy in the elective context. If the splenectomy is an emergency procedure, the patient should be immunized within 30 days after being discharged from the hospital.

Laparoscopic Splenectomy Although anterior, lateral, and posterior methods to laparoscopic splenectomy have been proposed, we believe that a semilateral approach provides the surgeon with more versatility and adaptability to spleens of various sizes and forms.

Laparoscopic Access and Initial Port Placement An orogastric tube is placed to decompress the stomach after induction of anesthesia and general endotracheal intubation. Because insertion of an orogastric tube while the patient is in the lateral decubitus position is difficult and generally ineffective, this is performed before the patient is positioned. Invasive monitoring with a central line or an arterial line is desirable but not necessary in most individuals. In every case, a Foley catheter is inserted. The strategy for additional perioperative hydrocortisone dosage is discussed with the anesthesiologist if the patient has been treated continuously with significant doses of steroids.

Positioning of the Patient The patient is positioned in the right semilateral decubitus posture (at a 45-degree angle to the operating table) on a beanbag on the operating room table. Positioning the patient in this manner, with the added stability provided by the beanbag, allows for correct adjustment during surgery, allowing the surgeon to reach a completely supine (anterior approach) or entirely lateral (lateral or posterior approach) posture at his or her choice. A more anterior approach is employed for spleens that are longer and larger and for those in which the splenocolic ligament is positioned more inferiorly. Furthermore, to successfully increase the space between the left costal margin and the anterior superior iliac spine of the pelvis, the patient is placed with his or her costal margin just hanging from the break of the operational table. This gives the most lateral port, which is implanted in the patient’s left flank, more mobility. The padding is then liberally applied to all pressure points.

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Port Placement

Extraction of the Spleen

A 5-mm incision is made 3 cm below the center of the left costal border after full neuromuscular paralysis. A Veress needle is placed, the abdomen is insufflated with 14 mm Hg of carbon dioxide, and a water drop test is done (CO2). The Veress needle is then withdrawn, and a 5-mm port is introduced into the abdominal cavity, followed by a 5-mm, 0-degree laparoscope. Following that, the laparoscope is replaced with a 5-mm, 30-degree laparoscope, and the additional trocars are inserted under direct view. Three 5-mm trocars are inserted anteriorly along the costal margin, spaced 10 cm each, and one 11-mm trocar that fits the endoscopic stapler is placed in the left flank, typically after the splenic flexure of the colon has been mobilized correctly, as is the case with longer spleens.

An effective manipulation of both the spleen and the bag can make this step a very rewarding conclusion to the operation. First, the spleen is separated from all of its attachments and carefully positioned away from the left diaphragmatic dome, often using operating table positioning. Then, through the most lateral, 11-mm port site, a strengthened, large plastic bag is introduced. The bag is unfolded and positioned in the shape of a “scorpion tail,” with the open end held superiorly by the assistant and inferiorly by the surgeon’s left hand, and the tail curled up slightly and nestled in the left upper quadrant. The spleen is then directed into the bag with a grasper held in the surgeon’s right hand (which holds the severed ligaments of the spleen, not its parenchyma), and the patient is placed in the Trendelenburg position. The spleen is guided into the open bag in this scenario, and the bag’s “tail” unfolds as the spleen enters. The strings of the bag are grabbed using an instrument inserted via the 11-mm port once the spleen has been safely put into the bag. The port is then withdrawn, allowing the bag to be opened and ring forceps to be inserted for morcellation and extraction. In known cases of ITP, it is always preferred to morcellate the spleen. In other cases, when an intact spleen should be sent to the pathology department, the surgeon can resort to one of two options. It is preferable to widen downward the most medial trocar incision, which is always positioned at the midline in the epigastrium, to execute a laparotomy small enough to recover the specimen in elderly patients. In young patients, the surgeon may offer the option of doing a Pfannenstiel incision before surgery for aesthetic reasons. Following the removal of the specimen, the abdomen is reinsufflated, and the dissection region is examined again to confirm hemostasis and rule out damage to the stomach, pancreas, diaphragm, and colon. All trocars are removed once the wound has stopped bleeding and the port sites have been appropriately managed. The 11-mm port site is always closed and infiltrated with local anesthesia using a figure-of-eight 2-0 absorbable suture. Drains are rarely used on a regular basis unless the pancreas has been accidentally damaged.

Mobilization of Splenic Ligaments For mobilization of the splenic ligaments, a vessel-sealing device is generally used. The surgery begins with the splenocolic ligament being divided, which contains the spleen’s inferior polar vessels. The ligaments are mobilized to the left once the inferior pole of the spleen has been fully mobilized by separating the most lateral part of the gastrocolic ligament to access the gastrosplenic ligament medially. The dissection proceeds superiorly and medially, dividing the short gastric vessels. As progress is made toward the apex of the spleen, the dissection proceeds upward toward the left pillar of the crus, with gentle medial retraction of the fundus of the stomach. The whole stomach is next folded medially to reveal the splenic hilum in its entirety. The orogastric tube, which was inserted preoperatively and left on low, continuous suction, considerably facilitates this maneuver. The superior pole of the spleen is totally mobilized at this point by dividing the highest part of the splenorenal ligament. The full mobilization of the spleen’s superior pole will therefore make vascular control of the splenic hilum easier. Following these procedures, a thorough search is conducted for accessory spleens, which are removed and put between the folded stomach and the left lobe of the liver for retrieval with the main specimen later. A clear view of the splenic hilum, upper pole, and lower pole is finally achieved at this point because of the use of proper operating table positioning, the effective use of gravity for retraction and exposure, and suspension of the spleen primarily by the splenorenal and phrenocolic ligaments, leaving the surgeon with the best strategy for addressing the hilar structures.

Management of Splenic Hilum The tail of the pancreas is first identified in connection to the hilar components of the spleen. The zone for transection of the splenic arteries is short when the tail of the pancreas reaches closer to the hilum of the spleen. Small (0.5-cm) hilar vessels can be sealed using the vessel sealing system in this scenario or when a scattered anatomy is present. In all other cases (e.g., difficult cases with a large amount of visceral fat and larger hilar vessels), we prefer applying careful serial firings of an endoscopic stapler loaded with vascular cartridges. Conversely, when a clear anatomy is present, the hilum is taken with one firing of an endoscopic stapler loaded with a vascular cartridge, provided that the tail of the pancreas is protected and that all hilar structures can be included between the jaws of the cartridge. The superior and inferior poles of the spleen must be sufficiently mobilized to allow a posterior window to form behind the hilum to accommodate the stapler. These steps can be accomplished by mobilizing the spleen anteriorly or posteriorly by tilting the operating table to the left or right and utilizing the stability provided by the beanbag. The surgeon can then choose the optimal approach to the splenic hilum based on the size, shape, vascular architecture, and connection of the spleen to the pancreatic tail. Finally, a major splenic artery and vein can be readily dissected separately. Energy devices are used to complete the remaining dissection of the splenorenal ligament and associated vascular structures away from all staple lines in all patients.

Posterior Approach The truly posterior approach is performed with the patient in a fully lateral position. It could be used for spleens that are more prominent anteriorly, obscuring the view to the hilum, and those in which a magistral branching pattern of the splenic artery is present. The lateral ligaments of the spleen (phrenicocolic and splenocolic) are transected to allow the spleen to descend and rotate medially, exposing the hilar arteries straight from behind. In some situations, this procedure is considered to enable a safer and less difficult dissection of the individual vessels.

Postoperative Care At the conclusion of the procedure, the orogastric tube and Foley catheter are removed. Intermittent parenteral opioids are used to manage pain before the patient is switched to oral pain medication. Patients are urged to walk as much as possible and are allowed an unrestricted diet as soon as feasible. The majority of patients are discharged on the first or second postoperative day and are encouraged to tailor their activities to their degree of comfort. Patients are often visited in the clinic two weeks after surgery for a full blood count. Administration of preventive immunization against overwhelming post-splenectomy infection (OPSI) and sepsis is warranted if the patient did not receive it before surgery.

Robotic Splenectomy Robotic surgery has been used in clinical practice for a number of laparoscopic purposes in recent years. Doubts have been raised regarding the suitability of laparoscopic splenectomy for patients with splenomegaly, advanced liver cirrhosis, and splenic tumors and

Sp l e e n

for those who will undergo a partial splenectomy. The benefits of robotic surgery have encouraged some of the most skilled laparoscopic surgeons to research its potential and expand its use in the minimally invasive surgery paradigm. Both straightforward splenectomies and complicated splenectomies in patients with cirrhosis or patients with splenomegaly have been described, and the high resolution of the robotic system allows safe and precise dissection of the splenic hilar vessels. The robotic system provides a stable camera platform with a better view as a result of three-dimensional imaging, instruments with more degrees of freedom, and a comfortable position for the surgeon. Concern was raised about the ability to control significant bleeding using the current limitation of three arms, with the need to convert emergently to open surgery in cases of major bleeding. In partial splenic resections requiring precise vascular dissection, recent research has revealed the advantages of robotic splenectomy.

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significance of post-splenectomy thrombocytosis and its role in the etiology of these events is still debated. Prophylactic antiplatelet therapy is not advocated. Mesenteric vein thrombosis is a well-documented complication of splenic vein ligation, occurring in up to 30% of cases in certain studies. The most common deadly late splenectomy consequence is OPSI. After a splenectomy, it can happen at any moment. The majority of infections that have been documented occur more than 2 years following surgery. The most frequently involved organisms are Streptococcus pneumoniae, H. influenzae, Neisseria meningitidis, and Salmonella spp. The standard of care today for post-splenectomy prophylaxis includes administration of pneumococcal vaccine polyvalent (Pneumovax 23), H. influenzae type b conjugate, and meningococcal polysaccharide vaccine within 2 weeks of splenectomy or before surgery.

S uggested R eadings Outcome and Complications Based on the time after the operation, post-splenectomy complications are usually classified into early and late complications. Surgery-related and non–surgery-related early complications include intraoperative and postoperative bleeding, left lower lobe atelectasis and pneumonia, left pleural effusion, subphrenic collection, and iatrogenic pancreatic, gastric, and colonic damage. Reactive thrombocytosis is a common side effect after splenectomy. Although post-splenectomy deep vein thrombosis, pulmonary embolism, and acute myocardial infarction have all been documented, the

Gamme G, Birch DW, Karmali S. Minimally invasive splenectomy: an update and review. Can J Surg. 2014;56(4):280. Ingle SB, Hinge Ingle CR, Patrike S. Epithelial cysts of the spleen: a mini review. World J Gastroenterol. 2014;20:13899–13903. Rubin LG, Schaffner W. Clinical practice. Care of the asplenic patient. N Engl J Med. 2014;371(4):349–356. Silver DS, Pointer Jr DT, Slakey DP. Solid tumors of the spleen: evaluation and management. J Am Coll Surg. 2017;224(6):1104–1111. Thipphavong S, Duigenan S, Schindera ST, et al. Nonneoplastic, benign, and malignant splenic diseases: cross-sectional imaging findings and rare disease entities. AJR Am J Roentgenol. 2014;203(2):315–322.

Hernia

Management of Inguinal Hernia James E. Wiseman, MD, MBA, and Gina L. Adrales, MD, MPH

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ore than 20 million inguinal hernia repairs are performed every year around the globe, placing this operation among the most common general surgical procedures (HerniaSurge Group, 2018). Although the use of mesh in inguinal hernia repair parallels a dramatic reduction in recurrence rates, chronic post-herniorrhaphy pain syndrome has simultaneously emerged as an important cause of morbidity in these patients, affecting up to 18% of patients (Reinpold, 2017). Further, the rapid and widespread adoption of robotic-assisted techniques has carried with it a steep learning curve with a renewed emphasis on patient selection, identification of appropriate surgical indications, and technical mastery of a variety of approaches to the surgical management of this condition.

INDICATIONS AND TIMING OF REPAIR Repair should be offered to all male patients with symptomatic inguinal hernias who are otherwise physically fit to undergo surgery. For those with no or minimal symptoms related to the presence of an inguinal hernia, it is well-accepted that watchful waiting is a safe and reasonable option for male patients. However, there is a time-dependent risk of development of nonemergent symptoms such as inguinal pain or progressive hernia enlargement, which will lead to a majority of patients seeking eventual surgical repair (Fitzgibbons et al., 2006). Other considerations that should influence the timing of repair include the increased complexity of repair associated with larger hernia defects as well as the greater risk of perioperative complications when performed in emergency settings, which is particularly relevant in patients with significant comorbidities or bleeding disorders. Watchful waiting is not currently recommended for female patients. Although inguinal hernias are much less prevalent in females, the risk of emergencies associated with observation in this group appears to be higher than for males. A contributing factor is the higher rate of femoral hernias in female patients with groin hernias—historically double the rate for male patients. However, the higher acuity of presentation of female patients may be caused, in part, by diagnostic challenges unique to this population that can lead to presentation or diagnosis at more advanced stages of the condition. Multiple population studies have estimated that 3% of female patients have groin hernias. However, a Swedish herniography study of female patients younger than 40 years of age identified hernias in 24%, suggesting that we gravely underdiagnose this condition (Kesek and Ekberg, 1999). When imaging is needed to evaluate the female patient with nonacute groin pain, standard ultrasound may not be

adequate. Pelvic magnetic resonance imaging is considered the best imaging modality in this population. It is important to note that evidence-based guidelines for female hernia patients are lacking, and future research efforts should focus on this demographic specifically.

CONSIDERATIONS IN SELECTING THE OPERATIVE APPROACH A variety of surgical repairs have been developed, all with their own unique benefit and risk profiles as well as characteristic learning curves. Selection of the appropriate technique is largely surgeondependent and based on experience, with the most favorable outcomes associated with the repair most frequently performed. Additionally, characteristics unique to each patient and the hernia should inform decision making regarding procedural selection. Although there are no absolute contraindications to minimally invasive repair, patients who are not candidates for general anesthesia are perhaps better suited for open techniques, which can be performed under spinal or local anesthesia with or without sedation. While laparoscopic inguinal hernia repair can be performed under epidural anesthesia, inadequate muscular relaxation can impose severe limits on the available working space. Accordingly, a large majority of these repairs are conducted with general endotracheal anesthesia to avoid this frustration. The choice of total extraperitoneal repair (TEP) versus transabdominal preperitoneal repair (TAPP) may also be largely dictated by patient characteristics or surgeon experience. For example, in the case of a surgeon comfortable with both TAPP and TEP techniques, the choice of pursuing a totally extraperitoneal approach in a given patient might be entirely dictated by features of that patient’s particular surgical or medical history. Individuals who have previously undergone abdominal surgery may have adhesions that make a transabdominal approach more challenging and perhaps even unsafe. Similarly, patients with a history of prostatectomy may have scarring of the preperitoneal space, rendering it unsuitable for an entirely extraperitoneal approach. There is compelling evidence to support minimally invasive posterior inguinal hernia repair for patients with bilateral inguinal hernias as well as recurrent inguinal hernias after prior open inguinal hernia repair. For the majority of inguinal hernia patients, open and minimally invasive mesh repairs are equivalent.

OPEN INGUINAL HERNIA REPAIR Tissue Repair Several pure tissue repairs have been described over the past century, but they were largely abandoned in favor of repairs utilizing mesh reinforcement in modern times. Although direct comparisons are limited and available randomized controlled trials are of low quality with concerns regarding standardization of technique, the Shouldice repair is the best nonmesh inguinal hernia repair technique with 663

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supporting level 1A evidence. Compared with other pure tissue repairs, the Shouldice confers lower recurrence, hematoma, and chronic pain rates (Shouldice 2003). Surgeon experience and meticulous technique have significant impact on outcomes. From a 2012 Cochrane systematic review, the recurrence rate for Shouldice was higher than Lichtenstein mesh repair, although substantial doubts about the uniformity of technique described in the Shouldice arms raise concerns about the validity of conclusions drawn from this review. Nevertheless, there was no significant difference in chronic pain, surgical site infection, or the incidence of postoperative seroma formation. Newer tissue repair techniques include the Desarda repair, a tension-free strategy that utilizes an autogenous patch of external oblique aponeurosis to reinforce the floor of the inguinal canal. Early data on recurrence and other traditional outcomes are promising for this repair. In a recent systematic review and meta-analysis of 14 randomized controlled trials comparing the Desarda or Shouldice with Lichtenstein repair, there were similar rates of recurrence for either tissue repair to Lichtenstein (Bracale, 2019). However, the recurrence rate was still higher for the tissue repair compared to Lichtenstein in these heterogeneous trials, with a threefold increased risk for the Shouldice repair (seven studies) and 40% higher for Desarda (three trials). Despite the higher rate of recurrence, public appetite for mesh-free repairs persists, and there remain circumstances in which the implantation of prosthetic mesh is inadvisable, such as contaminated cases and those involving strangulated bowel. All general surgeons should learn and maintain comfort with a pure tissue repair.

Lichtenstein Repair The most common open, mesh-based treatment is the Lichtenstein “tension-free” repair, which relies on the use of prosthetic mesh to reconstruct the posterior wall of the inguinal canal. Initially described in 1989, the repair involves fixation of mesh, usually polypropylene, to the internal oblique aponeurosis or muscle superiorly, the pubic tubercle medially, and the inguinal ligament inferiorly. The approach is via an incision inferior and medial to the anterior superior iliac spine, which is extended medially and obliquely for approximately 6 to 8 cm, ending just lateral to the symphysis pubis. Dissection is then carried down to the aponeurosis of the external oblique muscle, taking care to ligate or cauterize the superficial epigastric veins before opening the inguinal canal. The aponeurosis is then opened in the direction of the underlying fibers using Metzenbaum scissors, and the incision is extended through the external inguinal ring medially. The ilioinguinal nerve can now be visualized as it courses the inguinal canal, and this should be preserved. The interior oblique fibers are dissected bluntly from the overlying external oblique muscle flap, revealing the shelving edge of the inguinal ligament. The iliohypogastric nerve can be located by elevating the external oblique superior to the inguinal canal. This nerve courses along the anterior body of the internal oblique muscle before dividing into two cutaneous branches: anterior and lateral. The spermatic cord, along with an indirect hernia sac, if present, is commonly isolated using a Penrose drain for easy retraction. The hernia sac will usually be seen on the anterolateral surface of the cord structures and should be separated from the adjacent spermatic cord, which will often require division of surrounding fibers of the cremaster muscle. The genital branch of the genitofemoral nerve travels within the deep spermatic cord adjacent to the external spermatic vein, and it should be identified and preserved while separating the cord structures from the hernia sac. The posterior wall of the inguinal canal should be carefully assessed for weakness suggestive of the presence of a direct hernia. Repair of the hernia is initiated by securing the medial aspect of a prosthetic mesh to the aponeurotic tissue overlying the pubic tubercle with a single monofilament suture with an overlap of approximately 2 cm. The inferior edge of the mesh is then sewn to the inguinal ligament from medial to lateral. This can be done either in a running (“baseball stitch”) fashion or with the use of interrupted sutures. A second line of suture is placed

superiorly, securing the mesh to the aponeurosis of the internal oblique muscle or to the muscle itself. Interrupted suture limited to medial to the deep inguinal ring is recommended to limit the risk of nerve entrapment or injury. The mesh is divided along its long axis starting at the lateral edge, and these “tails” are then used to recreate the internal ring secured with a single nonabsorbable suture. The layers of the abdominal wall are then closed individually, starting with the aponeurosis of the external oblique muscle, Scarpa’s fascia, and finally the skin. Mesh fixation was initially described with nonabsorbable suture. Increasingly, long-acting absorbable monofilament suture is employed in an effort to limit the risk of chronic pain and inflammation. Alternatively, cyanoacrylate glue fixation and self-adherent mesh have been determined in randomized trials to be equal in hernia recurrence and chronic pain (Matikainen 2017, 2021). A modification of the Lichtenstein repair uses the addition of a mesh plug that is placed through the internal ring in the case of an indirect inguinal hernia. For a direct hernia, the plug is sutured to Cooper’s ligament (an extension of the inguinal ligament that forms the floor of the femoral canal), the inguinal ligament proper, and the internal oblique aponeurosis. International hernia guidelines note that the risk of mesh erosion and migration appear to be higher with the mesh plug versus flat mesh and therefore is not recommended (HerniaSurge Group, 2018). Additionally, bilayer mesh violates both the anterior and preperitoneal space, does not appear to be beneficial in reducing the risk of hernia recurrence, and may complicate future recurrence repair.

Local Anesthesia Block A local anesthetic block is safe and cost-effective as the primary method of anesthesia delivery during open repair as well as for postoperative analgesia. Regardless of whether general anesthesia is used, preemptive local anesthetic injection before performing the surgical incision may decrease postoperative pain by blocking the stimulation of local nociceptors. Lidocaine (1% or 2%), or bupivacaine (0.25% or 0.5%) may be used with or without epinephrine additive. The longer half-life of bupivacaine may confer advantages with respect to postoperative pain mitigation. Attempts should be made to inject local anesthetic in the intradermal, subdermal, and deeper subcutaneous layers. Regional blockade can also be achieved with injection just medial to the anterior superior iliac spine, although this risks causing a direct nerve injury. Additionally, injection of local anesthetic under the aponeurosis of the external oblique muscle following its closure will confer temporary analgesia to the peripheral inguinal nerves (ilioinguinal and genital branch of the genitofemoral nerve). Finally, patients are also likely to benefit from injection near the pubic tubercle and in the space just anterior to the internal oblique where the iliohypogastric nerve resides.

MINIMALLY INVASIVE INGUINAL HERNIA REPAIR Transabdominal Preperitoneal Repair The transabdominal preperitoneal inguinal hernia repair is performed with the patient in the Trendelenburg position tilted toward the contralateral side, which facilitates visualization of the operative field by allowing gravity to pull intrabdominal viscera cephalad. The abdomen is accessed in accordance with the individual surgeon’s standard practice. The presence of a concomitant umbilical hernia is not unusual and can be utilized for entry into the abdominal cavity. Although the existence of an umbilical hernia does not preclude a TEP repair, umbilical hernia repair is a convenient adjunct to the TAPP approach when the hernia is used for initial access to the abdominal cavity. Visual inspection of both inguinal regions allows for port placement adjustment to triangulate the instruments to the target surgical site. Bilateral hernias are approached via two 5-mm

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working ports placed approximately 6 cm lateral and slightly inferior to the umbilical port. For the unilateral repair, the ipsilateral 5-mm trocar is placed at the level of the umbilicus, whereas the contralateral 5-mm trocar is placed several centimeters lower than the umbilicus for ergonomic optimization (Fig. 1). Robotic-assisted TAPP can also be performed and has emerged as the preferred approach for adopters of this platform. The operation is typically performed with two working ports placed in mirror-image locations on either side of the abdomen, at least 8 to 10 cm lateral to the midline (often supraumbilical) camera port. To reduce the risk of midline port-site herniation, the port can be directed through the rectus abdominis sheath rather than the linea alba. The patient is placed in a flexed position to maximize the working space and clearance for the robotic arms. The operative and anesthesiology teams should be cognizant of the positioning of the arms during the procedure, and the patient’s upper extremities and face should be padded and protected to avoid inadvertent injury or extubation. After visualization of both inguinal sites and confirmation of the hernia(s), the mesh and suture for peritoneal closure can be inserted as appropriate before docking the robot to eliminate the later need for camera removal and repositioning to a lateral port. The robotic-assisted inguinal hernia repair can be performed with the fenestrated bipolar forceps, monopolar scissor, and suture-cut needle driver. Some variation of this instrumentation may be preferred according to the level of experience of the surgeon and the characteristics of the hernia, which may require bowel reduction with the more gentle Cadiere forceps. Regardless of the platform, wide exposure of the myopectineal orifice (MPO) is critical to safe and effective performance of this operation. The peritoneum is opened at least 4 cm above the internal inguinal ring, from just lateral to the anterior superior iliac spine to the medial umbilical ligament, and dissection is continued posteriorly until generous exposure of the psoas muscle is achieved. Dissection should take place in the avascular preperitoneal space, just deep to the transversalis fascia. Medially, the dissection is at the parietal layer of the transversals fascia, allowing the mesh to lay along the abdominal wall with separation from the bladder and full coverage over the obturator space. Laterally, the visceral and parietal transversalis fascia and fat overlying the nerve area should be preserved to reduce the risk of neuropathic postoperative pain. Recurrences of inguinal hernias commonly occur medially and posteriorly, so great care should be taken to ensure adequate posterior and medial dissection of the preperitoneal space, which in turn allows generous overlap of the mesh. Generally, if the spermatic cord structures lift up while the posterior peritoneal flap is elevated anteriorly, the posterior dissection is likely insufficient and should be continued until

FIG. 1  Myopectineal orifice.

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the cord structures have been completely freed from this layer. In the female patient, transection of the round ligament may be necessary to allow the peritoneal flap to come down adequately for wide mesh overlap. As the genital branch of the genitofemoral nerve may join the round ligament, transection should be performed close to the attachment at the peritoneum and not near the inguinal ring to limit the risk of nerve injury. The preperitoneal pocket should extend medially to the posterior surface of the symphysis pubis and laterally to just beyond the fibers of the transversus abdominis muscle as they come into the visual field superiorly and laterally near the anterior superior iliac spine. The preperitoneal “pocket” developed should be of sufficient size to allow identification of all hernia defects around the MPO and to facilitate wide mesh coverage of the area. Generally, all efforts should be made to ensure that this space is large enough to allow the mesh to lie flat, maximizing the surface area available for integration of the mesh into the abdominal wall. It may be useful to perform the medial and lateral dissections first as this will improve the mobility of the peritoneal flap and exposure, and it may assist in reduction of the hernia sac. A circumferential “margin” of 1 to 2 cm of clearance from the inner posterior edge of the peritoneum to the edge of the mesh will prevent folding of the mesh as the peritoneum is closed. Lipomas, which consist of incarcerated preperitoneal fat, should be fully reduced from the hernia defect as these are theoretically a source of compression and potential postoperative discomfort. Moreover, the presence of a retained lipoma could give patients the impression of a persistent hernia, diminishing their satisfaction with the outcome. The white edge of the attenuated transversalis fascia can be seen at the intersection of the spermatic cord and the lipoma, and it offers a visual cue for the proper plane of dissection (Fig. 2). Caution should be exercised to identify and preserve the corona mortis, the variably present aberrant vessels linking the epigastric and obturator arteries located below the direct defect at the ligament of Cooper. The external iliac vein should also be visible at this point, and the presence of overlying fat suggests an occult femoral hernia. If present, this should also be fully reduced before placement of the mesh. The hernia sac at the indirect space, if present, is then dissected from the cord structures while retracting the sac cephalad. One advantage of the TAPP approach, particularly during complex cases, is that it permits visualization of herniated viscera through both the preperitoneal and peritoneal spaces, which is often useful for

FIG. 2  The peritoneum is closed, taking care to leave no gaps through which mesh might be exposed to underlying bowel.

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determining the boundaries of the sac. The cord structures should be completely freed from hernia sac attachments, which might contribute to a subsequent hernia recurrence. With large direct defects (M3 EHS designated hernia), primary closure of the hernia can be undertaken to secure the iliopubic tract, composed of thickened fibers of the inferior edge of the transversalis fascia and musculoaponeurotic transverses abdominis, to the transversalis arch superiorly with incorporation of the attenuated transversalis fascia of the direct defect. This strategy should be used with caution, however, as it risks nerve entrapment if performed too anteriorly through the muscle wall and may contribute to the development of chronic postoperative pain. Meticulous attention to dissection can help reduce the risk of hernia recurrence. In the setting of larger direct hernias, inversion of the portion of transversalis fascia involved in the hernia not only decreases the likelihood of recurrence, but may also mitigate the potential for postoperative seroma formation. The size of the mesh selected should be large enough to offer wide coverage of the MPO as this may obviate the need for fixation in all but the largest defects. Additionally, although relatively pliant mesh is desirable, it should be substantial enough to resist herniation through the underlying defect. Lightweight mesh may not be adequate for a large indirect and particularly a large direct hernia. Mesh fixation in the setting of inguinal hernia repair is a matter of some controversy. No data currently exist that show a difference in recurrence rates directly attributable to the lack of fixation, regardless of the choice of platform. On the other hand, there exists some evidence associating fixation with both immediate and chronic postoperative pain. Given the current absence of definitive data supporting one strategy over the other, the decision to use fixation remains within the realm of surgeon preference at this time. For large defects, fixation may be prudent to prevent mesh migration or eventration. Implanted mesh should be completely excluded from the peritoneal cavity, including the elimination of any gaps in the suture line closure of the peritoneal flaps. Tears or rents in the peritoneum that result in exposed mesh likewise should be individually closed with absorbable suture. Although popular because of the expediency of their use, the barbs characteristic of “self-locking” sutures may impose a risk of small bowel obstruction, and care should be taken to ensure that these are adequately covered with native tissue. In circumstances in which the peritoneum cannot be sufficiently closed to adequately cover the mesh, omentum can be secured over the mesh as an alternative, though there remains a risk of interparietal hernia between the peritoneum and the mesh. The medial umbilical ligament can also be mobilized and used to cover the most medial portions of the preperitoneal space if necessary.

Total Extraperitoneal Repair Patient preparation is similar for both the TEP and TAPP approaches; the patient is placed in the supine Trendelenburg position, typically with the arms tucked as this is more convenient for pelvic laparoscopy. Patients should be asked to make an attempt to void before surgery, although some surgeons prefer the routine placement of a Foley catheter to ensure that the bladder is fully decompressed. Of note, postoperative urinary retention appears to be more common after laparoscopic and robotic-assisted repairs, particularly when bilateral repairs are performed. When this occurs, this may serendipitously denote the presence of underlying prostatic hypertrophy, and referral to a urologist might be prudent. There is also emerging evidence that the use of Sugammadex, which binds rocuronium and vecuronium, for reversal of anesthesia may prevent urinary retention. For the TEP approach, access to the preperitoneal space is gained via an infraumbilical 12-mm port. Under direct visualization, the anterior leaflet of the rectus sheath is incised just off of the midline, and the rectus muscle is split, revealing the underlying retrorectus space. This compartment is then developed bluntly, often through the use of commercially available balloon dissectors. Alternatively, this same space can be accessed while advancing an optical port under

camera visualization and may be aided by ultrasound guidance. This approach is particularly useful for surgeons who prefer the use of a 5-mm port and camera. Inadvertent tears in the peritoneum during the preperitoneal dissection may occur and occasionally require closure in order to proceed. Sutures, endoscopic clips, or Endoloops may be useful for this purpose. Additionally, a Veress needle or 5-mm port can be inserted into the abdominal cavity for decompression, allowing for selective insufflation of the preperitoneal space. Large tears may prevent insufflation of the preperitoneal space altogether, necessitating conversion to a TAPP or open approach. Insufflation pressures of 12 to 15 mm Hg are established before proceeding, and an angled laparoscope is recommended. Two 5-mm working ports are then placed in the midline under direct visualization, allowing for 5 cm between the lowest port and the symphysis pubis when possible, as well as adequate spacing between the ports. The lateral abdominal wall is identified first by bluntly dissecting away the filmy avascular tissue anterior to the hernia sac, but inferior to the epigastric artery and vein, which should be identified and preserved in situ anteriorly. Medially, Cooper’s ligament is identified and cleared of any overlying fat while taking care to avoid the venous circle of Bendavid and the femoral canal inferiorly. If injury to the deep venous circulation is not recognized and addressed, the result can be hematoma formation following the release of insufflation, with substantial postoperative morbidity. The spermatic cord and hernia sac can be grasped and retracted cephalad, which facilitates dissection of the preperitoneal space and reduction of any cord lipomas that may be present. Despite the notable benefits of a minimally-invasive procedure that does not violate the peritoneal cavity, the traditional TEP repair is limited by space constraints imposed by the architecture of the preperitoneum. These challenges are particularly exaggerated in patients with obesity, as well as those with large inguinal hernias. A modification of the conventional TEP was proposed in 2012 that substantially alleviates the difficulties associated with this limitation. (Daes, 2012) Known as the extended totally extraperitoneal repair (eTEP), this approach can be performed either laparoscopically or robotically. The primary innovation of this approach is the placement of a retromuscular optical port (12 mm laparoscopically or 8 mm robotically) in the upper quadrant on the same side as the hernia. This strategy takes advantage of the presence of the posterior rectus sheath above the arcuate line, which resists tearing, and promotes a much larger space in which to work. The retrorectus space is then dissected, either using a commercially available balloon dissector, or bluntly using the camera itself, taking care not to injure or disrupt the lateral neurovascular bundles or the linea semilunaris. Following this dissection, the space is insufflated to a minimum of 12 mm Hg pressure. In the original description of the procedure, 5-mm working ports were placed along the midline at the umbilicus and approximately halfway between the umbilicus and the symphysis pubis. However, a variety of port placement strategies can be successfully utilized depending on the presence of bilateral disease, a large unilateral hernia, or surgeon preference. The next key step in the procedure is division of the arcuate line, granting access to the preperitoneal space in the lower abdomen and pelvis. The hernia can then be identified and reduced, and the mesh can be placed as with a traditional TEP. This approach results in a markedly expanded view of the preperitoneal space, with ample additional room in which to work. Though originally described in the endoscopic treatment of inguinal hernias, the approach has become the basis for a multitude of retromuscular repairs of other hernia types, including midline ventral, incisional, and lumbar. There are limitations to the approach, however. Under the best of circumstances, eTEP is technically challenging. Development of the retromuscular space can be especially problematic in patients in whom this space has been damaged, such as those with prior history of colostomy or ileostomy. Additionally, eTEP should not be attempted in patients in whom retromuscular mesh is present.

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TAPP VERSUS TEP? The International Guidelines for Groin Hernia Management published by the HerniaSurge Group in 2018 and subsequently endorsed by multiple international hernia societies largely considers TAPP and TEP equivalent operations with similar operative time and cost, complication profiles, and recurrence rates. Conversion to open is more likely with a TEP approach, although this remains a relatively infrequent occurrence. Visceral injuries, while rare, are more common with the transabdominal approach, while the risk of vascular injuries is increased with the totally extraperitoneal approach. Port-site hernias are quite uncommon but tend to occur at the umbilical port. Given the similarities between the two approaches described here, the choice of technique should consider the surgeon’s skills, training, and experience. Some situations may be better suited for one approach over the other, however. For example, recurrent hernias following laparoscopic TEP may be more easily addressed via TAPP or an open (anterior) approach. TEP may be favorable in the setting of bilateral hernias given that there is no need for a peritoneal closure. Patients with prior surgery on the lower abdomen or pelvis, particularly when performed through a midline laparotomy incision; patients with a scrotal hernia, prior prostatectomy, or recurrence after previous use of a mesh plug; and patients in whom diagnostic laparoscopy would be beneficial may be preferred candidates for a TAPP procedure.

Risk Factors for Inguinal Hernia Development and Recurrence Patients with a family or personal history of inguinal hernia or prostatectomy, those of older age, male patients, and patients with collagen disorders resulting in decreased levels of mature type I collagen are at an increased risk of developing an initial inguinal hernia. Interestingly, obesity appears to be protective, as lower body mass index (BMI) is associated with a higher incidence of inguinal hernia, although this could be caused by a discrepancy in the rate of diagnosis. Factors related to surgical technique also appear to make a significant contribution to the overall risk of recurrence, as does surgeon volume, which is inversely related to recurrence rates. Direct and sliding hernias, in which part of the hernia sac is formed by the wall of a retroperitoneal organ, are likewise associated with poorer outcome. For reasons not completely understood, female patients are more likely to develop a recurrence.

CHRONIC PAIN AFTER INGUINAL HERNIA REPAIR Chronic pain after inguinal hernia repair has emerged as the most common complication of this operation, with rates ranging from 11% to 18%. Conventionally known as chronic post-herniorrhaphy pain syndromes, these are defined by surgery-related pain that persists beyond 3 months after the initial operation. This risk is higher with open approaches, and an effort should be made to identify the ilioinguinal, iliohypogastric, and genital branch of the genitofemoral nerves during open repairs with the intent of avoiding direct retraction of the nerves or injury to the perineurium. An international group of hernia experts convened in 2011 for the purpose of developing guidelines for the prevention and management of chronic pain after inguinal hernia surgery. The group found in a literature review that identification and preservation of all three peripheral nerves of the inguinal region reduced the risk of postsurgical pain syndromes to less than 1% (Alferi, 2011). If an injury to one of these nerves is suspected at the time of repair, a neurectomy proximal to the site of injury should be considered and the cut end implanted into muscle if performed. When tacks are used for fixation during

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laparoscopic repairs, these should not be implanted too deeply into the muscle to avoid injury to superficial nerves not visible from the posterior approach. Similarly, surgeons should consider performing “air knots” if suture fixation is utilized as this may help prevent nerve entrapment.

CONCLUSION Elective repair of symptomatic inguinal hernias is recommended; however, observation is appropriate in those patients with no discernible symptoms. The choice of minimally invasive or open techniques is primarily driven by surgeon preference, and the use of synthetic mesh significantly reduces the rate of hernia recurrence. The most common complication of inguinal hernia repair is the development of a chronic post-herniorrhaphy pain syndrome, the risk of which appears to be increased with the use of mesh and tack fixation. The risk of chronic pain must be balanced against that of recurrence in a thoughtful and transparent preoperative discussion with the patient regarding the necessity of repair and the available options.

S uggested R eadings Alfieri S, Amid PK, Campanelli G, et al. International guidelines for prevention and management of postoperative chronic pain following inguinal hernia surgery. Hernia. 2011;15(3):239–249. Amato B, Moja I, Panico S, et  al. Shouldice technique versus other open techniques for inguinal hernia repair. Cochrane Database Syst Rev. 2012;4:CD001543. Amid PK. The Lichtenstein open “tension-free” mesh repair of inguinal hernias. Surgery Today. 1995;25(7):619–625. Bracale U, Melillo P, Piaggio D, et al. Is Shouldice the best NON-MESH inguinal hernia repair technique? A systematic review and network metanalysis of randomized controlled trials comparing Shouldice and Desarda. Int J Surg. 2019;62:12–21. Claus C, Furtado M, Malcher F, et al. Ten golden rules for a safe MIS inguinal hernia repair using a new anatomical concept as a guide. Surg Endosc. 2020;34(4):1458–1464. Daes J. The enhanced view–totally extraperitoneal technique for repair of inguinal hernia. Surg Endosc. 2012;26(4):1187–1189. Daes J, Felix E. Critical view of the Myopectineal Orifice. Ann Surg. 2017;266(1):e1–e2. Fitzgibbons RJ, Giobbie-Hurder A, Gibbs JO, et al. Watchful waiting vs repair of inguinal hernia in minimally-symptomatic men: a randomized clinical trial. JAMA. 2006;295(3):285–292. HerniaSurge Group. International guidelines for groin hernia management. Hernia. 2018;22(1):1–165. Hu QL, Chen DC. Approach to the patient with chronic groin pain. Surg Clin North Am. 2018;98(3):651–665. Jacob BP, Chen DC, Ramshaw B, Towfigh S, eds. The Sages Manual of Groin Pain: Springer International Publishing; 2016. Lichtenstein IL, Shulman AG, Amid PK, et al. The tension-free hernioplasty. Am J Surg. 1989;157(2):188–193. Kesek P, Ekberg O. Herniography in women under 40 years old with chronic groin pain. Eur J Surg. 1999;165(6):573–578. McCormack K, Scott NW, Go PM, et  al. Laparoscopic techniques versus open techniques for inguinal hernia repair. Cochrane Database Syst Rev. 2003;1:CD001785. Matikainen M, Vironen J, Kösso J et al. Impact of mesh and fixation on chronic inguinal pain in Lichtenstein hernia repair: 5-year outcomes from the Finn Mesh study. World J Surg. 2021;45(2):459–464. Matikainen M, Kössi J, Silvasti S, et al. Randomized clinical trial comparing cyanoacrylate glue versus suture fixation in Lichtenstein hernia repair: 7-year outcome analysis. World J Surg. 2017;41(1):108–113. Reinpold W. Risk factors of chronic pain after inguinal hernia repair: a systematic review. Innov Surg Sci. 2017;2(2):61–68. Shouldice EB. The Shouldice repair for groin hernias. Surg Clin North Am. 2003;83(5):1163–1187.

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Management of Recurrent Inguinal Hernia

Management of Recurrent Inguinal Hernia Britta Jean Han, MD, MS, and Bethany C. Sacks, MD, MEd

INTRODUCTION Inguinal hernia surgery is one of the most common general surgery procedures performed in the United States. Recurrence rates after repair have been reported to be as high as 17%, with primary nonmesh repairs having even higher recurrence rates. Rates may be even higher than reported as long-term follow-up in the hernia population is often limited. Regardless, recurrent inguinal hernias are a problem that every general surgeon will encounter in training and practice (Fig. 1).

RISK FACTORS FOR RECURRENCE The etiology of recurrent inguinal hernias is complex and often multifactorial. Risk factors for recurrence include nonmodifiable and modifiable categories. Nonmodifiable risk factors include genetics such as connective tissue metabolism disorders, the type and location of inguinal hernia (direct vs. indirect, femoral), and female gender. In the following sections, we detail modifiable risk factors for recurrence, which are categorized into (1) patient factors, (2) technical factors, and (3) mesh factors. All factors should be aggressively optimized before repair of the recurrent hernia as each subsequent repair will increase the risk of hernia recurrence.

Patient Factors Several critical patient risk factors for hernia recurrence are those related to delayed wound healing. These factors include smoking, obesity, glucose control, and immunosuppression. The deleterious effects of smoking on wound healing are well known and documented. Smoking affects tissue oxygenation and aerobic metabolism and prolongs the effect of inflammation on healing. This ultimately delays wound healing and increases the

risk for surgical site occurrences such as wound infection, hematomas, or seromas, which all contribute to an increased risk of hernia recurrence. Of note, although nicotine replacement therapies seem to attenuate the inflammation phase of wound healing, these effects appear to be marginal according to a recent large observational cohort study and are also not associated with adverse postoperative outcomes. Thus, nicotine replacement therapies can be considered for patients who struggle with smoking cessation before undergoing redo repair. Obesity impacts risk of recurrence in two ways. First, increased mechanical strain and tension on the initial repair increase the risk of hernia recurrence. Second, obesity increases the risk of wound infection, another independent risk factor for recurrence. In fact, increasing body mass index (BMI) is associated with significantly increasing rates of surgical site infections. Poor glucose control is also a well-known contributing factor to poor postoperative wound healing. Hyperglycemia impairs neutrophil bactericidal activity and increases the risk of wound infection. Data suggest that for every 40-point increase from normoglycemia, there is a 30% increase in the rate of postoperative infections. Similarly, the use of immunosuppressive agents affects wound healing and increases the risk of wound infection.

Technical Factors Several key technical factors contribute to hernia recurrence. One is the failure to achieve a tension-free repair. The use of mesh is considered the gold standard because of its ability to provide a tension-free repair. Thus, primary tissue repair techniques such as Bassini, Halsted, and McVay have a 50% to 75% higher recurrence rate than mesh repairs. In recent meta-analyses and systematic reviews, recurrence rates by mesh weight are not significantly different. Other technical factors include inadequate dissection and reduction of the hernia sac or failure to identify concurrent indirect or direct hernia during the primary repair. Additionally, failure to resect a cord lipoma can present as pseudo-recurrence, so lipomas should be resected or adequately reduced during the initial repair. Finally, an ongoing debate centers around whether laparoscopic inguinal hernia repair is associated with higher rates of recurrence compared with the Lichtenstein open hernia repair. The data remain inconclusive. However, studies demonstrate that surgeon experience is most important in consideration for open versus laparoscopic repair. That is, recurrence rates for laparoscopic repairs decrease as surgeon experience with laparoscopy increases.

Mesh Factors As previously mentioned, tension-free mesh repairs remain the gold standard. Additionally, mesh products have evolved since their first inception and use. However, there remain several mesh factors that may contribute to recurrence. These factors include mesh shrinking after placement, mesh migration, mesh resorption, and mesh folding. Although any of these mesh events can occur even under the best of repairs, they highlight the importance of thoughtful mesh placement in the primary repair.

PREOPERATIVE EVALUATION

FIG. 1  Recurrent inguinal hernia.

Recurrent inguinal hernias are complex cases and warrant careful preoperative workup and operative planning. Native tissue planes and anatomy have often been distorted or obliterated because of scar tissue and prior mesh use, making repeat dissection challenging. This is particularly true in patients with multiple recurrent inguinal hernias.

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Defining Recurrent Inguinal Hernia

Management of Patient Expectations

Recurrent inguinal hernias that present within the first 3 to 6 months after primary repair are considered early recurrences. Patients presenting with recurrences after 6 months are considered late recurrences. Traditionally, early recurrences were often attributed to technical factors, and late recurrences were attributed to patient factors. However, this is not always the case. Both early and late recurrences can be caused by either technical, patient, or mesh factors (as described earlier).

Management of patient expectations is an important component for counseling patients with recurrent inguinal hernias. Patients should be made aware of the higher risk of complications in redo operations. Pain, particularly chronic pain, is a common symptom in both primary inguinal hernias and recurrent inguinal hernias. An honest conversation about pain will help prevent unrealistic postoperative expectations. Some patients will continue to experience chronic pain, even after a redo repair, or they may experience worsening pain because of the increased risk for nerve injury and damage to surrounding structures. Being realistic about the pain and potential for continued chronic pain can help allay patient disappointment or dissatisfaction after redo repair. In addition to management of expectations around pain, patients should also be well informed that recurrence rates after redo operations are even higher, regardless of the type of technique or mesh used.

Patient History and Physical Examination When patients present with a chief concern of recurrent inguinal hernia, a careful history and physical examination is crucial. Although some patients will present with an acute change to the groin (e.g., new bulging sensation, groin pain, or visible bulge), other patients will be asymptomatic. A detailed history, physical examination, and judicious use of imaging can help delineate a recurrence from other diagnoses that can present with similar symptoms. When a recurrent hernia diagnosis is confirmed, a thorough history of the inguinal hernia is important. The history should include any potential eliciting events to recurrence, number of prior recurrences with repair, history of mesh repair, and types of repairs performed. Ideally, the operative note(s) from the prior repair(s) will include details of the type of mesh used, the type of repair performed, and the dates of repairs. Finally, a history of surgical site infection and complex wound healing should be documented, especially a history of methicillin-resistant Staphylococcus aureus (MSRA). This should be accounted for in antibiotic prophylaxis if the patient undergoes recurrent inguinal hernia repair. Other components of the patient history should assess for risk factors listed previously. These should subsequently be optimized if the patient undergoes redo repair. Furthermore, these risk factors, in conjunction with other parts of the patient history, may determine whether a patient should undergo a redo operation at all. Although physical examination will be like that of a primary inguinal hernia, there are several examination maneuvers that may help distinguish a recurrent hernia from other diagnoses. In general, pain from a recurrent hernia can be elicited by palpating directly over the bulge or defect. Pain that is elicited with hip rotation or flexion/extension is generally not from a recurrent hernia. Constant pain can also have multiple etiologies that may be related to prior hernia repair (e.g., suture tacking, mesh fixation) but not actual hernia recurrence.

Management of Asymptomatic Recurrent Inguinal Hernia Not all recurrent inguinal hernias must be repaired immediately. A randomized multicenter trial in 2006 demonstrated that watchful waiting is an appropriate option for male patients with asymptomatic or minimally symptomatic inguinal hernias. This study found strangulation risk to be rare, with no significant changes to rates of postoperative complications. Of note, this study did not follow female patients. In this select group of patients, there may be time for not only watchful waiting, but also careful planning and, if needed, prehabilitation and optimization before undergoing a redo operation. Symptomatic patients should undergo repair (Fig. 2).

TECHNIQUES FOR REPAIR OF RECURRENCE Regardless of approach, all risk factors should be aggressively optimized, particularly smoking and obesity. If the patient is asymptomatic, more time is available for preoperative optimization. Repair of a recurrent inguinal hernia is complex and often more difficult than the initial operation because of distorted tissue planes and scar tissue. The cornerstones of recurrent inguinal hernia repair include (1) reinforcement of the entire inguinal canal, regardless of the size and location of recurrence, and (2) approaching the repair through unviolated tissue planes when possible.

Role of Imaging

Minimally Invasive Approaches

Although a history and physical examination may be sufficient to diagnose recurrent hernia, adjunct use of imaging can be helpful in both diagnosis and preoperative planning. When clinical diagnosis of recurrent hernia is difficult or the patient has a complex or unclear hernia history, imaging may be required. Clinically difficult to diagnose hernias are defined as occult hernias in literature. These hernias can present with chronic pain without a recurrent or palpable bulge. In these patients, imaging will be crucial to diagnosis. Traditionally, ultrasound is used as first-line imaging with computed tomography (CT) as follow-up imaging if ultrasound is inconclusive. However, in particularly challenging diagnoses such as occult hernias or complex clinical presentation, magnetic resonance imaging (MRI) can be used to further elicit a diagnosis. In one study, MRI demonstrated the highest sensitivity, specificity, and negative predictive value for occult hernias when compared with ultrasound and CT. In addition, MRI has increased sensitivity for neuromas or issues with implanted mesh.

Minimally invasive approaches are useful when a recurrence occurs following an open (anterior) inguinal hernia repair. This allows for surgeons to utilize unviolated native posterior tissue for dissection and mesh placement. However, as surgeons gain experience and comfort with laparoscopic approaches, many surgeons will approach a recurrent inguinal hernia with a laparoscopic approach regardless of the prior technique used. An additional advantage of laparoscopic re-repair is the ability to view all potential sites of recurrence and to examine the contralateral side for hernia presence. A recent retrospective study found that 96% of patients successfully underwent a second laparoscopic inguinal hernia repair for recurrent hernia with low rates of late re-recurrence. The most frequently utilized laparoscopic techniques include transabdominal preperitoneal repair (TAPP), total extraperitoneal repair (TEP), or extended-view total extraperitoneal repair (e-TEP). The approach will depend on surgeon preference and experience, patient surgical history, and hernia size. In a recent randomized prospective study, no differences were noted between the TAPP

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Management of Recurrent Inguinal Hernia

Recurrent Inguinal Hernia

Asymptomatic

Watchful waiting

Symptomatic

Prior tissue repair

Prior anterior repair

Prior posterior repair

Prior posterior and anterior repairs

Anterior or posterior repair

Posterior MIS repair

Anterior repair, consider repeat posterior MIS repair

Repeat posterior MIS repair versus IPOM

FIG. 2  Algorithm for management of recurrent inguinal hernia. IPOM, Intraperitoneal onlay mesh; MIS, minimally invasive surgery.

and TEP approaches in regard to quality of life, chronic groin pain, resumption of normal activities, or cost. TEP and e-TEP repairs minimize intraabdominal adhesions. Dissection of the preperitoneal tissue plane can be more challenging in patients with prior repairs and may lead to tearing of the peritoneum. In these cases, conversion to TAPP may be warranted. Thus, any surgeon attempting a TEP approach should be comfortable with both TEP and TAPP techniques. In particularly large and/or difficult to reduce recurrent hernias (e.g., inguinoscrotal), the TAPP approach provides improved visualization of incarcerated contents with concurrent ability to reduce the contents. Finally, in the case of difficult exposure or dense adhesions, conversion to open anterior or posterior repair is an option.

Open (Anterior) Approaches An open (anterior) approach can be considered for a patient with a prior posterior repair for the ipsilateral inguinal hernia (e.g., TAPP) to avoid previously dissected tissue. The most utilized technique is the Lichtenstein repair (tension-free mesh repair), though some surgeons will use an open preperitoneal repair (e.g., Stoppa). Other tissue-based repairs should be avoided when possible unless mesh is absolutely contraindicated, such as in the case of an active infection.

The Complex Recurrent Inguinal Hernia Patient Some patients will present with a multiply recurrent inguinal hernia. These patients may have undergone both open and laparoscopic repairs. Prior mesh may exist in more than one plane. Thoughtful preoperative evaluation should be completed with attempts to review all prior operative notes. These patients should undergo expectation management as risk of recurrence and postoperative complications increases with each subsequent repair. Additionally, these patients should be considered for referral to a high-volume, specialized hernia center for redo repair. For these patients, a laparoscopic approach is recommended as the initial approach. A diagnostic laparoscopy is helpful in identifying

the direct, indirect, and femoral spaces and can provide improved visualization. Finally, an intraperitoneal onlay mesh (IPOM) repair can be considered in the event that a repeat TAPP repair is difficult or the peritoneum is insufficient for mesh coverage. The mesh for these repairs is coated permanent mesh with an anti-adhesive barrier. Generally, IPOM is often considered a last resort after open and other laparoscopic approaches.

Mesh Considerations There is no clear consensus on the management of mesh from prior repairs. Some surgeons will advocate for removal of prior mesh whenever possible. If complete mesh resection is not feasible, it is ideal to remove as much as possible. This may facilitate new mesh placement. In our experience, the removal of prior mesh is often difficult, if not impossible, and often not necessary. Regardless, it is important to manage patient expectations around pain and discomfort thought to be secondary to either old mesh and/or recurrence. Mesh should be used in repairs of recurrent inguinal hernias. Patients presenting with hernia recurrence will already have weaker tissue because of prior repair and have a high likelihood of wound-healing abnormalities. The rare case of infected mesh is the only situation that may preclude the use of mesh. Traditionally, biologic mesh has been reserved for use in contaminated cases. Lightweight polypropylene mesh is an ideal option because of decreased pain, decreased mesh sensation, and increased ingrowth of mesh, leading to a more durable repair. Standard weight polypropylene may be considered for larger hernias that require a wider bridged repair to minimize the risk of postoperative mesh eventration or recurrence. Finally, there is no clear consensus on the role of mesh fixation in laparoscopic inguinal hernia repair. Some surgeons believe fixation can prevent mesh migration, folding, and recurrence, while other surgeons believe fixation only causes increased postoperative pain resulting from potential nerve injury. There is yet to be definitive data.

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CONCLUSION Recurrent inguinal hernia cases are complex and should not be taken lightly. Thoughtful preoperative evaluation and operative planning are crucial for recurrence risk optimization. Operative planning and approach should incorporate patient history and surgeon experience with plans for alternative intraoperative approaches if the initial selected approach cannot be safely completed. For patients with particularly complex recurrent hernias, consideration should be given to referring the patient to a high-volume specialized hernia center for evaluation and repair.

S uggested R eadings Bansal VK, Misra MD, Babu D, et al. A prospective, randomized comparison of long-term outcomes: chronic groin pain and quality of life following totally extraperitoneal (TEP) and transabdominal pre-peritoneal (TAPP) laparoscopic inguinal hernia repair. Surg Endosc. 2013;27(7):2373–2382.

Incisional, Epigastric, and Umbilical Hernias Hien T. Nguyen, MD, MBA, and Katherine McDermott, MD

I

ncisional, epigastric, and umbilical hernias account for the majority of ventral abdominal wall hernias. Over 400,000 ventral hernia repairs occur annually in the United States, with a trend toward more minimally invasive and outpatient procedures. Incisional hernias may develop in up to 28% of patients who have undergone laparotomy, which leads to a hospital cost of over $3 billion per year in the United States. Though VHR is a common surgical problem, it includes a wide spectrum of hernia size, complexity, and morbidity. Surgeon experience of 40 or more cases per year is associated with a 30% to 40% lower rate of reoperation for recurrence compared with low-volume hernia surgeons. Ventral hernias are generally repaired in the elective setting, and a watchful waiting approach may be appropriate for asymptomatic patients. Approximately 10% to 15% of patients under watchful waiting will cross over to require hernia repair. Factors associated with crossover include recurrent hernias, enlarging hernias, and BMI >30. There are no differences in outcomes and complications between patients who undergo initial surgery and elective crossover surgery, with low rates of emergent repair at 5 years among patients who participate in watchful waiting.

PATIENT SELECTION Smoking, diabetes, obesity, and COPD are the four most consistently demonstrated modifiable patient factors associated with recurrence or wound complication. Chronic smokers have a risk of surgical site infection (SSI) up to 50% higher compared with nonsmokers, but smoking cessation 4 weeks preoperatively is associated with decreased SSI; nicotine replacement therapy does not seem to diminish this benefit. There is significantly increased risk of 30-day SSI in patients with HbA1c >8.0%, but no clear increased risk of long-term complications. HbA1c is a better indicator for infection than a single glucose reading or insulin dependence. In our practice, the ideal preoperative goal of HbA1c is less than 7.0%, with >8.0% being a relative contraindication for elective repair. Recurrence rate is approximately

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Fitzgibbons Jr RJ, Giobbie-Hurder A, Gibbs JO, et  al. Watchful waiting vs repair of inguinal hernia in minimally symptomatic men: a randomized clinical trial. JAMA. 2006;295(3):285–292. HerniaSurge Group. The international guidelines for groin hernia management. Hernia. 2018;22(1):1–165. Holihan JL, Liang MK. Recurrent inguinal hernia. In: Cameron JL, Cameron AM, eds. Current Surgical Therapy. 13th ed. Philadelphia: Elsevier; 2020:631–637. Miller J, Cho J, Michael MJ, Saouaf R, Towfigh S. Role of imaging in the diagnosis of occult hernias. JAMA Surg. 2014;149(10):1077–1080. Roth S, Wennergren JE. Treating inguinal recurrences. In: Novitsky YW, ed. Hernia Surgery. Switzerland: Springer; 2016:491–496. Sereysky J, Parsikia A, Stone ME, Castaldi M, McNelis J. Predictive factors for the development of surgical site infection in adults undergoing initial open inguinal hernia repair. Hernia. 2020;24(1):173–178. Stefan MS, Pack Q, Shieh MS, et al. The association of nicotine replacement therapy with outcomes among smokers hospitalized for a major surgical procedure. Chest. 2020;157(5):1354–1361.

30% among patients with a BMI of 30 to 40 and up to 50% among those with a BMI greater than 40. A total body weight reduction of 7% may lead to a 50% absolute risk reduction in wound complication rate. COPD carries a twofold increased risk for recurrence and fourfold increased risk for postoperative respiratory insufficiency; therefore, preoperative optimization by a pulmonologist is recommended. Cirrhosis with ascites is associated with rates of umbilical and ventral hernia of up to 20% and a high risk of hernia complications as a result of poor nutrition and increased intraabdominal pressure. Inability to medically manage ascites is a relative contraindication to elective surgery, but elective repair of small and symptomatic hernias in optimized cirrhotic patients appears to be safe. Those who do not undergo elective repair have a 45% chance of requiring urgent repair, with a 15% mortality related to complications from urgent hernia surgery. Predictors of poor outcomes include high MELD or advanced Child classification, varices, age >65 years, and albumin 65 years), patients with a history of wound infection, obesity, malnutrition, smoking, immunosuppression, and chronic inflammatory disease. For open hernia repair we selectively use incisional NPWT, especially in patients with the aforementioned risk factors, long incisions, or large musculocutaneous flaps. The skin is closed with absorbable braided interrupted deep dermal sutures, a nonadherent contact layer is placed in a strip over the incision to protect the surrounding skin, and a sponge is placed over the nonadherent contact layer with care not to place the sponge directly onto the skin. We leave this dressing in place until postoperative day 4, and wound closure strips are applied to the incision once this dressing is removed. After discharge, patients are encouraged to optimize their level of activity with as much ambulation as possible. We also suggest a weight restriction of 15 lb for the first 2 weeks, and patients are asked to increase their maximal weight bearing by 5 to 10 lb per week until they are at their normal level of activity. Most patients are seen in the postoperative clinic 1 to 2 weeks after surgery. Additional follow-up is dependent on patient risk of developing an SSO. Any drains are typically removed by 2 weeks postoperatively when serosanguineous output is less than 25 mL/day.

COMMON COMPLICATIONS Most patients will develop a seroma, but only 10% to 30% of these are clinically significant, defined as symptomatic or persisting after 6 months from the time of surgery. Primary fascial closure in mesh repairs is the most consistently demonstrated strategy to prevent seroma/hematoma, and it is our practice to routinely excise the hernia sac. There are no strong associations between anatomic position of mesh placement or method of adhering mesh and rates of clinically significant seroma. Drains may decrease the rate of seroma formation but have not been shown to decrease the rates of seromas needing intervention, rates of hernia recurrence, or mesh explantation. For symptomatic seromas or those that persist at 6 months, percutaneous drain placement with removal when output is serous and minimal (90%) reported rates of success. Deep SSI, or “mesh infection,” requires positive cultures from the mesh itself or from fluid directly in contact with mesh for diagnosis. Overall rates of mesh infection are low at 1% to 2%, with risk factors including urgent or emergent repair, immunosuppression, and superficial SSI. The presence of a sterile seroma is not associated with development of mesh infection. Mesh salvage can be attempted in nonseptic patients with lightweight or macroporous mesh, especially if the mesh is in the retrorectus position. Key components of salvage include early systemic antibiotics, superficial debridement, mesh irrigation with antibiotic solution if mesh is visible, and NPWT. Factors predicting failure of salvage include onlay position of mesh, urgent initial repair, and enterotomy at time of initial repair; additionally, PTFE, microporous, or heavyweight mesh are strongly associated with failure to salvage; thus, we typically excise these mesh types upfront rather than attempting long-term conservative

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TABLE 1  Key Components of an Enhanced Recovery Protocol for Ventral Hernia Repair Preoperative risk stratification/preoperative counseling

Structured counseling about protocol should be provided at clinic visit

Preoperative bowel preparation

Bowel preparation (clear liquids × 2 days before surgery) recommended only to patients with colostomy

Prophylaxis against thromboembolism

Preoperative and postoperative chemoprophylaxis and intraoperative and postoperative sequential compression devices ordered and utilized

Methicillin resistant Staphylococcus aureus (MRSA) prophylaxis

Preoperative MRSA nasal swab, and if positive mupirocin intranasal ointment BID × 5 days preoperatively

Nutritional preparation

Consider nutritional consultation and preoperative supplementation if albumin 5y?

No Embolic

AOD

Embolic

No

AOD ET Yes

Open embolectomy

ROMS vs ET vs Bypass

Open embolectomy + Damage control laparotomy

ROMS/ET/ bypass + Damage control laparotomy

Open embolectomy/ ROMS/ Bypass

Yes

Good Nutrition?

No

Temporary closure

Second-look laparotomy FIG. 3  Algorithm for management of acute embolic/thrombotic mesenteric ischemia via open versus endovascular approach. CTA, CT angiography; AOD, atherosclerotic occlusive disease; ROMS, retrograde open mesenteric stenting; ET, endovascular therapy. (From Olson KA, Teixeira PG. Mesenteric Ischemia — How and When to Revascularize. Adv Surg 2021;55:75–87.)



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Greater omentum Marginal artery

Transverse colon

Celiac artery SMA (under pancreas)

Aorta Ascending branch of left colic artery

Duodenum

Graft

IMA Common Iliac artery Ureter

Superior rectal artery

FIG. 4  Operative exposure of the infrapancreatic SMA and IMA. (From Kazmers A. Operative management of acute mesenteric ischemia. Ann Vasc Surg. 1998;12:187–197.)

FIG. 6  Omental pedicle flap coverage of synthetic graft via a defect created in the transverse colon mesentery. (From Kazmers A. Operative management of acute mesenteric ischemia. Ann Vasc Surg. 1998;12:187–197.)

SMA

FIG. 5  Transverse arteriotomy for superior mesenteric artery embolism. (From Cronenwett, Johnston, editors. Rutherford’s Vascular Surgery and Endovascular Therapy, 8th ed. Philadelphia: Elsevier; 2014.)

for AMI. The graft is then tunneled in a retropancreatic plane to reach an unaffected portion of the SMA, and the anastomosis is created in an end-to-end or end-to-side fashion.

RETROGRADE BYPASS With suitable distal inflow, either from a nondiseased portion of the aorta or from the iliac arteries, a retrograde bypass may be performed. This approach avoids the added complexity of obtaining supraceliac aortic control and associated renal hypoperfusion. The traditional approach extends the incision in the mesentery used for SMA exposure down the aorta to the common iliac arteries. The use of a C-shaped supported synthetic conduit has been advocated to avoid “kinking” of venous graft (Fig. 8). An alternative approach, called the direct open retrograde revascularization (DORR) method, has been recently described. Rather than dividing the mesentery over the aorta, access to the iliac arteries is gained by incising the white line of Toldt and mobilizing the cecum or sigmoid colon medially. A venous conduit is utilized and an end-to-side anastomosis is performed. The vein graft is then tunneled through the small bowel mesentery, using blunt finger dissection from above and below,

directly to the SMA (Fig. 9). This serves the hypothetical advantages of using autologous vein graft, reducing graft redundancy, and decreasing operative time associated with transmesenteric dissection of the iliac vessels despite the time required for vein harvest.

RETROGRADE OPEN MESENTERIC STENTING A hybrid approach to revascularization has been described for patients undergoing laparotomy using endovascular techniques that can be employed using a C-arm without necessitating access to an endovascular suite. This allows for a thorough surgical exploration of the abdomen without the pitfalls associated with open bypass, particularly in patients with intraperitoneal contamination. After exposing and obtaining proximal and distal control of the SMA and its branches as described earlier, retrograde access via the SMA or a side branch is achieved with a micropuncture kit distal to the lesion. A guidewire and 6- or 7-Fr sheath are placed in a retrograde fashion. The lesion is then traversed, and a balloon expandable bare metal or covered stent is then deployed (Fig. 10). The arteriotomy is either closed primarily or with a vein patch. Success with this approach

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Intercostal arteries

A

B

C

D

E

FIG. 7  (A) The supraceliac aorta is exposed after division of the diaphragmatic crura. (B) Following systemic heparin, the supraceliac is clamped using either two aortic clamps or a Satinsky clamp. (C) A slightly oblique aortotomy is made for the proximal anastomosis of the bifurcated graft. (D) Note that the graft is gently beveled and that the right graft limb is anastomosed end-to-side to the celiac axis or hepatic artery. (E) The left limb of the graft is tunneled behind the pancreas. (From Sidawy AP, Perler B: Rutherford’s Vascular Surgery and Endovascular Therapy, 9th ed. Philadelphia: Elsevier, 2019.)

has shown to be similar to other revascularization techniques, with shorter operative times (189 vs. 302 minutes) compared with open mesenteric bypass. Patency rates of 76% were reported at 2 years.

OPEN ENDARTERECTOMY In patients with extensive AOD, multivessel disease, or acute on chronic mesenteric ischemia, open endarterectomy may be suitable.

Access and control of the SMA are described earlier. Meticulous dissection and isolation of the branching vessels is required. A longitudinal arteriotomy is performed over the diseased segment, and endarterectomy is performed in the subintimal plane. Care is taken to remove as much plaque from the branching vessels as possible. Autologous vein or pericardial patch may be used to close the arteriotomy. Figure 11 and Video 1 demonstrate this approach in a patient with SMA atherosclerosis, IMA occlusion, and atrial fibrillation who



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CA

SMA Prosthetic graft

FIG. 9  Direct open retrograde revascularization (DORR) technique. (From Huerta et al. J Vasc Surg. 2020;66:263–271 doi:10.1016/j.avsg.2020.01.019.)

FIG. 8  Retrograde bypass from the common iliac artery (CA) to the superior mesenteric artery (SMA).

FIG. 10  Retrograde open mesenteric stenting. (From Sidawy AP, Perler B. Rutherford’s Vascular Surgery & Endovascular therapy, 9th ed. Philadelphia: Elsevier, 2019.)

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Acute Mesenteric Ischemia

A

C

B FIG. 11  Patient with acute embolic mesenteric ischemia in the setting of chronic SMA atherosclerosis and IMA occlusion. (A) Exposure and control of SMA and its proximal branches. (B) Following completion of endarterectomy and saphenous vein patch. A side-branch of the saphenous vein was cannulated with an olive-tip syringe for angiography. (C) Atherosclerotic plaque removed from SMA.

developed AMI after discontinuing anticoagulation. The extent of atherosclerotic disease precluded candidacy for bypass.

ENDOVASCULAR APPROACHES While chronic mesenteric ischemia has been treated by endovascular approaches with some success, limited studies exist to support its widespread use in AMI. Careful selection is needed in identifying patients for endovascular revascularization and forgoing laparotomy (see Fig. 3). Early detection is essential, as extensive ischemia or peritonitis requires open laparotomy. A tortuous or highly angled SMA, proximal and distal landing zones ≤1 cm, and presence of disease at main arterial branches also preclude an endovascular approach. Because patency rates diminish with time, those patients with a life expectancy >5 years, should they survive hospitalization, are better suited for an open revascularization or hybrid technique. Therefore, exclusive endovascular techniques are highly reserved for a subset of patients at select facilities in capable hands. For those who are suitable for endovascular approaches, access via brachial or femoral approach can be used; however, a brachial approach is typically preferable given the difficulty accessing an angulated SMA from the

femoral artery. In such cases, an angled guidewire can be used. After directing the guide catheter to the origin of the SMA, a hydrophilic guidewire is used to traverse the lesion. Care should be taken in directing the guidewire to avoid damage to the branching arteries. Thrombosuction, mechanical thrombectomy, pharmacologic thrombolysis, angioplasty, and balloon-expandable stents can then be deployed. If satisfactory revascularization cannot be performed, the patient should be converted to an open procedure. In cases where revascularization is considered successful, a “second-look” diagnostic laparoscopy should be considered.

POSTOPERATIVE CARE In the acute postoperative period, patients should remain on heparin anticoagulation and broad-spectrum antibiotics, and be resuscitated before definitive abdominal closure. After open revascularization, a second-look laparotomy should be performed in 24 to 48 hours. Given the underlying comorbidities predisposing to AMI, lifetime anticoagulation is necessary. Patients who received endovascular stenting should be placed on dual antiplatelet therapy for 1 to 3 months and subsequently aspirin for life. Aspirin, at a minimum, is



Va s c u l ar S u r g e ry

required for patients with bypass grafting, though vitamin K antagonists and novel oral anticoagulants prescribed for comorbid disease are also suitable.

LONG-TERM FOLLOW-UP Lifestyle modification and addressing the patient’s medical comorbidities are essential to minimize disease recurrence. In patients with bypass grafts or stents, surveillance imaging via duplex US or CT angiography is recommended at 1, 6, and 12 months, and then annually thereafter. Early intervention on recurrent disease is paramount to long-term survival.

Chronic Mesenteric Ischemia Linda M. Reilly, MD

C

hronic mesenteric ischemia (CMI) results from inadequate perfusion of the abdominal viscera. The postprandial pain that is the hallmark of symptomatic CMI causes reduced oral intake, preventing adequate nutrition and leading to progressive weight loss. CMI is also believed to be a precursor to intestinal infarction. Therefore, the goals of treatment are (1) restoration of normal nutrition through durable relief of symptoms and (2) durable protection against visceral infarction. Successful management requires accurate diagnosis, assessment of disease extent, and selection of optimal treatment.

ETIOLOGY The most common etiology of chronic visceral ischemia is arterial occlusive disease, with atherosclerosis the most frequent form of the arterial pathology. Nonatherosclerotic arterial pathologies such as arteritis, fibromuscular dysplasia (FMD), segmental arterial mediolysis (SAM), or dissection (spontaneous, often in the setting of FMD or SAM, or posttraumatic) may also cause CMI but are fortunately much less frequent. The arteritides that may involve large and medium arteries include Takayasu’s arteritis, giant cell arteritis, polyarteritis nodosa, and Behçet’s arteritis, the latter to a variable degree. Abdominal pain in the setting of median arcuate ligament compression of the celiac axis is thought to have a component of mesenteric ischemia, although the mechanism is not defined and not easily differentiated from a possible neurologic etiology caused by ganglion tissue compression. The frequent observation of asymptomatic stenosis or even occlusion of a visceral artery in adults older than 65 years of age (about 20%) and the abundant potential routes of collateral flow to the viscera support the generally accepted belief that involvement of at least two of the three main visceral arteries is necessary to reduce visceral perfusion to the point of symptom development. Although it is clear that compromise of both celiac artery and superior mesenteric artery (SMA) flow can produce CMI, it is less predictable whether compromise of inferior mesenteric artery (IMA) flow and either celiac artery or SMA flow will produce symptoms of visceral ischemia. None of the patients we have treated developed symptoms with involvement of only the IMA and either the celiac artery or the SMA. The pattern of the flow-reducing lesions is also important in the development of symptoms: the more diffuse the distribution

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Suggested Readings Clair DG, Beach JM. Mesenteric Ischemia. The New England Journal of Medicine. 2016;374(10):959–968. Oderich GS, Macedo R, Stone DH, et al. Multicenter study of retrograde open mesenteric artery stenting through laparotomy for treatment of acute and chronic mesenteric ischemia. J Vasc Surg. 2018;68(2):470–480 e1. Olson KA, Teixeira PG. Mesenteric Ischemia – How and When to Revascularize. Advances in Surgery. 2021;55:75–87. Scali ST, Ayo D, Giles KA, et  al. Outcomes of antegrade and retrograde open mesenteric bypass for acute mesenteric ischemia. J Vasc Surg. 2019;69(1):129–140.

of lesions, the more likely that all potential collateral routes will be affected, and the more likely the patient will be symptomatic. There are three patterns of visceral artery involvement by occlusive processes: lesions involving the orifices and short segments of the proximal main visceral arteries, lesions involving long segments of the main visceral artery trunks (with or without orifice involvement), and lesions involving the branches of the visceral arteries (with or without proximal trunk/orifice) involvement. These patterns of disease determine which treatment method is applicable as well as the prognosis for a successful and durable reconstruction. The importance of establishing the arterial pathology is not limited to knowing the diagnosis but is also important to understanding the implication of a given pathology for successful treatment. For example, typical visceral atherosclerotic lesions are located at the vessel origin, actually representing aortic disease spilling into the visceral artery orifice. The involvement of the visceral artery is usually limited to the first 1 or 2 centimeters of the main trunk. In contrast, unusual pathologic processes involving the visceral arteries, such as an arteritis, generally affect longer segments of the arteries, less commonly involve the orifice, and can involve the main trunk, the branches, or both.

DIAGNOSIS AND EVALUATION The diagnosis of CMI often challenges the clinician primarily because initial symptoms may be subtle and vague without a recognizable or typical pattern. Progression is insidious, and there are few, if any, physical findings until the onset of weight loss. All too often symptoms are ascribed to anxiety, fed by a gender bias, because there is a 3:1 female-to-male ratio for CMI. The younger age at onset (50–60 years of age) and the low incidence of signs or symptoms of arterial disease in other beds (only about one-third of patients) leads clinicians away from this diagnosis, resulting in an average onset-to-diagnosis delay of 12 months or more. When objective findings do manifest (usually weight loss, hypoalbuminemia, anemia), malignancy is the most common clinical suspicion. Fortunately, at that point most patients will undergo computed tomographic (CT) imaging. Although this does not provide the best arterial imaging, it is valuable to eliminate many other potential etiologies, particularly malignancy. Once CMI is under consideration, duplex ultrasound (DUS) imaging should be performed to determine which vessels are involved and if any of the lesions are hemodynamically significant (cause a reduction in flow) (Fig. 1). The peak systolic velocity (PSV) threshold for hemodynamically significant disease will vary between imaging centers but is usually ≥200 to 250 cm/sec for the celiac artery, ≥275 to 300 cm/s for the SMA, and ≥200 cm/s for the IMA. Overall accuracy is improved by increasing the PSV threshold to 300 cm/s for the celiac trunk and 400 cm/s for the SMA. The end-diastolic velocity (EDV) threshold

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Chronic Mesenteric Ischemia

A

B

C

D

FIG. 1  Duplex ultrasound images. (A) Normal CE with normal flow velocities and waveform. (B) >70% CE stenosis with PSV = 319 cm/s and EDV = 100 cm/s. (C) Normal SMA with normal flow velocities and waveform. (D) >70% SMA stenosis with PSV = 360 cm/s and EDV = 75 cm/s. CE, Celiac axis; EDV, end-diastolic velocity; PSV, peak systolic velocity; SMA, superior mesenteric artery.

is less variable, generally ≥45 to 55 cm/s. Technician experience and patient body habitus affect the success of visceral artery DUS. Studies should be performed in the fasting state to reduce intestinal air, the most common reason for inadequate imaging. Because patients with CMI have usually lost significant weight, vessel depth is often less of a factor in study quality; however, DUS imaging will be less successful in a patient with a larger body mass index. Contrast-enhanced computed tomographic arteriography (CTA) provides the best visceral arterial imaging (Fig. 2). Studies should be performed with thin slices (1.25–2.00 mm). Oral contrast should not be administered during a CTA examination. CTA does not provide direct hemodynamic information, but the degree of collateralization provides inferential evidence of hemodynamically significant stenoses. Patients with chronic kidney disease are susceptible to further loss of renal function resulting from the contrast used in CTA. Magnetic resonance angiography (MRA) can also provide very good arterial imaging (Fig. 3) but cannot assess calcification or provide hemodynamic data, and a significant proportion of patients cannot tolerate the claustrophobic setting. As mentioned earlier, visceral atherosclerotic disease is often present in asymptomatic patients. Therefore, once visceral occlusive

disease has been identified, it is still important to be certain there is a causal relationship between the lesions and the symptoms. At this point, other investigations may be helpful (endoscopy, motility studies, malabsorption studies), but should be performed expeditiously because weight loss and physiologic deterioration will be ongoing.

REVASCULARIZATION OPTIONS There are basically two approaches to reconstruction for visceral arterial occlusive disease: endovascular techniques (angioplasty with or without stenting) and open surgical techniques (endarterectomy or bypass). The pattern of disease plays a major role in the selection of reconstruction technique. Although it is generally agreed that at least two visceral arteries must be involved by the occlusive process to produce symptoms, there is more debate regarding the number of visceral arteries that need to be treated to provide durable symptom relief and protection against visceral infarction. Some argue that durable symptom relief requires complete visceral revascularization (involving the celiac trunk and the SMA), whereas others report equivalent results with single-vessel revascularization. Among those who feel that single-vessel reconstruction is adequate, there is further



Va s c u l ar S u r g e ry

A

C

debate about the optimal single-vessel target, with most favoring the SMA. In fact, if all collateral pathways between the three main visceral arteries are intact, revascularization of any one vessel should be sufficient for relief of symptoms (Fig. 4). Practically speaking, if single-vessel reconstruction is chosen, either the celiac artery or the SMA should be the target artery as long as it is technically feasible. Single-vessel reconstruction to the IMA should be performed only if neither the celiac artery nor the SMA can be repaired. The technique of endarterectomy (transaortic) virtually requires that both the celiac artery and SMA be treated. Bypass can be performed to either single or multiple visceral vessels, but most surgeons will opt to revascularize more than one branch (assuming technically feasible) if for no other reason than to avoid subsequent reoperation. If an endovascular approach is chosen, the selection of the target vessel(s) can be more complicated. The less-invasive nature of the procedure favors treating both the celiac artery and the SMA during the same procedure, but it also allows a staged approach—treating one vessel (usually the SMA) and then waiting to see if intervention to treat the other branch is required. If either the celiac artery or SMA is occluded and the other branch is stenotic, some will reopen the occluded vessel first, concluding that it is lower risk (because

1169

B

FIG. 2  Selected CTAs showing different patterns of visceral occlusive disease. (A) Focal severe stenosis of the CE (arrow) and focal high-grade stenosis of the SMA (arrowhead). (B) Occlusion of the CE (arrow) with reconstitution at the level of the left gastric branch (dot) and critical stenosis of the very proximal SMA (arrowhead). (C) Severe long-segment SMA atherosclerosis. The CE is not occluded, just out of plane. Celiac celiac axis; SMA, superior mesenteric artery.

generally you cannot worsen an occluded vessel), whereas others might treat the stenotic vessel first, concluding that reopening an occlusion is technically more difficult, more likely to be unsuccessful, and may result in a much longer procedure if considerable time is spent attempting to reopen the occluded branch before accepting defeat and treating the stenotic branch.

Endovascular Techniques As in other locations, intraluminal endovascular treatment is optimal for focal visceral arterial lesions that are neither bulky nor heavily calcified. The most common visceral atherosclerotic lesion is actually aortic plaque that extends through the mesenteric artery origin and into the visceral artery for a short distance (1–2 cm), stopping before any major branch points. The focal involvement in the visceral branch favors an endovascular approach. Conversely, the aortic component of the plaque, the frequently observed dense calcification, the bulky nature of the lesions, or complete occlusion (especially flush occlusions) are unfavorable factors that may adversely affect procedural success and durability of an endovascular approach. The less-common patterns of visceral occlusive lesions (long segment main artery

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Chronic Mesenteric Ischemia

FIG. 3  MRA demonstrating celiac stenosis from compression by the median arcuate ligament.

involvement and/or branch involvement) are less likely to be successfully treated by an endoluminal approach. Compression of the celiac axis (and in rare cases of the SMA) by the very dense median arcuate ligament should not be approached endovascularly unless the ligament is first released. The ligament is too dense and will not respond to angioplasty, even if adjunctive stenting is performed. Simple angioplasty is rarely used to treat visceral atherosclerotic stenosis. The aortic component of the plaque and the frequent heavy calcification result in a poor response. Angioplasty with stenting is the most common endovascular approach. Balloon-expandable covered

stents have become the technique of choice for several reasons. Balloon-expandable stents exert high radial force, which is needed to push against the often heavily calcified, bulky, and circumferential lesions. Covered stents may reduce the risk of vessel injury from the high inflation pressures needed to adequately efface the stenosis. They may also reduce the risk of embolization by trapping the plaque against the arterial wall. Also, the intimal hyperplastic response to angioplasty and stenting can only occur at the distal end of a covered stent (the proximal end of the stent protrudes 1 to 2 mm into the aorta and is not in contact with any arterial wall). The ingrowth of intimal hyperplasia through the interstices frequently seen along the entire length of an uncovered stent is prevented by the fabric of the covered stent (usually expanded polytetrafluoroethylene [ePTFE]). This limits the risk of recurrent stenosis to the distal end of the covered stent. All of these factors may contribute to the reports by some investigators of lower restenosis and reintervention rates when covered stents are used. The stent should be longer than the stenosis. The stent is positioned to extend beyond the distal end of the plaque and to project into the aorta by 2 to 3 mm (Fig. 5A, B). It is important to “flare” the covered stent in the aorta to adequately treat the ostial aortic plaque (see Fig. 5C) a maneuver that has been reported to improve the midterm patency of mesenteric artery stents. The diameter of the covered stent should be about the same as the target visceral artery. Oversizing is not necessary and risks inflation injury of the branch or, worse still, of the junction of the branch with the aorta. Most currently available balloon-expandable covered stents can be dilated postdeployment to a slightly larger size by using a balloon slightly larger than the delivery balloon. This is far safer than oversizing. Visceral angioplasty and stenting can be performed from either a transfemoral or a transbrachial approach. The larger size of the common femoral artery reduces access site complications, but the angle of approach into the visceral branch is a disadvantage, particularly because the celiac artery and SMA frequently originate from the aorta at a downward angle. This anatomy can make recanalization of an occluded visceral branch more difficult and may impede tracking of any device (sheath, balloon, covered stent) into the branch. These challenges have been reduced significantly by the development of sheaths with conformable (deflectable) tips that can “aim” down and maintain that orientation, even while devices are inserted. Transbrachial access provides a more natural angle of approach to the

celiac axis

gastroduodenal artery

A

* * * ** * * *

SMA

B

FIG. 4  (A) Selective injection of the celiac axis results in opacification of the superior mesenteric artery via a very large gastroduodenal artery. In this case, revascularization of either the celiac axis or the SMA will provide perfusion to the entire visceral circulation (B). Intraoperative exposure of the gastroduodenal artery (asterisks) from the hepatic artery (arrow) to the SMA (arrowhead) during a Whipple procedure. A tight celiac stenosis was not recognized preoperatively. Because hepatic artery perfusion was dependent on this collateral pathway, it could not be sacrificed, prompting this unusual complete mobilization. SMA, Superior mesenteric artery.



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A

B

1171

C

FIG. 5  (A) Intraprocedural angiogram demonstrating optimal position of the celiac stent, extending a few millimeters into the aortic lumen. The proximal end of the stent is represented by the arrow. The aortic wall is represented by the dashed line. (B) Angiographic image of the celiac stent after pressuremonitored balloon inflation and stent deployment. (C) Angiographic image of deployed celiac stent showing the flared proximal end (arrow). The slight waist (arrowhead) represents the location of the aortic wall.

visceral branches. This is particularly important when recanalizing an occluded visceral artery or traversing a critical stenosis in a lesion with significant calcification. The mechanical advantage of pushing in a (more or less) straight line is significant. Using a brachiofemoral wire to stabilize sheath position further increases the in-line force that can be safely exerted to successfully treat challenging lesions or occlusions. In fact, we never conclude that we have failed to recanalize an occlusion or cross a complex lesion until we have tried both the transfemoral and the transbrachial approaches and have used a brachiofemoral wire. Whenever possible, the left brachial artery is used to avoid the disadvantage of traversing the entire aortic arch, with the associated risk of stroke resulting from manipulation across the origins of all the cerebral vessels. Access site complications are of course greater with the transbrachial approach, owing to the smaller size of the artery. One should not hesitate (unless one is a cardiologist) to perform open exposure of the brachial artery to allow safer access. Plaque fragment embolization is a risk associated with any endovascular procedure, but some arterial beds are more tolerant of this complication than others. The risk of visceral infarction resulting from plaque embolization during visceral angioplasty and stenting has prompted some to use distal embolic protection (filter devices). This adds complexity to an already complex procedure, and currently there are no data showing benefit. One should be aware of the embolization risk, particularly when recanalizing occluded visceral branches. Also, if the clinical scenario suggests subacute visceral branch occlusion (not too likely in patients with CMI), endovascular treatment should be approached very cautiously as the risk of thrombus embolization (as opposed to plaque fragment embolization) is very high. Any recent, relatively abrupt change in symptoms should be concerning. A shower of thrombus fragments can be fatal. A word of caution about endovascular treatment of the IMA: the IMA is a small and very fragile artery. Unfortunately, whenever there is IMA stenosis, there is always significant aortic plaque that is heavily calcified and circumferential around the IMA orifice and requires significant inflation pressure to overcome. There is often post-stenotic dilation of the IMA with flow-based enlargement (compensating for celiac artery and SMA disease), further increasing the fragility of the artery. Further, the IMA has a very short straight segment before it becomes tortuous. This combination of anatomic features very commonly results in dissection of the IMA when angioplasty and stenting is attempted. This is because the artery distal to the plaque and stenosis will not tolerate the amount of manipulation

needed to insert and deploy the stent and efface the stenosis. Because one does not usually treat the IMA unless neither the celiac artery nor the SMA can be treated, dissection of a dominant IMA can be catastrophic.

Hybrid Technique On occasion, it proves impossible to treat visceral artery stenosis or occlusion using the transfemoral or transbrachial approaches. Usually one then proceeds with an open surgical approach. However, if the patient is too high risk for standard open surgical visceral revascularization, the hybrid approach may provide the best treatment option. Commonly the SMA will be the target artery in this scenario. The artery is exposed through a midline laparotomy and then directly punctured distal to the stenosis or occlusion. Under fluoroscopy, a wire is advanced retrograde, crossing the lesion into the aorta. Angioplasty and stenting are performed in the standard manner. This circumstance is not often encountered with CMI, but is increasingly applied in the setting of acute mesenteric ischemia, particularly when laparotomy for bowel resection or assessment is needed.

Open Surgical Techniques Endarterectomy Endarterectomy was the earliest operative technique applied to visceral artery occlusive disease. However, the initial approach utilized the transarterial retrograde approach, through either the celiac artery, SMA, or both to remove the obstructing lesion. This approach resulted from the early failure to recognize the significance of the aortic involvement and was less successful because it did not allow complete removal of the aortic portion of the lesion. Currently endarterectomy is performed through the aorta, and the lesions extending into the visceral artery orifices are extracted by eversion endarterectomy. Aortic exposure is achieved through a transabdominal approach with medial visceral rotation (MVR) from the left. In this technique, I prefer to keep the left kidney in its anatomic position, while the plane behind the left colon, spleen, pancreas, and stomach is developed to allow displacement of these structures toward the midline. Others prefer to develop the plane behind the kidney as well because it is technically easier and faster. If needed, the entire aorta, from the distal thoracic level inferiorly, can be completely exposed in this manner (Fig. 6). During complete aortic occlusion and with control of any intervening intercostal branches, a U-shaped trapdoor

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SMA celiac axis left renal vein

diaphragm

* FIG. 6  Aortic exposure provided by a transabdominal approach with medial visceral rotation from the left. Note that the entire abdominal aorta from the diaphragm (under the narrow retractor blades; arrows) to the bifurcation of the iliac arteries can be exposed. Note that the left kidney (asterisk) remains in its anatomic position. The large vessel loop encircles the left renal vein, which can usually be left intact.

Endarterectomy is perhaps the most elegant approach to visceral artery occlusive disease, but it has significant limitations. It is most applicable to visceral artery lesions that are confined to the first 1 or 2 centimeters of the artery. Although longer lesions may be successfully treated with transaortic endarterectomy, in our experience endarterectomy in this setting is less durable. Endarterectomy is not applicable to lesions extending into branches of the visceral arteries. Transmural calcification of a visceral artery should generally be considered a contraindication to endarterectomy. A transmural lesion will force a very deep endarterectomy plane, usually resulting in inadequate integrity of the adventitia. Attempting endarterectomy in this setting usually results in extensive bleeding through the porous adventitia and prolonged visceral ischemia as a consequence of attempts to repair the bleeding artery—an invariably fatal combination. Endarterectomy is particularly appealing when there is occlusive disease involving the renal arteries because it is much faster than individual bypasses to all four arteries (celiac artery, SMA, and both renal arteries). Obviously if there are multiple renal arteries, it is even more attractive. Endarterectomy is often the most appropriate technique for occlusive disease involving the IMA. However, because of the smaller size of this artery and the less predictable location of the endpoint, I favor a longitudinal incision extending out the IMA to a disease-free segment and closure with a vein patch following the endarterectomy.

Bypass At least theoretically, bypass is the only reconstruction technique applicable to all patterns of arterial visceral occlusive disease. Practically, the more extensive the disease and the more branch involvement, the less feasible bypass becomes. Bypass to the mesenteric arteries may originate from the supraceliac aorta (antegrade bypass) or from the infrarenal aorta or iliac arteries (retrograde bypass).

Antegrade Bypass Proximal aortic exposure for antegrade bypass can be achieved using a transabdominal, transcrural approach (Fig. 8) or MVR from the

FIG. 7  A trapdoor aortotomy has been created to expose the aortic disease extending into the orifices of the celiac axis and the superior mesenteric artery. (From Ehrenfeld WK, Qvarfordt PG, Ronald J. Stoney RJ. Surgical techniques for visceral artery revascularization. In: Greenhalgh RM, ed. Vascular Surgical Techniques. Butterworth Heinemann; 1984).

aortotomy is placed to circumscribe the orifices of the celiac artery and SMA, and an endarterectomy is performed, removing the aortic wall lesion and its extensions into the visceral orifices (Fig. 7). In many cases, the significant aortic atheroma is confined to the ventral surface of the aorta immediately around the celiac artery and SMA orifices, and the aortic endarterectomy can be limited to the trapdoor segment itself. However, more diffuse aortic disease, frequently in the setting of associated renal artery occlusive lesions, requires extension of the aortotomy caudally to allow sleeve aortic endarterectomy and bilateral or unilateral renal artery endarterectomy. In this circumstance, the aortotomy takes the shape of a hockey stick rather than a trapdoor. Following completion of the endarterectomy, the aortotomy is closed with a running suture. If the disease extends well out into the visceral branches, it may be necessary to use a separate longitudinal arteriotomy in the visceral artery itself to allow complete removal of the disease. This visceral artery incision is then closed with a vein patch angioplasty.

FIG. 8  Transcrural exposure of the celiac axis and its branches (left gastric, hepatic, and splenic) and the superior mesenteric artery (SMA). Note the caudal retraction of the stomach and pancreas. Note also the complete division of the median arcuate ligament and the complete removal of the celiac ganglion and plexus from around the anterior surface of the aorta and the proximal trunks of the celiac axis and the SMA.



left. The transcrural approach is appealing because it is a less extensive exposure. However, it requires a relatively wide costal margin. It also may require a retropancreatic tunnel for the graft that will be anastomosed to the SMA, depending on the extent of the disease in that artery. Finally, the restricted exposure can make the aortic anastomosis somewhat difficult as the space is small, limiting visibility as well as movement. MVR provides much better exposure, but at the cost of a larger operation. Graft length and alignment are easier to determine with the transcrural approach and require more judgment with MVR. Regardless of the exposure, the proximal anastomosis of the antegrade bypass is placed in the disease-free supraceliac aorta and requires temporary total aortic occlusion. However, circumferential aortic mobilization is not routinely performed. The aortotomy is oriented slightly obliquely and must be of adequate length to allow a low profile for the graft. Sometimes a thin piece of the aortic wall is excised to facilitate wide opening of the anastomosis. The body of the graft should be short, and the bevel on the graft must be long and gradual to allow the graft to assume a low profile on the front of the aorta (Fig. 9). If the graft originates from the aorta with a high profile, it increases the chance of kinking. In addition, the aortotomy must be placed sufficiently proximal on the aorta to allow the graft limbs adequate space to assume a gentle course to the visceral artery. If the distance is too short, the graft limbs will kink. As depicted in Figure 9, we prefer to use a small-diameter bifurcated Dacron graft (12 mm × 6 mm) if both the celiac artery and SMA are to be revascularized. If only one artery requires reconstruction, we prefer to cut one limb from the body of the small bifurcated graft (if available), creating a nicely flanged proximal end to the single graft limb (Fig. 10). If no small-diameter bifurcated graft is available, we anastomose one 8-mm graft end-to-side to another 8-mm graft (or 6-mm graft, depending on the size of the target visceral artery) creating an appropriate customized bifurcated graft (Fig. 11). Whatever

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FIG. 10  Creation of flanged conduit from a small-diameter bifurcated graft when only one visceral vessel will be revascularized. (From Ehrenfeld WK, Qvarfordt PG, Ronald J. Stoney RJ. Surgical techniques for visceral artery revascularization. In Greenhalgh RM, ed. Vascular Surgical Techniques. Oxford, UK: Butterworth Heinemann; 1984).

the structure of the conduit, after completion of the proximal aortic anastomosis, aortic flow is restored, and an occluding clamp is placed across the limb(s) of the graft. If the transcrural exposure is used, the celiac artery and SMA are exposed above and behind the pancreas, which requires careful and complete dissection of the visceral arteries from the surrounding celiac ganglion tissue and the median arcuate ligament (see Fig. 8). Usually, the left graft limb will be anastomosed to the celiac axis, and the right graft limb will be anastomosed to the SMA. However, it is always wise to check the relative positions of the two visceral arteries before committing to this arrangement. When the MVR exposure is used, it may be better to perform the anastomosis to the SMA first. Usually, the anastomosis to the SMA is performed more distally on that artery than the anastomosis to the celiac axis. This is particularly so when the SMA lesion is more extensive. As a consequence, the SMA anastomosis may actually be performed under the graft limb to the celiac axis, restricting access and/or requiring significant retraction on the graft limb to the celiac axis. To avoid this situation, the anastomosis to the SMA should be performed first. The distal anastomoses are constructed in an end-to-end or end-to-side manner to the individual visceral arteries, beyond the point of atherosclerotic involvement. If the anastomosis is end-to-end, the visceral artery is almost always spatulated, and the conduit almost always has a short bevel. This provides for better alignment and lie for the grafts. The conduit is almost always prosthetic.

Retrograde Bypass FIG. 9  Completed antegrade bypass to the celiac axis and superior mesenteric artery (SMA). Note the very short body portion of the graft. Note that the orientation of the graft limbs prevents either limb from compressing the other. Also note the inferior retraction of the stomach and pancreas. Celiac anastomosis is indicated by the white arrowhead, and SMA anastomosis is indicated by the black arrowhead.

The infrarenal aorta, iliac artery, or a previously placed aortic bypass can also serve as inflow to the visceral arteries. This exposure utilizes the standard infracolic approach. If the SMA is the revascularization target, it is exposed in the root of the mesentery, beyond the disease, in preparation for an end-to-side anastomosis. The celiac axis itself is rarely the target for a retrograde bypass, in part because it is often too short to accommodate the anastomosis and in part because the graft

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Chronic Mesenteric Ischemia

FIG. 12  Retrograde bypass from the left external iliac artery to the superior mesenteric artery (SMA) using cryopreserved femoral vein. The SMA and its early branches are encircled by vessel loops. A tissue conduit was used because the patient underwent segmental small bowel resection at the same operation for a chronically ischemic bowel segment with changes consistent with contained perforation.

FIG. 11  Physician-constructed bifurcated graft. The dotted red line indicates where the graft has been incised to create a flanged end for the proximal anastomosis.

alignment would be awkward. More commonly, the bypass is anastomosed to a branch of the celiac artery, usually the hepatic artery, since hepatic and gastric perfusion are more important than splenic flow. Positioning and alignment are more difficult with retrograde conduits, making them more susceptible to twisting, kinking, and compression. To minimize this risk, most recommend that the conduit be constructed in the shape of a long, gentle backwards C-curve or candy-cane curve (Fig. 12).

OUTCOMES Since vascular surgeons began to incorporate endovascular techniques into practice and training, the use of these approaches to treat disease in all vascular beds has rapidly expanded. Mesenteric occlusive disease is no exception. Technical success rates for endovascular intervention (85%–100%) are competitive with but not quite as good as open surgical revascularization (97%–100%). Studies using data from the Nationwide Inpatient Sample (NIS) show that during the first 15 years of this century, between 70% and 80% of patients treated for CMI underwent endovascular intervention. Endovascular treatment surpassed open surgery to become the predominant treatment modality two decades ago. During the same time interval, the total number of patients treated for CMI increased from 1.8 per million to 5.6 per million, while the number of open surgical procedures remained constant. This suggests that the availability of endovascular treatment expanded the pool of patients for whom intervention was determined to be indicated and appropriate. Open surgery for CMI poses significant risks because the typical CMI patient has medical comorbidities and is malnourished. Even though the mortality of open surgery for CMI decreased by about 50% over the past two to three decades (from about 20% to about 10%), many studies report rates about threefold higher than the mortality of patients undergoing endovascular treatment for CMI

(about 10%–13% vs. 3%–5%). Both major adverse cardiovascular and cerebrovascular events and composite in-hospital complication rates are lower with endovascular treatment (major adverse cardiac and cerebrovascular events 8% vs. 16% and composite index 15% vs. 20%), which also has lower median costs and a shorter length of stay. These outcomes are even more notable when one considers that patients undergoing endovascular treatment tend to be older and have more medical comorbidities. For these reasons, most consider endovascular intervention to be the first-line treatment for CMI. Everything would be perfect in this story of progress if the benefit of reduced in-hospital mortality and morbidity with endovascular treatment of CMI were followed by long-term durability at least equal to open surgery. Unfortunately, this is not the case. Virtually all comparisons of open surgical and endovascular treatment for CMI show higher rates of recurrent stenosis, symptomatic recurrence, and reintervention following endovascular treatment. Reported recurrent stenosis rates are as high as 40%, with reintervention for recurrent symptoms needed in about one-half of that group. Factors associated with an increased risk of restenosis and reintervention include female gender, small-diameter arteries ( 32 mm diameter) is encountered, bilateral iliac vein filters or a Bird’s Nest type filter (Cook Inc.) may be used.

Special Considerations: Suprarenal Inferior Vena Cava Filter Clinical scenarios that call for a suprarenal IVC filter are rarely encountered. Indications are related to thrombus location, anatomic variations, and pregnancy. The most common indication is an IVC clot extending above the renal veins, which may occur above a previously placed infrarenal filter. Depending on the extent of the thrombus, thrombolysis or thrombectomy could be considered, with the use of a temporary IVC filter followed by deployment of a retrievable or permanent filter. Suprarenal IVC filters may be considered if either a duplicated IVC or short infrarenal IVC anatomic variants are encountered. Alternatively, bilateral iliac vein filters can be placed in these variants. When filters are indicated during pregnancy, suprarenal filters are preferred because of the caval compression by the gravid uterus and increased incidence of gonadal vein thrombosis. Similarly, large pelvic masses may result in iliofemoral DVT, and these patients may require interruption in anticoagulation for surgical intervention. In addition to caval compression, caval manipulation may occur during surgery. In some instances, isolated gonadal vein thrombosis may be treated with coil embolization. Regardless of the indication for suprarenal IVC filters, short dwelling times and retrievable filters are preferred. Indications for suprarenal IVC filter placement are shown in Box 2.

Contraindications for Placement of an Inferior Vena Cava Filter Contraindications for IVC filter placement are both technical and clinical. There are no absolute contraindications; however, there are a few relative contraindications. Technical reasons include a thrombosed/occluded IVC, a clot in the intrahepatic IVC, and no available venous access. Clinical contraindications include severe uncorrectable coagulopathy, severe prothrombotic state, and active bacteremia. Although active bacteremia is a contraindication to filter placement, the risk of seeding a filter has not been proven. If a filter is necessary in a patient with active bacteremia, then a retrievable one may be placed, and it should be removed as soon as not needed or replaced as soon as bacteremia resolves. A prothrombotic state increases the risk for in situ filter clot formation. It should not prevent filter placement if protection against potentially lethal PE is necessary. Hematology input is important to screen these patients and have a plan of action related to type of filter used, duration of protection, retrieval, and possibly concurrent systemic anticoagulation.

BOX 2  Indications for Suprarenal Inferior Vena Cava Filter Placement Thrombus Location • IVC thrombus to the level of the renal veins • Large thrombus extending above a previously placed infrarenal filter • Large gonadal vein thrombosis • Renal vein thrombosis Anatomic Considerations • Duplication of the IVC • Low renal vein insertion/short infrarenal IVC Pregnancy-Related Considerations • Placement during pregnancy



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TECHNIQUE Optimum performance requires catheter expertise, proper venous access selection, and appropriate filter type, as well as proper location and orientation of the deployed filter. Box 3 outlines an approach to IVC filter insertion.

Preoperative Planning Preoperative planning is crucial to successful IVC filter deployment and clinical outcomes. First, the clinical indication for IVC filter placement should be evaluated, and a proper history, review of records, and physical examination should be performed. As mentioned earlier, the clinical indication, patient factors (i.e., history of recurrent VTE, prognosis), and anatomy will guide filter selection. Laboratory tests should be reviewed for potential severe coagulopathy. Lastly, imaging should be reviewed with special attention on the thrombus location, venous anatomy, and IVC size. Preprocedural measurements are ideal as dehydration and bleeding may underestimate vessel size during venography. Selection of a suitable venous access route on either the right or left side will depend on

BOX 3  Inferior Vena Cava Filter Placement Techniques Review clinical indication History, physical examination, laboratory tests, and current imaging studies Selection of Filter Type • Retrievable filter for patients with expected temporary use • Permanent filter in select patients with lifelong indication • Temporary filter (used during high-risk endovascular cases) Access • Internal jugular vein favored • Patients with IVC, iliac, or complete CFV thrombus • Lower insertion site thrombosis • Does not require postprocedure bed rest • Common femoral vein • Popliteal vein • Brachial vein Inferior Vena Cava Venogram • IVC diameter and length • If > 28–30 mm and < 40 mm, consider a Bird’s Nest filter • Landing zone must accommodate filter type • Final filter selection depending on IVC diameter • IVC pathology • Thrombus • Narrowing • Consider IVUS when venogram findings are equivalent • IVC anomalies • Duplicated IVC • Renal vein identification for optimal filter tip position • Accessory renal veins Deployment Pre- and Post-Deployment Check • Filter location before deployment • Filter released from device post-deployment • Filter post-deployment; migration (90%. High-flow humidified oxygen via nasal cannula is an increasingly popular mode for oxygen delivery (i.e., 60 L/min at 100% FiO2) and may be delivered beneath the mask to provide additional oxygenation and some degree of positive end-expiratory pressure (PEEP). Oxygen therapy can then be deescalated accordingly after the patient has been assessed and stabilized, to a simple face mask (FiO2 35%–55%), a Venturi mask (FiO2 24%–60%), or a nasal cannula (FiO2 24%–44%). If the airway is compromised and the patient is not ventilating and oxygenating adequately, rapid noninvasive interventions are

BOX 1 Airway Parameters That May Predict Poor Visualization of the Vocal Cords During Direct Laryngoscopy • • • • • •

Prominent incisors or abnormal dentition Mandibular protrusion (see Figure 1) Mouth opening (>3 fingerbreadths, or 5–6 cm is normal) Mallampati classification (see Figure 2) Thyromental distance (>3 fingerbreadths, or 5–6 cm is normal) Cervical range of motion (should NOT be tested in any patient with a suspected C-spine injury) • Anatomic abnormalities (masses, swelling) • Thickness of neck • Length of neck (shorter neck associated with difficult intubation)

• Class C: The lower incisors cannot be brought edge to edge with the upper incisors MC

FIG. 1  The mandibular protrusion test. The test assesses jaw mobility. Class A portends better vocal cord visualization during direct laryngoscopy than Class B or C. (Modified from Munnur U, de Boisblanc B, Suresh MS. Airway problems in pregnancy. Crit Care Med. 2005;33:S259-S268.)

indicated during the interval preceding preparation for establishing a definitive airway. Bag-valve mask (BVM) ventilation with 15 L/ min of oxygen should be initiated (FiO2 90%–100%). Addition of a nasal cannula beneath the mask is advised when available to provide additional high-flow (>10 L/min) oxygen throughout the intubation procedure. This technique may help prevent desaturation during intubation by improving preoxygenation while also providing apneic oxygenation during the intubation attempt. Oropharyngeal or nasopharyngeal airways can be inserted to alleviate airway obstruction by the tongue. The most reliable technique for properly sizing an oral airway is to measure from the midpoint of the incisors to the angle of the mandible. Nasopharyngeal airways should not be used if the patient has a suspected craniofacial injury for fear of inserting the devices intracranially. The length of a nasopharyngeal airway should be selected based on the distance from the tip of the patient’s nose to the tip of the earlobe. The chin-lift maneuver, which is performed by gently lifting the mandible without hyperextending the neck, may help open the airway. Alternatively, the jaw-thrust maneuver can be performed by displacing the mandible forward while applying

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Airway Management in the Trauma Patient Class 1

Class 2

Class 3

Class 4

Grade 1

Grade 2

Grade 3

Grade 4

FIG. 2  The Mallampati classification. The higher the class, the worse the Cormack-Lehane view of the vocal cords during direct laryngoscopy. (From Lalwani AK, ed. Current Diagnosis and Treatment in Otolaryngology: Head and Neck Surgery. 2nd ed. New York: McGraw-Hill; 2007.)

pressure to both angles of the mandible. Either technique is preferable for trauma patients because both techniques can be performed during in-line cervical stabilization.

RAPID-SEQUENCE INDUCTION AND INTUBATION A definitive airway in a trauma patient is defined by the placement of a cuffed tube in the trachea, attached to a source of oxygen and properly secured. Endotracheal intubation, nasotracheal intubation, cricothyroidotomy, or tracheotomy can be performed to establish a definitive airway. In the majority of trauma patients, rapid-sequence induction and endotracheal intubation (RSII) is used to establish a definitive airway. RSII is predicated on the fact that the trauma patient has a full stomach, and excessive bag-valve mask ventilation will cause gastric insufflation with aspiration of gastric contents. RSII involves a highly organized sequence of events starting with preoxygenation for at least 3 minutes. The “6 P’s” of RSII describe the recommended sequence (Table 1). During the preparatory stage, a suction catheter is prepared and tested, an adequate source of oxygen is established and readied for connection, a pulse oximeter is attached to the patient, pharmacologic agents are prepared, and airway equipment is organized. It should be noted that proper performance of RSII ideally requires at least four providers: one to apply cricoid pressure or laryngeal manipulation, one to maintain in-line cervical stabilization, one to ventilate with a BVM and intubate, and one to administer drugs and assist with airway devices (Fig. 3). Although avoidance of BVM ventilation has been the traditional recommendation in RSII, many practitioners find that gentle mask ventilation (inspiratory pressure 18 mg/dL) in the absence of hypovolemia.

BOX 1  Sepsis Definitions • Sepsis: a life-threatening organ dysfunction caused by a dysregulated host response to infection • Organ dysfunction: an increase in the Sequential Organ Failure Assessment (SOFA) score of 2 points or more • Septic shock: a vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and serum lactate level greater than 2 mmol/L (>18 mg/dL) in the absence of hypovolemia

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TABLE 1  Sequential Organ Failure Assessment Score 0

1

2

3

4

PaO2/FiO2 ratio

>400

301–400

400