Current therapy in colon and rectal surgery [3 ed.] 9780323280921, 0323280927

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current therapy in colon and r e c ta l s u r g e r y

3

rd

edition EDITED BY

The Late Victor W. Fazio, MBBS, MS, MD (Hon), FRACS, FRACS (Hon), FACS, FRCS, FRCS (Ed), FASCRS, OA Formerly Rupert B. Turnbull, Jr., MD, Chair, Emeritus Emeritus Chairman, Department of Colorectal Surgery Cleveland Clinic Foundation Cleveland, Ohio

James M. Church,

MBChB, MMedSci, FRACS, FACS Victor W. Fazio Chair Department of Colorectal Surgery Cleveland Clinic Foundation Cleveland, Ohio

Ravi P. Kiran,

MBBS, MS, FRCS (Eng), FRCS (Glas), FACS Kenneth A. Forde Professor of Surgery Columbia University Medical Center and Mailman School of Public Health Chief and Program Director Division of Colorectal Surgery Director Center for Innovation and Outcomes Research New York-Presbyterian Hospital/Columbia University Medical Center New York, New York

Conor P. Delaney, MCh, PhD, FRSCI (Gen), FACS

Chairman, Digestive Disease and Surgery Institute Cleveland Clinic Cleveland, Ohio

For additional online content visit ExpertConsult.com

1600 John F. Kennedy Blvd. Ste 1800 Philadelphia, PA 19103-2899

CURRENT THERAPY IN COLON AND RECTAL SURGERY, THIRD EDITION

ISBN: 978-0-323-28092-1

Copyright © 2017 by Elsevier, Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions. This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein).

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. Previous editions copyrighted 2005 and 1990. Philip H. Gordon retains copyright for the original figures of Chapter 1: Anatomy and Physiology of the Colon, Rectum, and Anal Canal. Library of Congress Cataloging-in-Publication Data Names: Fazio, Victor W., 1940-2015, editor. | Church, James M., editor. |   Delaney, C. P. (Conor Patrick), editor. | Kiran, Ravi P., editor. Title: Current therapy in colon and rectal surgery / edited by the late   Victor W. Fazio, James M. Church, Conor P. Delaney, Ravi P. Kiran. Other titles: Current therapy series. 0831-8689 Description: Third edition. | Philadelphia, PA : Elsevier, [2017] | Series:   Current therapy | Includes bibliographical references and index. Identifiers: LCCN 2016035819 | ISBN 9780323280921 (hardcover : alk. paper) Subjects: | MESH: Colonic Diseases--surgery | Rectal Diseases--surgery |   Colon--surgery | Rectum--surgery Classification: LCC RD34 | NLM WI 650 | DDC 617.5/547--dc23 LC record available at https://lccn.loc.gov/2016035819 Executive Content Strategist: Michael Houston Senior Content Development Specialist: Ailsa Laing Publishing Services Manager: Patricia Tannian Senior Project Manager: Amanda Mincher Design Direction: Miles Hitchen Printed in China Last digit is the print number: 9 8 7 6 5 4 3 2 1

In Memoriam

Victor W. Fazio 1940–2015

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contributors

Cary B. Aarons, MD, FACS Assistant Professor Department of Surgery Division of Colon and Rectal Surgery University of Pennsylvania Philadelphia, Pennsylvania

David E. Beck, MD, FACS, FASCRS Professor and Chairmen Emeritus Department of Colon and Rectal Surgery Ochsner Clinic The University of Queensland School of Medicine New Orleans, Louisiana

Kareem Abu-Elmagd, MD, PhD Center for Gut Rehabilitation and Transplantation Transplant Center Cleveland Clinic Cleveland, Ohio

Elizabeth Berger, MD, MS General Surgery Resident Loyola University Medical Center Maywood, Illinois

Mary Jo Alberino, RD, LD, CNSC Registered Dietitian Center for Gut Rehabilitation and Transplantation Cleveland Clinic Cleveland, Ohio Preetha Ali, MD Attending Surgeon Colon and Rectal Surgery Overlake Hospital Medical Center Bellevue, Washington Dileep Atluri, MD, MRCP(UK) Nutrition Fellow Cleveland Clinic Cleveland, Ohio Knut Magne Augestad, MD, PhD Department of Gastrointestinal Surgery Akershus University Hospital Oslo, Norway H. Randolph Bailey, MD Professor of Surgery The University of Texas Health Science Center McGovern Medical School Houston, Texas David Bartolo, MS(London), FRCS, FRACS Consultant Colorectal Surgeon Fiona Stanley Hospital Murdoch, Western Australia, Professor of Surgery University of Western Australia Perth, Western Australia

Richard P. Billingham, MD Clinical Professor Emeritus Department of Surgery University of Washington Seattle, Washington Colin P. Bird, MD The University of Texas Health Science Center at Houston Houston, Texas Andrea Bischoff, MD Associate Professor of Surgery University of Colorado Assistant Director International Center for Colorectal Care Children’s Hospital Colorado Aurora, Colorado Jennifer Blumetti, MD, FACS, FASCRS Program Director Colon and Rectal Surgery Residency John H. Stroger Hospital of Cook County Chicago, Illinois Raul M. Bosio, MD Colorectal Surgeon Promedica Physicians General Surgery Sylvania, Ohio Marylise Boutros, MD, FRCSC Assistant Professor of Surgery McGill University Montreal, Quebec, Canada Aaron Brzezinski, MD, FRCP(C) Staff Gastroenterologist Digestive Disease and Surgery Institute Cleveland Clinic Foundation Cleveland, Ohio

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CONTRIBUTORS

Carol A. Burke, MD Department of Gastroenterology and Hepatology Cleveland Clinic Cleveland, Ohio

Tara M. Connelly, MD, MB, BCh, MSc Division of Colon and Rectal Surgery Milton S. Hershey Medical Center Hershey, Pennsylvania

Evie Carchman, MD Assistant Professor Department of General Surgery University of Wisconsin, Madison, Madison, Wisconsin

Guilherme Costa, MD, PhD Center for Gut Rehabilitation and Transplantation Transplant Center Cleveland Clinic Cleveland, Ohio

J. Andres Cervera-Servin, MD Minimally Invasive Colon and Rectal Surgery Fellow Swedish Medical Center/Swedish Cancer Institute Seattle, Washington

Benjamin Crawshaw, MD Research fellow Department of Colorectal Surgery University Hospitals Case Medical Center Cleveland, Ohio

George J. Chang, MD, MS Professor of Surgical Oncology Professor of Health Services Research Chief, Colon and Rectal Surgery Associate Medical Director, Colorectal Center Director of Clinical Operations Minimally Invasive and New Technologies in Oncologic Surgery Program Associate Professor The University of Texas, M.D. Anderson Cancer Center Houston, Texas James M. Church, MBChB, MMedSci, FRACS, FACS Victor W. Fazio Chair Department of Colorectal Surgery Cleveland Clinic Foundation Cleveland, Ohio Jose R. Cintron, MD, FACS, FASCRS Chief, Division of Colon and Rectal Surgery John H. Stroger Hospital of Cook County Chicago, Illinois Rhodri J. Codd, MB BCh, MSc, FRCS Consultant Colorectal Surgeon Royal Gwent Hospital Newport, Wales, United Kingdom Jeffrey L. Cohen, MD, FACS, FASCRS Chief Physician Officer Hartford HealthCare Medical Group System Vice President Physician and Provider Network Development Hartford HealthCare Clinical Professor University of Connecticut School of Medicine Hartford, Connecticut Fabio Cominelli, MD, PhD Professor of Medicine and Pathology Associate Dean for Program Development Chief, Division of Gastroenterology and Liver Disease Hermann Menges, Jr. Chair in Internal Medicine Director, Digestive Health Research Institute Director, NIH Cleveland Digestive Diseases Research Core Center Case Western Reserve University Chief Scientific Officer, Digestive Health Institute Cleveland, Ohio

Conor P. Delaney, MD, MCh, PhD, FRSCI (Gen), FACS Chairman, Digestive Disease and Surgery Institute Cleveland Clinic Cleveland, Ohio Peter G. Deveaux, MD, FACS Assistant Professor of Surgery University of Louisville Louisville, Kentucky Jonathan E. Efron, MD GI Ravitch Colon and Rectal Surgery Department of Surgery The Johns Hopkins Hospital Baltimore, Maryland Dan Eisenberg, MD, MS, FACS Assistant Professor Department of Surgery Stanford School of Medicine Director, Bariatric and Minimally Invasive Surgery Veterans Affairs Palo Alto Health Care System Palo Alto, California Theodore E. Eisenstat, MD, FACS, FASCRS Professor of Surgery Robert Wood Johnson Medical School New Brunswick, New Jersey Galal El-Gazzaz, MD Center for Gut Rehabilitation and Transplantation Transplant Center Cleveland Clinic Cleveland, Ohio C. Neal Ellis, MD, FACS, FASCRS, FACG Professor and Chairman Residency Program Director Texas Tech University Health Science Center–Permian Basin Odessa, Texas Paula Erwin-Toth, MSN, RN, CWOCN, CNS, FAAN President/CEO PETprojects Wound, Ostomy, and Continence Care Education and Advocacy Deerfield, Ohio

CONTRIBUTORS

Seraina Faes, MD Department of Visceral Surgery University Hospital of Lausanne Lausanne, Switzerland Sandy H. Fang, MD GI Ravitch Colon and Rectal Surgery Department of Surgery The Johns Hopkins Hospital Baltimore, Maryland Russell Farmer, MD Assistant Professor of Surgery University of Louisville Louisville, Kentucky Joanne Favuzza, DO Assistant Professor Section of Colon and Rectal Surgery Rush University Medical Center Chicago, Illinois †Victor W. Fazio, MB, MS, MD(Hon), FRACS, FRACS(Hon),

FACS, FRCS, FRCS(Ed), FASCRS, OA Formerly Rupert B. Turnbull, Jr., MD, Chair, Emeritus Emeritus Chairman, Department of Colorectal Surgery Cleveland Clinic Foundation Cleveland, Ohio

Daniel L. Feingold, MD, FACS, FASCRS The Dr. Stanley Edelman-Stephen Jarislowsky Associate Professor of Surgery Division of Colorectal Surgery Columbia University New York City, New York Josef E. Fischer, MD William V. McDermott Distinguished Professor of Surgery Harvard Medical School Boston, Massachusetts James Fleshman, MD Chief of Surgery Baylor University Medical Center Dallas, Texas Daniel P. Froese, MBChB, FACS, FASCRS Attending Surgeon Swedish Colon and Rectal Clinic Seattle, Washington Masato Fujiki, MD, PhD Center for Gut Rehabilitation and Transplantation Transplant Center Cleveland Clinic Cleveland, Ohio Susan Galandiuk, MD Professor of Surgery University of Louisville Director Price Institute of Surgical Research Louisville, Kentucky †Deceased.

Aurélie Garant, MD McGill University Montreal, Quebec, Canada Julio Garcia-Aguilar, MD, PhD Memorial Sloan Kettering Cancer Center New York, New York Susan L. Gearhart, MD Associate Professor of Surgery The Johns Hopkins Medical Institutions Baltimore, Maryland Dan Geisler, MD Colon and Rectal Surgery Allegheny General Hospital Pittsburgh, Pennsylvania Angelle M. Gelvin, MD Chief Resident Department of Surgery Louisiana State University Health Sciences Center New Orleans, Louisiana Bradley C. Gill, MD, MS Resident Physician Department of Urology Glickman Urological and Kidney Institute Clinical Instructor of Surgery Cleveland Clinic Lerner College of Medicine Cleveland, Ohio Philip H. Gordon, MD, FRCSC, FACS Professor of Surgery and Oncology Director of Colon and Rectal Surgery McGill University Jewish General Hospital Montreal, Quebec, Canada Lester Gottesman, MD, FACS, FASCRS Division of Colon Rectal Surgery Icahn School of Medicine and Mount Sinai New York, New York Henry R. Govekar, MD, FACS Colorectal and General Surgeon Tiesenga Surgical Associates, S.C. Suburban Surgery Center Elmwood Park, Illinois, Associate Staff Colorectal Surgeon Presence Health Resurrection Medical Center Associate Staff Colorectal and General Surgeon Community First Medical Center Chicago, Illinois, Active Staff Colorectal and General Surgeon West Suburban Medical Center Oak Park, Illinois, Associate Staff Colorectal and General Surgeon Westlake Hospital Melrose Park, Illinois Sharon Grundfest-Broniatowski, MD, FACS Associate Professor of Surgery Cleveland Clinic Lerner College of Medicine Case Western ­Reserve University Staff, Department of General Surgery Digestive Disease Institute Cleveland, Ohio

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CONTRIBUTORS

José G. Guillem, MD, MPH, FACS, FASCRS Professor of Surgery Weill Cornell Medical College Cornell University Memorial Sloan Kettering Cancer Center New York City, New York

Neil Hyman, MD, FACS Professor of Surgery Chief, Section of Colon and Rectal Surgery Co-director, Digestive Disease Center University of Chicago Medicine Chicago, Illinois

Dieter Hahnloser, MD Professor Department of Visceral Surgery University Hospital of Lausanne Lausanne, Switzerland

Terence Jackson, MD Case Western Reserve University School of Medicine University Hospitals Case Medical Center Cleveland, Ohio

Koji Hashimoto, MD, PhD Center for Gut Rehabilitation and Transplantation Transplant Center Cleveland Clinic Cleveland, Ohio Terrell C. Hicks, MD Vice-Chair Department of Colon and Rectal Surgery Ochsner Clinic New Orleans, Louisiana Andrew G. Hill, MBChB, MD, FRACS Department of Surgery University of Auckland Middlemore Hospital Auckland, New Zealand Edith Y. Ho, MD, MS Assistant Professor of Medicine Division of Gastroenterology Case Western Reserve University School of Medicine Director, Inflammatory Bowel Diseases Program Cleveland VA Medical Center Cleveland, Ohio Barbara J. Hocevar, MSN, RN, CWOCN Assistant Director, WOC Nursing Education R.B. Turnbull, Jr., School of WOC Nursing Cleveland Clinic Cleveland, Ohio Jennifer Holder-Murray, MD, FACS Assistant Professor of Surgery University of Pittsburgh Physicians Pittsburgh, Pennsylvania Vanessa W. Hui, MD General Surgery Resident Montefiore Medical Center Albert Einstein School of Medicine New York, New York Tracy Hull, MD Professor of Surgery Department of Colon and Rectal Surgery Cleveland Clinic Foundation Cleveland, Ohio Kimberly J. Hwa, NMS, PA-C Physician Assistant, Surgical Service Veterans Affairs Palo Alto Health Care System Palo Alto, California

Caroline C. Jadlowiec, MD Resident, Department of Surgery University of Connecticut Hartford, Connecticut Eric K. Johnson, MD Uniformed Services University of the Health Sciences Bethesda, Maryland, Multicare Healthcare System Tacoma, Washington Jeffrey R. Jorden, MD Assistant Professor Department of Surgery University of Louisville School of Medicine Louisville, Kentucky Matthew F. Kalady, MD Associate Professor of Surgery Krause-Lieberman Chair in Colorectal Surgery Department of Colorectal Surgery Digestive Disease Institute Cleveland Clinic Cleveland, Ohio Jeffry A. Katz, MD Professor of Medicine Case Western Reserve University School of Medicine Medical Director, Inflammatory Bowel Disease University Hospitals Case Medical Center Cleveland, Ohio Henrik Kehlet, MD, PhD Section of Surgical Pathophysiology Rigshospitalet Copenhagen University Copenhagen, Denmark Deborah S. Keller, MS, MD Colorectal Surgical Associates, LLP LTD Department of Surgery Houston Methodist Hospital Houston, Texas Robin H. Kennedy, MS, FRCS Department of Surgery St. Mark’s Hospital London and Department of Surgery and Cancer Imperial College London London, United Kingdom Ajai Khanna, MD, PhD Center for Gut Rehabilitation and Transplantation Transplant Center Cleveland Clinic Cleveland, Ohio

CONTRIBUTORS

Alok A. Khorana, MD Professor of Medicine Cleveland Clinic Lerner College of Medicine Case Western Reserve University Sondra and Stephen Hardis Chair in Oncology Research Vice Chair (Clinical Services and Strategy) Director GI Malignancies Program Taussig Cancer Institute Cleveland Clinic Cleveland, Ohio Ravi P. Kiran, MBBS, MS, FRCS (Eng), FRCS (Glas), FACS Kenneth A. Forde Professor of Surgery Columbia University Medical Center and Mailman School of Public Health Chief and Program Director Division of Colorectal Surgery Director Center for Innovation and Outcomes Research New York-Presbyterian Hospital/Columbia University Medical Center New York, New York Walter A. Koltun, MD, FACS, FASCRS Professor of Surgery Peter and Marshia Carlino Chair in IBD Chief, Division of Colon and Rectal Surgery Director, Inflammatory Bowel Disease Center Milton S. Hershey Medical Center Pennsylvania State College of Medicine Hershey, Pennsylvania Rodney J. Kratz, MD, FASCRS Attending Surgeon Swedish Colon and Rectal Clinic Seattle, Washington Ajit Krishnaney, MD Staff, Center for Spine Health Department of Neurosurgery Neurological Institute Cleveland Clinic Cleveland, Ohio Nicholas La Gamma, MD Assistant Professor of Surgery Hofstra Northwell School of Medicine Hempstead, New York Sergio Larach, MD, FACS Associate Professor of Colon and Rectal Surgery University of Florida Gainesville, Florida Philip A. Linden, MD Chief, Division of Thoracic and Esophageal Surgery University Hospitals Case Medical Center Associate Professor Case Western Reserve University School of Medicine Cleveland, Ohio Ian Lindsey, MBBS, FRACS Department of Colorectal Surgery John Radcliffe Hospital Oxford, United Kingdom

Walter E. Longo, MD, FACS, FASCRS Department of Surgery Yale University School of Medicine New Haven, Connecticut Kim C. Lu, MD, FASCRS Associate Professor of Surgery Division of Gastrointestinal and General Surgery Department of Surgery Oregon Health and Science University Portland, Oregon Kirk A. Ludwig, MD The Vernon O. Underwood Professor Professor of Surgery Chief, Division of Colorectal Surgery Department of Surgery Medical College of Wisconsin Milwaukee, Wisconsin Carole Macaron, MD Section of Gastroenterology Department of Veterans Affairs Louis Stokes Cleveland Medical Center Cleveland, Ohio Nikita Neha Machado, MD University Hospitals Case Medical Center Cleveland, Ohio Mark L. Manwaring, MD Assistant Professor of Surgery East Carolina University Greenville, North Carolina David A. Margolin, MD Ochsner Clinic Foundation New Orleans, Louisiana John H. Marks, MD, FACS, FASCRS Chief of Colorectal Surgery Main Line Health Systems Director Minimally Invasive Colorectal Surgery and Rectal Cancer ­Management Fellowship Lankenau Medical Center Professor Lankenau Institute of Medical Research The Lankenau Hospital Main Line Health System Wynnewood, Pennsylvania Beatriz Martin-Perez, MD Clinical Research Fellow Colon and Rectal Surgery Fellowship Florida Hospital Orlando, Florida Joseph Martz, MD, FACS, FASCRS Chief, Division of Colon and Rectal Surgery Mount Sinai Beth Israel, Associate Professor of Surgery Icahn School of Medicine at Mount Sinai New York, New York

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CONTRIBUTORS

Michael H. McCafferty, MD Professor Department of Surgery University of Louisville School of Medicine Louisville, Kentucky Robin S. McLeod, MD, FRCSC, FACS Professor Departments of Surgery and Health Policy, Management, and ­Evaluation University of Toronto Toronto, Ontario, Canada David S. Medich, MD Associate Professor of Surgery Chief, Section of Colon and Rectal Surgery University of Pittsburgh School of Medicine Pittsburgh, Pennsylvania Kurt Melstrom, MD, FACS, FASCRS Assistant Professor of Surgery City of Hope Duarte, California

Graham L. Newstead, AM, MB BS, FRACS, FRCS(Eng), FACS Hon FASCRS, Hon FRSM, Hon FACP (GB&I) Conjoint Associate Professor University of New South Wales Head, Colorectal Surgery Prince of Wales Private Hospital Sydney, Australia Tamim Niazi, MD, FRCP Jewish General Hospital McGill University Montreal, Quebec, Canada Pasha J. Nisar, MA, MBBChir, DM, FRCS (Gen Surg) Department of Colorectal Surgery St. Peter’s Hospital Chertsey, United Kingdom Marcus S. Noel, MD Assistant Professor of Medicine Wilmot Cancer Institute University of Rochester Rochester, New York

Victor L. Modesto, MD, FACS, FASCRS Orlando VA Medical Center Clinical Assistant Professor of Surgery University of Central Florida College of Medicine Orlando, Florida, Clinical Adjunct Assistant Professor of Surgery F. Edward Hebert School of Medicine Uniformed Services University of the Health Sciences Bethesda, Maryland

Joseph R. Notaro, MD, FACS, FASCRS Clinical Assistant Professor Surgery Robert Wood Johnson University Hospital New Brunswick, New Jersey

Drogo K. Montague, MD Center for Genitourinary Reconstruction Department of Urology Glickman Urological and Kidney Institute Professor of Surgery Cleveland Clinic Lerner College of Medicine Cleveland, Ohio

P. Ronan O’Connell, MD, FRCSI, FRCS(Glas), FRCS(Edin) Professor Section of Surgery and Surgical Specialties School of Medicine University College Dublin Dublin, Ireland

Grace A. Montenegro, MD Minimally Invasive Colon and Rectal Surgery Fellow Lankenau Medical Center Wynnewood, Pennsylvania

Guy R. Orangio, MD, FACS, FASCRS Associate Professor of Surgery Chief, Section of Colon and Rectal Surgery Department of Surgery Louisiana State University School of Medicine New Orleans, Louisiana

Harvey G. Moore, MD, FACS, FASCRS Assistant Professor of Surgery Section of Colon and Rectal Surgery Division of Advanced Oncology and Gastrointestinal Surgery Duke University School of Medicine Durham, North Carolina Jesse Moore, MD, FACS Assistant Professor of Surgery University of Vermont Medical Center University of Vermont College of Medicine Burlington, Vermont Mark Muhlmann, MBBS (hons), FRACS Conjoint Lecturer University of New South Wales Sydney, Australia

David P. O’Brien, MD, FASCRS Gastrointestinal and Minimally Invasive Surgery Division The Oregon Clinic Portland, Oregon

In Ja Park, MD, PhD Associate Professor Surgery, Division of Colon and Rectal Surgery University of Ulsan College of Medicine and Asan Medical Center Seoul, Korea Alberto Peña, MD Professor of Surgery University of Colorado Director International Center for Colorectal Care Children’s Hospital Colorado Aurora, Colorado Jason Penzer, MD, FACS Attending Surgeon Northwell Lenox Hill Hospital Clinical Assistant Professor of Surgery New York Medical College New York, New York

CONTRIBUTORS

Clayton C. Petro, MD General Surgery Research Scholar Case Comprehensive Hernia Center University Hospitals Case Medical Center Cleveland, Ohio Danielle M. Pickham, MD General and Colorectal Surgeon Kaiser Permanente San Jose Medical Center San Jose, California John Procaccino, MD, FACS, FASCRS Assistant Professor of Surgery Hofstra Northwell School of Medicine Hempstead, New York Siraj Rajaratnam, MBChB, FRACS Colorectal Unit North Shore Hospital Auckland, New Zealand Vikram Reddy, MD, PhD, FACS, FASCRS Department of Surgery Colon and Rectal Surgery Yale University School of Medicine New Haven, Connecticut Jonathan Rice, MD, PhD Senior Resident in Surgery University of Louisville Louisville, Kentucky Timothy J. Ridolfi, MD The Vernon O. Underwood Professor Professor of Surgery Chief, Division of Colorectal Surgery Department of Surgery Medical College of Wisconsin Milwaukee, Wisconsin John L. Rombeau, MD, FACS, FASCRS Emeritus Professor of Surgery Perelman School of Medicine University of Pennsylvania Philadelphia, Pennsylvania Michael J. Rosen, MD, FACS Professor of Surgery Lerner College of Medicine Cleveland Clinic Foundation Cleveland, Ohio Andrew J. Russ, MD University Colon and Rectal Surgery Department of Surgery University of Tennessee Graduate School of Medicine Knoxville, Tennessee Theodore J. Saclarides, MD Professor of Surgery Rush Medical College Head, Section of Colon and Rectal Surgery Rush University Medical Center Chicago, Illinois

Peter M. Sagar, MB ChB, FRCS, DM Consultant Colorectal Surgeon St. James’s University Hospital Leeds, United Kingdom Javier Salgado Pogacnik, MD Assistant Professor of Surgery Department of Colon and Rectal Surgery University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Dana R. Sands, MD, FACS, FASCRS Staff Surgeon Director, Colorectal Physiology Center Department of Colorectal Surgery Cleveland Clinic Florida Weston, Florida William Sangster, MD General Surgery Resident Department of Surgery Pennsylvania State University Hershey Medical Center Hershey, Pennsylvania Anthony J. Senagore, MD, MS, MBA Professor Chief of Gastrointestinal and Oncologic Surgery Department of Surgery University of Texas–Medical Branch at Galveston Galveston, Texas Skandan Shanmugan, MD Assistant Professor Department of Surgery Division of Colon and Rectal Surgery University of Pennsylvania Philadelphia, Pennsylvania Abdullah Shatnawei, MD Center for Gut Rehabilitation and Transplantation Transplant Center Cleveland Clinic Cleveland, Ohio Bo Shen, MD Professor of Medicine and the Ed and Joey Story Chair Center for Inflammatory Bowel Diseases Cleveland Clinic Foundation Cleveland, Ohio Christopher T. Siegel, MD, PhD, FACS Schulak Endowed Director of the Transplant Institute University Hospitals Case Medical Center Surgical Director, Liver Center of Excellence Digestive Health Institute Chief, Division of Hepatobiliary and Transplant Surgery Associate Professor of Surgery Case Western Reserve University Cleveland, Ohio Tim Slack, BSc, MBBS, FRACS Senior Lecturer University of Queensland Queensland, Australia

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CONTRIBUTORS

Nathan Smallwood, MD Research Fellow Department of Surgery Baylor University Medical Center Dallas, Texas Michael J. Snyder, MD Associate Professor of Surgery The University of Texas Health Science Center McGovern Medical School Houston, Texas Scott R. Steele, MD University Hospitals Case Medical Center Case Western Reserve University School of Medicine Cleveland, Ohio Ezra Steiger, MD Consultant Digestive Disease Institute Department of General Surgery Cleveland Clinic Cleveland, Ohio David B. Stewart, Sr., MD, FACS, FASCRS Associate Professor of Surgery Department of Surgery/Division of Colorectal Surgery Pennsylvania State University Hershey Medical Center Hershey, Pennsylvania Scott A. Strong, MD, FACS, FASCRS Chief, Gastrointestinal and Oncologic Surgery Surgical Director, Digestive Health Center Northwestern Medicine James R. Hines, MD, Professor of Surgery Northwestern University Feinberg School of Medicine Chicago, Illinois Paul H. Sugarbaker, MD, FACS, FRCS Director, Center for Gastrointestinal MalignanciesMedStar ­Washington Hospital Center Washington, D.C. Ursula M. Szmulowicz, MD, FASCRS Retired Staff Surgeon Department of Colorectal Surgery Cleveland Clinic Cleveland, Ohio Matthias Turina, MD, PhD Section Head, Coloproctology Division of Visceral and Transplant Surgery University of Zürich Hospital Zürich, Switzerland

Té Vuong, MD, FRCP Jewish General Hospital McGill University Montreal, Quebec, Canada Steven D. Wexner, MD, PhD (Hon), FACS, FRCS, FRCS (Ed) Professor and Chairman Department of Colorectal Surgery Director, Digestive Disease Institute Cleveland Clinic Florida Florida Atlantic University Florida International University Weston, Florida Mark H. Whiteford, MD, FASCRS Gastrointestinal and Minimally Invasive Surgery Division The Oregon Clinic Director of Colon and Rectal Surgery Providence Cancer Center Portland, Oregon Maria Widmar, MD, MPH Icahn School of Medicine at Mount Sinai Memorial Sloan Kettering Cancer Center New York, New York Kirsten Bass Wilkins, MD, FACS, FASCRS Clinical Assistant Professor Surgery Robert Wood Johnson University Hospital New Brunswick, New Jersey Jon Worsey, MBBS, FRCS, FACS, FASCRS Staff Surgeon Scripps Memorial Hospital La Jolla, California Massarat Zutshi, MD Associate Professor of Surgery Lerner College of Medicine of Case Western Reserve University Staff Surgeon Colorectal Surgery Cleveland Clinic Foundation Cleveland, Ohio

preface to the third edition

When this edition of Current Therapy in Colorectal Surgery was conceived, Editor-in-Chief Victor Fazio was an integral part of the team. Since then he has been lost to us, and we are the poorer for his loss. This book is akin to a festschrift in his memory. The new edition continues the surgical and educational philosophies espoused by Vic Fazio, philosophies that have made the book a unique volume much loved by surgical residents and surgeons managing colorectal diseases throughout the world. We, the current editors, have sought to achieve a uniform style that facilitates this edition’s use as a practical handbook of which Vic would be proud. This is not meant to be an all-inclusive encyclopedia of the literature on colorectal surgery; there are other books that serve that function. We aim to provide for the reader a very practical aid to the management of patients suffering from any of the conditions within the full spectrum of colorectal disease. We chose expert authors and asked them to focus on the practicalities of their topics, highlighting difficult and controversial issues. They were charged with providing advice in the same way that an experienced, worldly-wise surgeon shares wisdom with a young colleague. We hope that the book will not linger on the shelf, but rather will be in constant use in meeting the daily clinical challenges that are the essence of our profession. In this edition, we have maintained the emphasis on current practice in the light of recent developments in colorectal disease and provided a state-of-the-art understanding of the conditions. The same old chapters are here, with simple instruction in the basics of their

topics updated with the latest information. New chapters have been added with emphasis on the way that health care is heading into the 21st century. The chapters on risk assessment, operating on the highrisk patient, and outcomes in general address the increasing emphasis on quality, while the chapters on documentation and coding and enhanced recovery pathways are essential reading in this time of value-based reimbursement. We have a whole section on complications, because complications are inevitable in a busy colorectal surgical practice, and we all need help in minimizing their incidence and optimizing their management. There are five chapters dealing with rectal cancer, which reflects the major role that colorectal surgeons are expected to play in treating this condition. Other chapters that are well worth a read include those on short bowel syndrome, small bowel transplantation, pouchitis, and the medical management of IBD. The chapters relating to pouch creation and complications incorporate the techniques and principles developed and espoused by Vic; this was an area close to his heart and where his skills were superlative. The continually advancing area of hereditary colorectal cancer is also well, and helpfully, covered. Finally we hope that, in reading this, you will hear the gruff, Australian accent of Vic Fazio as he dispenses the wisdom and accumulated experience of his 40 years of practice. James M. Church, Conor P. Delaney, and Ravi P. Kiran

xiii

acknowledgments

To my wife, Lois Church, in appreciation of her selfless love and support. James M. Church To Clare for her love and support, and to my parents, without whose direction and support I would not have entered medicine. Conor P. Delaney To my wife, Madhu, for her love and support, and my parents for their guidance and encouragement. Ravi P. Kiran

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contents

1. Anal and Perianal Region

16. Pelvic Pain  73

1. A  natomy and Physiology of the Colon, Rectum, and Anal Canal  3

17. Anorectal Congenital Disorders  77

Marylise Boutros and Philip H. Gordon

Andrea Bischoff and Alberto Peña

18. Hirschsprung Disease 

2. Hemorrhoids  12

83

Andrea Bischoff and Alberto Peña

Anthony J. Senagore

3. Chronic Anal Fissure  16 Siraj Rajaratnam and Ian Lindsey

4. Anorectal Abscess  21

2. Rectal and Pararectal Region 19. Fecal Incontinence  93 P. Ronan O’Connell

Ravi P. Kiran

20. Rectal Stricture: Etiology and Management  98

5. Anal Fistula  24

William Sangster and David B. Stewart, Sr.

Mark L. Manwaring

6. Rectovaginal Fistula 

30

21. Management of Fecal Impaction  102 Sergio Larach and Beatriz Martin-Perez

Tracy Hull

7. Pilonidal Sinus 

Joseph R. Notaro and Kirsten Bass Wilkins

36

Tim Slack, Graham L. Newstead, and Mark Muhlmann

8. Perianal Hidradenitis Suppurativa  41 Mark L. Manwaring

9. Management of Pruritus Ani  43 J. Andres Cervera-Servin, Rodney J. Kratz, and Daniel P. Froese

10. Cause and Management of Anal Stenosis  48 Theodore E. Eisenstat and Jason Penzer

11. Management of Anal and Perianal Warts  53 Jennifer Blumetti and Jose R. Cintron

12. Anorectal Venereal Infections  57 Victor L. Modesto and Lester Gottesman

13. M  anagement of High-Grade Squamous ­Intraepithelial Lesion (Formerly Bowen Disease) and Paget Disease  62 Nicholas La Gamma and John Procaccino

14. A  nal Melanoma and Basal Cell Cancer of the Perianal Region  65 Kurt Melstrom and Joseph Martz

15. Anal Carcinoma  68 Timothy J. Ridolfi and Kirk A. Ludwig

22. Rectal Prolapse  107 Andrew J. Russ and Conor P. Delaney

23. Solitary Rectal Ulcer Syndrome  111 David Bartolo

24. Rectocele  114 Preetha Ali and Richard P. Billingham

25. Rectal Foreign Bodies  118 Joanne Favuzza

26. D  iagnosis and Management of Sacral and Retrorectal Tumors  121 Sharon Grundfest-Broniatowski and Ajit Krishnaney

27. Management of Rectal Villous Tumors  132 James M. Church

28. P  reoperative Evaluation of the Patient with Rectal Cancer: Staging and Strategy  135 Marylise Boutros and Steven D. Wexner

29. Cancer of the Rectum: Neoadjuvant Therapy  141 Té Vuong, Aurélie Garant, and Tamim Niazi

30. Cancer of the Rectum: Operative Management  146 Knut Magne Augestad, Benjamin Crawshaw, and Conor P. Delaney

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CONTENTS

31. Local Treatment of Rectal Cancer  152 Maria Widmar and Julio Garcia-Aguilar

32. L  ocally Recurrent Rectal Cancer: Management and Follow-up  157 Vanessa W. Hui, Harvey G. Moore, and José G. Guillem

33. Perineal Hernia  162 David E. Beck

49. Surgical Treatment of Diverticulitis and Its Complications  239 Raul M. Bosio and Conor P. Delaney

50. Lower Gastrointestinal Hemorrhage  244 Caroline C. Jadlowiec and Jeffrey L. Cohen

51. Large Bowel Obstruction  249 David P. O’Brien, Kim C. Lu, and Mark H. Whiteford

52. Colonic Volvulus  255 Deborah S. Keller

3. Colon 34. P  reoperative Preparation of the Patient for Colon and Rectal Surgery  167 Danielle M. Pickham, Terrell C. Hicks, and David A. Margolin

35. M  edical Treatment of Ulcerative Colitis and Other ­Colitides  174 Aaron Brzezinski

36. Chronic Ulcerative Colitis: Surgical Options  186 Ravi P. Kiran

37. M  anagement of Acute Toxic Colitis and Megacolon  191 Ursula M. Szmulowicz and Victor W. Fazio

38. P  elvic Pouch: Complications and Their Management  197 Ravi P. Kiran

39. P  ouchitis and Functional Complications of the Pelvic Pouch  201 Bo Shen

40. Continent Ileostomy  204 Jon Worsey and Victor W. Fazio

41. Unhealed Perineal Wound  209 Jesse Moore and Neil Hyman

42. Medical Management of Crohn Disease  213 Edith Y. Ho, Jeffry A. Katz, and Fabio Cominelli

43. Management of Crohn Colitis  217 Scott A. Strong

44. Management of Perianal Crohn Disease  222 James M. Church

45. Cecal Ulcer  226 Peter G. Deveaux and Michael H. McCafferty

46. Pseudomembranous Clostridium Difficile Colitis  228 Javier Salgado Pogacnik, Jennifer Holder-Murray, and David S. Medich

47. C  ytomegalovirus Ileocolitis and Kaposi Sarcoma in HIV/AIDS  231 Henry R. Govekar and Dana R. Sands

48. D  iagnosis and Management of Acute Colonic Diverticulitis  234 Daniel L. Feingold and Ravi P. Kiran

53. Colonic Pseudo-obstruction (Ogilvie Syndrome)  260 Theodore J. Saclarides and Elizabeth Berger

54. Management of the Malignant Polyp  264 Skandan Shanmugan and Cary B. Aarons

55. Colorectal Cancer Screening and Surveillance  267 Carole Macaron and Carol A. Burke

56. Molecular Genetics of Colorectal Cancer  273 James M. Church

57. Polyposis Syndromes 

275

James M. Church

58. Desmoid Disease  281 James M. Church

59. H  ereditary Nonpolyposis Colorectal Cancer and Lynch Syndrome  285 Matthew F. Kalady

60. Cancer of the Appendix and Pseudomyxoma Peritonei Syndrome  292 Paul H. Sugarbaker

61. Surgical Management of Cancer of the Colon  301 In Ja Park and George J. Chang

62. Management of Metastatic Colorectal Cancer  309 Marcus S. Noel and Alok A. Khorana

63. Management of Colorectal Liver Metastasis  314 Terence Jackson, Nikita Neha Machado, and Christopher T. Siegel

64. Colorectal Metastases to the Lung  320 Philip A. Linden

65. Nonepithelial Colorectal Tumors  323 Angelle M. Gelvin and Guy R. Orangio

66. Management of Colonic Ischemia  328 Vikram Reddy and Walter E. Longo

67. Colon and Rectal Trauma  334 Scott R. Steele and Eric K. Johnson

68. Endometriosis of the Colon and Rectum  341 H. Randolph Bailey, Michael J. Snyder, and Colin P. Bird

69. Pneumatosis Cystoides Intestinalis  345 Susan Galandiuk, Jonathan Rice, Peter G. Deveaux, and Russell Farmer

70. Constipation  349 Evie Carchman and Massarat Zutshi

CONTENTS

4. Small Intestine 71. Small Bowel Obstruction  359 Matthias Turina and Ravi P. Kiran

72. Medical Management of Short Bowel Syndrome  366 Mary Jo Alberino, Dileep Atluri, and Ezra Steiger

73. S urgery for Gut Failure: Auto-Reconstruction and Allo-Transplantation  372 Kareem Abu-Elmagd, Ajai Khanna, Masato Fujiki, Koji Hashimoto, Galal El-Gazzaz, Abdullah Shatnawei, and Guilherme Costa

74. C  rohn Disease of the Duodenum, Stomach, and Esophagus  385 Pasha J. Nisar and Ravi P. Kiran

75. Management of Small Bowel Crohn Disease  388 Scott A. Strong

76. Small Bowel Neoplasms  393 Susan L. Gearhart

77. N  euroendocrine Tumors of the Small and Large Intestine  396 Seraina Faes and Dieter Hahnloser

78. Enterocutaneous Fistulas  404 Josef E. Fischer

79. Acute and Chronic Mesenteric Ischemia  412 Susan Galandiuk, Jeffrey R. Jorden, Jonathan Rice, and Peter G. Deveaux

80. Radiation Enteritis and Proctocolitis  418 Sandy H. Fang and Jonathan E. Efron

5. Complications (and Other

­Miscellaneous Topics)

81. Colorectal Surgery in the High-Risk Patient  427 Walter A. Koltun and Tara M. Connelly

82. Reoperative Pelvic Surgery  434 Jon Worsey and Victor W. Fazio

xvii

83. Nutritional Support in Colorectal Surgery  439 John L. Rombeau, Kimberly J. Hwa, and Dan Eisenberg

84. Prevention and Management of Sepsis  445 Dan Geisler and C. Neal Ellis

85. Management of Anastomotic Leak  448 Nathan Smallwood and James Fleshman

86. Complications of Colonoscopy  452 Rhodri J. Codd and Peter M. Sagar

87. Management of Hemorrhage During Pelvic Surgery  456 John H. Marks and Grace A. Montenegro

88. Urologic Issues in Colorectal Surgery  462 Bradley C. Gill and Drogo K. Montague

89. P  revention and Treatment of Complications of Laparoscopic Colorectal Surgery  468 Benjamin Crawshaw, Knut Magne Augestad, and Conor P. Delaney

90. Prevention and Management of Ostomy Complications  472 Victor W. Fazio

91. S toma and Wound Considerations: Nursing Management  477 Paula Erwin-Toth and Barbara J. Hocevar

92. Measuring Outcomes  486 Robin S. McLeod

93. M  edical Documentation and Coding for the Colorectal Surgeon  490 Anthony J. Senagore

94. Enhanced Recovery Pathways After Colorectal Surgery  493 Henrik Kehlet, Andrew G. Hill, and Robin H. Kennedy

95. M  anaging Complex Ventral/Parastomal Hernias in Colorectal Surgical Patients  496 Clayton C. Petro and Michael J. Rosen

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ANAL AND PERIANAL REGION

1

1. Anatomy and Physiology of the Colon, Rectum, and Anal Canal   3

11. Management of Anal and Perianal Warts   53

2. Hemorrhoids   12

13. Management of High-Grade Squamous Intraepithelial Lesion (Formerly Bowen Disease) and Paget Disease  62

3. Chronic Anal Fissure   16 4. Anorectal Abscess   21 5. Anal Fistula   24 6. Rectovaginal Fistula   30 7. Pilonidal Sinus   36 8. Perianal Hidradenitis Suppurativa   41 9. Management of Pruritus Ani   43 10. Cause and Management of Anal Stenosis   48

12. Anorectal Venereal Infections   57

14. Anal Melanoma and Basal Cell Cancer of the Perianal Region  65 15. Anal Carcinoma   68 16. Pelvic Pain   73 17. Anorectal Congenital Disorders   77 18. Hirschsprung Disease   83

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Anatomy and Physiology of the Colon, Rectum, and Anal Canal*

1

Marylise Boutros and Philip H. Gordon

ANATOMY OF THE COLON AND RECTUM Colon The colon can be divided embryologically into the midgut (the transverse colon and portions proximal to it) and the hindgut (the distal half of the colon). The length of the colon is approximately 150 cm, and its diameter gradually diminishes from the cecum to the rectosigmoid junction. In appearance it is distinguished from the small bowel by its size and by its saccular or haustral look, a function of its unique arrangement of muscular layers. It has a complete inner circular muscle coat, but the longitudinal outer layer is condensed into three bands, the taenia coli. These bands run from the base of the appendix and merge in the distal sigmoid colon, and thus the rectum has a complete longitudinal muscle coat. The colon is also distinguished by the appendices epiploicae, a series of fatty appendages located on its antimesenteric surface. Course and Peritoneal Coverings The general topography of the colon varies from person to person (Fig. 1-1). The colon begins in the right lower quadrant of the abdomen where the terminal ileum enters its medial surface at the ileocecal valve. Below the level of the valve is the cecum, the broadest portion of the colon. The vermiform appendix projects from the lowermost part of the cecum, and the appendix orifice is the apex of the large bowel. The cecum is often entirely enveloped by peritoneum. The superior and inferior ileocecal ligaments help maintain the angulation between the ileum and the cecum at the ileocecal valve. From the ileocecal junction, the colon ascends on the right side of the abdomen to overlie the lower pole of the right kidney, a distance of about 20 cm. The ascending colon is invested by peritoneum on its anterior, lateral, and medial surfaces. The colon then turns acutely medially, downward, and forward, at the hepatic flexure. The transverse colon is the longest segment of the colon (40 to 50 cm), extending from the hepatic to the splenic flexure. It is invested with peritoneum and is mobile on its mesentery, the root of which overlies the right kidney, the second portion of the duodenum, the pancreas, and the left kidney. This posterior relationship is important because these structures are liable to injury during a right hemicolectomy. The stomach is immediately above and the spleen is to the left. The greater omentum arises from the greater curvature of the stomach and descends in front of the transverse colon to which it is attached. To mobilize the greater omentum or to enter the lesser sac, the fusion of the omentum *Text was modified from Philip H. Gordon and Santhat Nivatvong’s Principles and practice of surgery for the colon, rectum, and anus, 3rd edition. Informa Healthcare: New York, London. All rights reserved.

to the transverse colon mesentery must be dissected. Because the omental bursa becomes obliterated caudal to the transverse colon and toward the right side, this dissection should be started on the left side of the transverse colon. The splenic flexure takes an acute angle high in the left upper quadrant and lies anterior to the midportion of the left kidney. The descending colon (approximately 30 cm) passes downward and posteriorly from the splenic flexure, over the lateral border of the left kidney. The anterior, medial, and lateral portions of its circumference are covered by peritoneum. The sigmoid colon extends from just above the pelvis in the left lower quadrant of the abdomen, forms a loop in or above the pelvis, and becomes the rectum at the level of the sacral promontory. Its length varies dramatically from 15 to 50 cm. The lateral surface of the sigmoid mesentery is fused to the parietal peritoneum of the lateral abdominal wall, and the fusion plane is generally known as the ‘‘white line of Toldt.” The sigmoid is completely covered with peritoneum. The posterior surface is attached to the posterior wall of the abdomen by a fan-shaped mesentery, the base of which extends from the left iliac fossa, along the pelvic brim, and across the sacroiliac joint to the second or third sacral segment; in so doing, it forms the intersigmoid fossa, which serves as a valuable guide to the left ureter, lying just beneath. 

Rectum The rectum begins at the level of the sacral promontory and ends by passing through the levator ani muscles. The rectum differs from the colon in that the outer longitudinal muscle layer is complete. The rectum measures 12 to 15 cm in length and lacks sacculations and appendices epiploicae. The rectum has three lateral curves: the upper and lower curves are convex to the right, and the middle is convex to the left. On their inner aspect, these infoldings into the lumen are known as the valves of Houston. The middle fold is the internal landmark corresponding to the anterior peritoneal reflection. Peritoneal Relations and Fascial Attachments The rectum is divided into upper, middle, and lower thirds. The upper third is covered by peritoneum anteriorly and laterally, the middle third is covered only anteriorly, and the lower third is extraperitoneal. The location of the peritoneal reflection shows considerable variation between individuals and between men and women. In men, it is usually 7 to 9 cm from the anal verge, whereas in women it is 5 to 7.5 cm above the anal verge. The posterior and sometimes the lateral aspects of the rectum are covered by a layer of fat contained by the fascia propria of the rectum. This area is known as the mesorectum, and it contains arteries and veins of the rectal blood supply, along with lymphatic channels and nodes. It is continuous with the sigmoid mesentery and peters out just above the levator muscles. Total mesorectal excision implies the complete excision of all fat enclosed within the fascia propria. 3

4

ANATOMY AND PHYSIOLOGY OF THE COLON, RECTUM, AND ANAL CANAL

FIGURE 1-1  General topography

of the large bowel. A, Colon. B, Peritoneum and adjacent structures. (From Gordon PH, Nivatvongs S. Principles and Practice of Surgery for the Colon, Rectum and Anus. 3rd ed. New York: Informa Healthcare USA; 2007.)

A

The sacrum and coccyx are covered with a strong fascia that is part of the parietal pelvic fascia, known as Waldeyer fascia. The rectosacral fascia is a component of Waldeyer fascia that runs from the level of the fourth sacral segment to the fascia propria of the rectum. This fascia tethers the posterior rectum to the hollow of the sacrum and should be sharply divided for full mobilization (Fig. 1-2). Anteriorly, the extraperitoneal portion of the rectum is covered with a visceral pelvic fascia, the fascia propria, or investing fascia. Anterior to the fascia propria is a filmy delicate layer of connective tissue known as Denonvilliers fascia. It separates the rectum from the seminal vesicles and the prostate or vagina (Fig. 1-2). The distal rectum, which is extraperitoneal, is attached to the pelvic side wall on each side by the lateral ligaments, which are composed of the pelvic plexus, connective tissues, and minor branches of the middle rectal artery. 

ARTERIAL SUPPLY The arterial supply of the colon arises from the superior and inferior mesenteric arteries.

Superior Mesenteric Artery The ileocolic artery is the last branch of the superior mesenteric artery (SMA), arising from its right side and running diagonally around the mesentery to the ileocecal junction. It is always present and has two chief branches: the ascending branch and the descending branch. The origin of the right colic artery varies greatly: it may arise from the SMA, the middle colic artery, or the ileocolic artery, and it is absent in some people (Fig. 1-3, A). The middle colic artery normally arises from the SMA either behind the pancreas or at its lower border (Fig. 1-3, A). The artery curves toward the hepatic flexure and divides into a right branch that anastomoses with the ascending branch of the right colic artery and a left branch that anastomoses with the ascending branch of the left colic artery. 

Inferior Mesenteric Artery The inferior mesenteric artery (IMA) arises from the abdominal aorta approximately 3 to 4 cm above the aortic bifurcation, about 10 cm above the sacral promontory. The first branch is the left colic artery, arising 2.5 to 3 cm from its origin (Fig. 1-3, A). It bifurcates, and its ascending branch courses directly toward the splenic

B

Peritoneum Investing fascia of rectum Presacral fascia

Rectosacral fascia

Denonvilliers fascia

FIGURE 1-2  Peritoneal coverings and fascial attachments of the

rectum. (From Gordon PH, Nivatvongs S. Principles and Practice of Surgery for the Colon, Rectum and Anus. 3rd ed. New York: Informa Healthcare USA; 2007.)

flexure and anastomoses with the left branch of the middle colic artery, whereas the descending branch anastomoses with the sigmoid arteries. The sigmoid arteries usually originate from the IMA; the first sigmoid artery may arise from the left colic artery. The number of sigmoidal branches may vary up to six. The IMA proceeds downward, crossing the left common iliac artery and vein to the base of the sigmoid mesocolon to become the superior rectal artery (Fig. 1-3, B). It forms a rectosigmoid branch and an upper rectal branch and then divides into left and right terminal branches. The terminal branches extend downward and forward around the lower two thirds of the rectum to the level of the levator ani muscle. Most middle rectal arteries arise from the internal pudendal arteries (67%). The remainder come from inferior gluteal arteries (17%) and internal iliac arteries (17%). The inferior rectal arteries, which are branches of the internal iliac arteries, arise from the pudendal artery (in the Alcock canal). They traverse the ischioanal fossa and supply the anal canal and the external sphincter muscles. 

5

ANAL AND PERIANAL REGION

Middle colic artery Superior mesenteric artery Right colic artery

Ascending branch of left colic artery

Middle colic artery

Marginal artery

Superior mesenteric artery

Inferior mesenteric artery Left colic artery

Ileocolic artery Ileal branch Anterior cecal branch Median sacral artery Posterior cecal branch Appendicular artery Internal iliac artery

Arc of Riolan

Sigmoid arteries Left common iliac artery Bifurcation of superior rectal artery

Accessory middle rectal artery Middle rectal artery A Inferior rectal artery

FIGURE 1-4  Collateral circulation. (From Gordon PH, Nivatvongs S. Inferior mesenteric artery

Principles and Practice of Surgery for the Colon, Rectum and Anus. 3rd ed. New York: Informa Healthcare USA; 2007.)

Marginal arteries Median sacral artery Superior rectal artery Right common iliac artery Right external iliac artery Right internal iliac artery Right superior gluteal artery Right inferior epigastric artery Right obturator artery Right inferior gluteal artery Accessory middle rectal artery Right internal pudendal artery Right middle rectal artery Right inferior rectal artery

B

FIGURE 1-3  Arterial supply. A, Supply to the colon. B, Supply to the

rectum (posterior view). (From Gordon PH, Nivatvongs S. Principles and Practice of Surgery for the Colon, Rectum and Anus. 3rd ed. New York: Informa Healthcare USA; 2007.)

Collateral Circulation The marginal artery, generally known as the marginal artery of Drummond, is a series of arcades of arteries along the mesenteric border of the entire colon (Fig. 1-4). The arcades begin with the ascending colic branch of the ileocolic artery and continue distally to the sigmoid arteries (Fig. 1-4). A truly critical point exists at the splenic flexure, where the marginal artery is often small. This ‘‘weak point’’ has the potential to cause compromised blood supply. Another more proximal collateral is the “arc of Riolan,” found in about 7% of the population. It is a short loop connecting the left branch of the middle colic artery and the trunk of the IMA (Fig. 1-4) that serves as critical collateral for patients with a diseased SMA or IMA. 

VENOUS DRAINAGE The veins of the intestine follow their corresponding arteries and bear the same terminology.

Superior Mesenteric Vein The veins from the right colon and transverse colon drain into the superior mesenteric vein (SMV), which lies to the right and in front of the SMA. All ileocolic veins drain into the SMV. The right colic vein, if present, joins the SMV in 56% of persons and the gastrocolic trunk in 44% of persons. The middle colic vein (which is the most variable) and the right colic vein occasionally form a common trunk with the right gastroepiploic vein and/or the pancreaticoduodeinal vein. This common trunk is called the gastrocolic trunk. The middle colic vein drains directly into the SMV in 85% of persons, and the remainder drains into the SMV via the gastrocolic trunk. 

Inferior Mesenteric Vein The inferior mesenteric vein (IMV) is a continuation of the superior rectal vein. It receives blood from the left colon, the rectum, and the upper part of the anal canal. All the tributaries of the IMV closely follow the corresponding arteries but are slightly to the left of them. At the level of the left colic artery, the IMV follows a course of its own and ascends in the extraperitoneal plane over the psoas muscle to the left of the ligament of Treitz. It continues behind the body of the pancreas to enter the splenic vein (Fig. 1-5). 

LYMPHATIC DRAINAGE The extramural lymphatic vessels and lymph nodes follow the regional arteries and can be classified into four groups: epicolic, paracolic, intermediate, and main (principal) glands (Fig. 1-6). 

INNERVATION The large intestine is innervated by the sympathetic and parasympathetic systems, the distribution of which follows the course of the arteries. The peristalsis of the colon and rectum is inhibited by sympathetic nerves and is stimulated by parasympathetic nerves. Nerve fibers from the superior mesenteric ganglia supply the right colon, whereas the fibers to the descending colon, the sigmoid colon, and the upper rectum originate in the inferior mesenteric plexus. Parasympathetic innervation of the colon derives from two levels of the

6

ANATOMY AND PHYSIOLOGY OF THE COLON, RECTUM, AND ANAL CANAL

Superior pancreaticoduodenal vein Portal vein

Splenic vein

Superior mesenteric vein Inferior mesenteric vein

Right colic vein

Left colic vein

Ileocolic vein Superior mesenteric vein Inferior vena cava Right common iliac vein Right internal iliac vein Right external iliac vein Middle rectal vein Internal pudendal vein Inferior rectal vein

Testicular/ ovarian veins Sigmoid veins Middle sacral vein Superior rectal vein

Internal hemorrhoidal plexus External hemorrhoidal plexus

FIGURE 1-5 Venous drainage of the colon and rectum. Dark blue repre-

sents systemic venous drainage. Light blue shows portal venous drainage. (From Gordon PH, Nivatvongs S. Principles and practice of surgery for the colon, rectum, and anus, 3rd edition. Informa Healthcare, New York, London.  All rights reserved.)

each ureter. The hypogastric nerve on each side continues caudally and laterally, following the course of the ureter and the internal iliac artery along the pelvic wall. The hypogastric nerve joins the branches of the sacral parasympathetic nerves, or nervi erigentes, to form the pelvic plexus. During mobilization of the rectum, after the peritoneum on each side of the rectum is incised, the hypogastric nerves along with the ureters should be brushed off laterally to avoid injury. The key zones of sympathetic nerve damage are during ligation of the IMA and high in the pelvis during initial posterior rectal mobilization adjacent to the hypogastric nerves. The parasympathetic nerve supply is from the nervi erigentes, which originate from the second, third, and fourth sacral nerves on either side of the anterior sacral foramina. The fibers pass laterally, forward, and upward to join the sympathetic nerve fibers to form the pelvic plexus on the pelvic side walls (Fig. 1-7). The two types of nerve fibers are distributed to the urinary and genital organs and to the rectum. The branches of the pelvic plexus along with the blood vessels that supply the male genital organs are located posterolateral to the seminal vesicles and travel dorsolaterally in the lateral pelvic fascia between the prostate and rectum. To avoid nerve injury, the lateral ligament should be cut close to the rectal side wall. Key zones of risk to parasympathetic nerves are during lateral dissection in the pelvis near the pelvic plexus and during the anterolateral dissection deep in the pelvis while mobilizing the rectum from the seminal vesicles and the prostate. 

COLON AND RECTUM PHYSIOLOGY Colonic Physiology Major functions of the colon include storage and absorption of digestive material and propulsion of feces, in addition to digestion of carbohydrate and protein residues and secretion of mucus. Main nodes Intermediate nodes

Paracolic nodes

Absorption and Secretion In healthy persons, the colon absorbs water, sodium, and chloride, while secreting potassium and bicarbonate. It receives approximately 1500 mL of fluid material from the ileum over a 24-hour period and absorbs approximately 1350 mL of water, 200 mmol of sodium, 150 mmol of chloride, and 60 mmol of bicarbonate. The colon possesses enough reserve capacity to absorb an additional 3.5 to 4.5 L of ileal effluent, a feature that allows the large bowel to compensate for impaired absorption in the small intestine. The absorptive capacity is not homogeneous throughout the large intestine because of significant differences in the colonic segments. It has been shown that more salt and water are absorbed from the right colon than from the distal colon. 

Epiocolic nodes

Digestion FIGURE 1-6  Lymphatic drainage of the colon. (From Gordon PH,

Nivatvongs S. Principles and Practice of Surgery for the Colon, Rectum and Anus. 3rd ed. New York: Informa Healthcare USA; 2007.)

central nervous system: vagus nerve and sacral outflow. The vagus nerves descend to the preaortic plexus and then are distributed along the colic branches of the SMA that supply the cecum, the ascending colon, and most of the transverse colon. The splenic flexure and the descending and sigmoid colon are innervated from fibers of the sacral outflow. The sympathetic fibers to the rectum are derived from the first three lumbar segments of the spinal cord and form the superior hypogastric plexus, which divides into two hypogastric nerves (Fig. 1-7). The hypogastric nerves can be identified at the sacral promontory, approximately 1 cm lateral to the midline and 2 cm medial to

Digestion of food begins in the stomach and is almost accomplished when transit to the end of the small intestine is complete. However, a small amount of protein and carbohydrate is not digested during transit through the small bowel. The colon plays a role in salvaging calories from malabsorbed sugars and dietary fiber. The carbohydrate residues are broken down by anaerobic bacteria into short-chain fatty acids (SCFAs) and are absorbed in a concentration-dependent way. About 70% of colonic mucosal energy supply is derived from SCFAs originating in the lumen.  Propulsion and Storage The main functions of colonic and anorectal motor activity are to absorb water, store fecal waste, and eliminate them in a socially acceptable manner. The absorption of water is achieved by colonic segmentation and motor activity that propels colonic material forward

ANAL AND PERIANAL REGION

7

Sympathetic trunk Presacral nerve (superior hypogastric plexus)

Pelvic splanchnic nerves (nervi erigentes)

Vesicle plexus

Pelvic plexus

Dorsal nerve of penis

Pudendal nerve Perineal nerve Inferior rectal nerve

and backward over relatively short distances. Storage of fecal waste is facilitated by colonic and rectal compliance and accommodation, whereas elimination is regulated by the coordination of anorectal and pelvic floor mechanisms with behavioral and cognitive responses. Most of the water absorption occurs in the right colon, whereas the left colon is the storage organ for stool. The rectum is normally empty and is the organ of defecation. When a mass movement occurs, it strips down the left colon and propels the feces into the rectum. The increase in rectal volume and pressure sets in motion a series of reflexes and conscious sensations and decisions that lead to expulsion of the fecal bolus. 

ANAL CANAL ANATOMY The anal canal is the terminal portion of the intestinal tract. It begins at the anorectal junction, at the level of the levator ani muscles, and terminates at the anal verge as an anteriorposterior slit (Fig. 1-8). The length of the anal canal is approximately 4 cm; however, the lateral canal is significantly longer than the anterior and posterior canal. At the midpoint of the anal canal, approximately 2 cm from the anal verge, there is a saw-toothed epithelial junction referred to as the dentate line. As the rectum narrows into the anal canal, the tissue above the dentate line takes on a pleated appearance, creating longitudinal folds known as the columns of Morgagni (Fig. 1-8). At the lower end of the columns and between adjacent columns are small pockets referred to as the crypts of Morgagni. The anal glands open directly into the anal crypts at the dentate line. The average number of glands in a normal anal canal varies from 4 to 10. These crypts are

FIGURE 1-7  Nerve supply to the

rectum (lateral view). (From Gordon PH, Nivatvongs S. Principles and Practice of Surgery for the Colon, Rectum and Anus. 3rd ed. New York: Informa Healthcare USA; 2007.)

of surgical significance because foreign material may become lodged in them, obstructing the ducts of the anal glands and possibly resulting in sepsis.

Lining The lining of the anal canal consists of different types of epithelium at different levels. The mucosa of the upper anal canal is lined by columnar epithelium. Below the dentate line, the anal canal is lined by squamous epithelium. In between is a transitional zone where a gradual change in the mucosa, including columnar, transitional, or squamous epithelium, may be found over a distance of 6 to 12 mm. The rectal mucosa is pink, whereas the area just above the dentate line is deep purple because of the underlying internal hemorrhoidal plexus. Subepithelial tissue is loosely attached to the internal hemorrhoidal plexus, and at the anal margin, it contains the external hemorrhoidal plexus. The area approximately 1.5 cm below the dentate line is referred to as anoderm. This pale, smooth, thin, and shiny stretched tissue is not considered true skin because it is devoid of accessory skin structures (e.g., hair, sebaceous glands, and sweat glands). At the anal verge the lining becomes thicker and pigmented and acquires hair follicles, glands, and other histologic features of normal skin. A well-marked ring of apocrine glands is also present in this perianal area, which makes the area prone to hidradenitis suppurativa. Proximal to the dentate line, the epithelium is supplied by the autonomic nervous system, while distally the lining is richly innervated by the somatic nervous system. 

8

ANATOMY AND PHYSIOLOGY OF THE COLON, RECTUM, AND ANAL CANAL

Muscles of the Anorectal Region The musculature of the anorectal region may be regarded as two tubes, one surrounding the other (Fig. 1-8). The inner tube, being visceral, is smooth muscle and is innervated by the autonomic nervous system, whereas the outer funnel-shaped tube is skeletal muscle and has somatic innervation. This short segment of the intestinal tract is of paramount importance because it is essential to the mechanism of fecal continence and also because it is prone to many diseases. The internal sphincter is the downward continuation of the circular, smooth muscle of the rectum, which becomes thickened and rounded at its lower end. Its lowest portion is just above the lowest part of the external sphincter and is 1 to 1.5 cm below the dentate line (Fig. 1-8). The lowest portion of the external sphincter occupies a position below and slightly lateral to the internal sphincter (Fig. 1-8). A palpable groove at this level is referred to as the intersphincteric groove. The next portion (superficial) is attached to the coccyx by a posterior extension of muscle fibers that combine with connective tissue, forming the anococcygeal ligament. Above this level, the deep portion of the external sphincter is devoid of posterior attachments and proximally becomes continuous with the puborectalis muscle. Anteriorly, the high fibers of the external sphincter are inserted into the perineal body, where some merge and are continuous with the transverse perineal muscles. The anterior external anal sphincter is shorter in women than in men. Investigators have found that the median length and thickness of the female anterior external anal sphincter are 11 and 13 mm, respectively. These small dimensions explain why a relatively small obstetrical tear may have a devastating effect on fecal continence. Perineal Body The perineal body is the anatomic location in the central portion of the perineum where the external sphincter, bulbocavernosus, and superficial and deep transverse perineal muscles meet. This tendinous intersection gives support to the perineum and separates the anus from the vagina.  Pelvic Floor Muscles The pelvic floor muscles include the levator ani muscle and puborectalis. The levator ani muscle is broad, thin, and forms the greater part of the floor of the pelvic cavity. It consists of the iliococcygeus and the pubococcygeus muscles and is innervated by the fourth sacral nerve Longitudinal muscle Circular muscle

Innervation of the Anus Motor Innervation The internal anal sphincter is supplied by both sympathetic and parasympathetic nerves that presumably reach the muscle by the same route as that followed to the lower rectum. The parasympathetic nerves are inhibitory to the internal sphincter. The action of sympathetic nerves to the internal sphincter is conflicting. Some investigators found it to be inhibitory, whereas others reported a stimulating effect. The external sphincter is supplied by the inferior rectal branch of the internal pudendal nerve and the perineal branch of the fourth sacral nerve. The pudendal nerve passes through the greater sciatic foramen and crosses the sacrospinous ligament accompanied by the internal pudendal artery and vein. The pudendal nerve lies on the lateral wall of the ischioanal fossa, where it gives off the inferior rectal nerve, which crosses the ischioanal fossa with the inferior rectal vessels to reach the external sphincter posterolaterally. The puborectalis muscle is not supplied by the pudendal nerves but by a direct branch of the third and fourth sacral nerves, which lie above the pelvic floor. The levator ani muscles are supplied on their pelvic surface by twigs from the fourth sacral nerves and on their perineal aspect by the inferior rectal or perineal branches of the pudendal nerves.  Dorsal vein of penis

Valve of Houston

Levator ani muscle Puborectalis muscle Conjoined logitudinal muscle Deep External sphincter muscle

(Fig. 1-9). The puborectalis muscle, considered part of the external sphincter, is the third muscle of the pelvic floor. The puborectalis muscle arises from the back of the symphysis pubis and the superior fascia of the urogenital diaphragm, runs backward alongside the anorectal junction, and joins its fellow muscle of the other side immediately behind the rectum, where they form a U-shaped loop that slings the anorectal junction to the pubis. The iliococcygeus muscle arises from the ischial spine and posterior part of the obturator fascia, passes downward, backward, and medially, and becomes inserted on the last two segments of the sacrum, the coccyx, and the anococcygeal raphe, without any connections to the anal canal. The pubococcygeus muscle arises from the anterior half of the obturator fascia and the back of the pubis. The puborectalis and the levator ani muscles have a reciprocal action. During defecation, the puborectalis relaxes and the levator ani muscles contract, which causes the hiatus to widen, and the lower rectum and anal canal are elevated and straightened. When a person is in an upright position, the levator ani muscles support the viscera. The “anorectal ring” is a term coined by Milligan and Morgan to denote the functionally important ring of muscle that surrounds the junction of the rectum and the anal canal. It is composed of the upper borders of the internal sphincter and the puborectalis muscle. 

Urethra Levator hiatus

Pubococcygeus

Column of Morgagni

Obturator internus

Internal sphincter muscle Anal gland

Superficial

Anorectal junction

Iliococcygeus

Subcutaneous

Coccygeus Corrugator cuits ani muscle

External hemorrhoidal plexus

Anococcygeal raphe

Piriformis

FIGURE 1-8  Anal canal. (From Gordon PH, Nivatvongs S. Principles and

FIGURE 1-9  Levator muscles. (From Gordon PH, Nivatvongs S. Principles

Practice of Surgery for the Colon, Rectum and Anus. 3rd ed. New York: Informa Healthcare USA; 2007.)

and Practice of Surgery for the Colon, Rectum and Anus. 3rd ed. New York: Informa Healthcare USA; 2007.)

ANAL AND PERIANAL REGION

Sensory Innervation The sensory nerve supply of the anal canal is the inferior rectal nerve, a branch of the pudendal nerve. The epithelium of the anal canal is profusely innervated with sensory nerve endings, especially in the vicinity of the dentate line. Pain sensation in the anal canal can be felt from the anal verge to 1.5 cm proximal to the dentate line. The anal canal can sense touch, cold, and pressure. 

Arterial Supply of the Anus The inferior rectal arteries, which are branches of the inferior iliac arteries, arise from the pudendal artery (in the Alcock canal). They traverse the ischioanal fossa and supply the anal canal and the external sphincter muscles. No extramural anastomosis is found between the inferior rectal arteries and other rectal arteries. However, arteriography demonstrates an abundance of anastomoses among the inferior and superior rectal arteries at deeper planes in the walls of the anal canal and rectum. 

Lymphatic Drainage of the Anus Lymph from the lower part of the rectum drains cephalad via the superior rectal lymphatics to the inferior mesenteric nodes and laterally via the middle rectal lymphatics to the internal iliac nodes. It generally has been known that retrograde lymphatic spread in carcinoma of the rectum and anal canal occurs only after extensive involvement of the perirectal structures, serosal surfaces, veins, perineural lymphatics, and proximal lymphatic channels. Lymphatics from the anal canal above the dentate line drain cephalad via the superior rectal lymphatics to the inferior mesenteric nodes and laterally along both the middle rectal vessels and the inferior rectal vessels through the ischioanal fossa to the internal iliac nodes. Lymph from the anal canal below the dentate line usually drains to the inguinal nodes. It also can drain to the superior rectal lymph nodes or along the inferior rectal lymphatics through the ischioanal fossa if obstruction occurs in the primary drainage. 

Venous Drainage of the Anus Blood return from the anal canal is via two systems: portal and systemic. The superior rectal vein drains the rectum and upper part of the anal canal, where the internal hemorrhoidal plexus is situated, into the portal system via the inferior mesenteric vein. The middle rectal veins drain the lower part of the rectum and the upper part of the anal canal into the systemic circulation via the internal iliac veins. The inferior rectal veins drain the lower part of the anal canal, where the external hemorrhoidal plexus is located, via the internal pudendal veins, which empty into the internal iliac veins and hence into the systemic circulation. Controversy exists regarding the presence or absence of collaterals formed by these three venous systems. Current thinking supports the concepts of free communication among the main veins draining the anal canal and that there is no association between the occurrence of hemorrhoids and portal hypertension. 

ANAL CANAL PHYSIOLOGY Mechanisms of Continence Normal continence depends on a highly integrated series of complicated events.   

1.  Stool consistency plays an important role in anal continence. Some patients may be continent for solid stool but not for

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liquid stool or gas, or they may be continent for stool but not for gas. This fact is important in the management of patients with anal incontinence because the maneuver of changing stool consistency from liquid into solid may be sufficient to allow the patient to regain fecal control. 2.  The holding function of rectum arises from its adaptive compliance with its distensibility and capacity to accommodate, both of which are important factors for effective holding of stool. From a physiologic standpoint, differences in pressure patterns between the distal and proximal levels of the anal canal result in the development of a force vector in the direction of the rectum. Furthermore, the angulation between the rectum and anal canal, which is due to the continuous tonic activity of the puborectalis muscle, as well as the high-pressure zone in the anal canal, contribute to continence. 3. Although the rectum is devoid of sensory pathways, stretch receptors play an important role in defecation. The sensation of rectal distention initiates the sampling response (described in the section on defecation). 4.  Mechanical factors include the sphincters and the angle of the puborectalis muscle. Within the anal canal, the sphincters are responsible for producing a “high-pressure zone” between 2.5 and 3.5 cm in length. This zone is mainly a result of the continuous tonic activity of both sphincters, with the major contribution from the internal anal sphincter. Furthermore, the angulation of the anorectal system, which is due to the continuous tonic activity of the puborectalis muscle, is important. In the normal resting state, the lumen of the anal canal is occluded by the puborectalis sling and by the resting tone of the internal and external sphincters. As measured by defecography, the angle between the axis of the anal canal and the rectum in the resting state is about 90 degrees. During defecation, the puborectalis muscle relaxes, resulting in straightening of the anorectal angle, and the pelvic floor descends slightly (Fig. 1-10). 

Defecation The stimulus for initiating defecation is distention of the rectum. Rectal distention induces relaxation of the internal sphincter, which in turn triggers contraction of the external sphincter. This relaxation of the internal sphincter, allowing sampling of rectal contents, is called the sampling response (or recto-anal inhibitory reflex). If defecation is to be deferred, voluntary contraction of the external anal sphincter occurs and the rectum relaxes to accommodate the feces after an initial increase in pressure. If the defecation is appropriate, a squatting position is assumed, which causes the angulation between the rectum and the anal canal to straighten (Fig. 1-10). A Valsalva maneuver is the second semivoluntary stage. This maneuver overcomes the resistance to the external sphincter by voluntarily increasing the intrathoracic and intra-abdominal pressure. The pelvic floor descends, and the resulting pressure on the fecal mass in the rectum increases intrarectal pressure. Inhibition of the external sphincter permits passage of the fecal bolus, which is ideally driven by contraction of the rectal muscles. The complete longitudinal muscle coat of the rectum can generate powerful contractions, which are most effective when the first urge triggers defecation. Once evacuation has been completed, the pelvic floor and the anal canal muscles regain their resting activity, and the anal canal is closed. 

Physiologic Testing Anal Manometry Anorectal manometry is a means of quantifying the function of the internal and external sphincters by inserting a recording probe within the rectum and taking measurements upon withdrawal. The

10

ANATOMY AND PHYSIOLOGY OF THE COLON, RECTUM, AND ANAL CANAL Contraction

Defecation

Balloon Expulsion Test Rectal balloon expulsion may be used as an alternative to defecography because the inability to expel an intrarectal balloon can point to impaired rectal evacuation. However, many patients with electromyographic evidence of anismus are able to pass an inflated balloon, and patients with insufficient colonic contractility may have a confounded study.  Saline Continence Test

A

The saline continence test provides a more realistic assessment of fecal continence. The ability of a person to retain 1500 mL of saline solution infused into the rectum at a rapid rate (60 mL/min) can provide insights into the strength of the sphincter muscles.  Rectal Compliance

B FIGURE 1-10  Angulation between the rectum and the anal canal. A,

Lateral view. B, Anteroposterior view. (From Gordon PH, Nivatvongs S. Principles and Practice of Surgery for the Colon, Rectum and Anus. 3rd ed. New York: Informa Healthcare USA; 2007.)

high-pressure zone varies between 2.5 and 5 cm and is shorter in women than in men. The highest pressure is defined as the maximal resting anal pressure and typically ranges from 65 to 85 mm Hg above the rectal intraluminal pressure and is located 1 to 1.5 cm from the distal end of the sphincter. Resting pressure in the anal canal exhibits regular fluctuations that vary from day to night, by the presence or absence of fecal material in the rectum, and by posture. Closing pressure is the difference between maximum resting anal pressure and the resting pressure; it is an important determinant of anal continence. The patient is asked to squeeze at full strength to measure the maximal squeeze anal pressure. In a healthy person, intra-anal pressure is usually doubled during voluntary contraction.  Defecography by Fluoroscopy or Magnetic Resonance Imaging Defecography is a dynamic investigation of the defecation mechanism that can detect rectal intussusception, enterocele, sigmoidocele, rectocele, nonrelaxing puborectalis syndrome, and perineal descent. Conventional defecography is performed with introduction of a radiopaque semisolid contrast medium into the rectum while the subject is seated on a radiolucent commode to void the contrast material. With this technique, the anorectal angle, which depends on the tone of the puborectalis muscle, can be measured at rest and during straining. The position of the pelvic floor can be measured by calculating the distance between the anorectal junction and the pubococcygeal line. In this way, perineal descent at rest and during straining can be measured. The pubococcygeal line is drawn from the tip of the coccyx to the posteroinferior margin of the pubic ramus; normally, the pelvic floor lies at a plane approximately 1 cm below that of the pubococcygeal line. Magnetic resonance defecography is a nonradioactive imaging technique performed with the patient in the sitting position, thus permitting analysis of the rectal wall, in addition to the anorectal angle, the opening of the anal canal, the function of the puborectalis muscle, and the descent of the pelvic floor during defecation. 

Rectal compliance is the volumetric response of the rectum to stretch when subjected to an increase of intraluminal pressure. An infinitely compliant polyethylene balloon is used to measure rectal compliance. A volume–pressure curve is plotted, and the slope of this curve (dV/ dP) represents compliance. The elasticity and compliance of the rectum are closely interwoven with rectal sensation. A deficit of rectal sensory function together with increased rectal compliance has been observed in patients with constipation. Some investigators report maximum rectal capacity (MRC), the volume that can be infused into the rectum before the patient demands that the infusion stop. An MRC greater than 300 mL can be defined as megarectum. An MRC less than 100 is indicative of a very sensitive rectum and is typical of persons with severe irritable bowel syndrome or inflammatory bowel disease. Patients with inflammatory bowel disease, especially in the active phase, also may have a decreased distensibility of the rectum. Knowledge of this decreased rectal capacity may be of practical value in predicting which patients with Crohn disease would benefit from an ileorectal anastomosis.  Electromyography Electromyography records action potentials derived from motor units within contracting muscle. The external sphincter and the puborectalis are unique skeletal muscles because they show continuous tonic contractions at rest and cessation of contraction during defecation. Conventional concentric electromyography is performed by inserting a needle electrode directly into the external sphincter or the puborectalis muscle without a local anesthetic. With the muscles at rest, a basal low-frequency activity will be recorded between 2 to 50 mV. During squeezing and coughing, a burst of electrical activity, which is the consequence of increased frequency of motor unit firing and recruitment of new motor units, is recorded.  Nerve Stimulation Techniques Spinal nerve latency measures central motor innervation of the pelvic floor by placement of transcutaneous spinal stimulation at the level of L1 and L4 and use of a surface anal plug electrode or by an intramuscular needle electrode to detect sphincter function. The difference in the latencies from L1 and L4 has been called the spinal latency ratio, which is increased in patients with anal incontinence caused by a proximal lesion such as damage to the S3 nerve roots. Pudendal nerve terminal motor latency is used to assess the external anal sphincter. The electrodes are introduced into the rectum, and the tip is brought into contact with the ischial spine on each side. A supramaximal stimulus is delivered, and the latency between stimulus and external sphincter contraction is measured. The terminal motor latency of a normal pudendal nerve is of the order of 1.9 ± 0.2 msec. It is increased in patients with anal incontinence.

ANAL AND PERIANAL REGION

Suggested Reading Bollard RC, Gardiner A, Lindows S, et al. Normal female anal sphincter. Difficulties in interpretation explained. Dis Colon Rectum. 2002;45:171–175. Canessa CE, Miegge LM, Bado J, et al. Anatomic study of lateral pelvic lymph nodes: implications in the treatment of rectal cancer. Dis Colon Rectum. 2004;47:297–303. Carty NJ, Moran B, Johnson CD. Anorectal physiology measurements are of no value in clinical practice. True or false? Ann R Coll Surg Engl. 1994;76: 276–280. Church JM, Raudkivi PJ, Hill GL. The surgical anatomy of the rectum—a review with particular relevance to the hazards of rectal mobilization. Int J Colorectal Dis. 1987;2:158–166. Goligher JC. The blood supply to the sigmoid colon and rectum. Br J Surg. 1949;37:157–162. Gordon PH, Nivatvongs S. Principles and Practice of Surgery for the Colon, Rectum and Anus. 3rd ed. New York: Informa Healthcare USA; 2007.

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Havenga K, De Ruiter MC, Enker WE, Welvaart K. Anatomical basis of autonomic nerve-preserving total mesorectal excision for rectal cancer. Br J Surg. 1996;83:384–388. Heald RJ, Meran BJ. Embryology and anatomy of the rectum. Semin Surg Oncol. 1998;15:66–71. Lubowski DZ, Meagher AP, Smart RC, Butler SP. Scintigraphic assessment of colonic function during defecation. Int J Colorectal Dis. 1995;10:91–93. Matzel KE, Schmidt RA, Tangho EA. Neuroanatomy of the striated muscular and anal mechanism. Implications for the use of neurostimulation. Dis Colon Rectum. 1990;33:666–673. Miscusi G, Masoni L, Dell’Anna A, Montori A. Normal lymphatic drainage of the rectum and the anal canal revealed by lymphoscintigraphy. Coloproctology. 1987;9:171–174. Yamaguchi S, Kuroyanagi H, Milson JW, Sim R, Shimada H. Venous anatomy of the right colon. Precise structure of the major veins and gastrocolic trunk in 58 cadavers. Dis Colon Rectum. 2002;45:1337–1340.

2

Hemorrhoids Anthony J. Senagore

H

emorrhoids are vascular cushions that lie close to the anus and are subject to the stresses and strains of defecation. They are normal structures that become symptomatic when thrombosis or prolapse develops as a result of either a congenital weakness in the area or because of excessive or repeated straining. The challenges of managing patients with symptomatic hemorrhoids include making a correct diagnosis, persuading patients to improve their defecatory habits, and using the appropriate procedure to manage the problem at hand. In this chapter, external and internal hemorrhoids will be considered separately.

EXTERNAL HEMORRHOIDS The external hemorrhoidal plexus is a network of veins that run around the anus at the anal verge. The veins become symptomatic when they thrombose. Resolution of external hemorrhoid thrombosis may predispose to anal tags that are usually asymptomatic but are typically excised along with prolapsing internal hemorrhoids. Acute thrombosis of the external hemorrhoidal plexus is a painful condition that tends to follow straining, either during lifting, childbirth, or defecation. Affected patients are in considerable pain and have an edematous lump at the anal verge caused by the clot. Often the blue color of the clot confirms the diagnosis. Surgical excision of acutely thrombosed external hemorrhoids is warranted when the thrombosis is large, painful, and identified within 72 hours of onset. Sometimes the clot ulcerates through the skin and patients experience anal bleeding independent of bowel habits, with partial easing of the pain. This presentation is another indication for surgery. Small external hemorrhoidal thromboses are easily managed in the office setting with a local anesthetic and complete excision of the clot and vein, with or without skin closure. More extensive thromboses should be excised with use of a general anesthetic to allow careful planning of the excision and preservation of the anoderm. 

ANATOMY AND ETIOLOGY OF INTERNAL HEMORRHOIDS Internal hemorrhoids are vascular cushions lying above the dentate line under the mucosa of the low rectum. The classic orientation of the hemorrhoidal cushions is right anterior, right posterior, and left lateral, although intervening secondary hemorrhoidal complexes may blur this classic anatomy. The arterial blood supply, which contributes to the frequent symptom of bright red rectal bleeding, is derived from the superior rectal artery, a branch of the inferior mesenteric artery, the middle rectal arteries arising from the internal iliac arteries, and the inferior rectal arteries arising from the pudendal arteries. Above the dentate line the venous drainage enters the portal venous system, whereas below the dentate line it passes to the systemic venous system. This vascular anatomy creates the cushions that contribute to 12

anal continence and can be damaged by excessive straining, leading to the prolapse and bleeding typical of symptomatic hemorrhoids. An understanding of the stages of hemorrhoidal pathophysiology is the basis for developing a strategy for management of symptomatic hemorrhoids. The staging system is shown in Box 2-1. At the earliest stage of disease, transudation of blood through thin-walled, damaged veins and/or arterioles presents primarily as painless bleeding and can be managed with astringents or local ablation of the vessels. Later, as the damage progresses to significant disruption of the mucosal suspensory ligament, a technique capable of relocating the prolapsing tissue to its normal location and fixing the tissue at that location will be required. 

CLINICAL EVALUATION The typical constellation of hemorrhoidal symptoms includes bleeding, protrusion, and pain. However, only about one third of all patients with anorectal symptoms will actually have hemorrhoids as the cause of their symptoms. Hemorrhoidal bleeding, which typically occurs after bowel movements, is painless and visible as bright red blood either on the toilet paper or in the commode. The bleeding can become more severe as the hemorrhoids enlarge and are either partially or completely trapped in a prolapsed position. Patients with tight internal sphincters are prone to magnified hemorrhoidal symptoms because of the increased pressure in the anus. The history then addresses bowel habits, the frequency of straining upon defecation, recent changes in medications, diet, or lifestyle, and the presence of a family history of colorectal cancer. The patient should be asked about prior procedures performed to treat hemorrhoids, although the answer must be taken with a grain of salt unless it is supported by medical records. Examination of the patient with hematochezia, although tailored by the age of the patient, should include sufficient investigations to rule out a proximal source of bleeding such as inflammatory bowel disease or neoplasia. Hemorrhoids should not be accepted as the cause of iron deficiency anemia because this cause is rare. First, a careful digital examination of the anal canal and distal rectum should be performed, including palpation of the prostate in men. Inspection of the anus may reveal skin tags, bulging external ­hemorrhoidal cushions (clues to the presence of internal hemorrhoidal prolapse), or fourth-degree internal hemorrhoids. Other conditions may be present that mimic or co-exist with hemorrhoids, such as anal excoriation, anal neoplasms, condylomata, or fissure. If the patient does not have a fissure, an anoscopy is performed to determine the size and degree of prolapse of the hemorrhoids. Poking the cushions with a cotton-tipped swab gives an impression of the degree of redundancy and the suitability of the hemorrhoid for elastic band ligation. White plaques on the hemorrhoids (pseudoepitheliomatous hyperplasia) are an indication of chronic prolapse. Hemorrhoids should be classified as previously described to define

ANAL AND PERIANAL REGION

BOX 2-1:  The Standard Classification for Internal Hemorrhoidal Diseases Grade I = bleeding Grade II = protrusion with spontaneous reduction Grade III = protrusion requiring manual reduction Grade IV = irreducible protrusion of hemorrhoidal tissue the degree of mucosal irritation, prolapse, columns involved, and associated anal skin tags. If the patient has presented with bleeding, has an increased risk for colorectal cancer, or is at average risk but is overdue for screening, a colonoscopy is requested. No physical treatment should be performed without clearing the colon, because drop metastases from a cancer proximal to an anal canal wound can occur. 

NONEXCISIONAL OPTIONS Medical Management Many patients with symptomatic hemorrhoids strain during defecation for several reasons. If the straining is due to small-volume stools, they need more roughage in their diet. If the straining is due to hard stools, they need more roughage and perhaps a properistaltic agent such as prune juice. If the straining occurs because defecation is deferred, they need to respond to the urge to defecate when it is first perceived and not shut it down. An analysis of defecation and dietary habits and correction of problematic habits with the aim of avoiding straining may eliminate symptoms and allow patients to avoid a procedure. Correction of problematic habits is important in all patients, however, because straining after banding and after a ­hemorrhoidectomy may lead to recurrent symptoms. In at least 50% of patients, symptomatic internal hemorrhoids can be successfully managed by improving bowel habits. 

Sclerotherapy Sclerotherapy of symptomatic internal hemorrhoidal disease has been performed since the nineteenth century and remains a highly effective, low-risk means of managing stage I hemorrhoids. Treatment produces local tissue destruction, which simultaneously ablates small vessels in the submucosa and creates tissue fixation and atrophy of the hemorrhoidal complex. The sclerosing agents most commonly used are sodium morrhuate and sodium tetradecyl sulfate. Briefly, the procedure involves anoscopic identification of the hemorrhoidal complex followed by instillation of the sclerosant into the submucosa above the level of the dentate line using a 25-gauge spinal needle. Typically, 1 to 2 mL of sclerosant per location is adequate, and multiple locations can be treated during a single session. 

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the cost to acquire the machines and cleaning requirements between procedures should be considered. 

Hemorrhoidal Ligation with Rubber Bands In 1963, Barron became the first person to describe treatment of hemorrhoids with rubber bands. This technique has withstood the test of time, with multiple large-scale studies documenting both safety and efficacy, and it is a good option for grade II and III internal hemorrhoids. When the bands are applied correctly, pain is minimal both during and after the procedure. Banding is best performed with the patient in a prone jackknife position. Anoscopy is performed to assess the degree of h ­ emorrhoidal prolapse and to establish the sites of the worst and the least prolapse. A set of two bands is applied above the dentate line at the top of the hemorrhoidal column by pulling the prolapsing tissue into the applicator. An assistant is needed to hold the anoscope and may help by slightly easing it out when the hemorrhoid is pulled or sucked into the applier. The worst affected hemorrhoid is treated first, followed by the next worst affected hemorrhoid. It is wise to place a maximum of three sets of bands at once because discomfort due to the tightness can become severe. Patients are warned to expect to feel an urge to defecate after banding that may be quite uncomfortable and will last the remainder of the day. Some patients may experience vasovagal symptoms after banding and thus patients should be asked to lie down for 10 minutes after the procedure. Discomfort immediately after band placement may be reduced with the injection of a local anesthetic agent; however, this injection does not appear to provide a long-lasting benefit. Banding is associated with hemorrhage from the ulcers that occur at the band sites. This outcome is uncommon but can occur within the first 2 weeks of the procedure; it seems to be more likely if a large amount of ­tissue is pulled into the band. The presence of acute pain after banding means that the bands have been applied too low and sensory epithelium has been included in the band, in which case the bands should be removed. Finally, a rare but potentially fatal complication of perineal sepsis can occur, which is heralded by the symptoms of increasing rectal pain, fever, and the inability to void urine. It is essential to evaluate patients with these symptoms early and to treat them aggressively with broad-spectrum antibiotics and aggressive surgical drainage. The full effect of the bands is not noted for a month, by which time the ulcers at the sites of the band application have healed and scarring has occurred. Bayer and colleagues reported a series of 2934 patients who underwent elastic band treatment of internal hemorrhoids, with 79% experiencing complete relief of symptoms after a single session with treatment of only one or two locations. Multiple sessions were needed as follows: 2 sessions, 32%; 3 sessions, 17%; 4 sessions, 25%; and 5 sessions, 20%. Although the need for multiple sessions is a negative aspect of this technique, only 2.1% of patients required an excisional hemorrhoidectomy. Banding offers sustained, inexpensive relief of symptoms, with 69% of patients maintaining long-term relief and only 7.5% ultimately requiring an excisional hemorrhoidectomy. 

Energy-Based Destruction Bipolar diathermy converts electrical current into heat energy to coagulate the hemorrhoidal tissue, including the mucosa and submucosa. The machine generates a 2-second pulse of energy to ­accomplish the treatment. The technique produces the same basic effect as sclerotherapy, and therefore the indications for treatment are very similar. Other energy-based options include infrared coagulation and therapy with direct current (Ultroid; Ultroid Technologies, Inc., Tampa, Fla.). Infrared coagulation employs a tungsten halogen lamp that generates heat energy, generally for a 1.5-second period at a depth of penetration of 3 mm. Direct-current therapy uses electrical current applied for up to 10 minutes per complex treated. There is probably no advantage of one technique over the other, although

EXCISIONAL HEMORRHOIDECTOMY An excisional hemorrhoidectomy is indicated when the degree of prolapse of the internal hemorrhoids is too great to allow effective banding—that is, the bands themselves would ride up and down on the prolapsing hemorrhoids and would be too far away from the submucosa to fix the mucosa. Surgery effectively corrects the associated prolapse, bleeding, discomfort, anal seepage, and difficulties with anal hygiene. Excisional hemorrhoidectomy is the only option for gangrenous internal hemorrhoids. Several techniques have been described for excisional hemorrhoidectomy, including the Milligan-Morgan technique, the

14

Hemorrhoids

Ferguson closed hemorrhoidectomy, the Whitehead hemorrhoidectomy, and the more recently described stapled hemorrhoidectomy (or stapled hemorrhoidopexy). The procedures are usually performed in the operating theater after minimal preoperative preparation of the bowel, and excision can be performed with or without energy devices. The use of lasers for excisional hemorrhoidectomy offers no advantage and in fact causes delayed healing, increased pain, and increased cost. The anesthesiologist and patient usually decide which type of anesthetic will be used; however, a local anesthetic supplemented by the administration of intravenous narcotics and propofol is highly effective and short acting. The use of spinal anesthesia, although effective, may increase the risk of postoperative urinary retention because of a higher intraoperative administration of intravenous fluids. The Milligan-Morgan hemorrhoidectomy, which is widely practiced and described in Europe, includes resection of the entire enlarged internal hemorrhoid complex, ligation of the arterial pedicle, and preservation of intervening anoderm. The incision in the anal canal and perianal skin is left open. The closed Ferguson hemorrhoidectomy offers the benefit of primary wound closure with similar safety and efficacy. The following technical tips are related to the procedure: the entire internal/external hemorrhoidal complex should be removed with an hourglass-shaped excision (centered at the mid portion of the anoderm) with limited anoderm removal; the internal and external anal sphincters should be preserved; and primary closure of the entire wound should be performed. Occasionally it is necessary to undermine flaps of anoderm and perianal skin to allow removal of intermediate hemorrhoidal tissue while preserving the bridges of anoderm between pedicles. The Whitehead hemorrhoidectomy was devised to eradicate the enlarged internal hemorrhoidal tissue circumferentially with advancement of the prolapsed dentate line proximally to reconstruct the anal canal lining. This technique has been largely abandoned because of the high rates of mucosal ectropion and anal stricture resulting from the complexity of reconstruction.

(0.6%), urinary retention (2%), fissure (1%), and abscess/fistula (0.8%). Several subsequent prospective, randomized comparisons of diathermy with the Harmonic scalpel failed to confirm any differences between the two tools. 

Instrumentation for Excisional Hemmorrhoidectomy

A new technique that is gaining popularity is Doppler-guided hemorrhoidal artery ligation, or transanal hemorrhoidal ­dearterialization (THD). The Doppler-guided technique provides simultaneous reduction of the arterial blood flow, reduction of the prolapse (or mucopexy), and tissue destruction by oversewing the reduced hemorrhoidal tissue. A specifically designed proctoscope is used coupled with a Doppler transducer. At the distal end a small window allows suturing of the rectal mucosa 2 to 3 cm above the dentate line. The reduction of blood flow is thought to lead to shrinkage of the hemorrhoidal complex. In addition, a hemorrhoidopexy can be performed that lifts up the prolapsing tissue into its normal anatomic position. Giordano and colleagues published an extensive review of the current evidence on THD, looking specifically at safety and effectiveness of the technique. The technique appears safe and efficacious in trained hands, but it relies primarily upon suture plication of the hemorrhoidal complexes associated with reduction of the prolapse rather than excision of tissue. Therefore, it may be less painful than other techniques but requires additional operative cost for the disposable equipment. 

The increasingly critical emphasis on cost-effectiveness requires a thoughtful assessment of the need for advanced instrumentation in hemorrhoidectomy. The efficacy of conventional surgery is unquestioned, whereas the benefits of considerably more expensive energy devices are mostly theoretical. Standard monopolar electrocautery is relatively inexpensive and can be useful to control nuisance bleeding from the wound edges and small vessels. Suture ligation of the main pedicle is still required, and thermal spread is associated with increased pain. Laser technology has been evaluated both as a means of cutting hemorrhoidal tissue and as a technique for ablation, but it is simply another way of causing tissue destruction. Although some authors have suggested that patients experience less pain with the use of Nd:YAG laser for excision and coagulation, a prospective randomized trial demonstrated greater pain and slower healing when compared with sharp dissection. A bipolar cautery device capable of simultaneous tissue division and blood vessel coagulation has been compared with monopolar diathermy hemorrhoidectomy, with most of the data suggesting reductions in operative time and early postoperative pain. A metaanalysis compared hemorrhoidectomy with LigaSure (Medtronic, Minneapolis, Minn.) to conventional excisional techniques and found similar cure rates but shorter operative time, decreased pain, shorter time to wound healing, and less time off from work. A competing technology is the Harmonic scalpel (Ethicon Endo-Surgery, Cincinnati, Ohio), which relies on a rapidly reciprocating blade to generate heat for coagulation and tissue transection. Experience with the Harmonic scalpel suggests low rates of postoperative hemorrhage

PROCEDURE FOR PROLAPSING HEMORRHOIDS (STAPLED HEMMORHOIDOPEXY) Another option for advanced hemorrhoidal disease is the procedure for prolapsing hemorrhoids (PPH), which utilizes a circular stapler to reduce and fix the hemorrhoidal complex. The technique entails placement of a transanal purse-string suture 0.5 cm above the top of the hemorrhoidal complex to allow partial resection of the rectal mucosa in the less sensitive distal rectum above the hemorrhoidal tissue, with repositioning of both the anoderm and hemorrhoidal columns to the appropriate locations. Prospective randomized trials have been performed to compare this approach with excisional hemorrhoidectomy, although interest in the United States appears to be waning. Most of the data support the concept that PPH is associated with a lesser degree of early postoperative pain and a general reduction in the duration of this pain after surgery. Giordano and colleagues addressed the question of long-term outcome for PPH, ­demonstrating a significantly higher rate of prolapse recurrence in the PPH group and a higher rate of further treatment to correct recurrent prolapses compared with conventional hemorrhoidectomy. An additional concern associated with PPH is the risk of either closure of the rectal lumen as a result of failure to place the anvil proximal to the purse-string suture or sepsis as a result of rectal wall perforation. These complications can be life threatening and are difficult to correct and have reduced interest in the procedure in some circles. 

DOPPLER-GUIDED HEMORRHOIDAL DEARTERIALIZATION

POSTOPERATIVE MANAGEMENT AFTER HEMORRHOID SURGERY Postoperative management is primarily focused on effective analgesia and avoidance of urinary retention and constipation. Options include a combination of oral and parenteral narcotics, nonsteroidal agents, and local anesthetic blocks. Ketorolac has ­demonstrated considerable efficacy in managing posthemorrhoidectomy pain. The use of alternative administration routes for narcotics either by patch or subcutaneous pump has been successful in controlling

ANAL AND PERIANAL REGION

pain; however, the management of these routes of administration can be risky in the outpatient setting because of the risk of narcotic-induced respiratory depression, and therefore it is not recommended. Urinary retention is a frequent postoperative problem after hemorrhoidectomy, ranging in incidence from 1% to 52%. A variety of strategies have been used to treat the problem; the optimal approach is prevention by limiting perioperative fluid administration to 250 mL and avoiding both spinal anesthesia and anal packing. Early postoperative bleeding (within M Nocturnal/diurnal Abrupt onset and resolution Minimal radiation

+

LEVATOR SYNDROME

Reassurance, heat, NSAID, muscle relaxants

Observe

Radiograph/dynamic MRI/CT –

No response

+

Treat accordingly PROCTALGIA FUGAX

COCCYGODYNIA

Ca++ channel blocker, Botox

Orthopedic evaluation

Levator massage

? Coccygectomy

EGS, biofeedback

Inhaled Salbutamol

LEVATOR SYNDROME

Steroids/Botox Response + Observe

– Psychiatric evaluation Chronic pain management

FIGURE 16-1  Algorithm for the

management of pelvic/anorectal pain. Ca++, Calcium; CT, computed tomography; DRE, digital rectal examination; EGS, electrogalvanic stimulation; F, female; M, male; MRI, magnetic resonance imaging; NSAID, nonsteroidal antiinflammatory drug.

76

Pelvic Pain

Selected Readings Atkin GK, Suliman A, Vaizey CJ. Patient characteristics and treatment outcome in functional anorectal pain. Dis Colon Rectum. 2011;54:870–875. Chiaroni G, Nardo A, Vantini I, et al. Biofeedback is superior to electrogalvanic stimulation and massage for treatment of levator ani syndrome. Gastroenterology. 2010;38:321–329. Govaert B, Melenhorst J, van Kleef M, et al. Sacral neuromodulation for the treatment of chronic functional anorectal pain: a single center experience. Pain Prac. 2010;10:49–53. Jeyarajah S, Chow A, Ziprin P, et al. Proctalgia fugax, an evidence-based management pathway. Int J Colorectal Dis. 2010;25:1037–1046. Kamm MA, Hoyle CH, Burleigh DE, et al. Hereditary internal anal sphincter myopathy causing proctalgia fugax and constipation. A newly identified condition. Gastroenterology. 1991;100:805–810.

Kang YS, Jeong SY, Cho HJ, et al. Transanally injected triamcinolone acetonide in levator syndrome. Dis Colon Rectum. 2000;43:1288–1291. Nathan ST, Fisher BE, Roberts CS. Coccydynia: a review of pathoanatomy, aetiology, treatment and outcome. J Bone Joint Surg. 2010;92:1622–1627. Oliver GC, Rubin RJ, Salvati EP, et al. Electrogalvanic stimulation in the treatment of levator syndrome. Dis Colon Rectum. 1985;28:662–663. Rao SSC, Paulson J, Mata M, et al. Clinical trial: effects of botulinum toxin on levator ani syndrome—a double-blind, placebo-controlled study. Aliment Pharmacol Ther. 2009;29:985–991. Wald A, Bharucha AE, Enck P, et al. Functional anorectal disorders. In: Drossman DA, Corazziari E, Delvaux M, et al., eds. Rome III: The Functional Gastrointestinal Disorders. McLean, VA: Degnon Associates; 2006:639– 685.

Anorectal Congenital Disorders

17

Andrea Bischoff and Alberto Peña

A

norectal congenital malformations include a wide spectrum of defects, each of which requires a specific treatment and has a different functional prognosis. The main and most feared sequela is fecal incontinence, which is a devastating problem, although anal stenosis also may complicate some repairs. Approximately 70% of all affected patients who are properly treated will have voluntary bowel movements by the age of 3 years, although some will still experience occasional soiling. About 40% of all patients will be totally continent, meaning that they will have voluntary bowel movements and will never soil their underwear. Our goal in treating patients born with the potential for bowel control is to repair their malformation by preserving the anatomic elements of fecal continence. For patients who are born without the potential for bowel control, our goal is the anatomic repair of the defect followed by the implementation of a bowel management program aimed at keeping the patients constantly clean, giving them the best possible socially acceptable quality of life. This chapter is designed to help clinicians and surgeons find quick answers to practical therapeutic questions. Because of the existence of a spectrum of defects, any attempt to classify these malformations risks false generalizations. Table 17-1 lists the most conspicuous and common defects seen in everyday practice and correlates each with its prognosis for bowel control. This list may serve as a practical classification based on therapeutic and prognostic implications and includes benign defects (traditionally known as low defects), which are treated without a colostomy and with a small operation (anoplasty); 100% bowel control is achieved, and these defects are associated with a very low frequency of urinary malformations. On the other extreme of the spectrum are complex anorectal defects that are treated with a preliminary protective colostomy, followed by a major repair, with a high incidence of fecal incontinence. These patients also have a high incidence of associated urinary malformations. The term “high imperforate anus” is not used here because it includes malformations that require different treatments and have completely different prognoses (see Table 17-1). A significant portion of patients born with anorectal malformations also have other associated defects including genitourinary, sacrospinal, gastrointestinal, and cardiovascular defects. Early suspicion and expedited diagnosis and treatment of these defects will help avoid increased morbidity and mortality. Genitourinary defects represent the main source of death and morbidity, and therefore their presence should always be kept in mind. The frequency of associated defects varies depending on the specific type of anorectal defect (see Table 17-1). Establishing the final functional prognosis in patients with anorectal malformations is an important step in their management; it avoids false expectations from the parents and allows the early implementation of a bowel management program in patients with a poor functional prognosis. This approach also avoids the traditional

saga of fecally incontinent patients in search of a remedy that never comes, guided by a hope that has no factual basis. The prognosis can be established fairly accurately based on the type of defect. In addition, the accuracy of this prognosis can be enhanced by evaluating the integrity of the sacrum. Fig. 17-1 shows how to calculate the sacral ratio. Values of 0.7 and higher correlate with good prognosis for bowel control, whereas sacral ratio values of 0.4 and lower predict fecal incontinence.

DESCRIPTION OF DEFECTS Perineal Fistula A perineal fistula is the simplest of all defects and is seen with similar characteristics in male and female patients. The rectum opens into the perineum (always anterior to the location of the sphincter) and into an abnormal orifice, which is usually stenotic and therefore is called a fistula. Most of the rectum is surrounded by a good sphincter mechanism, except in its most distal part, where the rectum deviates anteriorly. The sacrum is almost always normal, the incidence of associated defects is low, and the functional prognosis is excellent (see Table 17-1). 

Rectal Atresia Rectal atresia occurs in only 1% of all male or female patients. Externally the anus looks normal, but an atresia or stenosis is located about 1 to 2 cm above the anal verge, at the junction of the anal canal with the rectum. The sphincter mechanism is normal, as is the sacrum. The incidence of associated defects is very low, and the prognosis is excellent (see Table 17-1). When a rectal stenosis is found, the surgeon should rule out the presence of a presacral mass. When a presacral mass is present, a sacral defect (hemisacrum or bifid sacrum) can be seen in the anteroposterior film of the sacrum, which changes the functional prognosis for bowel and urinary control. 

Vestibular Fistula A vestibular fistula is the most frequently seen defect in female patients. The rectum opens into the vestibule of the female genitalia immediately external to the hymen. Frequently, it is erroneously called a vaginal fistula. Most of the rectum is surrounded by a good sphincter mechanism, except for the lower part, which is frequently stenotic and is called a fistula. A common wall that exists between the rectum and the vagina must be separated during the surgical repair. Prior to the surgical repair it is important to confirm that the patient 77

78

Anorectal Congenital Disorders

TABLE 17-1:   Common Congenital Anorectal Defects, Their Treatment, and Their Prognosis Type of Defect

Colostomy

Main Repair

Prognosis for Voluntary Bowel Movements (%)

Frequency of UrinaryAssociated Defects (%)

Perineal fistula (male and female)

No

Anoplasty

100

1 cm bowel-skin distance

. Accessed March 21, 2016. Palmer G, Martling A, Cedermark B, Holm T. Preoperative tumour staging with multidisciplinary team assessment improves the outcome in locally advanced primary rectal cancer. Colorectal Dis. 2011;13(12):1361–1369. Pastor C, Subtil JC, Sola J, et al. Accuracy of endoscopic ultrasound to assess tumor response after neoadjuvant treatment in rectal cancer: can we trust the findings? Dis Colon Rectum. 2011;54:1141–1146. Skandarajah AR, Tjandra JJ. Preoperative loco-regional imaging in rectal cancer. ANZ J Surg. 2006;76:497–504. Smith NJ, Barbachano Y, Norman AR, et al. Prognostic significance of magnetic resonance imaging-detected extramural vascular invasion in rectal cancer. Br J Surg. 2008;95:229–236. Steele SR, Martin MJ, Place RJ. Flexible endorectal ultrasound for predicting pathologic stage of rectal cancers. Am J Surg. 2002;184:126–130. Wexner S, Berho M. The long overdue inception of accreditation of centres for rectal cancer surgery in the United States. Colorectal Dis. 2015;17(6):465–7.

Cancer of the Rectum: Neoadjuvant Therapy

29

Té Vuong,  Aurélie Garant, and Tamim Niazi

INTRODUCTION In the era of total mesorectal excision (TME) surgery, preoperative radiotherapy (RT) reduces local recurrence (LR) and can be administered either as long-course RT (LCRT) with a 5-fluorouracil (5-FU)– based regimen or as short-course RT (SCRT). For patients with a positive circumferential resection margin (CRM) at TME, tumor downstaging is highly desirable. In these circumstances, SCRT is not as effective as LCRT in preventing LR. To reduce radiation-related toxicity, field adjustments and new targeted radiation modalities should be explored. Radiation therapy was initially introduced as part of the treatment regimen of rectal cancer to improve local control in conjunction with surgery for patients with locally advanced disease. During the past two decades, neoadjuvant (NA) therapy has evolved significantly, not only through its application in serial randomized clinical trials (RCTs) but also as a result of advances in technology that include introduction of computerized imaging techniques. Currently, the treatment of patients with rectal cancer centers around a TME along with NA therapy. Locally advanced rectal cancers are those that are stage III and some that are stage II with extensive local tumor spread. Such patients are treated with similar strategies based on National Comprehensive Cancer Network recommendations (http://www.nc cn.org/clinical.asp). However, in the era of modern tumor imaging, rectal magnetic resonance imaging (MRI) in particular facilitates the precise estimation of involvement of the CRM, which is the most important factor predicting LR and systemic disease. The Mercury Trial investigators reported that for patients with a positive CRM on preoperative MRI, the risks of LR and systemic spread were significantly higher than for patients with a negative CRM. 

RADIOTHERAPY TRIALS Surgery remains the cornerstone of rectal cancer treatment for locally advanced (T3/T4) tumors. To further improve local control (LC) in rectal cancer, NA RT has been added to surgical treatment. The benefit of NA SCRT was first shown by the Swedish Rectal Cancer Group in the pre-TME era. After a median follow-up of 5 years, the LR risk was 11% in the group that underwent radiation and 27% in the group that did not undergo radiation, and the overall survival (OS) rates were 58% and 48%, respectively. In spite of these excellent results, the role of RT was questioned after the introduction of TME. In a Dutch TME study, the benefit of SCRT followed by immediate TME was demonstrated, with a 10-year LR rate of 11% for patients treated with TME alone versus 5% for patients treated with SCRT followed by TME. In the MRC-CR07 study, which has a comparable design, patients with resectable rectal cancer were randomized between NA SCRT followed immediately by surgery versus surgery alone. The patients in the group that underwent surgery alone received postoperative chemotherapy (CT)-LCRT when the CRM was involved.

The LR rate was 5% in the patients receiving NA SCRT and 12% in patients undergoing surgery alone (P 2.0 mg/dL). The total number of points correlates to predictive rates of major cardiac complications (Table 34-4). During this assessment, it is important to differentiate clinical risk factors from active disease. Active disease is defined as unstable coronary syndrome, including unstable or severe angina or recent (1 risk factor who will undergo intermediaterisk surgery 

Congestive heart failure

3

3.6

Statin

Cerebrovascular disease

≥4

9.1

Insulin-dependent diabetes 1

0.9

Indicated in: • Patients currently receiving statin therapy • Patients with ≥1 risk factor who will undergo intermediaterisk surgery 

Creatinine >2.0

0.9

Alpha-2 Agonist

1

BOX 34-1:   Indications for Preoperative Diagnostic Cardiac Tests

Electrocardiogram

Indicated in: • Patients with known CAD, PAD, or cerebrovascular disease who will undergo intermediate-risk surgery† • Patients with ≥1 clinical risk factor Not indicated in: • Asymptomatic patients undergoing low-risk surgery* 

Assess LV Function

Indicated in: • Patients with dyspnea of unknown origin • Patients with heart failure who have not had a recent (1 clinical risk factor and poor functional capacity who will undergo intermediate-risk surgery† Not indicated in: • Patients with no risk factors • Patients undergoing low-risk surgery * Low-risk surgery (3 hr) Head and neck surgery Emergent surgery Vascular surgery Induction of general anesthesia

Weak Evidence

Weight loss Impaired sensorium Cigarette use Alcohol use Abnormal chest examination

Perioperative transfusion

MANAGEMENT OF PATIENTS RECEIVING ANTITHROMBOTIC THERAPY

Insufficient Data

Obstructive sleep apnea Poor exercise tolerance

Esophageal surgery

Good Evidence AGAINST Being a Risk Factor

Well-controlled asthma Obesity

significantly reduce the risk of pulmonary complications, including atelectasis and pneumonia, and should be considered in patients who are unable to comply with deep breathing or incentive spirometry. In the presence of vomiting or abdominal distention, it is also appropriate to insert a nasogastric tube for gastric decompression, thus reducing the risk for gastric-related pulmonary compromise. Controlled asthma alone is not a risk factor for pulmonary complications but can be exacerbated by surgery. The National Asthma Education and Prevention Program (2002) recommends preoperative optimization of lung function, which may require the administration of steroids to reduce a postoperative inflammatory response. Finally, although it is well established that smoking leads to increased rates of pulmonary complications, quitting smoking in the immediate preoperative period does not reduce the risk for postoperative pulmonary complications. In fact, smoking cessation in close proximity to surgery increases complications because of a transient increase in mucus production and a reduction in coughing, possibly because of decreased airway irritation. Nonetheless, with overwhelming evidence demonstrating the negative health outcomes associated with smoking, it is the surgeon’s responsibility to encourage smoking cessation in all patient encounters. 

Hip surgery Genitourinary or gynecologic surgery

ASA, American Society of Anesthesiologists. Modified from Smetana GW. Postoperative pulmonary complications. Cleve Clin Med J. 76:s600-65, 2009.

The Respiratory Risk Index was described in 2007 to predict postoperative respiratory failure. This comprehensive assessment tool uses 28 independent predictors of postoperative respiratory complications to categorize patients into three groups. Predicted rates of respiratory failure correlate with these categories and are 0.2%, 1%, and 6.5% for patients at low, medium, and high risk, respectively. In 2006 the American College of Physicians published guidelines for Preoperative Pulmonary Assessment. A serum albumin level should be obtained for all patients with one or more risk factors, because low serum albumin (1 to 2 cm) sessile polyps, bowel resection, and cancer operations as having an increased risk for perioperative bleeding. The American Society of Gastrointestinal Endoscopy published guidelines in 2009 dividing endoscopic procedures into lowand high-risk procedures (Table 34-8). After defining the relative risks of clotting and bleeding, the surgeon must decide whether to withhold antithrombotic therapy and if bridging therapy is necessary. Preoperative use of warfarin should be discontinued for all persons undergoing major operations or procedures who

COLON

171

TABLE 34-6:  Thromboembolic Risk Stratification According to Indication for Therapy Risk Classification Indications for Therapy

High Risk (>10% Annual Risk)

Moderate Risk (5%-15% Annual Risk)

Low Risk (75 yr

Atrial fibrillation

CHADS score 5-6 Recent (within 3 mo) stroke or TIA Rheumatic valvular heart disease

CHADS score 3-4

CHADS score 0-2 without history of stroke or TIA

VTE

Recent (within 3 mo) VTE Severe thrombophilia: Protein C, S, or antithrombin deficiency or antiphospholipid antibodies

VTE within 3-12 mo Nonsevere thrombophilia: heterozygous factor V; Leiden or prothrombin gene mutation Recurrent VTE Cancer (treated in past 6 mo or palliative)

VTE >12 mo previous and no additional risk factors

Afib, Atrial fibrillation; CHF, congestive heart failure; DM, diabetes mellitus; HTN, hypertension; TIA, transient ischemic attack; VTE, venous thromboembolism. Modified from Gould MK, Garcia DA, Wren SM, et al. Prevention of VTE in nonorthopedic surgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 141(2 Suppl):e227S-77S, 2012.

TABLE 34-7:   CHADS Score Risk Factors

Points

Congestive heart failure

1

Hypertension

1

Age >75 yr

1

Diabetes

1

Stroke or transient ischemic attack

2

TABLE 34-8:   Bleeding Risk Associated with Endoscopic Procedures Low Risk

High Risk

Flexible sigmoidoscopy ± biopsy Colonoscopy ± biopsy Endosonography

Polypectomy Laser ablation and coagulation Pneumatic dilation Treatment of varices

are determined to have a moderate to high risk of bleeding. Typically warfarin is withheld for 5 days prior to surgery and for 24 hours after surgery. The international normalized ratio should be obtained on the day of surgery to ensure adequate clearance of the drug. The decision regarding use of an antithrombotic bridge is based on the patient’s risk of thromboembolism. Table 34-9 summarizes indications for bridging. Traditionally, unfractionated heparin has been used for bridging therapy. Although effective, it has the drawback of requiring inpatient hospitalization. Recently, low molecular weight heparin (Lovenox) has been used for bridging therapy. In addition to being efficacious, it has a good safety profile and can be used in the outpatient setting. Regrettably, the published data have not been strong enough to obtain Food and Drug Administration approval. Within the past few years, many new oral antithrombotic medications have been used with increased frequency. Unlike warfarin, these medications work independently of the vitamin K pathway and instead target thrombin or Factor Xa. New oral antithrombotic agents have a

quick onset and stable pharmokinetics and therefore do not require close monitoring. However, their anticoagulation effect is not reversible with fresh frozen plasma or vitamin K. For this reason, emergency surgery is ideally delayed until the drug is cleared. After surgery, bridging therapy is not necessary, and the medication can be started 4 to 6 hours after surgery. The first dose should be a reduced dose, after which the usual maintenance dose is resumed. Table 34-10 provides a summary of these medications and perioperative recommendations. As with anticoagulation, patients with cardiovascular disease who are being treated with antiplatelet therapy also may require preoperative interruption in their therapy. Management of this antiplatelet therapy is dependent on the patient’s cardiac risk and should only be made after a comprehensive assessment of risk is ascertained in conjunction with either the cardiologist or neurologist who prescribed the therapy. Because of the necessity of the drug therapy, a guiding principle is to minimize antiplatelet therapy interruption when possible, especially in patients with increased cardiac risk. Table 34-9 provides further recommendations to guide antiplatelet therapy management. 

MANAGEMENT OF PREOPERATIVE ANEMIA Many gastrointestinal diseases result in blood loss, and thus anemia is common in patients undergoing colon and rectal surgery. It is estimated that more than 50% of patients with colon cancer are anemic, with rates reaching 76% in patients with advanced cancer. Anemia is not unique to patients with colorectal cancer. Approximately 22% of patients with ulcerative colitis are anemic, with the prevalence tripling to 67% in the emergency setting. Although most patients are asymptomatic from chronic anemia, when combined with acute surgical blood loss, fluid shifts, and perioperative medications, an anemic patient may require allogenic blood transfusions postoperatively. However, perioperative blood transfusions are associated with increased adverse outcomes. Among patients with colon and rectal cancer, transfusion has been linked to decreased overall survival, higher recurrence rates, and increased morbidity. Whether a true causal relationship exists between blood transfusions and adverse outcomes is a contentious topic, and concerns are being raised regarding the risk of untreated preoperative anemia. Studies of patients with a hematocrit less than 28% who required prostate or vascular surgery showed an increased risk for

172

Preoperative Preparation of the Patient for Colon and Rectal Surgery

TABLE 34-9:   Management of Antithrombotic Therapy in Patients Undergoing High/Moderate Bleeding Risk Operations Thromboembolism or Cardiac Risk Indications for Antithrombotic Medication

High Risk

Moderate Risk

Low Risk

Hold anticoagulation

Hold anticoagulation

Hold anticoagulation

Bridge with LMWH or UFH

Consider bridge

No bridge necessary

 

Defer surgery if possible

Hold anticoagulation

Hold anticoagulation

VTE

Bridge with LMWH or UFH

Consider bridge

Consider bridge if immobilized

 

Consider IVC filter if bridge contraindicated

Antiplatelet therapy for cardiovascular disease

Continue ASA through surgery

Consider holding ASA

Hold clopidogrel (Plavix) and ASA for 7-10 days prior to surgery

Stop clopidogrel (Plavix) 7-10 days prior to surgery

Stop clopidogrel (Plavix) 7-10 days prior to surgery

Resume within 24 hr

Mechanical heart valve or atrial fibrillation

 

Resume clopidogrel (Plavix) within 24 hr

ASA, Aspirin; IVC, inferior vena cava; LMWH, low molecular weight heparin; UFH, unfractionated heparin; VTE, venous thromboembolism.

TABLE 34-10:   Oral Antithrombotic Medication Summary and Perioperative Management Perioperative Recommendations Based on Procedural Bleeding Risk*

General Information Medication (Brand)

Target

Standard Dose

Half Life, hr

Low Risk

High Risk

Apixaban (Eliquis)

Factor Xa

5 mg twice a day

10-14

Stop 24 hr prior (48 hr if CrCl 90

Hemoglobin

Normal

30

Abdominal radiograph

—

Edema

Dilatation 38.5°C Tachycardia >120/min Leukocytosis >10.5 × 109/L Hemoglobin 6 months after proctectomy

Small, superficial sinus tracts or wounds may respond to serial unroofing and curettage; the wound tends to get progressively smaller, and adequate symptomatic relief may be achieved, even if complete healing does not occur. Excision and saucerization to change the shape of the defect from a deep, narrow sinus to a broader wound with a flatter surface may also help. Skin grafting of the resulting wound can be performed simultaneously or at a future time. Healing rates of 55% to 77% have been reported with this technique.

Asymptomatic or improving

Observe/local treatment

Symptomatic, not improving Superficial Workup: Exam under anesthesia ± CT/MRI ± Fistolography

Deep

Excision/curettage (± skin graft)

Excision/curettage of cavity and muscle flap (e.g., gracilis)

FIGURE 41-4  A proposed algorithm for treatment of patients with an unhealed perineal wound. CT, Computed tomography; MRI, magnetic resonance imaging.

212

Unhealed Perineal Wound

structures. The coccyx often must be excised and the lower two segments of the sacrum can be safely resected if necessary to provide a tension-free closure of nonfibrotic tissue. In wounds that require a bulkier flap, an omental pedicle flap or VRAM may be preferable. The VRAM flap has a success rate between 50% and 100%. 

SUMMARY

FIGURE 41-5  A perineal wound with a gracilis flap harvested from the

left leg ready to be positioned. (Photo courtesy Robert Nesbit, MD.)

Deep, large cavities will likely require transposition of healthy, well-vascularized tissue flaps to fill the space. Tissue flaps generally can be divided into those that do and do not require a laparotomy. A laparotomy is necessary to create omental pedicle flaps or rectus abdominis myocutaneous flaps. A laparotomy carries the risk of inadvertent enterotomy, repeat pelvic dissection, and an increased risk of hernia. The rectus abdominis flap may have an impact on subsequent stoma siting if the need for revision arises. For most of the deep wounds extending into the pelvis, we favor the gracilis flap (Fig. 41-5). The morbidity of a gracilis muscle harvest is low, and the effect on ambulation or extremity function is minimal. Gracilis flaps have a success rate of 20% to 75%. The gracilis is harvested initially with the patient in the lithotomy position, with the muscle insertion division distally. The muscle is then tunneled to the perineal wound and the patient is placed in the prone jackknife position. The perineal wound is carefully inspected and debrided with care to avoid injuring other

Sphincter-saving techniques have diminished the number of proctectomies being performed both for IBD and malignancy. ­ ­Nonetheless, an unhealed perineal wound remains a problem, with significant morbidity and impact on quality of life. Proper preoperative management prior to proctectomy and good surgical technique provide the best chance of avoiding a UPW. When a UPW develops, it may respond to patient, nonoperative therapy. Deep, chronically fibrotic pelvic cavities require debridement and the use of a muscle flap such as the gracilis.

Suggested Reading Collie MH, Potter MA, Bartolo DC. Myocutaneous flaps promote perineal healing in inflammatory bowel disease. Br J Surg. 2005;92(6):740–741. Genua JC, Vivas DA. Management of nonhealing perineal wounds. Clin Colon Rectal Surg. 2007;20(4):322–328. Ip B, Jones M, Bassett P, Phillips R. Factors affecting the healing of the ­perineum following surgery. Ann R Coll Surg Engl. 2013;95(4):252–257. Menon A, Clark MA, Shatari T, et  al. Pedicled flaps in the treatment of ­nonhealing perineal wounds. Colorectal Dis. 2005;7(5):441–444. Pemberton JH. How to treat the persistent perineal sinus after rectal excision. Colorectal Dis. 2003;5(5):486–489. ­ erineal Shibata D, Hyland W, Busse P, et al. Immediate reconstruction of the p wound with gracilis muscle flaps following abdominoperineal r­esection and intraoperative radiation therapy for recurrent carcinoma of the ­rectum. Ann Surg Oncol. 1999;6(1):33–37.

Medical Management of Crohn Disease

42

Edith Y. Ho, Jeffry A. Katz, and Fabio Cominelli

INTRODUCTION Crohn disease (CD) is a chronic, relapsing, idiopathic inflammatory condition that primarily affects the gastrointestinal tract. The severity and location of CD are variable. CD, a transmural inflammation of the bowel characterized by skip lesions that may involve any section of the gastrointestinal tract, is sometimes complicated by strictures and fistula formation. In about 50% of cases, CD affects the terminal ileum and colon; in 20% of cases, it affects the colon only; and in 30% of cases, it affects the small bowel only. Perianal complications develop in about 20% of persons with CD. Treatment paradigms for CD are rapidly evolving as newer agents become available. Treatment with 5-aminosalicylates (5-ASA) is no longer recommended, and anti–tumor necrosis factor (TNF) therapies are initiated earlier in the course of disease to induce mucosal healing. The primary treatment goal is induction and maintenance of steroid-free remission while minimizing drug toxicity. This target has been associated with a better quality of life and a lower likelihood of requiring hospitalizations or surgery. “Deep remission,” defined as both clinical and endoscopic remission, might become the ultimate therapeutic goal in the future. 

MEDICAL THERAPIES Multiple options exist for the medical treatment of CD. The choice of therapy is guided by the efficacy of any given agent in inducing and/or maintaining remission, as well as by the severity and extent of the disease. Serious adverse effects of medical treatment are rare, but risks and benefits should be carefully weighed in selecting the appropriate treatment strategy.

5-Aminosalicylates 5-ASA drugs, such as mesalamine and sulfasalazine, are no longer recommended for the treatment of CD. Sulfasalazine alone has shown moderate benefit in treating active disease, but it has not been shown to be effective in maintaining remission. Nevertheless, many physicians prescribe ASA drugs for mild CD because of their low toxicity, low cost, and familiarity. In particular, mesalamine (Pentasa), a controlled-release formulation of 5-ASA, is a favorite drug for CD involving the small bowel and colon because it releases approximately 50% of 5-ASA in the small intestine and the remaining 50% in the colon. Mesalamine suppositories and enemas are also used for distal left-sided disease. 5-ASA agents have a relatively safe toxicity profile. Kidney function may be checked annually because of a low risk of renal insufficiency. Interstitial nephritis is considered an idiosyncratic reaction and is not dose dependent. Rarely, a hypersensitivity reaction can occur, causing worsening abdominal pain, diarrhea,

or hematochezia, which should prompt discontinuation of the drug. Although many physicians and patients still elect to use 5-ASA, it has not been proved that these agents affect the course of CD. 

Antibiotics No strong evidence exists to support the use of antibiotics in persons with active CD. However, antibiotics may be beneficial in treating suppurative disease, perianal complications, or hospitalized patients who have signs of infection. A common practice is to prescribe a 2-week course of ciprofloxacin, 500 mg by mouth twice a day, and metronidazole, 500 mg by mouth twice a day. 

Corticosteroids Corticosteroids are highly potent antiinflammatory medications used to achieve clinical remission in patients with active CD. They should not be used as long-term therapy because of their adverse effects. Short-term adverse effects include mood disturbances, fluid retention, hypertension, and weight gain. Long-term consequences include thinning of skin, poor wound healing, cataracts, diabetes, osteoporosis, adrenal insufficiency, and increased risk of infections. Corticosteroids can be administered parenterally, orally, or topically. Severely ill, hospitalized patients with CD benefit from intravenous corticosteroids, such as hydrocortisone, 300 mg per day, or methylprednisolone, 40 to 60 mg per day. Prednisone is the most commonly used oral corticosteroid, starting at 40 to 60 mg per day, and tapering by 5 to 10 mg every 5 to 7 days once remission is achieved. Entericcoated budesonide, an analog of conventional corticosteroids, is an excellent and effective alternative for ileal and right-sided colonic CD. Because of its high first-pass metabolism in the liver, only 10% to 15% of budesonide is systemically bioavailable, thus conferring less toxicity than conventional steroids. Studies have shown that budesonide is effective in inducing remission or delaying relapse for up to 9 months, but evidence for its use in maintaining remission is lacking. The optimal dose to induce remission is 9 mg per day, followed by a 3 mg taper every 4 weeks. Physicians and patients should develop a management plan that aims to maintain steroid-free remission on a long-term basis, which typically includes the use of an immunomodulator or a biologic agent. 

Immunomodulators Thiopurines (e.g., azathioprine and 6-mercaptopurine [6-MP]) are the most common immunomodulators in the treatment of moderate to severe CD disease and are primarily used for the maintenance of remission. Because of their slow onset of action (up to several weeks), 213

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Medical Management of Crohn Disease

immunomodulators are not effective in inducing remission. Therefore, in patients with active disease, immunomodulators with a more rapid onset of action such as corticosteroids are typically prescribed. The standard dose of azathioprine is 2 to 2.5 mg/kg/day, whereas the dose of 6-MP is 1 to 1.5 mg/kg/day. Azathioprine is a prodrug that is converted to 6-MP, which is then metabolized into an active metabolite, 6-thioguanine nucleotide (6-TGN). Excess production of the 6-TGN metabolite can cause myelotoxicity and increased risk of infection. Excess production of the 6-methylmercaptopurine (6-MMP) metabolite can lead to hepatotoxicity. Therefore, before starting therapy, thiopurine methyltransferase (TPMT) enzymatic activity should be checked to assess potential risk for drug sensitivity and toxicity. Thiopurine is not recommended for patients with a low or undetectable TPMT level. In patients with low to intermediate TPMT activity, the dosage should be reduced, usually by 50%. No standard method exists for monitoring blood tests. We recommend weekly complete blood cell count and liver function tests for the first month, then every other week for 1 month, then every 3 months. If the white blood cell count is less than 3000 per mm3 or if transaminases are greater than three times the upper limits of normal, the dosage should be reduced or the drug should be discontinued. One key drug interaction is allopurinol, an inhibitor of xanthine oxidase, which interferes with the metabolism of azathioprine and 6-MP. This drug-drug interaction can elevate plasma levels of 6-TGN, which can suppress bone marrow function. Therapeutic drug monitoring for 6-TGN and 6-MMP are now commercially available. These tests are particularly useful in patients who did not respond to thiopurine treatment despite an adequate duration and dose of immunomodulator therapy. 6-TGN levels of greater than 235 pmol/8 × 108 red blood cells correlate with a higher likelihood of response, whereas 6-MMP levels of greater than 5700 pmol/8 × 108 red blood cells correlate with a higher likelihood of hepatoxicity. Before initiating immunosuppressive therapy, patients are screened for latent tuberculosis and chronic hepatitis B. Age-appropriate vaccinations may be considered prior to initiating immunomodulators, especially live vaccines, given the risk of reactivation or dissemination in an immunocompromised host. There is also an increased risk of nonmelanoma skin cancers and a four- to fivefold increased risk of non-Hodgkin lymphoma. Therefore, annual skin surveillance is often recommended along with routine blood work. Methotrexate, another immunomodulator, is often used in conjunction with a biologic agent to reduce antibody formation. Although less commonly used as monotherapy for CD, a reasonable amount of placebo-controlled data shows that methotrexate is effective for the induction and maintenance of remission. The dose is 25 mg once weekly administered subcutaneously, which is then lowered to 15 mg after 8 to 12 weeks if the patient improves. Because methotrexate is a folate antagonist, it is usually taken with folic acid, at a dose of 1 mg daily. The risk of infection and malignancy is slightly increased. Complete blood cell count and liver function tests are checked regularly. Methotrexate is classified as a category X drug in pregnancy because it has been associated with miscarriage and birth defects. Patients are counseled to use contraception while undergoing therapy and are advised to discontinue the drug for 6 months before planning for conception. 

Biologic Agents The introduction of biologic agents has substantially improved the care of patients with CD by effectively inducing and maintaining remission and reducing the need for hospitalization and surgery. Monoclonal anti–tumor necrosis factor (anti-TNF) antibodies are designed to bind to human TNF-α, thereby impairing binding to TNF-α receptor sites and resulting in downregulation of the cytokine-driven inflammatory response. Multiple studies have shown that anti-TNF agents are effective in inducing and maintaining remission in persons with moderate to severe CD. Additionally, anti-TNF

therapy is the treatment of choice for perianal fistulas. Currently, three anti-TNF medications have been approved for the treatment of CD in the United States: infliximab, adalimumab, and certolizumab pegol. Infliximab and adalimumab are approved for the induction and maintenance of remission, but certolizumab has a higher failure rate in inducing remission. Infliximab is administered via intravenous infusion, whereas adalimumab and certolizumab are injected subcutaneously. These agents differ by their chemical structure but share similar adverse effects. The most common include infusion reaction or injection site reactions, which can be addressed easily. Most serious adverse effects include an increased risk of infection and non-Hodgkin lymphoma, especially with exposure to thiopurines concurrently or in the past. Anti-TNF monotherapy does not appear to be associated with an increased risk of lymphoma, but it is associated with melanoma. Latent tuberculosis, active hepatitis B, or fungal infections should be ruled out before starting biologic agents. Age-appropriate vaccinations and live vaccines may be initiated prior to starting biologic agents because of the potential risk of reactivation. Patients may be monitored with routine blood work every 3 to 6 months and with annual skin examinations. Commercially available tests to detect therapeutic levels and the presence of antibody toward infliximab and adalimumab can be helpful in persons with a poor response to anti-TNF therapy to determine the optimal dosage, interval of administration, or need to consider an alternative biologic agent. Another therapeutic option is natalizumab, a humanized monoclonal antibody directed against cell adhesion molecule α4β1 and α4β7 integrins, which prevents T-lymphocyte adhesion to vascular cell adhesion molecule–1 and mucosal addressin–cell adhesion molecule–1 (MAdCAM-1), thus downregulating inflammation. Natalizumab was first shown to be effective in the treatment of multiple sclerosis but has since been shown to be effective in inducing and maintaining remission of moderate to severe CD. Use of this drug has been limited by the risk of progressive multifocal leukoencephalopathy (PML), and thus the U.S. Food and Drug Administration has restricted it to patients who have not responded to anti-TNF drugs. Before treatment with natalizumab is initiated, patients must be tested for the JC virus antibody to assess their risk of the development of PML. Vedolizumab, a humanized monoclonal immunoglobulin G1 antibody, specifically binds to integrin α4β7 but does not inhibit α4β1 or αEβ7. The agent inhibits adhesion of a gut-specific subset of T lymphocytes to MAdCAM-1 but not to vascular cell adhesion molecule–1. Because MAdCAM-1 resides almost exclusively in the gastrointestinal tract, vedolizumab does not affect systemic immune response or affect T-cell migration to the central nervous system and therefore may be the first gut-specific CD treatment. It does not appear to be associated with risk of PML, which is a significant advantage compared with natalizumab. The pivotal GEMINI 2 study demonstrated the efficacy and safety of vedolizumab in treating CD, which led to approval by the U.S. Food and Drug Administration in 2014. Many new agents, including ustekinumab and etrolizumab, are in development, and ongoing research continues to expand our repertoire of therapies for CD. 

Combination Therapy The Study of Biologic and Immunomodulator Naïve Patients in Crohn’s disease (SONIC), a single randomized controlled trial, demonstrated that combination therapy of immunomodulators and antiTNF was superior to monotherapy in persons with moderate to severe CD. In this trial, combination therapy of azathioprine and infliximab was more effective than infliximab monotherapy, which, in turn, was more effective than azathioprine alone at maintaining clinical and endoscopic remission at 26 and 54 weeks. It is not clear whether azathioprine compounds antiinflammatory effects, but it does appear to enhance the response to infliximab by decreasing anti-infliximab

COLON

antibodies and increasing infliximab levels. Combination therapy was not associated with a higher risk of serious infections during the trial, and evidence in subsequent studies was insufficient to conclude whether combination therapy increases the risk of opportunistic infections or malignancies. Furthermore, the risks and benefits beyond 1 year are not known. Expert opinion states that results from SONIC can be extrapolated to adalimumab. Controversy exists about duration of combination therapy and whether combination therapy provides benefit for persons who have failed to respond to immunomodulator therapy. Some patients might elect monotherapy because of a higher value of avoiding any potential risk of serious complications or malignancies compared with an increased chance of inducing and maintaining remission. 

PERIANAL AND FISTULIZING CROHN DISEASE Perianal/perirectal abscess and acute suppuration are indications for surgical drainage with or without placement of setons. Patients with nonsuppurative perianal complications, such as recurrent fistulization

or fissuring, can first try metronidazole alone or in combination with ciprofloxacin, followed by immunosuppressive agents upon resolution of infection. In patients with fistulizing disease that is refractory to antibiotics, corticosteroids, or immunomodulators, a series of 5 mg/kg infliximab infusions at 0, 2, and 6 weeks can enhance closure of CD fistulae. Continuation of 5 mg/kg infliximab at 8-week intervals showed durable benefit. 

APPROACH TO MANAGEMENT OF CROHN DISEASE Treatment recommendations depend on disease severity, the extent of involvement, and the complexity of the disease. The therapeutic goal is to induce and then maintain clinical remission. This approach is outlined in Figure 42-1. To assess disease severity, two systems commonly used in clinical trials are suitable, including the Crohn’s Disease Activity Index (CDAI) and the Harvey-Bradshaw Index, which is a simplified version of the CDAI. A drop in the CDAI of 100 points corresponds to a drop in the Harvey-Bradshaw Index by 3 points. In general, patients with mild to moderate CD disease (CDAI

Assess disease severity

Mild to moderate

Moderate to severe

Oral steroids

Induction of remission

Budesonide ±5-ASA (PO/PR)

Response?

No

Yes

Response? Yes

OR

No

Anti-TNF ± thiopurine

Response? Yes

Severe to fulminant/ refractory

OR

No

IV steroids

Oral steroids + Anti-TNF ± Thiopurine

Response?

No

Yes

Response? Yes

No

Surgery

Maintenance of remission

Oral steroids + Anti-TNF ± Thiopurine

±5-ASA

Thiopurine or methotrexate

Anti-TNF ± Thiopurine

Post-operative prophylaxis 5-ASA or thiopurine or anti-TNF

FIGURE 42-1  Approach to management of Crohn disease by disease severity. 5-ASA, 5-Aminosalycilic acid; IV, intravenous; PO, by mouth; PR, per

rectum; TNF, tumor necrosis factor.

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Medical Management of Crohn Disease

50-200) are ambulatory and able to maintain adequate nutrition without significant symptoms. Patients with moderate to severe CD disease (CDAI 200-450) have failed to respond to treatment for mild to moderate disease and are dependent on systemic corticosteroids for symptom control. They present with fever, weight loss, nausea or vomiting, abdominal tenderness, and/or anemia. Severe to fulminant disease (CDAI >450) refers to patients who present with alarming symptoms such as high fevers, persistent vomiting, peritonitis, bowel obstruction, or abscess formation. They are refractory to conventional glucocorticoids or biologic agents. 

SURGERY Most patients with CD require surgery over the course of their disease, and a subset may require multiple surgeries. Except for total colectomy and ileostomy for CD limited to the colon, surgery is rarely curative because CD recurs in most patients within 5 years. The most common indications for surgery are refractory disease that is not responsive to medical therapy or intolerability of the adverse effects of medications. Surgery is also indicated for penetrating and stricturing CD causing perforation or bowel obstruction, abscesses not amenable to percutaneous drainage, complex perianal or internal fistulas, uncontrolled hemorrhage, high-grade dysplasia, or malignancy. 

POSTOPERATIVE RECURRENCE Recurrence of CD disease after surgery occurs in most patients. Postoperative recurrence can be defined by endoscopy, symptoms, or the need for another surgery. Because endoscopic recurrence generally precedes clinical symptoms, it is recommended that an endoscopic assessment be performed 6 to 12 months after surgery to identify recurrence and assess risk. Disease patterns (e.g., jejunal or extensive ileal-colonic disease, fistulization, and perianal involvement) and patient-specific variables (e.g., a shorter preoperative disease duration or initial presentation requiring surgery, prior surgeries, age younger than 30 years, failure of medical management, and current history of smoking) appear to increase risk. Patients with high-risk features might benefit from aggressive and early prophylaxis within 30 days of surgery and continue to receive lifelong therapy. To date, no consensus exists regarding optimal medical strategies for preventing recurrence. Treatment options include 5-ASA, imidazole antibiotics, azathioprine, 6-MP, and anti-TNF biologic agents. 

SMOKING CD is more likely to develop in past and current smokers than in persons who have never smoked. Smoking also increases the risk of exacerbations, fistulizing and stricturing disease, reduced response to medical therapy, and postoperative recurrence. Persons with CD therefore should stop smoking. 

NUTRITION Nutritional therapy alone has not been a reliably effective treatment for CD. In general, patients experiencing a CD flare can follow a lowresidue diet divided into small, frequent meals. Nonabsorbable fibers

such as raw vegetables can exacerbate symptoms. Patients in clinical remission can follow a healthy diet that is low in saturated fat and red meat but high in fish and vegetables. Patients with more than 100 cm of diseased or resected ileum experience bile salt malabsorption but not depletion. The large amount of unabsorbed bile salts entering the colon causes choleraic diarrhea, which can be symptomatically controlled by bile salt sequestrants such as cholestyramine. In patients with more than 100 cm of terminal ileum that is diseased or resected, the liver is unable to compensate for bile salt losses, and fat malabsorption ensues. In these cases, a low-fat diet supplemented with medium-chain triglycerides (medium-chain triglyceride oil) is recommended. These patients also may require parenteral replacement of vitamin B12. Fat-soluble vitamins (A, D, and E) should be checked and supplemented. Vitamin K status can be assessed by international normalized ratio. In prolonged and severe cases of CD, zinc, chromium, and selenium deficiency also may develop, and parental or enteral nutrition may be needed to correct these nutritional deficiencies.

Suggested Reading Cheifetz AS. Management of active Crohn disease. JAMA. 2013;309(20): 2150–2158. Colombel JF, Sandborn WJ, Reinisch W, et  al. Infliximab, azathioprine, or combination therapy for Crohn’s disease. N Engl J Med. 2010;362(15): 1383–1395. Ford AC, Sandborn WJ, Khan KJ, et  al. Efficacy of biological therapies in inflammatory bowel disease: systematic review and meta-analysis. Am J Gastroenterol. 2011;106(4):644–659; quiz 660. Hanauer SB, Sandborn WJ, Rutgeerts P, et al. Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn’s disease: the CLASSICI trial. Gastroenterology. 2006;130(2):323–333; quiz 591. Lichtenstein GR, Feagan BG, Cohen RD, et al. Drug therapies and the risk of malignancy in Crohn’s disease: results from the TREAT™ Registry. Am J Gastroenterol. 2014;109(2):212–223. Lichtenstein GR, Hanauer SB, Sandborn WJ, et  al. Management of Crohn’s disease in adults. Am J Gastroenterol. 2009;104(2):465–483; quiz 464, 484. McLeod RS, Wolff BG, Steinhart AH, et  al. Risk and significance of endoscopic/radiological evidence of recurrent Crohn’s disease. Gastroenterology. 1997;113(6):1823–1827. Osterman MT, Kundu R, Lichtenstein GR, Lewis JD. Association of 6-thioguanine nucleotide levels and inflammatory bowel disease activity: a meta-analysis. Gastroenterology. 2006;130(4):1047–1053. Patel V, Wang Y, MacDonald JK, et al. Methotrexate for maintenance of remission in Crohn’s disease. Cochrane Database Syst Rev. 2014;8:CD006884. Sandborn WJ. Current directions in IBD therapy: what goals are feasible with biological modifiers? Gastroenterology. 2008;135(5):1442–1447. Sandborn WJ, Colombel JF, Enns R, et al. Natalizumab induction and maintenance therapy for Crohn’s disease. N Engl J Med. 2005;353(18):1912–1925. Sandborn WJ, Feagan BG, Rutgeerts P, et al. Vedolizumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med. 2013;369(8): 711–721. Sandborn WJ, Feagan BG, Stoinov S, et al. Certolizumab pegol for the treatment of Crohn’s disease. N Engl J Med. 2007;357(3):228–238. Sands BE, Anderson FH, Bernstein CN, et al. Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med. 2004;350(9):876–885. Seow CH, Benchimol EI, Griffiths AM, et al. Budesonide for induction of remission in Crohn’s disease. Cochrane Database Syst Rev. 2008;(3):CD000296. Toruner M, Loftus EV, Harmsen WS, et al. Risk factors for opportunistic infections in patients with inflammatory bowel disease. Gastroenterology. 2008;134(4):929–936.

Management of Crohn Colitis

43

Scott A. Strong

C

rohn disease can affect any segment of the intestinal tract, and the colon will be involved in approximately half of afflicted patients. Crohn disease of the colon can entail disease of the large bowel alone or of the large bowel plus the terminal ileum. The behavior of the disease varies and can be categorized as predominantly inflammatory, stricturing, or penetrating. Furthermore, disease of the anal canal or perineum can complicate any of these behavior patterns. Understanding the distribution and behavior of the disease is critical to the creation of an individualized treatment plan that usually begins with medical therapy but ultimately includes surgery in many patients.

MEDICAL MANAGEMENT The appropriate treatment of a patient with Crohn disease of the colon or ileocolon generally begins with individual or combination medical therapy in the form of antibiotics, 5-aminosalicylic acid (5-ASA) compounds, glucocorticoids, immunomodulators, or biologic agents. The 5-ASA compounds and glucocorticoids can be orally or topically delivered, depending on the disease location. The medications are conventionally prescribed in an escalating or “bottom-up” fashion in which the next level of medication is implemented when the disease shows itself to be unresponsive to the current therapy. However, more recent studies suggest that early aggressive or “top-down” treatment might be more effective with quicker and greater control of mucosal inflammation and disease symptoms. Regardless of the medical treatment, surgery is ultimately required in many patients with large bowel disease. The incidence of surgery, however, is lower than that for terminal ileal or small bowel Crohn disease. 

OPERATIVE INDICATIONS The indications for surgery in a patient with Crohn disease are generally categorized as failed medical therapy or disease-associated complications. Medication failure can be defined as the persistence of symptoms despite appropriate medical therapy, failure as a result of poor compliance, intolerance of medications, debilitating adverse effects, or concern for potential risks/complications. Disease complications can be classified as acute (e.g., abscess, free perforation, hemorrhage, and severe colitis) or chronic (e.g., growth retardation, neoplasia, and obstruction). 

PREOPERATIVE CONSIDERATIONS Any patient requiring surgery for large bowel disease requires routine laboratory studies to exclude anemia and electrolyte abnormalities. Assessment of nutrition-related proteins (e.g., albumin, transferrin, and prealbumin) is reserved for a patient with recent poor caloric

intake or substantial weight loss (>10% of the patient’s weight when well). Simple deficits such as hemoglobin less than 7. 0 g/dL, hypokalemia, and hypomagnesemia should be corrected. Malnutrition secondary to systemic inflammatory mediators will not improve with hyperalimentation, but 7 to 10 days of parenteral nutrition should be considered in elective situations if the cause of malnutrition is poor caloric intake. Smoking cessation should be strongly encouraged and supported when appropriate because of the negative impact of smoking on operative morbidity and disease recurrence. Regardless of the setting, a patient who may or will require fecal diversion should undergo marking in at least one abdominal quadrant in an area that is easily visible and remote from bony structures, scars, and creases despite the patient’s position (e.g., lying, sitting, and standing). A patient with anorectal sepsis in whom a proctectomy is planned will usually benefit from preliminary drainage of the sepsis. A patient scheduled for elective surgery should generally undergo endoscopy and selective imaging if these investigative studies have not been performed recently. Colonoscopy is warranted to determine the distribution of disease, but upper endoscopy is usually not necessary. Magnetic resonance imaging or computed tomography (CT) enterography is performed to evaluate small bowel involvement in a patient with suggestive symptoms. Rectal compliance and anal sphincter function should be assessed if preservation of the rectum and anal canal is considered. The compliance and sphincter strength can be objectively measured using anorectal physiology testing and subjectively assessed by observing distensibility of the rectum with insufflation during endoscopy and digital examination. A patient who can retain a 150-mL saline enema for at least 5 minutes should experience minimal problems with urgency or seepage after an operation that spares the rectum and anal canal. The colon is responsible for absorption of water and salt from stool, and the majority of this activity occurs in the midgut portion of the large bowel. This physiologic role helps protect patients against dehydration and electrolyte imbalances. Although the large bowel is dispensable and patients undergoing a colectomy have a normal life expectancy, attempts at preservation of the colon are justified. 

OPERATIVE APPROACH Laboratory, endoscopic, and imaging studies are used to plan the operation so that unanticipated findings are rare. However, patients with large bowel disease must be emotionally prepared for the possibility of a permanent stoma during their lifetime. The incurable nature of the disease causes physicians and surgeons to redirect efforts toward safely restoring a normal quality of life, and many patients equate this goal with avoidance of a permanent stoma. Patient education or experience with a temporary ileostomy often helps alter a patient’s outlook and enables her or him to appreciate that a permanent stoma does not negatively affect quality of life for most ostomates. 217

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Management of Crohn Colitis

FIGURE 43-1  Retroileal passage of the short colonic limb ensures a

tension-free colorectal anastomosis. (Reprinted with permission, Cleveland Clinic Center for Medical Art & Photography. Copyright 1998-2016. All Rights Reserved.)

A laparoscopic approach to large bowel Crohn disease is associated with an acceptable conversion rate and is generally favored in the elective setting for a patient undergoing a first-time operation for uncomplicated disease. Compared with a conventional open procedure, this laparoscopic approach is associated with reduced postoperative pain, lessened operative morbidity, better cosmesis, and decreased length of stay without an increased risk for disease recurrence. 

OPERATIVE OPTIONS The surgical options that are used for large bowel Crohn disease include resection with or without fecal diversion. Diversion (i.e., an ileostomy or colostomy) can be temporary or permanent. A temporary ileostomy is used to avoid or protect an anastomosis in a patient with coagulopathy, debilitating comorbid conditions, high-dose glucocorticoid usage, or severe malnutrition, as well as someone requiring an operation associated with undrained sepsis, purulent or feculent peritonitis, or excessive blood loss. Unlike in persons with small bowel Crohn disease, strictureplasty is not generally advocated for large bowel strictures because approximately 7% of colonic strictures harbor a malignancy and colonic strictureplasty does not provide better postoperative function or quality of life compared with resection.

Disease of the Colon Alone Colonic disease can be managed by segmental resection with creation of a primary anastomosis or by a total colectomy with construction of an ileorectal anastomosis. Disease that is limited to the ascending colon with or without terminal ileum involvement is best treated by resection, but the resultant anastomosis can abut against the second portion of the duodenum and expose the patient to risk of a complex fistula involving the duodenum or retroperitoneum if disease recurs at the ileocolic anastomosis. Accordingly, omentum is interposed between the anastomosis and duodenum or the distal resection margin is moved into the mid transverse colon to create separation from the duodenum.

Disease affecting the ascending colon and transverse colon is also managed with limited resection, but a tension-free anastomosis is best assured by rotating the midgut mesentery counterclockwise to bring the terminal ileum into close proximity of the descending colon. The small bowel will accordingly lie medial to the hindgut mesentery and occupy the right side of the abdomen. Disease of the transverse colon, descending colon, and sigmoid colon can be treated by either segmental resection with creation of a colorectal anastomosis or a total colectomy with construction of an ileorectal anastomosis. The latter approach is generally preferred, but a more limited resection is favored if the patient is older (>50 years) or has undergone significant (>50 cm) small bowel resection. In both scenarios, preservation of the ascending colon may significantly improve the patient’s function because absorptive colonic mucosa is retained. Problems with reach of the colonic segment associated with a limited resection can be overcome by passing the colon through a window created between the superior mesenteric and ileocolic vessels in the midgut mesentery (Fig. 43-1). Disease of the entire colon is best managed with a total colectomy and construction of an ileorectal anastomosis. The anastomosis is created using sutures or stapling instruments in any manner of configuration (e.g., end-to-end or side-to-end), but an anastomosis to the side of rectum is usually avoided. A hand-sewn end-to-end anastomosis can be challenging if a marked discrepancy exists between the diameters of the two lumens. A Cheatle slit along the antimesenteric margin of the terminal ileum can be used to reduce the size difference (Fig. 43-2), or a side-to-end anastomosis can be created. The method used to construct and configure the anastomosis does not seem to significantly affect the risk for early complications or later recurrence. 

Disease of the Rectum Alone Disease limited to the rectum that requires surgery is usually managed with resection of the entire large bowel and creation of an end ileostomy. However, proctectomy alone with construction of a colostomy has been advocated by some centers with acceptable recurrence rates. This option is attractive in a patient who would benefit from retained water and salt absorption, such as someone who is older (>50 years) or has undergone significant (>50 cm) small bowel resection. In a highly selected young patient with no history of anoperineal disease, a coloanal anastomosis can be safely performed to avoid a stoma in the short term. However, the patient is at significant risk for recurrent disease that would necessitate complex reoperative pelvic surgery and creation of a permanent ileostomy. 

Disease of the Colon and Rectum Disease affecting at least portions of the colon and the entire rectum is typically treated by resection of the entire large bowel and creation of an end ileostomy. The proctectomy is usually performed in an endoanal fashion with excision of the internal sphincter and preservation of the external sphincter and muscles of the pelvic floor. These structures are closed in a layered manner (Fig. 43-3), with the skin left to heal by secondary intention if an anorectal abscess or fistula is present. Regardless of the closure technique used, normal healing of the perineal wound occurs in only half of patients, and approximately 25% will demonstrate a persistent wound after 6 months of follow-up. Superficial wounds will eventually close, as opposed to sinus tracts that extend into the pelvis, which often require a repeat operation with debridement and use of omental pedicle or muscle flaps to achieve healing. For young patients afflicted with proctocolitis who do not have any history or evidence of small bowel or anoperineal disease, a restorative procedure such as a proctocolectomy with creation of an ileal pouch–anal anastomosis is an option. The procedure is usually performed in two or three stages depending on the clinical scenario.

COLON

219

FIGURE 43-2  A Cheatle slit of the terminal ileum facilitates c­ onstruction of an ileorectal anastomosis. (Reprinted with permission, Cleveland Clinic Center

for Medical Art & Photography. Copyright 1998-2016. All Rights Reserved.)

If the disease affects portions of the colon and upper rectum, selected patients without significant small bowel or anoperineal disease can be managed with resection of the colon and upper rectum and creation of an ileal pouch–rectal anastomosis. The ileal pouch measures 10 cm in length, is configured in a J shape, and is joined to the remaining normal rectum near the peritoneal reflection. Although the likelihood of disease recurrence is relatively high with this procedure, the function is acceptable and the patient can often avoid a permanent ileostomy during her or his early adult years. 

SPECIAL SITUATIONS Medications High-dose glucocorticoid usage has been linked to an increased risk for postoperative complications (e.g., infection and poor healing), and a patient requiring high-dose prednisone (>20 mg daily) should be counseled about the possible need for temporary fecal diversion. The impact of biologic agents on the risk for infectious complications has been argued, but the risk is likely linked to serum levels of the drug that is metabolized at varying patient-dependent rates. Regardless, it is likely advisable to schedule an elective procedure when the patient is due for her or his next scheduled infusion or injection of the agent. 

Abscess Intra-abdominal abscesses associated with penetrating disease usually arise from the left colon. These abscesses are best managed by parenteral antibiotics plus CT-guided drainage if the abscess measures greater than 3 cm or by aspiration if the abscess is 3 cm or smaller and the patient has been treated with glucocorticoids. Reimaging is recommended if the patient’s condition worsens or does not improve within 3 to 5 days of treatment onset. A sinogram through the existing drain should be performed every few weeks, followed by

FIGURE 43-3 Layered closure of the perineal wound following

­endoanal proctectomy. (Reprinted with permission, Cleveland Clinic Center for Medical Art & Photography. Copyright 1998-2016. All Rights Reserved.)

repeat CT imaging in all patients at 6 weeks to ensure resolution of the abscess. Whether the patient’s condition is subsequently managed with long-term medical therapy or surgery is the topic of debate and depends on the interplay of multiple factors. 

Severe Colitis Any patient with severe colitis should be resuscitated and evaluated for peritonitis with physical examination and for perforation with abdominal imaging (Fig. 43-4). After stool studies for Clostridium difficile, lower endoscopy is conducted with minimal insufflation.

220

Management of Crohn Colitis Severe colitis

Severe endoscopic findings No

Peritonitis or perforation

Yes

No

Infliximab

Glucocorticoids No

Yes

Response by day 7

No

Operation

Response by day 3

Yes

Yes

Discharge on medical therapy FIGURE 43-4 Treatment algorithm for severe colitis.

The severity of mucosal inflammation is assessed and biopsy specimens are obtained to exclude cytomegalovirus infection. High-dose glucocorticoids are typically started, and the patient is frequently assessed with abdominal examinations and daily abdominal roentgenograms. If the patient shows signs of deterioration or no improvement after 3 days of therapy, rescue therapy or surgery is recommended. Infliximab is the agent most commonly used for rescue therapy, and the patient should experience improvement within 5 to 7 days. An operation is indicated if rescue therapy fails to resolve disease-related symptoms and signs. In patients with “severe” endoscopic inflammation, infliximab is often used as first-line therapy instead of glucocorticoids. Regardless the setting, infliximab is not prescribed in a patient in whom severe disease developed while he or she was being treated with immunomodulators or biologic agents. If an operation is warranted, the procedure of choice is a laparoscopic colectomy with creation of an end ileostomy. The distal transected bowel can be managed in a variety of ways. Intraperitoneal closure of a rectal stump is complicated by dehiscence and an intraabdominal abscess in approximately 10% of cases. This complication can be avoided by leaving a longer stump that is closed and implanted above the fascia level in the lower abdomen. Dehiscence of the stump with this approach occurs in one quarter of the cases but results in a mucous fistula that can be easily managed. Rarely, the stump cannot be closed because the tissue is too fragile. In this instance, a short (5-cm) segment of the transected sigmoid colon is exteriorized. The short segment is amputated and a mucous fistula is created after 7 to 10 days. A definitive operation is planned 6 months later when the patient has recovered and has usually discontinued all medical therapy. 

Growth Retardation Growth retardation is a disease- or medication-related complication seen in prepubescent children afflicted with Crohn disease of the large bowel. Surgery can return growth velocity to normal, but catchup growth is often incomplete. In some affected children, delayed puberty may compensate for poor growth experienced earlier in life, and significant growth can still occur. Surgery may have a favorable impact on growth in the short term, but final height often remains less than predicted. 

Fistula Fistulas complicating Crohn disease of the large bowel most often arise from the transverse colon and target the stomach. Surgery is usually

required because the fistula is often symptomatic or at risk for associated complications. The diseased large bowel is resected, and the edges of the stomach are excised to healthy tissue and primarily closed. 

Neoplasia Dysplasia and adenocarcinoma can develop in any segment of chronically inflamed large bowel, and the risk for malignancy is generally estimated at 0.5% per year after 8 to 10 years of disease symptoms. The risk is greatest in patients with extensive disease, severe disease, or sclerosing cholangitis. Patients in whom at least one-third of the large bowel is affected by disease are surveyed every 1 to 2 years with a colonoscopy that includes targeted biopsies of any suspicious lesions or masses, as well as four-quadrant random biopsies obtained every 10 cm. Strictures should be extensively biopsied, and cytologic brushing should be considered. If the entire bowel at risk cannot be surveyed because of a stricture or atrophy associated with out-of-circuit rectum, prophylactic resection is usually advised if adequate surveillance has not been performed for more than 5 years. Oncologic resection of the diseased bowel and its lymphatic drainage basin is recommended for any finding of dysplasia that cannot be endoscopically resected or adenocarcinoma. Continued surveillance is generally suggested for patients with indefinite dysplasia and adenoma-like dysplasia but is debated for unifocal dysplasia arising in flat mucosa found during surveillance. Colonic dysplasia or carcinoma in a patient with rectal sparing is usually managed with a colectomy and construction of an ileorectal anastomosis. If the rectum is the site of neoplasia or is inflamed, a total proctocolectomy is warranted. 

OUTCOME A segmental colectomy and total colectomy are associated with comparable 30-day operative morbidity rates of approximately 14%. The overall 30-day mortality rate is approximately 0.4% for elective procedures but higher for emergency operations. Although the surgical recurrence rates are similar for the two procedures, patients undergoing a segmental resection exhibit recurrence an average of 4.4 years earlier than those who undergo a total colectomy. Moreover, patients with at least two colonic segments involved by disease tend to do better if they undergo a total colectomy with construction of an ileorectal anastomosis. Fortunately, permanent fecal diversion is required in only a small number (18%) of patients, but the presence of anoperineal disease portends a greater risk.

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Proctocolectomy with creation of an ileal pouch–anal anastomosis in appropriately selected patients with large bowel Crohn disease has an acceptable outcome. Most of these patients do as well as persons undergoing the same operation for presumed ulcerative colitis who were later diagnosed with Crohn disease after pathologic examination of the resected specimen. Specifically, the ileal pouch failure rate is approximately 15% after 10 years of follow-up. 

SUMMARY Crohn disease of the colon and ileocolon is initially managed with medical therapy, but surgery is eventually warranted in many patients. Patients requiring an elective procedure should be evaluated with endoscopic and imaging studies and should undergo optimization as dictated by their clinical condition. Whether a laparoscopic segmental colectomy, total colectomy, or proctocolectomy is performed depends on the patient’s age, operative indication, distribution of disease, severity of disease, and condition of the rectum, anal canal, and perineum.

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Suggested Reading Baumgart DC, Sandborn WJ. Crohn’s disease. Lancet. 2012;380:1590–1605. Dyson JK, Rutter MD. Colorectal cancer in inflammatory bowel disease: what is the real magnitude of the risk? World J Gastroenterol. 2012;18: 3839–3848. Feagins LA, Holubar SD, Kane SV, Spechler SJ. Current strategies in the management of intra-abdominal abscesses in Crohn’s disease. Clin Gastroenterol Hepatol. 2011;9:842–850. Melton GB, Fazio VW, Kiran RP, et al. Long-term outcomes with ileal pouchanal anastomosis and Crohn’s disease: pouch retention and implications of delayed diagnosis. Ann Surg. 2008;248:608–616. Rosenfeld G, Qian H, Bressler B. The risks of post-operative complications following pre-operative infliximab therapy for Crohn’s disease in patients undergoing abdominal surgery: a systematic review and meta-analysis. J Crohns Colitis. 2013;7:868–877. Tekkis PP, Purkayastha S, Lanitis S, et al. A comparison of segmental vs subtotal/total colectomy for colonic Crohn’s disease: a meta-analysis. Colorectal Dis. 2006;8:82–90. Umanskiy K, Malhotra G, Chase A, et  al. Laparoscopic colectomy for Crohn’s colitis. A large prospective comparative study. J Gastrointest Surg. 2010;14:658–663.

44

Management of Perianal Crohn Disease James M. Church

INTRODUCTION Perianal disease is the presenting symptom in 5% of patients with Crohn disease, but overall up to 80% of patients experience anal symptoms. An understanding of the pathophysiology of the anal disease is basic to appropriate management and successful control of symptoms. The purpose of this chapter is to present a rational approach to dealing with perianal disease in patients with Crohn disease. 

PATHOPHYSIOLOGY The key to successful treatment of perianal Crohn disease is recognition of perianal Crohn disease, in which the anoderm and perineal skin are affected by Crohn disease at a microscopic level. The Crohn disease–related inflammation, including granulomas, is in the perianal and perineal tissues themselves. When this is the case, incisions do not heal and local surgery is doomed to fail. Perineal Crohn disease does respond well to anti–tumor necrosis factor (TNF)-α therapy, however. Perineal Crohn disease can be diagnosed clinically by the appearance of the tissues. Waxy perineal edema, spontaneous ulceration, painless fissures, large edematous tags, and a split in the skin of the natal cleft are characteristic findings. Figg and Church describe these appearances, some of which are shown in Figure 44-1. Histologically, granulomas can be found in most patients. The proportion of patients with these extremely symptomatic findings is likely to vary between studies and centers, accounting for some of the variation in results achieved by surgery or anti-TNF-α treatment. The presence of perineal Crohn disease has the following implications:   

  

1. Surgical incisions will not heal. 2. Symptoms will respond to biologic agents. 3. After a proctectomy, the perineal wound still may not heal and biologic agents might still be needed.

The alternative pathophysiology in patients with Crohn disease in whom perianal disease develops is cryptoglandular sepsis, chronic diarrhea-induced anal stenosis, hemorrhoidal disease, or the “common” fissure made more common and more severe by diarrhea related to Crohn disease. Here the perianal skin and anoderm look normal, and treatment for the manifestations can be the same as the standard treatment in patients without Crohn disease. Incisions will heal, but biologic therapy will be ineffective. It is obvious that the success rate of biologic agents and surgery in the management of perianal disease in any series will depend on the proportion of patients with perineal Crohn disease in any treatment group. The combination of biologic agents first and then surgery is ideal for patients with perineal Crohn disease.  222

OTHER CONSIDERATIONS Other considerations in the management of perianal Crohn disease are the small bowel and colon, the rectum, and the anus itself. If patients have had a functionally significant amount of bowel removed, the impact of stooling on the anus is magnified. In this case, “significant” means loss of enough bowel to cause chronically more frequent or more liquid stools. If the rectum is affected by active Crohn disease, the symptoms of urgency and tenesmus may be added to stool frequency. In addition, ulcerations in the low rectum preclude any surgery. The anus itself can be affected by Crohn disease or by treatments that others might have performed. Anal stenosis is a common finding in patients with chronic diarrhea because the constant liquid stools do not have the dilating effect of normal, formed stools. The anal stenosis makes access to the anal canal difficult for surgeons and endoscopists. At the other end of the spectrum, anal laxity—a consequence of ill-advised surgery, childbirth, or aging—produces incontinence or mucus seepage that aggravates any symptoms from the Crohn disease itself. 

PRESENTATIONS Anal Sepsis Perianal abscess and fistula are the most common manifestations of perianal disease in patients with Crohn disease. The abscess often follows an accelerated course, especially when perineal disease is present. Spontaneous or therapeutic drainage leads to a fistula. Crohn fistulas are atypical in that the internal opening(s) can be eccentric and multiple, and tracts can be complex. Patients with Crohn disease seem to have reduced resistance to spread of sepsis in the perineum, which makes early control of the sepsis important. Uncontrolled sepsis spreads across the perineum, creating new external openings and complex cavities. 

Anal Tags Large “elephant ear” anal tags are diagnostic of Crohn disease and cause irritation for patients. Because of the possibility of perineal Crohn disease, they should not be excised. Hemorrhoidal tags also may be present but generally need no treatment. 

Fissures Painful anal fissures are generally due to diarrhea and are indicative of underlying anal sphincter hypertonicity. They can be treated in the same way as most fissures: with nitric oxide donor

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223

FIGURE 44-2  Controlling the sepsis: use of Penrose drains in a patient

with extensive, Crohn disease–related, perianal sepsis. FIGURE 44-1 What happens when an incision is made in the peri-

neum of a patient with perineal Crohn disease.

ointments or a sphincterotomy. Painless fissures are a sign of perineal Crohn disease and should be left alone. 

Stenosis Anal stenosis in a patient with Crohn disease may be the effect of chronic diarrhea. In this case there is no point in dilation because the stenosis will always recur. It is usually not symptomatic because it is an adaptation to the diarrhea. However, the anus must be dilated to gain access for procedures involving the anoderm or anal canal. 

Perianal Skin Irritation Chronic wetness due to discharge or seepage damages the perianal skin and causes pruritus. Scratching then further damages the skin. The only way to correct this condition is to minimize physical trauma and keep the perineum dry. 

Internal Hemorrhoidal Prolapse Treatment of internal hemorrhoids in patients with Crohn disease can be tricky. Diagnosis of perineal Crohn disease is key because it mandates against any sort of surgery. In the absence of evidence of perineal or anal Crohn disease, hemorrhoidectomy could be performed. However, removal of the anal cushions can predispose to seepage. Elastic band treatment is also possible, although the chances of a normal bowel habit will determine its success. 

TREATMENT OF SEPSIS: ABSCESS AND FISTULA The top priority in a patient with Crohn disease–related anal sepsis is to control the sepsis, which means providing adequate drainage. Provision of adequate drainage is almost always accomplished during an examination after induction of anesthesia. Probing and cutting in an awake patient is usually not helpful, and anesthesia with a local anesthetic is difficult to achieve in a patient with perianal sepsis.   

Step 1: Perform an inspection. After induction of anesthesia, with the patient in the lithotomy position, the anus is inspected,

which should reveal any abscess or draining external fistula opening. It also should show asymmetry of tissue contours, which is a sign of deeper sepsis. A bluish coloration of the anus and the presence of edematous tags suggest perineal Crohn disease. Waxy edema of the perineal skin and spontaneous ulcerations in the perineum or natal cleft confirm this suspicion. Scars from prior operations also may be present. Step 2: Perform a digital examination. Digital examination reveals the tone and length of the anus and any distortions or evidence of active disease or prior surgery. Sometimes subcutaneous fistula tracts can be palpated. The presence of an anal stenosis becomes obvious. Hard nodules in a patient with chronic perianal Crohn disease should be biopsied to exclude malignancy. Step 3: Perform anoscopy. Anoscopy shows the status of the anoderm, the anal transition zone, and the lower rectal mucosa. Rectal ulcerations mean that advancement flap repair will be impossible and are an indication for anti-TNF-α treatment to obtain healing. Large prolapsing hemorrhoids may be seen, and there may be indications of internal openings feeding an abscess or fistula. Step 4: Drain the abscess. If the abscess is pointing, the site of drainage is obvious. If there is a choice, drainage should be performed as close to the anus as possible. Sometimes the abscess has created a shallow subcutaneous cavity that can be unroofed, although if concern about perineal disease exists, one should be conservative. If the abscess leads to a fistula, drainage will be completed by insertion of a seton drain. If there is no obvious fistula, a mushroom drain can be used. Probing of a freshly drained abscess in a patient with Crohn disease must be performed carefully because it is possible to create false tracks in the fragile, edematous tissues. Nonetheless, probing should be performed because insertion of a seton drain is important in controlling the sepsis. In addition, gentle probing in all directions helps identify extensions. Extensive sepsis requires extensive drainage, often with Penrose drains (Fig. 44-2). These drains can be changed to vessel loop seton drains in the office in 10 to 14 days (Fig. 44-3). Step 5: Find the fistula. Effective, safe probing of a fistula tract is performed gently and sensitively, with a finger in the anus as a guide. It is analogous to picking a lock. The probe is encouraged to follow the fistula tract in all its convolutions. Sometimes the tract is easy to follow because it is straight and wide; other times it is difficult to follow, with twists and turns in multiple planes. Goodsall’s rule does not apply to patients with Crohn disease, and there is a rare possibility that the external

224

Management of Perianal Crohn Disease

biopsy confirm perineal Crohn disease, patients should be treated with anti-TNF medications for some months prior to any attempt at repair. If it seems unlikely that perineal Crohn disease is present, and if the rectal mucosa is normal, an advancement flap repair can be scheduled. If repair is not an option, long-term seton drainage can provide symptomatic relief. 

RECTO/ANOVAGINAL FISTULA

FIGURE 44-3  A more long-term way of controlling sepsis: use of a mushroom catheter to drain a cavity and a seton drain to control a fistula.

opening is being fed by a loop of small bowel or sigmoid colon that has perforated against the pelvic floor. Narrow tracts require thin probes, and tract dilation is a good technique. Knowing the site of the internal opening allows a probe to be inserted from within the anus, which can then be encouraged to meet up with a probe in the fistula. If the tract cannot be identified, one should ensure that the external sepsis is well drained. Step 6: Locate openings. Patients with chronic perianal Crohn disease sometimes have multiple openings. Usually one internal opening, or maybe two, feeds them all. The internal openings are key. Seton drains must be used for drainage of these internal openings. Seton drains can also be placed into various other subcutaneous and perineal sinuses, but they will be able to be removed later. Step 7: Administer antibiotics. Ciprofloxacin and metronidazole are mainstays in the management of perianal Crohn disease. In addition to their antibiotic effect, they have calming effects on the perianal sepsis. Patients should take these antibiotics until it is clear that the sepsis is controlled. Step 8: Manage uncontrolled sepsis. If the perianal sepsis cannot be controlled by local measures, fecal diversion is necessary, which is usually performed by loop ileostomy. Once the perianal disease is under control, it can subsequently be repaired, and there is a chance that the ileostomy can be reversed. Step 9: Control proximal disease. It is difficult to control perineal Crohn sepsis when ileitis or colitis is active and causing pain, diarrhea, and malnutrition. Pari passu with the treatment of the anal disease is effective management of the abdominal disease. This treatment could be medical or surgical. Step 10: Provide definitive treatment. Once the sepsis is controlled, usually a minimum of 2 months after effective seton/ drain placement, consideration is given to managing the fistula. At the initial examination after induction of anesthesia, the presence or absence of perineal Crohn disease is determined. If the appearances or the finding of granulomas on

Anovaginal fistula in a patient with Crohn disease is difficult to treat because the symptom of gas and stool per the vagina is disabling. Fecal diversion is used more often for symptom control, and using seton drains is pointless because the tract is short and usually not infected. The same principles regarding perineal Crohn disease apply here, however, and they determine the role of preoperative anti-TNF therapy. Flap repair is the first choice of surgery as long as a normal perineum is present. If the perineum is thin, a sphincteroplasty should be performed at the time of repair. 

OTHER MANIFESTATION OF PERIANAL CROHN DISEASE Tags: Leave them alone. Tags are an indication of perineal Crohn disease, and the wounds caused by their excision may not heal. Hemorrhoids: Leave them alone, unless they are very symptomatic. Elastic band ligation is a reasonable option for prolapsing, bleeding hemorrhoids. Fissure: Painless fissures are an indication of perineal Crohn disease. Leave them alone and leave the sphincter alone. Anti-TNF therapy will heal the fissure. Painful fissures can be treated in the same manner as any painful fissure (see Chapter 3). Stenosis: If the stenosis is due to chronic diarrhea, leave it alone. If it is due to active sepsis, treat the sepsis. An anus with scarring due to past surgery should be dilated if it is symptomatic. A steroid injection into the scar may prolong the time to the next dilation. Anoplasty in a patient with perineal Crohn disease is potentially disastrous. Chronic skin problems: Patients with Crohn disease are prone to chronic skin problems, including irritation, lichenification, and pruritus because of the seepage and discharge that is often present. Controlling the discharge and keeping the skin clean and dry is the best way of helping the condition settle down. 

SUMMARY Patients with Crohn disease who have perianal symptoms may have perineal Crohn disease or may have a basically normal perineum with anorectal disease superimposed by their inflammatory bowel disease–related stooling abnormalities. This differentiation is key in providing the correct treatment in the correct sequence and obtaining the best outcomes. Control of sepsis is paramount. An algorithm summarizing the decision-making process is provided in Figure 44-4.

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Suggested Reading

EUA ± biopsy, drain sepsis Sepsis controlled

No

Yes

Divert

EUA or definitive management

Perineal Crohn

El-Gazzaz G, Hull T, Church JM. Biological immunomodulators improve the healing rate in surgically treated perianal Crohn’s fistulas. Colorectal Dis. 2012;14(10):1217–1223. Figg RE, Church JM. Perineal Crohn’s disease: an indicator of poor prognosis and potential proctectomy. Dis Colon Rectum. 2009;52(4):646–650. Hyder SA, Travis SP, Jewell DP, et  al. Fistulating anal Crohn’s disease: results of combined surgical and infliximab treatment. Dis Colon Rectum. 2006;49(12):1837–1841. Jarrar A, Church J. Advancement flap repair: a good option for complex anorectal fistulas. Dis Colon Rectum. 2011;54(12):1537–1541.

Proximal disease

No

Yes

Drain/repair

Anti-TNF

No

Yes

Treat

Healed?

No

Yes

FIGURE 44-4  An algorithm for the management of perianal Crohn

disease. EUA, Examination under anesthesia.

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45 Cecal Ulcer Peter G. Deveaux and Michael H. McCafferty

INTRODUCTION Solitary ulcer of the cecum was first described by Cruveilhier in 1832. The subject of cecal ulcers is confusing and complicated because they are uncommon and have multiple causes. A variety of terms, including solitary cecal ulcer, acute cecal ulcer, and benign solitary cecal ulcer, have been used to describe these lesions. Case inclusion varies. For example, Ong et  al, in a recent review of “solitary caecal ulcer syndrome,” excluded cecal ulcers associated with colon cancer, infectious causes, nonsteroidal antiinflammatory drug (NSAID) use, and inflammatory bowel disease, whereas the case report and literature review of “benign solitary cecal ulcer” by Chi and Hanauer described a case that was caused by an infectious agent. Perhaps it is more useful to consider cecal ulcers in the context in which they are found, after which the potential causes can be considered and treatment can be tailored. Knowledge of the possible causes is essential to this approach. 

CAUSES Box 45-1 provides an outline of possible causes of cecal ulceration. With so many possibilities, cecal ulceration is likely the end point of several pathologic pathways. A detailed history including current medications, family history of irritable bowel disease or colon cancer, immune status, and travel history, correlated with presenting symptoms, may point to a possible cause. Cecal cancer can be confused with less common causes of cecal ulcer, such as ulcerated submucosal tumors, mycobacterial or ischemic strictures with ulceration, and drug-induced ulceration. These conditions can cause profound inflammation with a mass effect so as to suggest an ulcerated cancer. In an aging society, drug-related cecal ulcers are common. NSAIDs can damage the stomach, small bowel, and colon. Colonic ulceration is predominantly right sided. Possible mechanisms of injury include reactive oxygen species and Na+/H+ exchange alteration with resultant increased acidification. A variety of infections can produce cecal ulcers, especially in immunocompromised patients who are prone to cytomegalovirus (CMV)-induced cecal ulcers. 

ulceration also may be present. The cecal ulceration can be solitary or multiple. Upon colonoscopy, these ulcers are commonly found on the anterior wall of the cecum or on the antimesenteric border within 2 cm of the ileocecal valve. Significant edema typically surrounds these ulcers, which may have the appearance of a simple peptic ulcer. Biopsy results are nonspecific, but fibrinous granulation tissue and lymphocyte and fibroblast infiltration with disruption and thickening of the muscularis mucosae have been described. Microvascular thrombosis in submucosal vessels due to fibrin deposition may be seen. In patients with CMV infection, viral inclusions within endothelial cells and fibroblasts in the lamina propria are seen. Some patients with cecal ulcers will present with right lower quadrant (RLQ) pain simulating acute appendicitis. A history of NSAID use or immunosuppression should at least lead to consideration of the possibility of a cecal ulcer as a cause of the pain. A strong family history of colon cancer potentially related to Lynch syndrome raises suspicion of a right-sided colon cancer. The usual evaluation of a patient with RLQ pain includes a complete blood cell count and differential, routine chemistries, and imaging studies. Computed tomography BOX 45-1:   Causes of Cecal Ulcers Neoplastic Adenocarcinoma Ulcerated submucosal tumor Pharmacologic Nonsteroidal antiinflammatory drugs Methotrexate Oral contraceptives Infectious Cytomegalovirus Mycobacteria Entamoeba histolytica Campylobacter jejuni Vascular Vasculitis Chronic kidney disease Cecal diverticulitis Inflammatory bowel disease Ischemia Idiopathic

DIAGNOSIS Cecal ulcers can be identified at the time of colonoscopy or during the evaluation of symptoms (Box 45-2). The former scenario is probably most commonly seen in patients taking NSAIDs. Occult blood loss or blood loss anemia may also be seen in asymptomatic patients who take NSAIDs. About 3% of regular NSAID users have colonic ulcers, which are more common with enteric-coated formulations and usually are found in the cecum or right colon. Terminal ileal 226

BOX 45-2:   Cecal Ulcer Presentations Asymptomatic Abdominal pain Perforation Bleeding

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scan findings are nonspecific but include cecal wall thickening, inflammation (streaky or dirty fat) in the adjacent mesocolon, and occasionally the appearance of a cecal mass, which suggests cancer. In the appropriate clinical scenario, appendicitis and Crohn disease may be considered. A barium or water-soluble enema may similarly suggest cancer. Cecal ulcers, whether idiopathic or associated with a known cause, can appear to be ulcerated colon malignancies, and an ulcerated lipoma can mimic an ulcerated colonic malignancy. Colonoscopy with a biopsy will help settle this differential, although the clinical setting will dictate whether a colonoscopy is deemed to be safe. Nonoperative management and delayed colonoscopy is often prudent. 

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BOX 45-3:   Management of Cecal Ulcer • Take full medical history, especially nonsteroidal antiinflammatory drug use, inflammatory bowel disease, immunosuppressive drugs, and cytomegalovirus infection • Stool cultures • Evaluate bleeding, iron deficiency, anemia • Colonoscopy (biopsy ulcer edge) • Complete resuscitation • Computed tomography scan • Treat infectious cause, if found • For poor or no control of pain or bleeding by nonoperative methods, (rare) cecectomy or right colectomy

MANAGEMENT Cecal ulcers can present with localized perforation or free perforation. Management algorithms used for diverticulitis can be applied. The patient with diffuse peritonitis or extensive free air and fluid will require emergency surgery. For the patient who is neither immunosuppressed nor malnourished and who is hemodynamically stable, resection with primary anastomosis is preferred. The extent of resection will be dictated by the level of concern that the surgeon has about the possibility of cancer. The immunosuppressed or profoundly malnourished patient will need a resection with an ileostomy. Percutaneous drainage coupled with antibiotics, gut rest, and delayed colonoscopy is a standard approach to the patient who presents with RLQ pain and a pericecal abscess. Usually, the patient with a small pericecal abscess or contained extraluminal gas can undergo successful management with antibiotics and gut rest alone, followed later by a colonoscopy. Colonoscopy findings in the setting of recovery after successful treatment of an abscess or contained perforation vary and may result in no clear diagnosis. Discontinuation of potentially causative medications, most notably NSAIDs, is important. Cecal ulcers can present with acute lower gastrointestinal (GI) bleeding or occult bleeding and anemia. In acute lower GI bleeding, the evaluation includes a detailed history, ruling out an upper GI source, and a lower GI evaluation that varies depending on the magnitude of the bleeding and hemodynamic stability of the patient. If the patient is stable, colonoscopy will visualize a cecal ulcer and allow biopsy and control of the bleeding. More massive bleeding can require angiography for localization. Embolization or selective vasopressin infusion are angiographic options if a bleeding site is found. The decision for surgery versus angiography is dependent on local expertise and the patient’s characteristics. For example, bleeding related to CMV infection in a debilitated and immunosuppressed patient would be associated with a high operative mortality, thereby favoring angiography. Occult bleeding is evaluated by colonoscopy. A cecal ulcer should be biopsied at the periphery and the base. Biopsy results coupled with the history will often suggest the cause. If no evidence of cancer is demonstrated and a drug-related cause is possible, the potentially causative drug should be discontinued and follow-up blood work and colonoscopy in 6 to 8 weeks should be arranged. Patients who

are asymptomatic or have less common symptoms, such as diarrhea or constipation, and have a cecal ulcer at the time of colonoscopy can undergo similar management. The finding of a normal appendix coupled with focal thickening and inflammation of the cecum during an operation for a clinical diagnosis of appendicitis is an occasional scenario for encountering a cecal ulcer. It may be difficult to differentiate the real cause from cecal diverticulitis or cancer. Resection of the diseased bowel cures the problem and settles the diagnostic confusion. A cecal ulcer is rarely the presumptive diagnosis. Box 45-3 outlines diagnostic and management decisions. 

CONCLUSION Cecal ulcers are uncommon. The diagnosis is not usually made until a colonoscopy or operation is performed (and then only after the specimen is opened). True idiopathic, solitary ulcers occur, but they are usually related to NSAID or other drug use or to infectious causes. Cecal ulceration and its myriad causes can produce RLQ pain and perforation, bleeding and anemia, and diarrhea or constipation. Evaluation of these presentations occasionally reveals the diagnosis of a cecal ulcer(s). Consideration of the possible causes and the status of the individual patient directs diagnostic and treatment decisions.

Suggested Reading Atila K, Gῢler S, Gonen C, et  al. Benign solitary cecal ulcer: a condition that mimics plastron appendicitis. Turkish J Trauma Emerg Surg. 2010;16(6):579–581. Chi KD, Hanauer SB. Benign solitary cecal ulcer: a case report and review of the literature. Dig Dis Sci. 2003;48(11):2207–2212. Cruveilhier J. Un beau cas de cicatrisation d’un ulcere de l’intestin gae le clatant d’une douzaine d’armels. Bull Soc Anat. 1895;7:1–2. Nagar AB. Isolated colonic ulcers: diagnosis and management. Curr Gastroenterol Rep. 2007;9:422–428. Nagaria N, Kansagra A, Ahlawat S. Idiopathic cecal ulcer. J Clin Gastroenterol. 2010;44(10):720. Shah S, Sangman P, et al. Solitary rectal ulcer. Case report and literature review. Oncol Gastroenterol Hepatol Hosp Rep. 2013;2(2).

46

Pseudomembranous Clostridium Difficile Colitis Javier Salgado Pogacnik, Jennifer Holder-Murray, and David S. Medich

INTRODUCTION Clostridium difficile was originally described as a component of the normal intestinal flora of newborn infants by Hall and O’Toole in 1935, who also demonstrated that this organism produced a toxin extremely lethal to mice. However, the “C. difficile era” began in 1974 when Tedesco et al reported high rates of pseudomembranous colitis in patients exposed to clindamycin at Barnes Hospital in St. Louis, Mo. Furthermore, this study was the first to use endoscopy as a diagnostic tool for patients with antibiotic-associated diarrhea. C. difficile–associated diarrhea (CDAD) is presently the most common form of nosocomial diarrhea in the United States. According to the Centers for Disease Control and Prevention, the annual incidence of C. difficile infection (CDI) exceeds 250,000 hospitalized cases, and the prevalence measured by the National Hospital Discharge Survey is estimated to be 9.4 cases per 1000 discharges with a mortality rate of 1% to 2.5%. On the basis of current incidence rates, annual costs for management of CDI range between $800 million and $3.2 billion in the United States per year. Although CDI primarily is considered to be a nosocomial infection, recent population and hospital-based studies have reported an epidemiologic shift during the previous decade, including an increased incidence among outpatient cohorts as well as hospitalized patients. Furthermore, new studies discovered that these changes in the epidemiology were connected with the development of hypervirulent strains of C. difficile, currently recognized as NAP1/BI/027 strains. C. difficile, a spore-forming gram-positive bacterium, is a normal component of gastrointestinal flora in up to 3% of healthy adults and is present in up to 20% of persons who are receiving antibiotic treatment. In several studies, the period between exposure to C. difficile and the occurrence of CDI has been estimated to be a median of 2 to 3 days. The primary mode of C. difficile transmission resulting in disease is person-to-person spread through the fecal-oral route, principally within inpatient health care facilities. C. difficile spores are resistant to gastric acidity and are able to evolve into the vegetative form in the small intestine after ingestion. Colonization of the colon then occurs after the normal flora is disrupted by the use of antibiotics or other predisposing host factors. Once the colonization is accomplished, the bacteria produces exotoxins and other virulence factors that are toxic to colonic mucosa and initiate local and systemic inflammatory cascades. Clinical presentation ranges from asymptomatic infection or diarrhea when the injury is limited to the colonic mucosa to severe fulminant colitis when the consequences of the toxemia become systemic. Major risk factors for the development of CDAD are advanced age (>65 years), prior hospitalization, and use of antibiotics. Certain antibiotics have been associated with nosocomial CDI, such as clindamycin, second- and third-generation cephalosporins (especially ceftriaxone), and fluoroquinolones. When subdividing antibiotics for outpatient cohorts, the use of phenoxymethylpenicillin, dicloxacillin, and penicillins with extended spectra remained statistically 228

significant in a multivariable model analysis as a risk factor for the development of CDAD. However, neither the antibiotic dosage nor the length of administration has been found to correlate with the development of CDI. Other risk factors associated with CDAD include admissions to long-term care facilities, immunosuppression, postoperative state, use of proton pump inhibitors, elemental diets, inflammatory bowel disease, and chemotherapy. 

PRESENTATION OF CLOSTRIDIUM DIFFICILE INFECTION The severity of symptoms of CDI is highly variable, ranging from diarrhea to life-threatening colitis and systemic toxemia. The severity of the disease is likely determined by host factors in combination with the virulence of the toxin produced by the infecting strain. Typical features include watery diarrhea, with as many as 15 to 30 bowel movements per day, and leukocytosis. Many patients report abdominal pain or cramps (30% to 60%) and fever (28%). Some patients do not present with diarrhea and instead demonstrate an ileus. The peripheral leukocyte count is usually 10,000 to 20,000 leukocytes/mm3 but may approach 50,000 leukocytes/mm3. Hypoalbuminemia is a common feature over time because CDI is a protein-losing enteropathy, and patients who are already malnourished for other reasons may be at higher risk of contracting CDI. In rare circumstances, patients experience ileus, toxic megacolon, and colonic perforation. 

DIAGNOSIS The diagnosis of CDI is based on a combination of signs and symptoms. CDI is confirmed by microbiological evidence of C. difficile toxin and toxin-producing C. difficile in stools or by colonoscopic or histopathologic findings that demonstrate pseudomembranous colitis without another cause. Numerous laboratory tests are currently available. Testing for C. difficile or its toxins should be performed only on diarrheal (unformed) stool. Anaerobic culture and bacterial glutamate dehydrogenase antigen tests detect the presence of both nontoxigenic and toxigenic strains of C. difficile. Toxigenic culture and polymerase chain reaction for toxin genes detect only the presence of bacteria capable of making toxin; however, these tests cannot separate active disease from colonization. Enzyme immunoassay testing for C. difficile toxin A and B is rapid but is less sensitive than the cell cytotoxin assay, and thus it is considered suboptimal compared with molecular methods for the diagnosis of CDI. Repeat testing during the same episode of diarrhea is of limited value and should be discouraged. Colonoscopy can identify pseudomembranes, which are a hallmark of CDAD. Nonetheless, a considerable number of patients with CDAD do not demonstrate pseudomembranes, and false-negative rates quoted in larger series are 10% to 25%. Colonoscopy may be

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beneficial for patients in whom the clinical suspicion of CDAD is high, yet laboratory test results continue to be negative. Even though the sensitivity and specificity of a computed tomography (CT) scan to identify colonic abnormalities in these patients is 52% to 85% and 48% to 93%, respectively, various studies have suggested that the early use of CT scanning is highly effective in determining whether patients have fulminant colitis. Typical CT findings include severe colonic wall thickening, dilation, the “accordion sign” (i.e., oral contrast material attenuation in the colonic lumen alternating with an inflamed mucosa with low attenuation), ascites, and pericolonic stranding. 

MEDICAL MANAGEMENT Guidelines from the Society for Healthcare Epidemiology of America (SHEA) currently recommend discontinuing therapy with the inciting antibiotic as soon as possible because this may influence the risk of CDI recurrence. The treatment of an initial episode of mild to moderate CDI (defined by the Infectious Disease Society of America as a white blood cell count [WBC] 20,000 or 35,000 or 5 4. Cardiopulmonary failure 5. Renal failure 6. Mental status change Predictors of mortality after surgical management 1. Advanced age 2. Cardiopulmonary failure 3. Acute renal failure 4. Coagulopathy 5. Hypoalbuminemia 6. Peripheral vascular disease 7. Congestive heart failure 8. Chronic obstructive pulmonary disease 9. Mental status change 10. Surgery more than 3 days after admission requiring mechanical ventilation or vasopressors (7 points), and diffuse abdominal tenderness (6 points). A score greater than 6 was predictive of fulminant disease. The authors suggest careful evaluation and early surgery in this patient cohort. 

CONCLUSION CDI is increasing worldwide, and hypervirulence is emerging. Although most patients resolve the CDI with medical therapy alone, those with severe, fulminant disease have a worse prognosis, and mortality remains high in this cohort. Surgical treatment should be performed earlier in the disease course for improved outcomes.

Surgical options include total abdominal colectomy with end ileostomy or diverting loop ileostomy and intraoperative colonic lavage. This newer strategy of loop ileostomy with colonic lavage offers promising results.

Suggested Reading Adams SD, Mercer DW. Fulminant Clostridium difficile colitis. Curr Opin Crit Care. 2007;13(4):450–455. Bouza E. Consequences of Clostridium difficile infection: understanding the healthcare burden. Clin Microbiol Infect. 2012;18(suppl 6):5–12. Butala P, Divino CM. Surgical aspects of fulminant Clostridium difficile colitis. Am J Surg. 2010;200(1):131–135. Cammarota G, Ianiro G, Gasbarrini A. Fecal microbiota transplantation for the treatment of Clostridium difficile infection: a systematic review. J Clin Gastroenterol. 2014;48(8):693–702. Dallal RM, Harbrecht BG, Boujoukas AJ, et al. Fulminant Clostridium difficile: an underappreciated and increasing cause of death and complications. Ann Surg. 2002;235(3):363–372. Halabi WJ, Nguyen VQ, Carmichael JC, et al. Clostridium difficile colitis in the United States: a decade of trends, outcomes, risk factors for colectomy, and mortality after colectomy. J Am Coll Surg. 2013;217(5):802–812. Hensgens MP, Dekkers OM, Goorhuis A, et  al. Predicting a complicated course of Clostridium difficile infection at the bedside. Clin Microbiol Infect. 2014;20(5):O301–O308. Klein EJ, Boster DR, Stapp JR, et  al. Diarrhea etiology in a children’s hospital emergency department: a prospective cohort study. Clin Infect Dis. 2006;43(7):807–813. Koss K, Clark MA, Sanders DS, et al. The outcome of surgery in fulminant Clostridium difficile colitis. Colorectal Dis. 2006;8(2):149–154. Lungulescu OA, Cao W, Gatskevich E, et  al. CSI: a severity index for Clostridium difficile infection at the time of admission. J Hosp Infect. 2011;79(2):151–154. Neal MD, Alverdy JC, Hall DE, et al. Diverting loop ileostomy and colonic lavage: an alternative to total abdominal colectomy for the treatment of severe, complicated Clostridium difficile associated disease. Ann Surg. 2011;254(3):423–427. discussion 427–429.

Cytomegalovirus Ileocolitis and Kaposi Sarcoma in HIV/AIDS

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Henry R. Govekar and Dana R. Sands

INTRODUCTION An unusual outbreak of Kaposi sarcoma (KS) and Pneumocystis carinii pneumonia among young homosexual men was first reported by the Centers for Disease Control and Prevention (CDC) in 1981. By the end of 1982, the term acquired immune deficiency syndrome (AIDS) was born. In 1983, two research groups published their findings of the retrovirus thought to be responsible for AIDS. Initially referred to as human T-lymphotrophic virus III and lymphadenopathy-associated virus, it turned out both researchers were dealing with the same virus, renamed human immunodeficiency virus (HIV) in 1986. AIDS and HIV are global pandemics. By the end of 2011, the World Health Organization estimated that 34 million people were living with HIV. This number varies from country to country, with African nations being the most severely affected; 4.9% of the African population is living with HIV. More than 2.5 million new cases of HIV were diagnosed in 2011, and the World Health Organization estimates that 1.7 million people worldwide succumbed to AIDSrelated illnesses in 2011. Heterosexual spread is the most common mode of transmission, although in the Western world, homosexual men are still the most frequently affected. HIV infections and the syndrome of AIDS are big public health problems in the United States. The CDC estimated that in the United States in 2010 there were 47,500 new HIV infections and that 872,990 people were living with HIV. The CDC also reported that in the United States in 2010, a total of 32,052 people were diagnosed with AIDS and 487,692 people were living with AIDS. The number of AIDS-related deaths in the United States in 2010 was 15,529, and the estimated total AIDS-related deaths through 2010 was more than 636,048. Gay and bisexual persons and men who have sex with men are the most frequently affected individuals in the United States. White men having sex with men account for 11,200 of the new infections, followed by black men having sex with men at 10,600. HIV is spread through exposure to infected blood (transfusions, needle sticks, or needle sharing), sexual contact (including oral, vaginal, and anal sex), and transmission from pregnant mothers to fetuses. The risk varies depending on the type of exposure and the surrounding circumstances. Direct exposures to infected blood or needle sticks still carry the highest risk. Varying sexual acts carry differing risks of infection, with receptive anal intercourse having the highest risk. The rectum is a well vascularized organ with fragile mucosa, allowing for easier transmission of the virus. Multiple publications have shown that the presence of other sexually transmitted diseases increases the risk of HIV transmission. Primary HIV infection often presents with a short flu-like illness that lasts around 14 days. This illness is accompanied by fever, malaise, and lymphadenopathy. Seroconversion, the period when antibodies are produced by the body’s immune system, occurs in 4 to 10 weeks in most patients but can take up to 6 months. In this “window” period, antibody tests may give false-negative responses. Rapid antibody tests

are available and used for point of care tests to aid in the diagnosis of HIV infection. The Food and Drug Administration has recently approved the use of a rapid in-home test for this purpose. Further testing is required to confirm the diagnosis, and a negative result may not be reliable in the “window” period. The enzyme-linked immunosorbent assay tests the patient’s serum against a plate of HIV antigens. If antibodies are present, the test is confirmed via Western blot. The current immunoassay for detection of HIV is in its fourth generation. It uses a synthetic peptide or recombinant protein antigens that are designed to detect immunoglobulin (Ig)M and IgG antibodies and p24 antigen. A positive result is tested to differentiate HIV-1 antibodies from HIV-2 antibodies. Patients with a positive result from this second test should be considered positive to either HIV-1 or HIV-2 and should seek medical care for further testing for viral load and resistance assays. The introduction of antiretroviral therapy, more commonly referred to as highly active antiretroviral therapy (HAART), has helped improve the outcomes of patients infected with HIV. HAART medication is made up of three categories of drugs: protease inhibitors, non-nucleoside reverse transcriptase inhibitors, and nucleoside reverse transcriptase inhibitors. The combination of these drugs has allowed patients to live longer, increasing life expectancy from months to decades. A recent study from the HIV Prevention Trials Network confirmed that HAART therapy can reduce the risk of sexual transmission of HIV from one partner who is infected with HIV to his or her noninfected partner by 96%. 

CYTOMEGALOVIRUS COLITIS Cytomegalovirus (CMV) is a double-stranded DNA virus first isolated in 1956. It is a member of the herpes virus family, often establishing a latent infection after the initial exposure. Recent statistics suggest that at least 60% of the U.S. population has been exposed to CMV. CMV infection is thought to occur most frequently in immunosuppressed patients. The risk of exposure increases with the age of the patient and varies according to geographic location. CMV, the most common colonic infection in patients with HIV, is found in up to 10% of cases. Clinical disease often occurs when the CD4 counts have fallen below 100 cells/mm3. Prior to the introduction of HAART medication, the incidence of CMV end organ dysfunction was greater than 20% per year among patients with HIV and AIDS. According to reports from recent AIDS literature, the proportion is now 3.2% to 5% per year. The role of CMV in the development of colitis remains unclear. The question is whether the virus itself is the source or acts as a promoter or cofactor for other infections. Infection often produces a vasculitis affecting the capillaries and arterioles, leading to thrombosis and subsequent ischemia, thrombosis, or ulceration. One study of the mechanism of CMV colitis suggested that the CMV virus helped block the macrophage inhibition of the HIV-1 infection, enhancing inflammation and tumor necrosis factor-α release. 231

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The most common symptoms of CMV colitis are bloody diarrhea and abdominal pain. Patients may present with hemorrhage but also can have fever, weight loss, and anorexia. Diarrhea is a symptom of other opportunistic infections in the AIDS population, such as cryptosporidium, Giardia, and shigella. Stool cultures are important. Perianal ulceration may occur and must be distinguished from herpes simplex. Patients presenting with suggestive symptoms will often undergo extensive workup including radiographs, computed tomography scan, and colonoscopy. The computed tomography findings may include colonic wall thickening, localized edema, and fat stranding. These findings are suggestive of colitis, but the diagnosis cannot be confirmed without endoscopic evaluation. A barium enema was often performed in the past, with findings including diffuse mucosal ulceration, skip areas, and thumbprinting. The gold standard for diagnosis for CMV colitis is colonoscopy with biopsy. Endoscopic findings include submucosal hemorrhage and diffuse ulcerations that measure 3 to 5 mm. Random biopsies are recommended to distinguish CMV from other causes of colitis. The ulcers may be seen throughout the colon but can also be patchy, commonly clustering in the right colon. In one study, in 13% of patients, disease was only found in the right colon. For that reason, a full colonoscopy rather than a flexible sigmoidoscopy is important. CMV lesions can resemble those of ulcerative colitis and occasionally have findings of a whitish membrane similar to pseudomembranous colitis. Diagnosis of CMV colitis is confirmed via biopsy. The pathognomonic finding on histology, often described as “owl eyes,” is the presence of large basophilic intranuclear cytomegalic viral inclusion bodies. As the cells infected with the virus necrose, the inclusion bodies become less clear and take on a blue-red appearance, which is highly suggestive of CMV colitis. CMV can be detected by antigen pp65 testing and polymerase chain reaction assays. However, viremia may be present in the absence of colitis, suggesting latent infection. Treatment of patients with CMV but without evidence of colitis is not recommended. Treatment should start with the initiation of HAART therapy by HIV specialists. The treatment of choice for CMV colitis is ganciclovir, and improvement is often seen in the first week. Ganciclovir is a competitive inhibitor of deoxyguanosine triphosphate incorporation into DNA. Treatment dose is 5 mg/kg by intravenous (IV) administration every 12 hours for 14 to 21 days. Adverse effects include neutropenia, anemia, thrombocytopenia, fever, diarrhea, and liver dysfunction. In pre-HAART studies, maintenance therapy was frequently required for patients with evidence of CMV colitis. This maintenance therapy was often given as an oral preparation of valganciclovir or an IV maintenance dose of ganciclovir every 4 to 6 weeks. More recent studies from the National Institutes of Health challenge those recommendations. Current literature does not support the use of lifelong maintenance therapy, although it should be considered if relapse occurs. Foscarnet is a DNA chain inhibitor of phosphorylation that is active against herpes simplex virus and CMV virus. It is often used against ganciclovir-resistant strains of the CMV virus. Foscarnet is given at a dose of 90 mg/kg by IV administration every 12 hours for 14 to 21 days. Foscarnet is nephrotoxic, so the patient must stay well hydrated during treatment to avoid renal impairment. Adverse effects include anemia, headache, nausea, and neurologic toxicities. Other drugs, including oral valganciclovir, can be used when symptoms are less severe. No evidence exists that preemptive therapy with antiviremic medications is necessary in high-risk patients. CMV disease is best prevented by utilization of HAART to keep CD4 counts above 100 cells/mm3. The treatment of CMV retinitis includes newer medications such as cidofovir that have not been adopted for the treatment of CMV colitis. Since the advent of HAART in 1996, the incidence of opportunistic infections, including CMV, has significantly decreased. 

SURGERY Although most patients will respond to medical therapy, emergency surgery may be needed. An initial study from 1988 that examined patients with AIDS who were undergoing intra-abdominal surgery found that CMV colitis was the indication in two thirds of these patients. Mortality was 86% at 6 months. The most common symptoms in these patients were diffuse uncontrolled hemorrhage and perforation, often leading to a subtotal colectomy. In 1994, Soderlund et  al reported their findings on elective resection of patients with CMV colitis for whom medical therapy failed. Within 30 days of surgery, only two minor complications occurred among the eight patients, along with one death. Mean survival was 13 months, and four patients had recurrent or persistent symptoms of CMV enterocolitis within 1 year. Indications for surgery include diffuse hemorrhage, perforation, or toxic megacolon. If emergency surgery is needed, a subtotal colectomy with an end ileostomy is the procedure of choice. 

KAPOSI SARCOMA KS is the most common malignant tumor in patients with AIDS. It is now known to be a vascular tumor caused by the human herpes virus type 8. KS was originally described by Hungarian dermatologist Dr. Mortiz Kaposis in 1872. Prior to the AIDS epidemic, KS was seen in elderly men of Mediterranean descent as a bluish-red skin lesion with a benign course. In the mid 1980s the incidence began increasing in the homosexual community. The AIDS-associated (epidemic) form of KS is the fourth variant of the disease. The disease can be found affecting skin, lymph nodes, and the intestinal tract. Often asymptomatic, gastrointestinal disease can be found in up to 40% of patient with AIDS. The transmission of KS in the AIDS population is thought to be related to anal receptive intercourse because the incidence is 50% higher in homosexual males with AIDS compared with heterosexual males with AIDS. KS commonly appears as a pink to purple skin lesion. These cutaneous lesions can be found in up to 50% of patients with AIDS. The gastrointestinal tract is rarely the sole site affected; most patients present with raised nodular skin lesions on the foot. The most common presenting symptoms of colonic KS are abdominal pain, nausea, obstruction, and gastrointestinal bleeding. Endoscopic findings in patients with KS of the colon vary from small patchy hemorrhagic lesions to papules and nodular lesions projecting into the lumen. Biopsy can reveal spindle-shaped cells and hemosiderin-laden macrophages. Treatment is palliative, aimed at improving symptoms as disease progresses. First and foremost, HAART therapy should be initiated if it is not already in use. Studies have shown a decrease in cases of AIDS-related KS and regression in the size and burden of disease in patients with KS lesions. Publications in the early 1990s showed that the use of radiation therapy can help treat rectal lesions but is of no use for disseminated disease. Topical and local therapies have been used for superficial lesions, which often is not the case in colonic disease. A 0.1% alitretinoin is a topical agent approved for local therapy, but skin irritation may be limiting. Local therapy includes intralesional chemotherapy, cryotherapy, and photodynamic treatment. Vinblastine has shown a response rate of 70% on intralesional injections. Systemic chemotherapy is used for cases of widespread disease. Liposomal anthracyclines (doxorubicin) have become first-line treatment for disseminated KS. The treatment dose for doxorubicin is 20 mg/m2 every 3 weeks. Adverse effects can be mild, including alopecia and neuropathies. A trial looking at 54 patients with AIDS-related KS showed that 82% of patients had a complete or partial response in 6 weeks with a combination of HAART and liposomal doxorubicin. Taxanes, specifically paclitaxel, showed response rates up to 71% in patients with AIDS who had KS. Standard doses are 135 to 175 mg/m2

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given every 3 weeks. Adverse effects were one of the limiting factors, with arthralgias, alopecia, and myelosuppression being the main effects. Low-dose paclitaxel (100 mg/m2 every 2 weeks) produced tumor regression in patients who did not respond to chemotherapy. A complete or partial response was seen in 56% of the patients. Patients were shown to have improved quality of life and tolerated the adverse effects; neutropenia was the most dramatic adverse effect with an incidence of 35%. Interferon alpha, a biologic response modifier, has been available for treatment of KS, especially residual cutaneous lesions. One study showed that high-dose interferon alpha along with zidovudine had a 31% response rate compared with 8% in the low-dose group. Another study showed that liposomal doxorubicin was better tolerated and had less toxic effects than the low-dose treatment of interferon alpha. Surgery is only recommended for uncontrolled hemorrhage, perforation, or obstruction. Surgery should be limited to the diseased segment and may require fecal diversion.

Suggested Reading Arora M, Goldberg E. Kaposi sarcoma involving the gastrointestinal tract. Gastroenterol Hepatol. 2010;6(7):459–462. Centers for Disease Control and Prevention. Diagnoses of HIV infection in the United State and dependent areas, 2011; July 24, 2013. < http://www.cdc.gov/ hiv/library/reports/surveillance/2011/surveillance_Report_vol_23.html >. Centers for Disease Control and Prevention. Monitoring selected national HIV prevention and care objectives by using HIV surveillance data—United States and 6 U.S. Dependent Areas—2010; July 24, 2013. < http://www.cdc.gov/hiv/ surveillance/resources/reports/2010supp_vol17no3/index.htm >. Cohen MS, Makhema J, Elharrar V, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011;365(6):493–505. Dezube BJ. Management of AIDS-related Kaposi sarcoma: advances in target discovery and treatment. Exp Rev Anticancer Ther. 2002;2(2):193–200. Erice A, Tierney C, Hirsch M, et  al. Cytomegalovirus (CMV) and human immunodeficiency virus (HIV) burden, CMV end organ disease, and survival in subjects with advanced HIV infection (AIDS Clinical Trials Group Protocol 360). Clin Infect Dis. 2003;37(4):567–578.

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Kaplan JE, Benson CA, Holmes KK, et al. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Atlanta, GA: Department of Health and Human Services, Centers for Disease Control and Prevention; 2009. Karakozis S, Gongora E, Caceres M, et  al. Life-threatening cytomegalovirus colitis in the immunocompetent patient. Dis Colon Rectum. 2001;44(11):1716–1720. Lichterfeld M, Qurishi N, Hoffmann C, et al. Treatment of HIV-1-associated Kaposi sarcoma with pegylated liposomal doxorubicin and HAART simultaneously induces effective tumor remission and CD4+ T cell recovery. Infection. 2005;33(3):140–147. Maheshwari A, Smythies LE, Wu X, et al. Cytomegalovirus blocks intestinal stroma-induced down-regulation of macrophage HIV-1 infection. J Leukocyte Biol. 2006;80(5):1111–1117. Marques Jr O, Averbach M, Zanoni EC, et  al. Cytomegaloviral colitis in HIV positive patients: endoscopic findings. Arquivos Gastroenterologia. 2007;44(4):315–319. Soderlund C, Bratt GA, Engstrom L, et al. Surgical treatment of cytomegalovirus enterocolitis in severe human immunodeficiency virus infection. Dis Colon Rectum. 1994;37(1):63–72. Tulpule A, Scadden DT, Gill PS, et  al. Multicenter trial of low-dose paclitaxel in patients with advanced AIDS-related Kaposi sarcoma. Cancer. 2002;95(1):147–154. Welles L, Saville MW, Lietzau J. Phase II trial with dose titration of paclitaxel for the therapy of human immunodeficiency virus-associated Kaposi’s sarcoma. J Clin Oncol. 1998;16(3):1112–1121. Wexner SD, Smithy WB, Trillo C, et al. Emergency colectomy for cytomegalovirus ileocolitis in patients with the acquired immune deficiency syndrome. Dis Colon Rectum. 1988;31(10):755–761. Wilcox C, Chalasani N, Lazenby A, Schwartz D. Cytomegalovirus colitis in acquired immunodeficiency syndrome: a clinical and endoscopic study. Gastrointest Endosc. 1998;48(1):39–43. World Health Organization. HIV/AIDS; 2016. < http://www.who.int/gho/hiv/en/ >.

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Diagnosis and Management of Acute Colonic Diverticulitis Daniel L. Feingold and Ravi P. Kiran

INTRODUCTION Colonic diverticula are false diverticula—that is, pockets composed of mucosa and submucosa that have herniated through weaknesses in the colon wall at the points where intramural vasa recta penetrate the inner circular muscle of the bowel (Fig. 48-1, A and B). The generally accepted pathophysiology of diverticulitis centers on a diverticular microperforation causing a bacterial infection. A possible alternative mechanism suggesting that diverticulitis may be a primary inflammatory process has been proposed. When the inflammation resolves uneventfully, the diverticulitis is described as uncomplicated. In contrast, patients who experience clinical sequelae as a result of diverticulitis are described as having complicated diverticulitis (Box 48-1). The presence of a phlegmon or simple extraluminal gas demonstrated on cross-sectional imaging is not considered complicated disease. This chapter will focus on specific aspects of sigmoid diverticulitis, including presentation, diagnostic evaluation, and clinical management. 

PRESENTATION The severity of presentation of diverticulitis ranges from mild to life threatening, depending on the extent and duration of inflammation and peritoneal contamination. Patients with sigmoid diverticulitis typically describe worsening left lower quadrant abdominal pain. According to the lay of the sigmoid loop, some patients may experience right-sided or suprapubic pain, and nonspecific symptoms such as anorexia, nausea, vomiting, constipation, fever, or diarrhea may be present. Dysuria may be reported in cases in which the inflamed colon abuts the bladder, and small bowel obstruction may occur when a loop of small bowel is kinked by an inflammatory attachment to the colon. Patients with fistulizing disease may describe pneumaturia, fecaluria, abnormal vaginal discharge, or a draining skin sinus. Physical examination typically reveals a febrile patient distressed by pain with tenderness in the lower abdomen. Signs of localized peritoneal inflammation, such as rebound tenderness and guarding, often can be elicited. A phlegmon may be appreciated upon palpation. Psoas or obturator signs also may be present because of the inflammatory process. Patients with severe diverticulitis can be hemodynamically unstable with signs of diffuse peritonitis, whereas at the other end of the spectrum, patients with recurrent episodes may recognize an attack early and present when signs are still minimal. 

DIAGNOSTIC EVALUATION Although the constellation of left lower quadrant tenderness, fever, and leukocytosis is suggestive of sigmoid diverticulitis (especially in patients with recurrent diverticulitis whose diagnosis has been 234

previously confirmed), other possible diagnoses should be considered (Box 48-2). Urinalysis and plain abdominal radiographs are helpful in excluding urinary tract infection, kidney stones, and bowel obstruction. Because of the superiority of cross-sectional imaging compared with other types of evaluation, a computerized tomography (CT) scan of the abdomen and pelvis is the most appropriate initial imaging in patients with suspected diverticulitis. Multislice CT imaging with intravenous and intraluminal contrast material has excellent sensitivity and specificity that is reported to be as high as 98% and 99%, respectively. CT findings consistent with diverticulitis may include colon wall thickening, mesenteric fat stranding, phlegmon, extraluminal gas, abscess, stricture, and fistula (Fig. 48-2, A-D). Patients who have early or mild diverticulitis and immunocompromised patients whose ability to mount an appropriate inflammatory response is limited may not demonstrate these typical inflammatory changes. A major benefit of CT imaging is its ability to diagnose other disease processes that may mimic the presentation of diverticulitis. An additional unique benefit provided by CT scanning is the ability to grade the severity of diverticulitis, which has been shown to correlate with risk of failure of nonoperative management, recurrence of infection, persistence of symptoms, and the long-term development of strictures and fistulas. Transabdominal, high-resolution ultrasound can be a useful alternative to CT imaging in patients with relative contraindications to CT scanning such as pregnancy, renal insufficiency, or allergy to contrast material. Although the diagnostic accuracy may be as high as 97%, ultrasound is a more subjective test and is less effective in evaluating alternative diagnoses compared with CT imaging. The utility of ultrasound also can be limited in patients with abdominal tenderness because the use of the transducer probe requires compression. The quality of ultrasound imaging may be reduced in obese patients, as well. Magnetic resonance imaging (MRI) is potentially a better alternative to CT than ultrasound, with a sensitivity and specificity as high as 94% and 92%, respectively, in the setting of diverticulitis. The use and popularity of MRI colonography in this setting may increase, especially in patients requiring serial imaging, because its use does not involve exposure to ionizing radiation. A water-soluble contrast enema, which has been largely supplanted by cross-sectional imaging, may still be useful in evaluating select patients (Fig. 48-3). Use of barium is contraindicated in the acute setting and in patients with a suspected leak because barium extravasation may lead to chemical peritonitis. Although a water-soluble contrast enema can expedite surgery by detecting an occult colon cancer, physicians tend to be reluctant to utilize contrast enemas early in the course of diverticulitis because of fear that a contained perforation will convert into a free perforation. A contrast enema is particularly useful when evaluating certain diverticular fistulas, in cases with equivocal CT findings, when colonoscopy is incomplete because of a rigid tortuous colon, and when a stricture of the sigmoid colon is suspected (Fig. 48-4, A and B).

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BOX 48-1:   Complications of Diverticulitis Free perforation Abscess Sepsis Intestinal obstruction Ureteral obstruction Colon stricture Fistula Lower gastrointestinal bleeding

BOX 48-2:   Diverticulitis: Differential Diagnosis Colon cancer Appendicitis Irritable bowel syndrome Inflammatory bowel disease Ischemic colitis Bowel obstruction Gynecologic disease Urologic disease diagnosis cannot be overstated. A diagnostic colonoscopy is usually performed within 6 to 8 weeks of resolution of the acute episode in patients who have not had a recent colon evaluation. CT colonography may be considered as an alternative. 

A

B FIGURE 48-1  A, Colonic diverticulosis seen in cross-section shows

mucosa/submucosa protruding through openings in the muscular bowel wall where vasa recta penetrate. B, Numerous diverticula seen on colonoscopy.

Although flexible endoscopy is not usually performed in a patient with acute diverticulitis because of concern about the possibility of disrupting a contained perforation, it may be helpful in patients with unresolved questions regarding diagnosis. The main role of colonoscopy in managing patients who have recovered from an episode of presumed diverticulitis is to evaluate the colon to exclude neoplasia, confirm the diagnosis, and rule out any coexisting conditions that may influence management. Although the chance of finding colonic neoplasia in this setting is low, the importance of an accurate

MEDICAL MANAGEMENT In general, patients with uncomplicated disease who tolerate oral antibiotics can be treated initially as outpatients, and the vast majority of patients who are treated in this manner recover. The need for antibiotics in this treatment paradigm has recently been called into question by randomized controlled studies that have demonstrated no significant differences in clinical outcomes between groups of patients treated with and without antibiotics. Patients who do not respond to outpatient management or who have complicated presentations or significant comorbidities are hospitalized and treated with bowel rest and intravenous antibiotics covering gram-negative and anaerobic colonic flora. Nonoperative inpatient treatment is successful in as many as 91% of patients. Once a patient recovers from a bout of diverticulitis, a variety of agents have been suggested to help decrease the risk of recurrent diverticulitis. Although the use of supplemental fiber, rifaximin, antispasmodic agents, mesalamine, and probiotics have been studied in this setting, the efficacy of these types of products remains questionable, and their role in prevention remains to be defined. Patients with diverticulitis and an associated abscess resulting from a contained perforation are usually first treated nonoperatively. Most small abscesses up to about 3 to 4 cm will resolve with standard medical therapy without requiring drainage. Patients who do not improve clinically without drainage and those with large abscesses should undergo placement of percutaneous drains, which allows most patients to avoid urgent surgery. An interval, elective, one-stage colectomy can be considered. Predictors of failed medical therapy without drainage include fever higher than 101.2° F on presentation, location of an abscess in the pelvis, and an abscess size larger than about 5 cm. Patients without an adequate window for percutaneous access may be candidates for laparoscopic drainage. 

SURGICAL MANAGEMENT Patients with generalized peritonitis need emergency surgery. On the way to the operating room, intravenous hydration and antibiotics are administered. Although many of the less urgent indications for

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A

B

C

D

FIGURE 48-2  A, A computerized tomography (CT) scan with mesenteric fat stranding and extraluminal gas. B, A CT scan with pelvic abscess and small bowel obstruction with dilated proximal bowel and decompressed distal bowel. C, A CT scan with thickening of the colon wall with a diverticulum. D, A CT scan with mesenteric abscess and fat stranding.

surgery listed in Box 48-3 are self-evident, some remain controversial and deserve specific mention. The recommendation to proceed with an elective colectomy after two or three attacks of uncomplicated diverticulitis has been called into question, and the decision to recommend sigmoidectomy in this setting should be individualized. This practice recommendation is based on a modern understanding of the clinical outcomes from diverticulitis. The recurrence rate after recovering from an episode of diverticulitis is low, and the likelihood of requiring emergency surgery with stoma creation as a result of recurrent diverticulitis is 1 in 2000 patient-years of follow-up. The practice of recommending an elective colectomy to prevent a future recurrence requiring emergency surgery with stoma creation should be discouraged. Nonetheless, patients in certain situations with recurrent, uncomplicated disease may choose to undergo elective resection. Such instances include patients with multiple repeat attacks clustered over a short time interval, patients with chronic symptoms related to prior bouts of diverticulitis (“smoldering” disease), and patients with certain socioeconomic influences. Transplant patients and those whose immunity is otherwise compromised have a significantly greater risk of recurrent diverticulitis that requires emergency surgery compared with the remainder of the population, and it is commonly recommended that these patients undergo definitive, semielective resection after an episode of diverticulitis. It is generally recommended that patients who experience an episode of complicated diverticulitis have an elective resection. Although patients with a fistula or stricture most commonly require a colectomy for symptom resolution, patients who recover after having an abscess are often asymptomatic, and the recommendation

FIGURE 48-3  Multiple diverticula seen with use of an air-contrast enema.

for surgery in this setting remains controversial. Although low-level evidence suggests that the diverticulitis recurrence rate after having an abscess treated to resolution may be as high as 40%, expectant, nonoperative management in this group of patients has been supported by other reports. Large-scale prospective research is needed

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A

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B

FIGURE 48-4  A, A contrast enema demonstrating a diverticular stricture. B, A contrast enema demonstrating a colovesical fistula.

to better determine the criteria for resection in this setting. However, in patients who are poor operative candidates, nonoperative management even in the setting of complicated diverticular disease should be considered. Young patients (typically considered younger than 50 years at the time of their initial episode of diverticulitis) deserve special mention. Historically, young age has been associated with more severe disease and worse clinical outcomes, and young patients have been counseled to undergo resection after a single bout of uncomplicated diverticulitis. More recent literature demonstrates similar disease severity across age groups in terms of the need for resection at the initial hospitalization and emergency surgery or stoma creation during subsequent attacks. For these reasons, routine elective resection based entirely on young age is no longer recommended.

Surgery A laparoscopic approach to an elective colectomy is preferred because the short-term outcomes and hernia rates are superior to those of open surgery. However, given the degree of technical difficulty of laparoscopic colectomy, the open approach to surgery for diverticulitis should be performed at the discretion of the surgeon. Regardless of the operative approach, the extent of elective resection involves removing the entire sigmoid colon, leaving margins of healthy colon and rectum. It is important that the distal line of transection, and hence the anastomosis, be at the level of the proximal rectum because recurrent diverticulitis may develop in a segment of retained distal sigmoid colon. During the operation, the main sigmoidal artery is usually ligated, or the vessels can be taken at the mid mesentery, sparing the superior hemorrhoidal artery. Preserving the blood supply to the rectum may reduce the risk of anastomotic failure but may not be feasible depending on the postinflammatory anatomy. Patients for whom neoplasia has not been excluded preoperatively should undergo a cancer-type resection. In the setting of urgent surgery in patients with diverticulitis, the surgeon has several options once the inflamed segment has been resected. These options include primary colorectal anastomosis with or without a proximal stoma and end colostomy with

BOX 48-3:   Diverticulitis: Current Indications for Surgery* One episode of complicated diverticulitis Lack of improvement with inpatient medical management Chronic symptoms related to diverticulitis (“smoldering diverticulitis”) Recurrent attacks of uncomplicated diverticulitis Inability to exclude cancer Fistula formation Generalized peritonitis Colon obstruction as a result of a stricture Secondary small bowel obstruction *The decision about whether to perform surgery needs to be individualized.

oversewing of the rectum (the Hartmann procedure). The risk of an anastomotic leak is weighed against the recognition that end colostomy reversal is typically a technically challenging operation with its own risk of morbidity and that many end colostomies are never reversed. The decision to perform a colorectal anastomosis with or without proximal diversion or to create an end colostomy must incorporate patient characteristics (e.g., body mass index, severity of peritonitis, immunosuppression, and the condition of the patient), intraoperative factors (e.g., Hinchey grade, acidosis, and hemodynamic instability), and surgeon preference. Because of the risk of stoma creation and morbidity from an urgent colectomy for diverticulitis, laparoscopic lavage has been suggested as a possible alternative to resection. Until randomized clinical trials determine the utility of lavage, it is not appropriate for patients with purulent or feculent peritonitis to be treated in this way, because the septic focus remains and risks ongoing and recurrent infection.

Suggested Reading Ambrosetti P. Acute diverticulitis of the left colon: value of the initial CT and timing of elective colectomy. J Gastrointest Surg. 2008;12:1318–1320. Chabok A, Påhlman L, Hjern F, et al. Randomized clinical trial of antibiotics in acute uncomplicated diverticulitis. Br J Surg. 2012;99:532–539. Dharmarajan S, Hunt SR, Birnbaum EH, et  al. The efficacy of non-operative management of acute complicated diverticulitis. Dis Colon Rectum. 2011;54:663–671.

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Elagili F, Stocchi L, Ozuner G, et  al. Outcomes of percutaneous drainage without surgery for patients with diverticular abscess. Dis Colon Rectum. 2014;57(3):331–336. Feingold DL. Laparoscopic lavage for Hinchey grade III sigmoid diverticulitis. Semin Colon Rectal Surg. 2011;22:173–179. Feingold D, Steele SR, Lee S, et al. Practice parameters for the treatment of sigmoid diverticulitis. Dis Colon Rectum. 2014;57:284–294. Janes S, Meagher A, Frizelle FA. Elective surgery after acute diverticulitis. Br J Surg. 2005;92:133–142.

Maconi G, Barbara G, Bosetti C, et al. Treatment of diverticular disease of the colon and prevention of acute diverticulitis: a systematic review. Dis Colon Rectum. 2011;54:1326–1338. Rogers AC, Collins D, O’Sullivan GC, Winter DC. Laparoscopic lavage for perforated diverticulitis: a population analysis. Dis Colon Rectum. 2012;55:932–938. Schwenk W, Haase O, Neudecker JJ, Müller JM. Short term benefits for laparoscopic colorectal resection. Cochrane Database Syst Rev. 2005;2:CD003145.

Surgical Treatment of Diverticulitis and its Complications

49

Raul M. Bosio and Conor P. Delaney

INTRODUCTION Surgical management of patients presenting with complications of diverticular disease can be elective, semi-elective, or an emergency, depending on the severity of the disease and patient comorbidities. A laparoscopic sigmoid resection is the preferred procedure in the elective setting, whereas two-stage procedures (e.g., the Hartmann procedure [HP] and primary resection with anastomosis and diversion [PRA]) are better choices in the semi-elective and emergency setting. Performing either the HP or PRA laparoscopically results in decreased morbidity and mortality rates, as well as a shorter length of hospital stay. However, a significant shift in the surgeon’s mindset is required because data suggest that minimally invasive techniques are rarely used in emergencies—in as few as 6% of cases. Although patient characteristics may preclude use of minimally invasive procedures, it is fair to say that the primary limiting factor is usually a lack of familiarity with these techniques. Laparoscopic peritoneal lavage (LPL) may be an alternative option to resection in the emergency setting, especially for Hinchey stage III patients. Although this procedure has been associated with lower morbidity and mortality rates than either laparoscopic or open HP and PRA, further studies are required to determine its role in the treatment algorithm of this disease. The objective of the present chapter is to provide a clear and concise surgical algorithm for the management of diverticulitis, including both elective and emergency operations. Surgical management of patients presenting with recurrent episodes of diverticulitis or those who show inadequate response to optimal medical management will be discussed. Complicated diverticulitis will be reviewed separately. 

UNDERSTANDING DIVERTICULAR DISEASE AND ITS MANAGEMENT From a practical treatment standpoint, acute diverticulitis can be classified into uncomplicated and complicated disease. Generally speaking, uncomplicated disease includes patients who become asymptomatic with medical treatment. Despite being at risk of recurrent episodes, elective surgery is not indicated unless quality of life is significantly affected by the frequency or severity of these episodes. In contrast, complicated diverticulitis is usually an indication for surgery. Complicated diverticulitis includes patients presenting with an associated abscess, fistula (colovesical, colovaginal, or colocutaneous, among others), acute colonic obstruction, or diffuse purulent or feculent peritonitis. Treatment ranges from semi-elective to emergency procedures. In some cases, emergency situations can be temporized by placement of a percutaneous drain or stent. Patients who have persistent symptoms after an acute episode of uncomplicated diverticulitis and those in whom symptoms of partial obstruction develop will require an elective operation. Management of diverticular disease is summarized in Table 49-1. 

ACUTE UNCOMPLICATED DIVERTICULITIS The prevalence of diverticular disease ranges from 5% to 45% and increases with age. Eighty percent of patients respond to outpatient medical management. Treatment consists of broad-spectrum antibiotics and dietary changes once the acute event is resolved. Although the role of antibiotics during acute episodes of diverticulitis has been questioned on the basis of some recent data, antibiotics remain the primary treatment for this disease. The percentage of patients requiring hospitalization is small (20%), but this still means approximately 300,000 admissions per year at an annual cost of $1.8 billion (direct medical cost). Up to 30% of these patients will subsequently experience recurrent episodes or progress to complicated disease requiring surgery.

Who Requires Elective Surgery after Uncomplicated Diverticulitis? As previously discussed, elective resection is indicated for patients with recurrent episodes of diverticulitis that significantly affect their quality of life. Previous practice guidelines recommended surgery after a first episode of diverticulitis in patients 50 years or younger and after two episodes of diverticulitis at any age. Current practice parameters for the treatment of sigmoid diverticulitis published by the American Society of Colon and Rectal Surgeons in 2014 are more conservative. These recommendations are now aligned with a large body of literature that has demonstrated that age at the time of the first episode of diverticulitis is not a predictor of more aggressive disease. Recommendations based on the number of prior episodes of uncomplicated diverticulitis have also come under scrutiny, and the number of prior episodes is no longer a major indicator of the need for surgery. Whereas a total of four attacks was set as a threshold at which the risk of surgery would be acceptable to reduce the number of ostomies or mortalities caused by the disease, in practice, the absolute number may not be so important. For example, four attacks over four decades is a very different situation to three attacks in 6 months. Thus indications for elective surgery in persons with uncomplicated disease should be individualized based on the severity, frequency, and the impact of these recurrences. Patients with persistent symptoms of acute diverticulitis or chronic obstruction despite adequate medical management would benefit from elective surgery. Immunocompromised patients (e.g., transplant patients, patients with collagen-vascular diseases, or patients with chronic use of steroids) constitute a separate subgroup; in this population, surgery should be considered during the first episode of diverticulitis, although surgery is not always necessary in our experience. Laparoscopic sigmoid resection is the preferred technique for elective sigmoid colectomy because an abundance of data have shown significant differences in morbidity, mortality, length of hospital stay, and 239

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TABLE 49-1:   Diverticular Disease: Management Algorithm Surgical Management

Disease Classification

Presentation

Initial Management

Uncomplicated diverticulitis

First episode Recurrent episode

Not indicated Antibiotics and dietary changes Colonoscopy or BE after resolution of symptoms

Recurrent episodes affecting quality of life Nonresolving episode Immunocompromised patients

Antibiotics and dietary changes Colonoscopy or BE to rule out IBD, IBS, and cancer

Elective laparoscopic sigmoid resection

With abscess formation

Antibiotics and percutaneous drainage as needed Colonoscopy or BE once recovered

Laparoscopic sigmoid resection

With fistula formation

Antibiotics and dietary changes Colonoscopy or BE to rule out IBD, IBS, and cancer

Laparoscopic fistula takedown and sigmoid resection Consider omental flap

With purulent peritonitis (Hinchey stage III)

Antibiotics and sepsis-directed therapies Emergent procedure required

Laparoscopic or open resection and anastomosis with/without loop ileostomy or laparoscopic Hartmann vs. open procedure Consider laparoscopic lavage

With feculent peritonitis (Hinchey stage I-V)

Antibiotics and sepsis-directed therapies Emergent procedure required

Laparoscopic or open resection and anastomosis with/without loop ileostomy or laparoscopic Hartmann vs. open procedure

Chronic partial obstruction

Evaluation of colon: colonoscopy or BE Rule out IBD, IBS, and cancer

Laparoscopic sigmoid resection with or without temporary diversion depending on proximal colon quality

Acute colonic obstruction

Stenting as a bridge to surgery (controversial) Correct overall patient’s status Emergent procedure may be required

Laparoscopic resection and anastomosis with/without loop ileostomy or laparoscopic Hartmann vs. open procedure

Acute colonic obstruction— closed-loop obstruction

Emergent procedure required Special considerations: intact vs. necrotic cecum

Laparoscopic vs. open segmental colectomy vs. total colectomy with ileorectal anastomosis or end ileostomy (necrosis present)

Complicated diverticulitis

BE, Barium enema; IBD, inflammatory bowel disease; IBS, irritable bowel syndrome.

cost in favor of minimally invasive procedures. Combining laparoscopic technique with enhanced postoperative recovery programs contributes even further to optimize patient care and reduce cost and resource utilization. “Converting a hospital” from open to minimally invasive surgery is feasible as a short-term goal. This endeavor requires the addition of surgeons trained in minimally invasive colorectal procedures to the staff. Putting enhanced recovery pathways in place requires educating surgeons, patients, nurses, ancillary staff, residents, and anesthesia colleagues and allows an institution to maximize patient care and resource utilization. A decrease in cost is a direct by-product of this process. Although both single-port minimally invasive procedures and robotic approaches have been described in the treatment of diverticular disease, these techniques may be associated with higher morbidity (i.e., hernia formation after single-site surgery) and increased overall cost and operative time (robotic surgery) when compared

with conventional laparoscopy. The technical aspects of a laparoscopic sigmoid colectomy will be discussed later in this chapter. 

COMPLICATED DIVERTICULITIS Acute Diverticulitis Complicated by Abscess Formation: Converting an Emergency Situation into a Semi-Elective Procedure Clinical presentations vary from one patient to another and may be masked by immunosuppression, steroid use, and the location of the infectious process (e.g., a small abscess confined to the mesocolon or deep in the pelvis versus a large superficial left lower quadrant

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abscess). The Hinchey classification system helps surgeons identify patients who may benefit from medical management versus those requiring resection. Hinchey stage I-II includes patients who present with either an associated abdominal (I) or pelvic (II) abscess, whereas Hinchey stage III-IV represents a diffuse purulent (III) or fecal (IV) peritonitis. Patients presenting with an episode of diverticulitis complicated by an abscess usually respond to medical management that includes intravenous fluid hydration and broad-spectrum antibiotics. Computed tomography (CT) performed with use of oral and intravenous contrast material is the diagnostic tool of choice to evaluate the severity of the disease and to help determine the need and feasibility of placing a drain. Most patients (>80%) will respond to antibiotic treatment; however, persistent fever, abdominal pain, and leukocytosis after treatment with intravenous antibiotics for 48 to 72 hours should prompt reevaluation and a decision about whether percutaneous drainage is indicated. Findings upon admission that are suggestive of a high failure rate without a drain are fever higher than 101.2°F, the presence of a pelvic abscess (in contrast with an abdominal or “intra” mesocolonic abscess), or an abscess larger than 4 cm. Overall, 75% to 95% of these patients will respond to medical treatment and avoid emergency surgery. In a retrospective analysis of 136 patients who presented with perforated diverticulitis, five patients had free air and nonloculated free fluid at presentation and underwent surgical exploration upon admission. Of the remaining 129 patients, 109 had an abscess and limited areas of free air on an initial CT scan. Only 28% of these patients required percutaneous drain placement. Combined medical and percutaneous drainage was successful in 95% of the cases, with failure occurring in only seven patients (5%) who required a semi-elective operation. Patients who recover from an episode of complicated diverticulitis may become candidates for an elective laparoscopic sigmoid resection, although most surgeons would not operate on a patient who had one simple abscess that resolved easily. 

Acute Diverticulitis Complicated by Purulent or Feculent Peritonitis: Surgical Options in the Emergency Setting Acute diverticulitis presenting with free intra-abdominal perforation carries significant morbidity and mortality. Patients presenting with signs of peritonitis or a rigid abdomen and intra-abdominal free air visible on plain radiographs require emergency surgery. In patients where physical examination findings and initial imaging studies are inconclusive, a CT scan is indicated. Findings of free air and diffuse, nonloculated fluid suggest diffuse purulent or fecal peritonitis, which is an indication for surgical exploration. Depending on patient comorbidities and time from onset of symptoms to presentation at the emergency department, signs of sepsis or even of septic shock may already be present. Intravenous broad-spectrum antibiotics and aggressive fluid resuscitation should be started promptly. Open diversion without removal of the source (a classic threestage operation) is no longer recommended because it has a much higher rate of morbidity and mortality than other procedures. An exploratory laparotomy with planned resection is standard procedure in most of these cases. A nonresective exploratory laparoscopy and peritoneal lavage (LPL) has been described as an alternative, although this approach is supported mainly by results from small series. Several prospective trials are currently underway in Europe. Investigators performing a prospective randomized trial in which patients were enrolled in either an LPL arm versus an HP or PRA arm recently closed the LPL arm because of safety concerns; although the data leading to this decision are not yet available, LPL cannot be recommended as a valid surgical alternative at this time. Thus a laparoscopic/open HP or a PRA, often with a protective loop ileostomy, are the two operations a surgeon should consider in the setting of purulent peritonitis and in selected patients with

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feculent peritonitis. When treating patients who are immunocompromised, malnourished, and/or taking steroids or vasopressors (the use of these medications at the time of surgery should raise concern for organ failure and septic shock), and in most cases of a diffuse feculent peritonitis, an HP is the better option. Such patients have a poor response with any further complications, especially an anastomotic dehiscence, even with a protective loop ileostomy in place. This is also true when treating patients with chronic life-threatening conditions such as severe congestive heart failure. However, for some patients, a “temporary” Hartmann colostomy will end up being permanent. As long as patients are hemodynamically stable, we favor a laparoscopic approach because it transforms recovery and minimizes issues with wound management. If a stoma is required, the specimen often can be removed through the ostomy site. Obviously this approach depends on the experience of the surgical team. The literature favors a laparoscopic approach whenever patient characteristics and surgical expertise are suitable. A final and important factor in whether patients have an anastomosis or temporary ostomy is the quality of the distal rectum. Some patients, even with a Hinchey stage II history, have so much rectal inflammation that the rectum is not suitable for anastomosis, or a much lower transection is required. We do not favor such a low transection in an emergency setting because of its effect on the patient’s bowel function. 

Hartmann Procedure and Reversal When an ostomy is being considered in patients undergoing semielective or emergent operations, the ostomy site should be marked preoperatively. Division of the rectum just distal to the rectosigmoid junction is ideal, avoiding any presacral mobilization. This approach prevents a more difficult second operation. In these cases we deliberately try not to divide the inferior mesenteric artery because the distal rectum then retracts low in the pelvis, particularly with laparoscopic approaches. Although the lack of adhesions after laparoscopic surgery usually means the distal rectum is easy to find at a second procedure, if the first operation is performed open, placement of nylon sutures makes finding the rectal stump easier. Proximally, the colon is divided in an area where the colonic wall is not thickened and hypertrophied, and ideally in a section where no diverticulae are present. It is important to ensure that the colon has been mobilized enough so that it will reach through the abdominal wall without tension. The splenic flexure is almost never mobilized at this operation and is left as a fresh plane for the second surgery. Using the ostomy site as the extraction site and dividing the colon extracorporeally is our preference, unless the phlegmon is extremely large. Another option for much larger specimens is to divide the colon proximally using endostaplers. The specimen can be then extracted through a Pfannenstiel incision while the proximal end is brought up through the ostomy site and matured at the end of the procedure, once all wounds are closed. If the initial resection is performed open and the patient is obese, it may be difficult to make the end colostomy reach the abdominal wall. In this case, the end of the colon can be stapled across and a loop transverse colostomy can be constructed, which avoids the need to mobilize the splenic flexure. Under these circumstances the closure should be performed within 6 months or the diverted segment of colon may atrophy and make colostomy takedown difficult. Reversal of the end colostomy is also performed laparoscopically, even when the initial procedure required open surgery. The procedure starts with end colostomy mobilization and insertion of an anvil into the proximal healthy bowel. This is returned to the abdomen, and a port is inserted to insufflate the abdomen. The remaining ports are inserted. The proximal colon is mobilized adequately, and the distal rectum is defined. If the distal rectum is

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healthy enough, a direct anastomosis is performed. If it is thickened or in any way abnormal, it is resected and a primary anastomosis is performed. The resected stump is removed through the ostomy site at completion of the case. 

COMPLICATED DIVERTICULITIS WITH FISTULA FORMATION Although fistulas are almost always managed electively, they add a level of complexity to surgical management. Colovesical (65%), colovaginal (25%), and colocutaneous are the most common types. Coloenteric, colouterine, and some other forms of fistulas have been described but are fairly rare and tend to follow similar management principles. As with any patient with suspected diverticulitis, preoperative evaluation of the colon is necessary to rule out other possible causes such as inflammatory bowel disease and cancer.

Colovesical Fistulas: Diagnosis and Management Patients with diverticular disease complicated by a colovesical fistula usually present with a history of pneumaturia and even fecaluria, with or without (recurrent) urinary tract infections. A history of previous episodes of diverticulitis is common. Clinical manifestations vary from patient to patient, and urosepsis could be the presenting symptom in elderly or debilitated patients. Appropriate rehydration, drainage of the bladder with a Foley catheter, and broad-spectrum antibiotics may convert an emergency into an elective situation, ­allowing for correction of nutritional and electrolyte/ metabolic abnormalities (i.e., renal dysfunction) prior to surgery. Urinalysis is usually abnormal, and a CT scan may show air in the bladder with no history of bladder instrumentation. Cystoscopy is usually not necessary, except when malignant invasion of the bladder is suspected. When treating colovesical fistulas, the bladder defect is usually not identifiable, and if it is, it doesn’t require repair. It is usually located near the dome of the bladder. The bladder is routinely filled in a retrograde fashion through the Foley catheter to assess for the presence of a defect that might require repair. If none is found, the Foley catheter is kept in place for 48 hours and a cystogram is obtained prior to removal and subsequent hospital discharge. In cases in which a leak is seen, the edges are debrided laparoscopically, and laparoscopic placement of reabsorbable sutures is performed. In these cases, the Foley catheter is maintained in place after surgery for 2 weeks before obtaining a cystogram. Interposing omentum between the bladder and the colorectal anastomosis may decrease the chance of a fistula recurring in the setting of an anastomotic leak. 

Colovaginal Fistulas: Diagnosis and Management Colovaginal fistulas may develop in women who have a history of recurrent episodes of diverticulitis. These patients have almost always undergone a hysterectomy. In many cases, the fistula opening is very small and difficult to identify. Patients may report passing gas and even stool through the vagina. Complaints of brown malodorous discharge and recurrent urinary tract infections are common. Vaginal examination may show some brown discharge, granulation tissue, or umbilication of the vaginal wall. Numerous diagnostic studies such as a CT scan, contrast enema, flexible sigmoidoscopy, and vaginoscopy have been used to ensure a correct diagnosis prior to surgery, although we often confirm the diagnosis at surgery without multiple additional tests. A thorough anorectal examination rules out an anovaginal fistula. Because of the more indolent and chronic nature of this problem, patients may present with significant weight loss and various degrees of malnutrition, and improving the patient’s overall

status prior to surgery may help avoid the need to construct a protective loop ileostomy. In the management of a colovaginal fistula, placing a healthy wellvascularized tissue, such as the omentum, between these two organs once the fistula has been taken down may help decrease the chance of fistula reformation. Laparoscopic creation of an omental flap to interpose between the vagina and the newly constructed colorectal anastomosis is technically easy. The omentum is divided very close to the stomach wall, preserving the gastroepiploic pedicle. Vessels from the greater curvature of the stomach to this pedicle can be safely divided with the use of advanced bipolar devices. The vaginal defect itself is sutured with absorbable sutures if feasible. 

Colocutaneous Fistulas: Diagnosis and Management Colocutaneous fistulas are uncommon and generally occur in patients with previous placement of a percutaneous drain for an abscess during a previous episode of acute diverticulitis. In the absence of a persistent infectious process or distal colonic obstruction, these fistulas may close over time. When they persist, treatment follows the same principles that are discussed in the following sections. In these cases, however, adequate drainage of the fistula tract and healing by secondary intention is important to prevent abdominal wall complications. 

ACUTE COLONIC OBSTRUCTION: PATIENT SELECTION FOR EMERGENT VERSUS SEMI-ELECTIVE OPERATIONS Recurrent episodes of diverticulitis can lead to chronic obstruction of the sigmoid colon, with patients requiring a semi-elective operation. A superimposed inflammatory/infectious process may cause these patients to present with symptoms of acute large bowel obstruction that may require emergency surgical treatment. In cases in which the ileocecal valve is incompetent and the small bowel is dilated, initial treatment with intravenous fluids, nasogastric tube decompression, and intravenous antibiotics may allow the acute inflammatory process to resolve. This initial treatment allows time to correct electrolyte abnormalities and improve renal function. Often these patients have been vomiting and are dehydrated when they present to the emergency department. A competent ileocecal valve, on the other hand, creates a closed-loop obstruction that could lead to necrosis and perforation of the cecum, as dilation progresses and cecal diameter reaches 12 cm or more. Changes in operative planning and decision making are usually required. In cases in which patchy necrosis or serosal tears at the level of the cecum are present, the surgeon is faced with the need to perform a total colectomy with either an end ileostomy or an ileorectal anastomosis with or without a diverting loop ileostomy. A controversial option that may function as a bridge to a more elective surgery is placing a stent through the stenotic segment. The length of the stenosed segment in diverticular disease is usually longer than that caused by cancer and may be very technically challenging to stent. However, as expertise with stents increases, placing a stent through the stenotic segment could represent an alternative approach in these cases. Relieving the closed-loop obstruction may allow time to correct metabolic abnormalities and improve overall patient status. As the colon recovers tone and caliber, the risk of perforation when manipulated during surgery, especially if a minimally invasive approach is planned, may decrease. Although it is not mandatory, patients may be able to tolerate a bowel preparation and undergo a more selective laparoscopic resection. Nevertheless, performing a segmental resection and anastomosis without prior mechanical preparation has been demonstrated to be safe in numerous publications, and it does not mandate a protective loop ileostomy. On-table colonic lavage is currently not a mandatory step prior to construction of an anastomosis in the management of obstructive

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disease. These points are discussed in more detail in the chapter on large bowel obstruction. 

RECURRENT DIVERTICULITIS IN PATIENTS WHO HAVE PREVIOUSLY UNDERGONE RESECTION FOR DIVERTICULAR DISEASE Recurrent diverticulitis is rare after adequate resection. In many cases, the reason for these new episodes of diverticulitis can be traced to the initial operation. Although removal of all the diverticuli is not necessary, failure to perform a complete sigmoid resection increases the risk of the development of recurrent diverticulitis from 4% to 16% as a result of leaving the high pressure zone of the rectosigmoid. It is critical that distal bowel division take place in the upper rectum, just distal to the rectosigmoid junction. Patients with recurrent diverticulitis should have a colonoscopy to exclude Crohn disease or a newly diagnosed colon cancer. Irritable bowel syndrome also can mimic diverticulitis, and ascertaining a correct diagnosis can be difficult, especially when investigative studies such as a contrast CT or a barium enema show diverticulosis and a poorly distensible colon near the anastomotic site. Whenever an elective repeat operation is recommended, it is important to manage patient expectations preoperatively. When irritable bowel syndrome is present, some of the symptoms may not improve after resection. Having this conversation “after the fact” may lead to a breakdown of the patient-surgeon relationship; it is therefore recommended that prior to a repeat operation, alternative treatments such as probiotics, nonabsorbable antibiotics, and 5-aminosalicylic acid compounds be discussed.

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Suggested Reading Biondo S, Lopez Borao J, Millan M, et  al. Current status of the treatment of acute colonic diverticulitis: a systematic review. Colorectal Dis. 2012;14(1):e1–e11. Delaney CP, Brady K, Woconish D, et  al. Towards optimizing perioperative colorectal care: outcomes for 1,000 consecutive laparoscopic colon procedures using enhanced recovery pathways. Am J Surg. 2012;203(3): 353–355. Dharmarajan S, Hunt SR, Birnbaum EH, et  al. The efficacy of nonoperative management of acute complicated diverticulitis. Dis Colon Rectum. 2011;54(6):663–671. Feingold D, Steele SR, Lee S, et al. Practice parameters for the treatment of sigmoid diverticulitis. Dis Colon Rectum. 2014;57(3):284–294. Klarenbeek BR, Veenhof AA, de Lange ES, et al. The Sigma-trial protocol: a prospective double-blind multi-centre comparison of laparoscopic versus open elective sigmoid resection in patients with symptomatic diverticulitis. BMC Surg. 2007;7:16. Regenbogen SE, Hardiman KM, Hendren S, Morris AM. Surgery for diverticulitis in the 21st century: a systematic review. JAMA Surg. 2014. Senagore AJ, Duepree HJ, Delaney CP, Brady KM, Fazio VW. Results of a standardized technique and postoperative care plan for laparoscopic sigmoid colectomy: a 30-month experience. Dis Colon Rectum. 2003;46(4):503–509. Stulberg JJ, Champagne BJ, Fan Z, et al. Emergency laparoscopic colectomy: does it measure up to open? Am J Surg. 2009;197:296–301. Swank HA, et al. The Ladies trial: laparoscopic peritoneal lavage or resection for purulent peritonitis and Hartmann’s procedure or resection with primary anastomosis for purulent or faecal peritonitis in perforated diverticulitis (NTR2037). BMC Surg. 2010;10:29. Turley RS, Barbas AS, Lidsky ME, Mantyh CR, Migaly J, Scarborough JE. Laparoscopic versus open Hartmann procedure for the emergency treatment of diverticulitis: a propensity-matched analysis. Dis Colon Rectum. 2013;56(1):72–82.

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Lower Gastrointestinal Hemorrhage Caroline C. Jadlowiec and Jeffrey L. Cohen

INTRODUCTION Lower gastrointestinal hemorrhage refers to blood loss originating distal to the ligament of Treitz that is symptomatic and necessitates hospital admission. It is a serious and potentially life-threatening situation. Although rectal hemorrhage can be seen in any age group, most patients requiring admission to the hospital are elderly and have coexistent medical problems. Because of these comorbidities, management is complex. Many patients stop bleeding spontaneously, but up to 30% experience bleeding again during or after their hospitalization. In the adult population, diverticulosis and vascular ectasias cause more than 90% of cases of lower gastrointestinal hemorrhage. Other less common causes are listed in Box 50-1. Although the focus of this chapter will be on general evaluation and management of lower gastrointestinal hemorrhage, it is worthwhile to briefly examine and contrast the two most common causes. 

ETIOLOGY In Western society, up to 65% of the population will have diverticulosis by age 85 years. Twenty percent of patients with diverticulosis coli will present with bleeding during their lifetime, and 5% will experience a severe hemorrhage. Although almost all of these patients stop bleeding spontaneously, bleeding will recur in 25%. Most diverticula are located in the sigmoid and descending colon, likely as a result of the sigmoid colon’s high intraluminal pressure. Despite this leftsided predilection, diverticular bleeding is distributed fairly equally between the right and left sides of the colon. The pathogenesis is believed to be injury to the submucosal arterial branches of the vasa recta that become stretched over the diverticulum and are then subject to trauma by the passage of stool. It has been speculated that the wider necks of the right-sided diverticula permit a greater length of the artery to be exposed to injury, thus increasing the percentage of bleeding from proximal diverticulosis. Diverticulitis is not usually associated with bleeding vasa recta. Vascular ectasias of the colon are also believed to be acquired lesions because they are rarely observed in patients younger than 40 years. Also known as angiodysplasia or arteriovenous malformations, these lesions are predominantly located on the right side of the colon. It is likely that the increased wall tension of the cecum accounts for the presence of these lesions. As described by Boley, repeated lowgrade obstruction of the submucosal veins over many years leads to the characteristic tortuous, dilated, thin-walled vessels, which can be identified both grossly and histologically. Arteriovenous connections occur relatively late in this process and result from increased pressure, leading to disruption of the precapillary sphincters. A high incidence of cardiac disease, especially aortic stenosis, has been observed in patients with vascular ectasias, and as many as 25% of patients who present with bleeding arteriovenous malformations are noted to have 244

aortic stenosis. First described in 1958, Heyde syndrome describes a triad of aortic stenosis, an acquired coagulopathy, and anemia occurring as a result of intestinal angiodysplasia. Although bleeding has been reported to cease with aortic valve replacement, gastrointestinal hemorrhage is not an indication for open heart surgery. Rather, the decision to perform aortic valve replacement should be made on the basis of traditional indications, with surgery for lower gastrointestinal bleeding proceeding first if critical aortic stenosis is not present. Bleeding from vascular ectasias tends to be venous and, therefore, is not usually as brisk as that seen with diverticulosis. In more than 90% of patients, bleeding will stop spontaneously, but repeated episodes of bleeding are common, with an incidence that approached 85% in one study. 

INITIAL EVALUATION AND RESUSCITATION Because many patients who present with lower gastrointestinal hemorrhage lose a large amount of blood, resuscitation must accompany the initial evaluation. Despite the varied causes for lower gastrointestinal hemorrhage, the initial approach is standard. In trying to quantify the degree and characteristics of a patient’s bleeding, it is important to realize that even small amounts of blood in the toilet can appear massive to the patient. Because blood is a cathartic, more importance can be attached to the frequency of bloody bowel movements prior to presentation than in trying to quantify the exact amount of blood loss. Significant lower gastrointestinal bleeding often causes hemodynamic instability, and it is essential to treat this condition while evaluating underlying causes. A lack of hemodynamic instability does not necessarily imply a minor bleed, however. A study from our institution revealed that, at presentation, 90% of patients with positive findings of an arteriogram were normotensive or hypotensive, and only 30% were tachycardic. As the initial evaluation progresses, the basics of cardiopulmonary resuscitation must be followed. Large-bore intravenous catheters should be placed with infusion of a balanced salt solution. Blood samples are drawn for laboratory studies, including hemoglobin, hematocrit, coagulation studies, blood typing, and crossmatching. Attempts should be made to keep the patient normothermic. Placement of a Foley catheter permits accurate assessment of urinary output and assists in fluid replacement. Patients with massive hemorrhage, severe cardiac disease, or multiple comorbidities require intensive monitoring, which may include systemic arterial, pulmonary arterial, electrocardiographic, and oximetric monitors. Early in the evaluation, a nasogastric tube should be placed. In many studies of lower gastrointestinal bleeding, as many as 10% of patients initially believed to be bleeding from a colonic source were ultimately determined to be bleeding from an upper gastrointestinal lesion. If clear bile is not returned upon nasogastric aspiration, an

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BOX 50-1:   Cause of Colonic Hemorrhage Diverticular disease Vascular ectasias Colonic neoplasms Ischemic colitis Radiation colitis Infectious colitis Inflammatory bowel disease Trauma Hematologic disorders Rectal varices Hemorrhoids Anal disease Endometriosis Solitary rectal ulcer Postpolypectomy bleeding

upper endoscopy should be performed as part of the evaluation. Even if clear bile is noted upon lavage, upper gastrointestinal bleeding can be seen in up to 16% of patients. The nasogastric tube can be left in place to use as access for a rapid mechanical bowel preparation to expedite a colonoscopy. While resuscitation is proceeding, important information should be obtained from the patient’s history in relation to the risk for continued or recurrent bleeding. Asking about alcohol or aspirin ingestion, a prior history of gastrointestinal bleeding, the presence of any bleeding diathesis, coagulopathy from anticoagulation therapy, and comorbid diseases is extremely important. Upon physical examination, particular attention should be directed to identifying stigmata of advanced liver disease. In addition, the presence of an abdominal mass may indicate an unsuspected colon carcinoma. Although diverticulitis is not commonly seen with bleeding diverticulosis, a finding of abdominal tenderness may suggest that possibility. More likely, however, would be a diagnosis of ischemic colitis or inflammatory bowel disease when a patient presents with abdominal pain, tenderness, and lower gastrointestinal hemorrhage. Finally, rigid sigmoidoscopy is essential early in the evaluation of patients with lower gastrointestinal bleeding. It is generally performed in the emergency department to rule out an anorectal source of bleeding. Hemorrhoids associated with portal hypertension can bleed massively, and other low rectal or anal sources of bleeding may be treatable in the acute setting. Additionally, observation of the rectal mucosa may suggest a possible source of bleeding, such as infectious, inflammatory, or ischemic proctocolitis. 

DIAGNOSTIC TESTING The diagnostic phase of lower gastrointestinal bleeding usually proceeds once the patient has been stabilized. However, because of the dynamic nature of colonic hemorrhage, diagnostic testing occasionally must be initiated while the patient is still being stabilized. In fact, aggressive diagnostic maneuvers can have the benefit of localizing bleeding before it has stopped. Identifying the source of bleeding matters, especially for the 25% to 30% of patients who will experience significant recurrent bleeding. Early aggressive diagnostic procedures may achieve this goal and permit nonoperative therapeutic maneuvers as well. The most commonly used diagnostic studies performed for lower gastrointestinal bleeding are radionuclide scanning, multidetector computed tomography (CT angiography), angiography, and colonoscopy. In many patients, a combination of these tests will be needed, and occasionally, because of recurrent bleeding, it will be necessary to repeat them. Both angiography and colonoscopy can be of potential

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therapeutic benefit, and this advantage adds to their usefulness as diagnostic modalities.

Scintigraphy Two types of radionuclide scans are available to image gastrointestinal bleeding. Initially, sulfur colloid was used as an intravascular marker that could not return to the vascular compartment once bleeding into the intestine had taken place. However, its rapid clearance by the reticuloendothelial system results in two distinct disadvantages. First, the patient must be actively bleeding at the time of the injection because more than 90% of the trace is cleared within 7 minutes. Second, accumulation of activity by the liver and spleen obscures evidence of bleeding from the colonic flexures. A second technique, injection of technetium-labeled red blood cells, has supplanted sulfur colloid scanning as the nuclear medicine technique of choice. It is equally safe and effective, and its only disadvantage is the 30 to 40 minutes required to label the red blood cells. Technetium-labeled red blood cell scans are reported to be sensitive to bleeding rates as low as 0.05 to 0.1 mL per minute. The tagged red blood cells have an extended half-life, and scanning can take place for 24 hours after injection. Although tagged red blood cell scanning has gained wide acceptance as a modality to detect gastrointestinal bleeding, it is arguable whether scintigraphy can localize a bleeding site reliably. In a review of 72 technetium-labeled red blood cell scans performed at our institution, 71% of the positive scans accurately localized the site of bleeding as confirmed by surgery, angiography, or endoscopy. This finding is supported by other studies in the literature, which average a false localization rate of 25%. Recently, it has been reported that the accuracy of scanning can be enhanced by performing dynamic scintigraphy, with stratification of results based on early radionuclide blushing. Ideally, scintigraphy should be performed while the patient has active bleeding, yet despite a national trend toward increased 24-hour hospital staff coverage, accommodating on-request scintigraphy continues to be problematic in many hospitals. Even in large centers that employ on-call nuclear medicine technologists, it is difficult to perform scintigraphy in a timely manner during nights and weekends. This suboptimal usage of scintigraphy has resulted in an increased number of false-negative studies. Additionally, despite the theoretical benefit of prolonged bleeding observation (repeat scintigraphy), it has been suggested that scans that are positive within several hours of injection produce more accurate localization, whereas, because of the rapid antegrade and retrograde movement of extravasated blood, the accuracy of delayed-positive scans decreases substantially. Given these factors, the relatively high false localization rate for scintigraphy is not surprising. Therefore, basing a bowel resection on the results of red blood cell scintigraphy alone should be discouraged, and confirmation should be obtained prior to surgery if possible. Radionuclide scanning has also been suggested as a cost-effective screening tool prior to angiography. Given its increased sensitivity, relative safety, and decreased cost compared with angiography, scintigraphy should be an ideal test to perform to increase the yield of positive angiograms. Unfortunately, it has been difficult to support this supposition in practice, possibly because the delay in obtaining an angiogram while performing scintigraphy allows the “window of opportunity” to find a bleeding vessel to pass. A review of our experience with angiography showed that a prior positive nuclear scan did not increase the percentage of positive angiograms compared with use of angiography as the initial diagnostic procedure, although successful anatomic localization did permit diminished contrast material administration during angiography. In conclusion, the exact role of radionuclide scanning remains unclear. The examinations are minimally invasive and inexpensive, have low complication rates, and may alert physicians to patients who are likely to require surgery. However, at this point, it is not safe to limit a workup and plan treatment based on the results of a

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radionuclide scan alone. Furthermore, its value as a screening test for the cost-effective use of angiography remains questionable, and many institutions are now using alternative modalities as first-line diagnostic tools. 

Multidetector Computed Tomography In recent years, contrast-enhanced multidetector computed tomography (MDCT) increasingly has been described as being useful in the diagnosis of active lower gastrointestinal bleeds. Studies have found that MDCT is capable of detecting colonic bleeding at rates between 0.3 and 0.4 mL per minute. This finding is significant because the rate of bleeding detected is lower than the 0.5 mL per minute detected by mesenteric angiography and approaches bleeding rates detected by radionuclide scanning. Additional benefits include the 24-hour availability of MDCT at most hospitals, as well as decreased artifact from bowel gas and peristalsis that can result in false-positive results, specifically during mesenteric angiography. A review of the literature shows that MDCT has a greater than 85% sensitivity and 95% specificity, with 95% overall accuracy for localizing gastrointestinal bleeding. Increased accessibility to MDCT results in a greater likelihood that the study will be performed while the patient has active bleeding, and it theoretically increases the likelihood of having a positive localizing study. After a positive MDCT study, patients should undergo mesenteric angiography and embolization. Concerns of precipitating renal insufficiency as a result of use of this algorithm have been raised because patients receive duplicate intravenous contrast dye loads. In our experience, however, these concerns have not been substantiated. Similar to scintigraphy, we have found that positive localization on MDCT allows for decreased dye administration with the ability to target mesenteric angiography to a specific vascular territory. 

Angiography Selective mesenteric angiography has become widely used for lower gastrointestinal hemorrhage because it has the benefit not only of being diagnostic but also frequently therapeutic. By localizing bleeding to a specific vessel, angiography tremendously facilitates surgery. Furthermore, transcatheter therapy, either pharmacologic or by embolization, can successfully treat the source of bleeding, thus avoiding surgery. Minimal preparation is necessary for angiography, but because it must be assumed that the patient is actively bleeding, continuous monitoring is necessary. Resuscitation should be continued while a Foley catheter prevents the bladder from filling with contrast material. Selective injection is performed first through the superior mesenteric artery, because bleeding is most likely in this distribution. Injections of the inferior mesenteric artery and celiac axis follow because the ultimate source is proximal to the ligament of Treitz in up to 10% of patients with presumed lower gastrointestinal bleeding. Bleeding can be detected at rates as low as 0.5 to 1.0 mL per minute. Although extravasation of contrast material is unequivocal evidence for a bleeding source, angiography also can detect other lesions such as a tumor blush or angiodysplasia. Extravasation is seen in fewer than 15% of patients with vascular ectasias; however, angiographic signs of their presence include a prominent early-filling vein, a vascular tuft, or a late-draining vein. When angiography documents a bleeding site, transcatheter therapy can be instituted in an attempt to stop the bleeding. The two alternatives are intra-arterial infusion of vasopressin or transcatheter embolization of the vessel. Superior mesenteric arterial infusion of vasopressin reduces splanchnic blood flow by up to 65%, thus, it is hoped, allowing a hemostatic plug to form in the bleeding vessel. Vasopressin infusion is initiated at 0.2 units per minute with repeat angiography performed 20 minutes later to document the effectiveness of the infusion. If necessary, the rate can be increased to 0.4 units

per minute, after which the marginal benefit is offset by its adverse effects. Because cardiac complications are reportedly as high as 43%, these patients require continuous cardiac monitoring, preferably in an intensive care unit. Although success rates up to 90% have been reported, up to 50% of patients will experience recurrent bleeding upon cessation of therapy. Our experience of a 41% rebleeding rate has led us to conclude that the major benefit of vasopressin is in stabilizing a patient’s clinical situation, thus permitting a semi-elective resection to be performed. An alternative to vasopressin infusion is transcatheter embolization of the affected vessel. This technique provides permanent control of the bleeding vessel and avoids the troublesome adverse effects of vasopressin. Early techniques used temporary agents placed in a fairly central location so as to spare distal communicating vessels and permit their eventual recanalization. Although theoretically transcatheter embolization was expected to reduce the complication of intestinal ischemia, ischemia still occurred in up to 20% of cases. The development of small-caliber angiographic catheters has permitted superselective catheterization of peripheral vessels. This advance has permitted a more selective therapeutic intervention and has limited the potential for widespread intestinal ischemia. Platinum-fibered coils or polyvinyl alcohol particles are used as permanent embolic agents. To date, we have used this approach in nearly 200 patients with angiographically proven lower gastrointestinal bleeding. In our experience, recurrent bleeding after seemingly successful selective embolization occurred in approximately 10% of patients. For these patients, repeat embolization remains an option. Similarly, approximately 8% of patients at our institution experienced postembolization ischemia requiring urgent surgical intervention. 

Colonoscopy Colonoscopy is an extremely valuable diagnostic tool in the evaluation of lower gastrointestinal bleeding. With few exceptions, it should be performed at some time in the evaluation of any patient presenting with acute rectal bleeding. The major issue relates to timing of the colonoscopy during the patient’s hospitalization. There are many proponents of immediate colonoscopy upon admission to the hospital without a colonic preparation. This approach is theoretically possible because blood is an excellent cathartic, and early colonoscopy with “jet” irrigation of the colon has a high likelihood of determining the site of bleeding. A large amount of residual clot is usually present, but the bleeding site can be distinguished either by spurting blood or bright red blood. Blood can travel retrograde up the colon, and thus a clot in the cecum does not necessarily mean that the bleeder is there. However, if the blood stops at a certain level, then the bleeding site is at least distal to that place. Success rates in finding the bleeding site as high as 80% have been reported, but it should be noted that this examination is technically very difficult and has several drawbacks. Even with highly skilled endoscopists performing “emergency” colonoscopy, the cecal intubation rate is less than that for elective procedures. Furthermore, patient instability can severely limit the ability to administer sedatives and analgesics. Finally, residual blood markedly reduces the ability to visualize mucosal detail, which is critical in the diagnosis of angiodysplasia. A preferable approach is to decide whether a patient has stopped bleeding early in the evaluation period. If the patient is hemodynamically stable and not passing fresh blood per rectum, the patient is prepared for an “urgent” colonoscopy. Polyethylene glycol is administered over 4 to 6 hours, preferably through a nasogastric tube if it has been left in place. A colonoscopy then can be performed in a much more controlled setting. The patient is now hemodynamically stable and can be sedated, permitting a safer procedure. Mucosal detail is usually comparable to that of elective procedures, although highpressure irrigation to remove an adherent clot must be available. It is unusual to detect an actively bleeding lesion during colonoscopy performed in this setting. However, suspicious lesions other

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than diverticula have been reported in up to 50% of patients. Neoplastic lesions can be removed or biopsied at the time of the colonoscopy. Areas of ulceration or active colitis also can be biopsied. Some controversy exists about whether angiodysplastic lesions that are not actively bleeding should be treated prophylactically. We treat them if no other potential bleeding sources are found during the patient’s evaluation and if there is a high degree of suspicion that the vascular ectasia has recently bled. When numerous nonbleeding angiodysplastic lesions are present, their distribution is noted and no active treatment is undertaken. The method of coagulation that is preferred in our gastrointestinal unit is to use the heater probe to cauterize around the lesion and finally to cauterize the central area. Care is taken to use low-power settings, especially in the right colon, which has a relatively thin wall. Other methods of coagulation that can be utilized are bicap electrocautery, needle injection, argon plasma coagulation, and neodymium: yttrium-aluminum-garnet (Nd:YAG) laser therapy. When a diverticulum has stigmata of bleeding, endoscopic clipping has become a favored treatment. Typically, epinephrine is injected into the diverticulum to evert it for better access. This maneuver is then followed by clipping of the vessel or the entire diverticular orifice. Tattooing of suspected bleeding sites is also recommended for future localization should recurrent bleeding occur. It is important to perform colonoscopy in all patients who have undergone therapeutic angiography. Although the patient may have stopped bleeding after either administration of vasopressin or embolization, there is a 5% to 30% incidence of neoplastic lesions in this setting. Furthermore, the mucosa can be evaluated for evidence of ischemia, especially if abdominal pain or tenderness develops. 

SURGERY Most patients with lower gastrointestinal bleeding stop bleeding spontaneously and never require surgery. Surgery is reserved for the 10% to 25% of patients who continue to hemorrhage despite nonoperative attempts to control bleeding or who have massive repeat episodes of bleeding. It has been shown that patients requiring four or more units of blood in the first 24 hours of treatment have a 50% chance of requiring an operation. However, because there are no absolute predictors of who will require surgery for lower gastrointestinal bleeding upon admission, all patients with a massive hemorrhage should be evaluated and treated as though they may eventually require exploration and bowel resection. Every effort should be made to localize the bleeding source preoperatively. If the patient is stable, as many investigations as necessary should be used to accurately localize the source of bleeding and guide surgical treatment. Not only is blind laparotomy of a bleeding patient a frustrating and often futile exercise, it is also dangerous. Emergency colectomies for nonlocalized bleeding are associated with a mortality rate of 10% to 30%, and if a segmental resection is performed in this setting, the recurrence rate of bleeding is as high as 33%. Subtotal colectomies have become the preferred option for nonlocalized bleeding; however, this option should still be the last resort. In an emergency, a subtotal colectomy is performed without an anastomosis, with an end ileostomy. Then, if recurrent bleeding occurs, it will come from either the stoma or the rectum. The alternative, a total abdominal colectomy with ileorectostomy, can be a debilitating procedure in the older population, for whom it is frequently necessary. Frequent loose stools associated with varying degrees of incontinence can severely affect quality of life. Moreover, creation of an anastomosis within the setting of an acute gastrointestinal bleed is contraindicated. During the past 15 to 20 years, the ability to localize sites of lower gastrointestinal hemorrhage preoperatively has improved greatly, reducing the need for blind resections. A subtotal colectomy should be reserved for patients with significant recurrent bleeding in whom repeated attempts to localize bleeding have failed and in whom gastric, small bowel, and rectal sources have been ruled out. Patients in this situation may benefit from intraoperative enteroscopy prior to resection.

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When the bleeding site has been localized, segmental resection is the preferred treatment option. The mortality rate in this setting is less than 10%, and studies have demonstrated rates of rebleeding ranging from 0 to 14%. The decision to perform an anastomosis depends on intraoperative conditions, as well as the patient’s stability and comorbid conditions. Of these factors, continued hemodynamic instability remains the most important determinant in the performance of a diverting ostomy at the time of the operation. Because many of these patients are older and have coexistent disease, prolonging the operation and creating a risky anastomosis is not wise. Should the situation be equivocal, performing a primary anastomosis with a temporary proximal diverting ileostomy is a useful alternative. The surgeon is occasionally faced with the dilemma of the patient who has had bleeding localized to the right colon but also has extensive left-sided diverticulosis. The option of a subtotal colectomy is considered, but the most appropriate procedure in this setting remains a right hemicolectomy. Multiple studies have shown that the rebleeding rate from left-sided diverticulosis is quite low. An alternative consideration in such circumstance is the creation of either an end colostomy or ileostomy. The theoretical advantage of this technique is that it often can be performed laparoscopically with minimal morbidity to the patient and can facilitate more definitive localization of an uncertain bleeding source. Using this technique, an ostomy is created and the patient is then observed. When recurrent bleeding occurs, a higher degree of certainty regarding its source is based on whether the bleeding is from the ostomy (a proximal source) or the rectum. Although described as a treatment for gastrointestinal bleeding, this operative technique likely plays a minimal role in the setting of life-threatening hemorrhage because it is not therapeutic. Rather, this technique may be of some utility in the diagnosis of intermittent recurrent gastrointestinal bleeding. In our experience, if a patient has recurrent bleeding but remains hemodynamically stable, waiting and permitting successful localization in other more conventional ways provides an overall benefit. 

THE PROBLEM PATIENT: INTERMITTENT RECURRENT GASTROINTESTINAL BLEEDING Occasionally, patients experience acute, self-limited gastrointestinal bleeding from a source that cannot be localized with multiple diagnostic studies. It must be emphasized that as long as the patient remains hemodynamically stable, continued diagnostic evaluation is indicated. Blind exploration has virtually no role in this setting. Bleeding scans, angiography, or endoscopic procedures may need to be repeated several times. For patients who do not bleed massively and have significant comorbidities, conservative treatment with intermittent transfusions ultimately may be the most appropriate course. One of the challenges in the evaluation of recurrent gastrointestinal bleeding has been the lack of effective investigations for evaluation of the small bowel. The introduction of video capsule endoscopy and spiral enteroscopy represents a significant technological advance. Video capsule endoscopy facilitates the successful identification of obscure bleeding sites that have otherwise been difficult to detect. This evaluation has been especially beneficial in diagnosing abnormalities of small bowel mucosa, specifically ectasias, which are the most common source of lower gastrointestinal bleeding when other tests prove to be negative. More recently, the development of spiral enteroscopy has led to a significant change in the treatment algorithm for small bowel bleeding. Prior to the development of this technique, endoscopic treatment of small bowel bleeding was limited to intestine accessible by push enteroscopy and retrograde ileoscopy. In combination with capsule endoscopy, spiral enteroscopy now provides the potential for treatment. Reported diagnostic yield for spiral enteroscopy ranges from 65% to 80%, with the most common disease being small bowel angioectasia, inflammation, and neoplasia.

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Argon plasma coagulation ablation is a suitable treatment for most of these lesions. As a result, these noninvasive modalities have largely replaced surgery, thereby resulting in a significant change in the diagnosis and management of recurrent gastrointestinal bleeding. As a last resort, either provocative angiography or intraoperative enteroscopy can be performed. Provocative bleeding studies combine the use of visceral angiography with the intra-arterial administration of vasodilators or anticoagulants. A review of published results shows that this technique can increase the yield of positive angiograms from 32% to 65%. Despite the improved success, the overall diagnostic benefit of provocative angiography remains low, with bleeding identified in only a small proportion of patients. Additionally, caution must be used, with the patient’s understanding that immediate surgical exploration may be required. Alternatively, although operative enteroscopy is technically difficult, success rates of greater than 50% in finding and treating the cause of bleeding have been reported. Unlike conventional colonoscopy, the bowel mucosa should be inspected in an antegrade fashion because significant trauma can occur to the bowel wall, thereby obscuring visualization of potential lesions. An advantage of this

technique is the ability to transilluminate the bowel, thereby potentially demonstrating mucosal lesions. With current advances in endoscopy, however, the role for this surgical technique has markedly diminished.

Suggested Reading Boley SJ, Brandt LF. Vascular ectasias of the colon—1986. Dig Dis Sci. 1986;31(suppl):265–425. Browder W, Cerise EJ, Litwin MS. Impact of emergency angiography in massive lower gastrointestinal bleeding. Ann Surg. 1986;204:530–536. Lewis BS, Wenger JS, Waye JD. Small bowel enteroscopy and intraoperative enteroscopy for obscure gastrointestinal bleeding. Am J Gastroenterol. 1991;86:171–174. Pennoyer WP, Vignati PV, Cohen JL. Management of angiogram positive lower gastrointestinal hemorrhage in the lower gastrointestinal tract in adults: diagnostic imaging and interventions. Am J Roentgenol. 1993;161:703–711. Zink AI, Ohki SK, Stein B, et al. Noninvasive evaluation of active lower gastrointestinal bleeding: comparison between contrast-enhanced MDCT and 99mTc-labeled RBC scintigraphy. Am J Roentgenol. 2008;191(4):1101–1114.

Large Bowel Obstruction

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David P. O’Brien, Kim C. Lu, and Mark H. Whiteford

INTRODUCTION A large bowel obstruction results from a narrowing of the colorectal lumen that restricts passage of gas and stool. It is a relatively common surgical emergency. Because the condition may be the result of many combinations of causes, locations, and settings, each case is unique, making the choice of treatment challenging. The most common cause of large bowel obstruction is colorectal adenocarcinoma, which accounts for more than 50% of cases. Most obstructions occur on the left side of the colon because the lumen is more narrow there and the stool is more solid. The age at presentation parallels that of colorectal cancer, with most patients in the seventh decade of life. Other causes of large bowel obstruction include carcinoma of noncolorectal origin, diverticulitis, volvulus, and inflammatory bowel disease (Box 51-1). Iatrogenic causes of obstruction are the ischemia that may follow surgery, an anastomotic stricture, and radiation. A number of attempts have been made to classify large bowel obstruction, but the aim of treatment in each patient is to safely relieve the obstruction while attempting to preserve normal bowel function. Urgent surgery is often performed under suboptimal conditions and includes a bowel resection and then creation of either a temporary or permanent stoma. Newer techniques, including temporary placement of an endoluminal stent, have permitted conversion of an emergency procedure into an elective operation, lowering risks and enhancing recovery. This delay or bridge may be critical for patient stabilization and optimization, delivery of neoadjuvant therapies, and minimizing the need for a stoma. 

CLINICAL AND DIAGNOSTIC EVALUATION Symptoms of a large bowel obstruction range from mild to severe depending on the degree of obstruction and the length of time it has been present. Most patients first note a change in caliber or a decrease in the volume of stool. They may report constipation. Abdominal distension, associated with bloating and cramping abdominal pain, is a sign of progressive obstruction. As the obstruction worsens, patients become reluctant to eat or drink and are prone to dehydration. In extreme cases, patients may present with peritonitis and/or hemodynamic collapse from colonic ischemia or perforation. Patients presenting with a more chronic obstruction often have weight loss and experience malnutrition. The goal of the initial evaluation should be to differentiate a complete obstruction with possible ischemia and impending perforation from a stable, partial obstruction. A complete history and physical examination should be performed, including a review of prior radiographic studies and endoscopic procedures, including water-soluble or barium enema studies, computed tomography (CT) scans of the abdomen and pelvis, flexible sigmoidoscopy, and colonoscopy.

The history can identify any potential precipitating factors, such as abdominal surgery, constipation, bowel obstruction, or specific conditions such as colorectal neoplasia, diverticulitis, and inflammatory bowel disease. A detailed history of changing bowel habits helps assess the acuity of the presentation, and the ability to pass gas means that the presentation is likely not urgent. Rectal bleeding is an important clue that may indicate cancer. A physical examination should focus on vital signs, the general appearance of the patient, and a careful abdominal examination. Inspection may reveal distension, and percussion confirms tympani. Distal colonic obstruction causes the transverse colon to distend, which is obvious in slim patients. Volvulus can produce massive distension, and tenderness over the colon is concerning. A thorough rectal examination is performed. In the absence of peritonitis, abdominal imaging should be performed, and in some cases, more than one imaging study may be required. In reality, many patients presenting via the emergency department have already had a CT scan of the abdomen and pelvis, but a plain abdominal radiograph can be performed quickly, is inexpensive, can usually differentiate large bowel from small bowel obstruction, may demonstrate free air, and can suggest a specific diagnosis such as volvulus. It will show the diameter of the cecum, which is important because a large cecal diameter is associated with preferentially increased wall tension for a given intraluminal pressure. Cecal dilatation above 9 cm carries an increased risk of perforation and death. Although such information will assist in triaging and expediting care, plain films may not confirm a specific diagnosis, and thus more testing may be required. A water-soluble contrast enema study, which can be performed relatively quickly and is inexpensive, is effective in locating the site and cause of obstruction, especially distal obstruction. It also can exclude nonanatomic obstructions such as colonic pseudo-obstruction. In fact, only 60% to 63% of mechanical obstructions suggested by plain radiographs are confirmed by a water-soluble enema. Limitations of water-soluble contrast enemas are that they miss small nonobstructing lesions and provide limited or no information about the bowel proximal to the level of obstruction (Fig. 51-1). In stable patients, a CT scan can provide more information than either plain films or a contrast enema. CT scans can confirm the diagnosis of large bowel obstruction and pseudo-obstruction in more than 90% of patients. Furthermore, a CT scan may identify the location and length of the stricture, as well as evidence of inflammation/abscess, local visceral invasion, and the potential cause. CT also excludes or confirms the presence or absence of metastases and carcinomatosis, and it provides information about the more proximal large and small bowel. CT colonography could also play a role in evaluating patients whose preoperative colonoscopy was incomplete by assisting in the detection of proximal synchronous colon cancers. This information could alter surgical management. However, CT colonography is most accurate after full colonic preparation, and thus its application is often limited in these cases. 249

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BOX 51-1:   Causes of Large Bowel Obstruction

Benign

• Diverticulitis • Crohn disease • Volvulus • Ischemic stricture • Radiation stricture 

Malignant

• Colorectal adenocarcinoma • Carcinomatosis • Gastrointestinal stromal tumor • Carcinoid tumor • Lymphoma • Extrinsic tumors (gynecologic, urologic)

History and physical examination

Blood work Plain films Resuscitation

Perforation or unstable patient

Emergent surgery

Stable patient

Water soluble contrast Enema CT scan

Volvulus

CO2 colonoscopy

Malignant or diverticular stricture

FIGURE 51-1  Initial evaluation of a large bowel obstruction. CO2,

Carbon dioxide; CT, computed tomography.

Endoscopy is risky in patients with an obstruction because air insufflation during the procedure can result in worsening colonic distension above the blockage. For a distal obstruction, endoscopy can provide an accurate and histologic diagnosis. It should be performed with gentle carbon dioxide insufflation instead of air to reduce the risk of barotrauma. 

SURGICAL MANAGEMENT Basic surgical principles apply to the initial management of any acute surgical emergency. These principles include adequate intravenous access, rehydration, and correction of electrolyte abnormalities. Some patients with large bowel obstruction may also have distended small bowel loops. Nasogastric tube decompression should be performed if any concern exists about aspiration. During resuscitation, a surgical strategy can be developed, based on history, including endoscopy and imaging, the patient’s current medical condition, latest imaging results, and the likely diagnosis. Unstable patients or those with peritonitis require an emergency operation. The patient and family must be counseled realistically about the aims of the surgery, the alternatives, and the consequences of various possible findings. Stoma site

marking is a part of the preoperative preparation. Other complexities, including unresectable tumors and difficulties in providing relief of obstruction in the setting of carcinomatosis and prior colorectal resection, must be anticipated. The need for a prolonged stay in the intensive care unit, postoperative mechanical ventilation, a multistage procedure, management of an open abdomen, and other potential complications should be discussed. Unfortunately, much may be unknown prior to the operation, and it is often difficult to anticipate all potential outcomes. In semi-elective situations, endoscopic treatment options can be considered. Endoscopic preoperative resolution of the obstruction may prevent the need for an ostomy and multiple abdominal operations to restore intestinal continuity. Endoscopic decompression and sigmoid tube insertion should be performed for sigmoid volvulus if possible. However, endoscopic decompression is less effective for cecal volvulus, and an operation should be recommended. The use of stents for the urgent decompression of large bowel strictures is controversial. The stent may serve as either a bridge to definitive surgical therapy or as palliation in the unfit surgical candidate or in the case of an advanced malignancy. Volvulus and the role of endoscopic stenting in treating large bowel obstruction are discussed in greater detail later in this chapter. Perioperative antibiotics and deep vein thrombosis prophylaxis are administered, and patients are placed in the lithotomy position because of a possible need for rectal access, intraoperative endoscopy, and/or on-table colonic lavage. Ureteral catheters should be considered in cases of significant lower abdominal inflammation, bulky pelvic tumors, or tumors overlying the ureters. In select cases the laparoscopic technique may be used, although in patients who have markedly dilated bowel, laparoscopy may not be feasible because of a lack of abdominal domain and risk of bowel injury. Additionally, laparoscopy is contraindicated in the unstable patient because it may contribute to hemodynamic collapse. In cases of malignancy, oncologic principals need to be followed, including lymphadenectomy and en bloc resection of involved organs. One of the most difficult intraoperative decisions can be whether to perform an anastomosis or create a stoma. In making this decision, the surgeon must consider the underlying health of the patient, his or her history of radiation and hemodynamic stability, the level of contamination, intestinal viability, technical feasibility, and the potential need for adjuvant therapies. No simple algorithm exists for making this decision. Choices for temporary diversion include an end colostomy or a loop ileostomy. Because emergency end colostomies sometimes become permanent, a diverting loop ileostomy protecting a distal anastomosis is preferred. On-table lavage can remove the column of stool proximal to this anastomosis, thus avoiding significant contamination in the event of an anastomotic leak. 

MALIGNANT AND BENIGN OBSTRUCTION Stricturing large bowel obstructions may be benign or malignant. Sometimes a definitive diagnosis cannot be made preoperatively, and in this case, it is prudent to consider cancer as the most likely diagnosis and conduct an oncologic resection. If perforation or peritonitis is present, emergency surgery is indicated. In the absence of an emergency, there should be time to obtain a detailed history, which will help individualize care. The patient and family should be counseled regarding the risks of routine bowel surgery and the added risk in patients with large bowel obstructions of having a protracted hospital or intensive care unit course, a permanent colostomy, and mortality (at a rate of nearly 10%). These risks are higher in elderly patients and in patients with significant comorbidity. Preoperative ostomy siting and counseling with a wound ostomy continence nurse should be performed in anticipation of a temporary or permanent ostomy.

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251

History and physical exam

Stricture on imaging

Right sided

One stage surgery: • Right colectomy • Extended right colectomy Two stage surgery: • Right colectomy, ileostomy

Left sided

Malignant with palliative intent Malignant with curative intent, age ≥70, ASA≥3

Consider definitive or bridge to surgery SEMS

Malignant with curative intent, age 3 • Hemodynamic instability • Significant acute or chronic comorbidities • Pre-existing chronic diarrhea or fecal incontinence • Chronic immunosuppression or steroid use • Presence of metastatic disease • Malnutrition 

Local Bowel Factors Identified Intraoperatively



FIGURE 51-3  Set up for on-table colonic lavage.

is connected to sterile cystoscopy tubing and a Foley catheter. The Foley catheter is inserted into a controlled enterotomy in the terminal ileum, or an appendectomy is performed with a catheter placed into the appendiceal stump. Sterile anesthesia tubing is tied into the distal open end of the colon and passed off the field into a bucket. A saline solution lavage is performed until the colon is clear of solid stool (Fig. 51-3). Bowel anastomosis with an air leak test, with or without a protecting stoma, is then created. Left-sided bowel obstruction may lead to significant proximal distention, with barotrauma and ischemic injury to the right colon. This condition may be severe enough to mandate a subtotal or total colectomy, with a primary anastomosis or an ostomy as appropriate. A small proportion of patients will present with a locally advanced and unresectable rectosigmoid tumor. This unfortunate situation may best be managed with proximal loop diversion alone, which palliates the acute obstruction and avoids the morbidity of a nontherapeutic major resection. Factors determining the procedure of choice will depend on the location of the obstruction, the stage of the tumor, the age, condition, and comorbidities of the patient, the degree of viability or severity of dilation of the proximal bowel, and the surgeon’s experience (Box 51-2). Direct tumor invasion into adjacent organs or peritumoral adhesions should be resected en bloc with the primary tumor whenever possible. Malignant cells can be present in up to 40% of peritumoral adhesions, and with no reliable intraoperative method to distinguish between benign and malignant adhesions, adjacent adhesions should be excised en bloc. The most common organs involved by direct tumor spread are the small bowel, abdominal wall/retroperitoneum, urinary bladder, and gynecologic organs. Multivisceral resections carry with them a higher risk of perioperative complications, but operative mortality is similar to standard resection, and cure remains a realistic possibility. Carcinomatosis is often underestimated by preoperative imaging and may not be discovered until surgery. In such cases, cytoreductive tumor debulking does not improve patient survival and is not indicated. Instead, the goals are palliation of current or likely future

• Proximal bowel dilation, bowel wall fragility, or edema • Marginal vascular supply, ischemia • Proximal fecal load • Tension on or technically nonoptimal anastomosis • Localized infection or sepsis • Distal location of anastomosis • Abnormal air leak test

symptoms. Surgical options to relieve obstructive symptoms in the setting of carcinomatosis include (1) primary resection and anastomosis, (2) enterocolic bypass, (3) proximal loop ostomy without resection, and (4) venting tube gastrostomy. To avoid a potential closed loop obstruction, a proximal Hartmann procedure (without a distal mucous fistula) should not be considered. 

Self-Expanding Metallic Stents Morbidity, mortality, and ostomy rates after emergency colon surgery are substantially higher than after elective surgery. These discouraging statistics suggest that a combined endoscopic and fluoroscopic placement of self-expanding metallic stents (SEMS) is a worthwhile option to avoid emergency surgery in left-sided colon obstruction. The theoretic advantage of SEMS is rapid decompression of the obstructed colon, turning an emergency situation into an elective procedure. SEMS can be utilized in two roles: as a bridge to surgery in potentially curative cancer or as a definitive procedure for palliation of incurable or unresectable cancer. As a bridge to surgery, SEMS facilitates relief of the acute obstruction, permitting decompression of the dilated and often ischemic proximal bowel. The urgent condition is averted, allowing time to optimize the patient’s condition, comorbidities, and nutritional status, followed by elective single-stage definitive surgery. SEMS has generally been reserved for patients with left-sided malignant obstructions and should be performed by experienced teams. The site of the obstruction must be endoscopically accessible, traversable using endoscopic and/or fluoroscopic means, with minimal bowel angulation, and room for a 2-cm proximal and distal stent flange overlap. SEMS is generally not indicated in other parts of the large intestine or for asymptomatic strictures. Right-sided obstruction can usually be managed with a right colectomy with relatively low morbidity and ostomy rates. Use of SEMS is discouraged for rectal cancers because of significant patient discomfort and a high stent migration rate. Use for benign or extrinsic strictures carries an unacceptably high rate of perforation. Initial case series with SEMS demonstrated high clinical success rates along with decreased morbidity, colostomy rates, and length of stay compared with urgent resection for symptomatic left-sided malignant strictures. These results popularized SEMS as a bridge to surgery in patients with obstructing left colon cancers who are candidates for curative operations. Unfortunately, several recent small, randomized controlled studies with long-term oncologic followup have been less optimistic. Three studies were terminated early

COLON

History and physical exam

Decompression

Elective sigmoidectomy

No decompression

Urgent sigmoidectomy

253

CO2 endoscopy

Plain films +/– water soluble contrast enema, CT scan

Sigmoid

Volvulus

Resuscitation

Cecal

Urgent right colectomy

FIGURE 51-4  Management of a large bowel obstruction resulting from volvulus. CO2, Carbon dioxide; CT, computed tomography.

because of a high rate of adverse events in the stent arm and one was terminated early because of a high anastomotic leakage rate in the primary surgery arm. Although short-term results favor SEMS, a meta-analysis revealed that mean morbidity rates were similarly high for both groups: 10.7% for SEMS as a bridge to surgery and 12.4% for emergency surgery. Even more concerning data were the long-term oncologic outcomes, which showed a marked increase in local recurrence rates for patients managed with SEMS versus surgery (50% to 53% vs. 15% to 28%). Reflecting the need to balance short-term morbidity and mortality with long-term oncologic outcomes, the latest European Society of Gastrointestinal Endoscopy guidelines recommend primary surgery for the management of malignant left colon obstruction, with use of SEMS reserved for patients deemed to be at particularly high risk (i.e., American Society of Anesthesiologists score ≥3, age >70 years, and the presence of significant comorbidities) or for palliation of unresectable/incurable cancer. 

COLONIC VOLVULUS Colonic volvulus is a twisting of a mobile loop of colon around a narrow mesentery. This phenomenon causes a complete, closed-loop, large bowel obstruction and a physiologic continuum of changes of increased luminal pressure, venous occlusion, arterial occlusion, thrombosis, and necrosis, with eventual perforation. The most common sites are the sigmoid colon (60%) followed by the cecum (35%). Colonic volvulus is more common in developing countries where fiber intake is much higher. Clinical presentation typically includes acute onset of colicky abdominal pain, distention, nausea, vomiting, and obstipation. Pain out of proportion to physical findings increases the concern for strangulated bowel. Unfortunately, the clinical assessment of ischemia is challenging and nonspecific. 

SIGMOID VOLVULUS Patients with sigmoid volvulus are more likely to be male, older, institutionalized, taking psychiatric medications, and/or constipated (Fig. 51-4). After volume and electrolyte resuscitation, the diagnosis can be suggested with an abdominal plain film. Typically, a very distended loop of colon is present within the right upper quadrant with the thinnest/sharpest contour pointed toward the left lower quadrant. Plain films alone may not distinguish between other causes of large bowel obstruction. A retrograde, water-soluble enema can show the classic “bird’s beak” deformity at the site of the twist in the rectosigmoid (Fig. 51-5).

FIGURE 51-5  A retrograde water-soluble enema showing the “bird’s

beak” appearance in a patient with sigmoid volvulus.

Observation of free air on imaging or peritonitis mandate immediate surgery. The stable patient should undergo decompression urgently with flexible sigmoidoscopy utilizing either water or carbon dioxide insufflation, because air insufflation may increase the risk of barotrauma. Rigid proctoscopy is an acceptable alternative if the twist is within reach. After endoscopically seeing the twist or point of obstruction, one should gently push. The colon should decompress as the scope tip passes the point of obstruction and enters a cavernous loop of bowel. A large amount of fluid and air will evacuate. The mucosa should be inspected; necrosis mandates emergency sigmoid resection. A rectal tube can then be placed endoscopically to maintain colonic decompression, followed by medical optimization and a plan for an elective sigmoid colectomy during the same admission. The risk of recurrence with nonoperative management has recently been stated to be 67%. The decision to anastomose the colon depends on the quality of the bowel, patient nutrition, patient stability, and medical comorbidities. 

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or use of a cecostomy tube have been described, they are rarely indicated or performed. Rare forms of colonic volvulus involve the transverse colon, the splenic flexure, and ileosigmoid knotting. For the first two presentations, one should proceed directly to either a segmental colectomy or an extended right colectomy if indicated on the basis of bowel viability. The last very rare type, ileosigmoid knotting, is treated via urgent surgery. There, if the ileum can be detorsed from the sigmoid, resection can be limited to the compromised bowel segment(s) only. However, often detorsion is not possible and en bloc resection is mandated.

Suggested Reading

FIGURE 51-6  A plain abdominal radiograph of cecal volvulus.

CECAL VOLVULUS Patients with cecal volvulus tend to be younger and female. The abdominal plain film may show a very distended, kidney-bean– shaped loop of colon within the left upper quadrant, with the inner curvature of the loop pointed toward the right lower quadrant (Fig. 51-6). Should the patient be seen in the emergency department and sent directly for a CT scan, a cecal volvulus often shows dilated small bowel, a large dilated loop of colon, and whorling of the ileocolic mesentery. Unlike patients with sigmoid volvulus, endoscopic decompression is unlikely to be successful, and the American Society for Gastrointestinal Endoscopy recommends proceeding with an urgent right colectomy. Although colopexy and/

ASGE Standards of Practice Committee, Harrison ME, Anderson MA, Appalaneni V, et  al. The role of endoscopy in the management of patients with known and suspected colonic obstruction and pseudo-obstruction. Gastrointest Endosc. 2010;71(4):669–679. Atamanalp SS. Treatment of sigmoid volvulus: a single-center experience of 952 patients over 46.5 years. Tech Coloproctol. 2013;17(5):561–569. Bruzzi M, Lefevre JH, Desaint B, et al. Management of acute sigmoid volvulus: short- and long-term results. Colorect Dis. 2015;17(10):922–928. Buechter KJ, Boustany C, Caillouette R, Cohn Jr I. Surgical management of the acutely obstructed colon. A review of 127 cases. Am J Surg. 1988; 156(3 pt 1):163–168. Chang GJ, Kaiser AM, Mills S, et al. Practice parameters for the management of colon cancer. Dis Colon Rectum. 2012;55(8):831–843. Finan PJ, Campbell S, Verma R, et  al. The management of malignant large bowel obstruction: ACPGBI position statement. Colorectal Dis. 2007;9(suppl 4):1–17. Gingold D, Murrell Z. Management of colonic volvulus. Clin Colon Rectal Surg. 2012;25(4):236–244. Park SH, Lee JH, Lee SS, et al. CT colonography for detection and characterisation of synchronous proximal colonic lesions in patients with stenosing colorectal cancer. Gut. 2012;61(12):1716–1722. Rakinic J. Colonic volvulus. In: Beck DE, Roberts PL, Saclarides TJ, et  al., eds. The ASCRS Textbook of Colon and Rectal Surgery. 2nd ed. New York: Springer Science+Business Media; 2011. [chapter 23]. Sabbagh C, Browet F, Diouf M, et al. Is stenting as “a bridge to surgery” an oncologically safe strategy for the management of acute, left-sided, malignant, colonic obstruction? A comparative study with a propensity score analysis. Ann Surg. 2013;258(1):107–115. van Hooft JE, van Halsema EE, Vanbiervliet G, et al. Self-expandable metal stents for obstructing colonic and extracolonic cancer: European Society of Gastrointestinal Endoscopy (ESGE) clinical guideline. Gastrointest Endosc. 2014;80(5):747–761. e1-75.

Colonic Volvulus

52

Deborah S. Keller

INTRODUCTION In this chapter, we review the presentation, diagnostic strategy, and treatment algorithms for colonic volvulus. Colonic volvulus is the torsion of a mobile loop of bowel with an elongated mesentery and a narrow pedicle. The twisting of the bowel around its mesenteric blood supply leads to acute luminal obstruction and decreased blood flow to the bowel wall that can progress to ischemia, infarction, and, eventually, perforation. Volvulus is rare in developed countries, where it is the cause of 2.5% of all cases of large bowel intestinal obstruction (LBO). However, volvulus causes up to 80% of LBO cases worldwide and remains the third leading cause of LBO behind cancer and diverticulitis. Volvulus must be distinguished from all other causes of colonic distention, including neoplasms, diverticulitis, inflammatory bowel disease, Ogilvie syndrome, Hirschsprung disease, and ileus. Two main types of volvulus present in adults: sigmoid and cecal. Historically, 60% of colonic volvulus cases were sigmoid, with cecal volvulus accounting for 20% to 40%. However, the incidence of cecal volvulus has been increasing in developed countries, while the incidence of sigmoid volvulus remains stable. A recent United States– based study found cecal volvulus in approximately 60% of patients and sigmoid volvulus in 40%. Less common is transverse colon volvulus, which occurs in 2% to 4% of cases. The types of volvulus differ dramatically in their patient population and management. 

and ascending colon twist 180 to 360 degrees around each other along the longitudinal axis of the ascending colon. This torsion is similar to sigmoid volvulus, except it occurs in a clockwise direction. This form has a high mortality, because the mesenteric torsion is associated with vascular compromise, which can lead to ischemic gangrene and perforation. The cecal bascule subtype presents in one third of cecal volvulus cases. The cecum folds on itself anteromedially over the ascending colon, creating a ball-valve type obstruction at the level of the ileocecal valve. Because no torsion of the ileocolic mesentery is present, vascular compromise is rare and occurs only when significant distention prevents the cecum from unfolding into its normal position. Several risk factors have been identified, including congenital bands, cathartics, a high-fiber diet, previous pelvic surgery, and pregnancy. 

Signs and Symptoms Cecal volvulus presents with symptoms of a distal small bowel obstruction—colicky abdominal pain, nausea, vomiting, and obstipation. Eighty-five percent of affected patients have acute obstruction at presentation. A constricting band is found across the ascending colon intraoperatively. 

Diagnostic Imaging

CECAL VOLVULUS Background and Demographics Cecal volvulus presents when there is both an abnormally mobile ascending colon and a fixed point for the mobile segment to twist around. The main predisposing condition is failed fusion of the ascending colon to the retroperitoneum, a congenital anomaly found in 10% to 22% of individuals. This condition creates a mobile, intraperitoneal ascending colon that can twist around its own mesentery. Other risk factors are adhesions from previous surgery and an abdominal mass that serves as a fulcrum for rotation. No geographic distribution has been identified, but incidence is increased in developed countries with higher rates of previous abdominal surgery. Compared with sigmoid volvulus, cecal volvulus occurs more frequently in a younger (mean age 53 years), female population. 

Pathophysiology Two classic volvulus patterns exist—axial torsion (true cecal or cecocolic) and mesentericoaxial (cecal bascule). Axial torsion presents in two thirds of cecal volvulus cases. In this subtype, the distal ileum

On an abdominal radiograph, the small bowel is distended, whereas the distal colon is decompressed. The classic radiograph finding is a round loop of air-distended bowel with haustral markings directed toward the left upper quadrant (Fig. 52-1). In axial torsion, the medially placed ileocecal valve indents the dilated cecum, giving the characteristic “coffee bean” shape. With cecal bascule, the redundant cecum flips up medially into the upper abdomen, causing a dilated cecum and small bowel. Plain radiographs are insufficient to confirm cecal volvulus in 33% to 85% of cases. Barium enema demonstrates a “bird’s beak” or column cutoff sign in the right colon and is diagnostic in 88% of cases. However, performance of this study may unnecessarily delay surgery, so it should not be used routinely. A computed tomography (CT) scan is the test of choice. Pathognomonic CT signs include dilated small bowel and cecum centered on the whirled mesentery (“the whirl sign”) and an ileocecal twist. CT delineates the cause and level of high-grade obstruction and provides evidence of closed-loop obstruction or ischemia, facilitating timely management. However, almost 50% of cases are not diagnosed until laparotomy. 

Treatment Prompt diagnosis and surgery can prevent the complications of cecal volvulus, which include closed-loop bowel obstruction and 255

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countries, and in persons of advanced age, explaining the anatomic basis, higher male occurrence, and higher rates of failed colonoscopic reduction among older patients. 

Pathophysiology In persons with sigmoid volvulus, the redundant sigmoid colon rotates around its mesentery, causing distension and obstruction. When distended, the antimesenteric border lengthens more than the mesenteric border, and the sigmoid twists to accommodate. Further distension occurs in the closed loop from hyperperistaltic emptying of the proximal colon and bacterial fermentation. Luminal obstruction occurs when the torsion reaches 180 degrees, and vascular compromise occurs at 360 degrees. The distal obstruction can cause progressive cecal dilatation, and eventual perforation can occur in patients with a competent ileocecal valve. 

Signs and Symptoms

FIGURE 52-1  Radiographic findings of cecal volvulus.

vascular compromise, gangrene, perforation, and death. The overall complication rate (17%) and mortality rate (25% in a mixed gender population aged ≥50 years or >30% for men and >20% for female patients older than 50 years). The ADR is defined as the proportion of screened subjects in whom at least one adenoma is detected. Endoscopists who meet these standards have decreased interval cancer rates. Compared with physicians who have an ADR greater than 20%, the hazard ratios for interval CRC based on ADRs of less than 11%, 11% to 14.9%, and 15% to 19.9%, were 10.94, 10.75, and 12.50, respectively (P = .02 for all comparisons). In a recent study published, Corley and colleagues

Also known as virtual colonoscopy, CT colonography (CTC), a promising CRC screening modality, does not require sedation and has very low immediate test-related complications. However, CTC currently is not covered by Medicare or by many commercial payers, it requires an extensive bowel preparation, and it has poor discrimination for colorectal lesions less than 6 mm, flat lesions, and serrated lesions. A meta-analysis by Mulhall and colleagues showed that the sensitivity of CTC improved as the polyp size increased, with a sensitivity ranging from 48% for polyps less than 6 mm to 85% to 93% for polyps larger than 9 mm. Similar findings were reported in a more recent randomized controlled trial. The American College of Radiology Imaging Network National CT Colonography Trial assessed the accuracy of CTC for detecting histologically confirmed colorectal neoplasms (adenomas and cancers), using colonoscopy as the reference standard. Although CTC had a sensitivity of 90% for the detection of large lesions, its sensitivity for the detection of adenoma or cancers was 65% for lesions larger than 5 mm, 78% for lesions 6 mm or larger, and 84% for lesions 7 mm or larger. Nonrandomized controlled studies show that the detection rate for advanced neoplasia was similar between screening patients undergoing CTC (3.2%) or colonoscopy (3.4%), with a 7.9% referral rate for follow-up colonoscopy after CTC. The Special Interest Group in Gastrointestinal and Abdominal Radiology (SIGGAR) study, a recent large randomized study of symptomatic patients, showed that the yield for colorectal cancer or large polyps was identical with CTC and colonoscopy with a very low miss rate (1 of 29 in the CTC group). However, the referral rate for colonoscopy after CTC was unexpectedly high (30%), a fact that has major cost implications. Adherence to CTC has been shown to be higher than adherence to colonoscopy in some studies. In one analysis, significantly more

COLON

patients accepted the invitation to have a CTC than to undergo colonoscopy (34% vs. 22%). Radiation exposure and radiation-related cancer risk should be considered, especially with repeated scanning. Other limitations of CTC include the need for a standardized technique, a consensus in reporting the findings, and the dilemma posed by the number of incidental extracolonic findings identified on imaging, which are present in up to 16% of patients. The USMSTF recommends that CTC screening begin at age 50 years; however, the interval for repeat examination after a negative CTC is uncertain. The authors state that it is “reasonable to repeat exams every 5 years if the initial CTC is negative for significant polyps until further studies are completed and are able to provide additional guidance.” The USMSTF guidelines recommend surveillance colonoscopy as opposed to CTC for patients with polyps 6 mm or larger detected with CTC. 

CANCER DETECTION TESTS Fecal Occult Blood Tests Fecal occult blood tests (FOBTs) are stool-based tests designed to detect occult blood loss from colorectal neoplasms. They are based on the concept that large adenomatous polyps and early-stage colon cancer intermittently bleed, and this blood may be detected with occult blood tests. Two major types of FOBTs exist: the guaiac-based test (gFOBT) and the FIT. The gFOBT detects blood through the peroxidase activity of heme or hemoglobin, which converts the colorless guaiac to a blue color. The FIT uses an antibody that reacts with human globin. The gFOBT protocol requires the collection of two stool samples from each of three consecutive bowel movements at home. Multiple stool samples increase the yield because colorectal neoplasms tend to bleed intermittently. Prior to testing with a sensitive guaiac-based test, persons should be instructed to avoid eating red meat, some fruits, and some raw vegetables because of a false-positive reaction due to the presence of peroxidase or pseudoperoxidase in these foods. Medications such as high-dose aspirin and nonsteroidal antiinflammatory drugs may cause occult bleeding and therefore should be avoided for 7 days prior to testing. Vitamin C and antioxidants may interfere with the reaction and cause false-negative results by blocking the peroxidase reaction. The sensitivity of gFOBT for CRC varies among the available tests, from the low test sensitivity gFOBT (such as Hemoccult II, Beckman Coulter, Brea, Calif.), with a sensitivity of 37.1%, and the high test sensitivity gFOBT (such as Hemoccult SENSA, Beckman Coulter), with a sensitivity of 79.4%. Five large randomized controlled trials with gFOBT have demonstrated a significant reduction in CRC mortality of 15% to 33%. Because FIT detects human globin, it is more specific for human blood than guaiac-based tests. It is not subject to interactions with diet and is more specific for lower gastrointestinal bleeding, because globin is degraded by digestive enzymes in the upper intestinal tract. Although no randomized controlled trials are available for FIT, cohort studies report a one-time sensitivity for CRC of 60% to 85% and a sensitivity for advanced adenoma of 20% to 50%. Multiple studies have compared different types of FIT with Hemoccult SENSA (high-sensitivity gFOBT). There is no clear superiority in overall test performance between highly sensitive gFOBT and FIT. The sensitivity of FIT and gFOBT was 81.8% and 64.3%, respectively, in a recent study by Allison and colleagues. In terms of specificity, FIT tends to be superior to gFOBT, with a specificity of 97% for distal cancer. Annual screening with high-sensitivity gFOBT (such as Hemoccult SENSA) or with FIT has been shown to detect a majority of prevalent CRC in an asymptomatic population and is an acceptable

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option for colorectal screening in average-risk adults aged 50 years and older who refuse to undergo a colonoscopy. Patients should be advised that any positive FOBT test should be followed up with a colonoscopy. 

Stool DNA Stool DNA testing relies on the fact that adenomas and carcinomas continuously shed cells that contain altered DNA into the bowel lumen. Because no single gene mutation is shed by all cells in all tumors, a multitarget stool DNA test is needed to improve sensitivity. The currently available stool DNA assay requires the entire stool specimen (30 g minimum) to ensure an adequate stool sample for evaluation. The sensitivity of fecal DNA testing varies from 52% to 93%, with the lower performance attributed to inadequate stability of the stool DNA, as well as imperfect extraction. The most recent version of the test (Cologuard, Exact Sciences, Madison, Wis.) has a sensitivity of 93% for CRC, 43% for advanced adenoma, and 42% for sessile serrated adenomas/polyps. It has recently been approved by the Food and Drug Administration, and the cost of the test is reimbursed by Medicare for average-risk patients older than 50 years every 3 years. Although the USMSTF recommends stool DNA as an acceptable option for CRC screening, further research is needed to determine the interval between negative stool DNA tests. At this time, the appropriate interval is unknown. Cologuard is currently recommended for average-risk patients who refuse to undergo a colonoscopy or who for some reason cannot have a colonoscopy. 

SCREENING IN PERSONS AT AN ABOVE-AVERAGE RISK FOR COLORECTAL CANCER Persons with a personal or family history of CRC, precancerous colorectal polyps, or inflammatory bowel disease are at a moderately increased risk for CRC. Approximately 80% of CRC arises from conventional adenomas through the adenoma-carcinoma pathway as a result of chromosomal instability. Observational data suggest that the adenoma-carcinoma sequence takes approximately 10 years. Adenomas are dysplastic lesions histologically characterized as tubular, villous, or a mixture of the two (tubulovillous), based on the percentage of villous component in their glandular architecture. An advanced adenoma is an adenoma with high-grade dysplasia, an adenoma 10 mm or greater, or an adenoma with a greater than 25% villous component.

Surveillance Colonoscopy in Patients with Adenomatous Lesions at Baseline Strong evidence has shown that baseline polyp characteristics predict the recurrence of advanced neoplasia. Lower risk adenoma-bearing persons have one to two tubular adenomas measuring less than 10 mm. Higher risk persons have more than 2 adenomas or one or more advanced adenomas. The National Cancer Institute pooling project found that with each additional polyp, there is a linear increase in the risk of advanced neoplasia on follow-up. Patients with three or more adenomas have a risk of metachronous advanced neoplasia (OR, 1.32) comparable with that of patients who have an advanced adenoma (OR, 1.4). Recurrence of advanced neoplasms has been shown to be nearly twofold higher in the higher versus low-risk cohorts. In its 2012 guideline, the USMSTF risk stratifies patients based on the findings at the baseline colonoscopy and alters the colonoscopy interval accordingly (Table 55-3). It is recommended that low-risk patients with an adenoma have their next colonoscopy in 5 to 10 years and that higher risk patients have their next colonoscopy in 3 years. 

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TABLE 55-3:   2012 U.S. Multi-Society Task Force Recommendations for Surveillance and Screening Intervals in Patients with Adenomatous Lesions Surveillance Interval (Yr)

Quality of Evidence

5-10

Moderate

3-10 tubular adenomas, or ≥10 mm in size, or high-grade dysplasia, or presence of villous component

3

Moderate High Moderate Moderate

Patients with colorectal cancer

Colonoscopy at 1 yr; if normal, repeat colonoscopy at 3 yr, and if that is normal, then repeat in 5 yr Every 3-6 mo, flexible sigmoidoscopy or endoscopic ultrasound for the first 2 yr after low anterior resection of rectal cancer

Moderate

10 mm) and location in the colon (proximal) and synchronous advanced adenomas elsewhere in the colon. Only a few studies assessed the risk of serrated polyps for metachronous neoplasia. Schreiner and colleagues found that persons with small proximal serrated polyps at baseline have a similar risk of advanced adenoma on follow-up colonoscopy as patients with a nonadvanced adenoma at baseline (5.1% vs. 6.3%). The same study showed that patients with coexisting serrated polyps and advanced adenomas at baseline had a 28.9% risk of advanced adenoma on follow-up compared with 14.7% in patients with only an advanced adenoma at baseline. With the current evidence suggesting that size greater than 10 mm, histologic features, and proximal location may be associated with an increased risk of CRC, the USMSTF recommends that an SSP greater than 10 mm, an SSP with dysplasia, or traditional serrated adenoma (TSA) be managed like an advanced adenoma, whereas small SSPs (20 mm) or sessile adenomas that are resected piecemeal return for a repeat colonoscopy in 2 to 6 months with biopsy of the scar at the polypectomy site to ensure complete removal of the polyp. Once the resection is completed, subsequent surveillance should be individualized based on the endoscopist’s judgment. 

COLON

Surveillance Colonoscopy after Endoscopic Resection of a Malignant Polyp A malignant polyp is a polyp with invasive cancer invading the submucosa (pT1). An invasive adenocarcinoma arising in a pedunculated or sessile polyp may be adequately treated by endoscopic en bloc polypectomy alone if the cancer invades only the submucosa and possesses favorable histologic features. Favorable histologic features include well or moderately differentiated tumors, absence of lymphatic or vascular invasion, and negative resection margins. If any adverse histologic features are noted, the risk of lymph node involvement is increased substantially and surgical resection is required. If the lesion is removed piecemeal and the adequacy of resection cannot be confirmed, surgical resection should also be considered. National recommendations for the postpolypectomy intervals for persons who have adenomas with invasive cancer and favorable prognostic features may be as short as 3 to 6 months to ensure that no residual polyp tissue remains. 

Surveillance Colonoscopy in Patients with Colorectal Cancer Surveillance of patients with resected CRC has two potential roles. One is the detection of recurrences of the primary cancer at an early stage, allowing curative treatment, and the second is the detection of metachronous colorectal neoplasms. Colonoscopy performed at annual or shorter intervals has not been shown to provide a survival benefit in persons with colon cancer, likely because of the relatively low rates of anastomotic or intraluminal recurrence (2% to 4% in the case of colon cancer), and because the majority of recurrences detected are incurable. Therefore, the primary benefit of surveillance colonoscopy is detecting and resecting metachronous neoplasms, particularly in the first 2 years after surgical resection. Patients with colon cancer that has been resected to achieve a cure should undergo a high-quality preoperative colonoscopy to rule out synchronous lesions. According to the USMSTF, in the case of an obstructive cancer, the colonoscopy should be performed 3 to 6 months after surgery if no unresectable metastasis was found during surgery. Subsequent surveillance colonoscopy should be performed 1 year after surgical resection or after the initial colonoscopy that was performed to clear the colon of synchronous neoplasia. If results are normal, the colonoscopy is repeated at 3 years, and if findings of that colonoscopy are normal, then the subsequent examination should be performed in 5 years. Many clinicians distinguish between rectal and colon cancer because local recurrence rates for rectal cancer can be 10 times that of colon cancer. The USMSTF recommends that patients treated with low anterior resection for rectal cancer undergo endoscopic ultrasound or flexible sigmoidoscopy at 3- to 6-month intervals for the first 2 years after resection for the purpose of detecting a surgically curable recurrence. 

Surveillance Colonoscopy in Patients with Inflammatory Bowel Disease Patients with inflammatory bowel disease are at increased risk of CRC. The degree of risk depends on the duration and anatomic extent of the inflammation. After 10 years of pancolitis, the risk of CRC has been reported to rise by 0.5% to 1% per year. The ACG recommends annual or biannual surveillance colonoscopy after 8 to 10 years of colitis or after 12 to 15 years of left-sided colitis. Patients with primary sclerosing cholangitis and ulcerative colitis have an increased risk of CRC, and a colonoscopy is advisable at the diagnosis of primary sclerosing cholangitis and then annually. 

271

Surveillance Colonoscopy in Patients with a Family History of Colorectal Cancer or Adenomatous Polyps Patients with a family history of either CRC or adenomatous polyps in a first-degree relative before age 60 years or in 2 or more first-degree relatives at any age should begin colonoscopy at age 40 years or 10 years before the youngest case in the family. The recommended interval for colonoscopy is every 5 years if the examination is normal. In patients with a family history of either CRC or adenomatous polyps in a first-degree relative after age 60 years or in more than two second-degree relatives, it is recommended that screening begin with any average-risk option. The ACG advocates colonoscopy every 10 years as the preferred CRC screening strategy, and in this group, it recommends beginning at age 50 years rather than at the USMSTF suggested age of 40 years. The interval for colonoscopy should be altered according to the size, number, and pathologic features of lesions detected on each examination. 

WHEN SHOULD SCREENING AND SURVEILLANCE STOP IN THE AVERAGE-RISK POPULATION? With age, the risk of colonoscopy increases and its benefits wane. Both screening and surveillance should stop when the risk outweighs the benefit. The USPSTF recommends against screening in patients 85 years or older and suggests individualized decisions in patients between 75 and 85 years based on patient comorbidities and life expectancy. The USMSTF recognizes that persons with advanced neoplasia are at an increased risk of metachronous CRC and are a group that could benefit from colonoscopy after the age of 85 years. Decisions about ongoing colonoscopy need to be individualized. 

CONCLUSION CRC incidence and mortality have been steadily declining in the United States, which is attributed to increases in the use of CRC screening and removal of colorectal polyps. Colonoscopy every 10 years is considered the gold standard CRC prevention screening test but must be considered within the preference of the patient. The optimal and most effective screening test is the one that is actually performed. Randomized controlled trials demonstrate both a reduction in CRC incidence and mortality with the use of fecal occult blood testing and flexible sigmoidoscopy. Ultimately, the effectiveness of screening depends on adherence and the performance of high-quality examinations. It is recommended that all endoscopists monitor key colonoscopy quality indicators.

Suggested Readings Ahlquist DA, Zou H, Domanico M, et al. Next-generation stool DNA test accurately detects colorectal cancer and large adenomas. Gastroenterology. 2012;142(2):248–256, quiz e25–e26. Allison JE, Sakoda LC, Levin TR, et  al. Screening for colorectal neoplasms with new fecal occult blood tests: update on performance characteristics. J Natl Cancer Inst. 2007;99(19):1462–1470. Atkin W, Dadswell E, Wooldrage K, et al. Computed tomographic colonography versus colonoscopy for investigation of patients with symptoms suggestive of colorectal cancer (SIGGAR): a multicentre randomised trial. Lancet. 2013;381(9873):1194–1202. Atkin WS, Edwards R, Kralj-Hans I, et al. Once-only flexible sigmoidoscopy screening in prevention of colorectal cancer: a multicentre randomised controlled trial. Lancet. 2010;375(9726):1624–1633. Baxter NN, Goldwasser MA, Paszat LF, et al. Association of colonoscopy and death from colorectal cancer. Ann Intern Med. 2009;150(1):1–8.

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Corley DA, Jensen CD, Marks AR, et al. Adenoma detection rate and risk of colorectal cancer and death. N Engl J Med. 2014;370:1298–1306. Davila RE, Rajan E, Adler D, et al. ASGE guideline: the role of endoscopy in the diagnosis, staging, and management of colorectal cancer. Gastrointest Endosc. 2005;61(1):1–7. Hawkins NJ, Ward RL. Sporadic colorectal cancers with microsatellite instability and their possible origin in hyperplastic polyps and serrated adenomas. J Natl Cancer Inst. 2001;93(17):1307–1313. Kaminski MF, Regula J, Kraszewska E, et al. Quality indicators for colonoscopy and the risk of interval cancer. N Engl J Med. 2010;362(19):1795–1803. Kim DH, Pickhardt PJ, Taylor AJ, et al. CT colonography versus colonoscopy for the detection of advanced neoplasia. N Engl J Med. 2007;357(14): 1403–1412. Leggett B, Whitehall V. Role of the serrated pathway in colorectal cancer pathogenesis. Gastroenterology. 2010;138(6):2088–2100. Levin B, Lieberman DA, McFarland B, et al. Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. Gastroenterology. 2008;134(5):1570–1595. Lieberman DA, Rex DK, Winawer SJ, et al. Guidelines for colonoscopy surveillance after screening and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology. 2012;143(3):844–857.

Pohl H, Srivastava A, Bensen SP, et  al. Incomplete polyp resection during colonoscopy-results of the complete adenoma resection (CARE) study. Gastroenterology. 2013;144(1):74–80.e1. Rex DK, Johnson DA, Anderson JC, et al. American College of Gastroenterology guidelines for colorectal cancer screening 2009 [corrected]. Am J Gastroenterol. 2009;104(3):739–750. Robertson DJ, Lieberman DA, Winawer SJ, et al. Colorectal cancers soon after colonoscopy: a pooled multicohort analysis. Gut. 2014;63(6):949–956. Schoen RE, Pinsky PF, Weissfeld JL, et  al. Colorectal-cancer incidence and mortality with screening flexible sigmoidoscopy. N Engl J Med. 2012;366(25):2345–2357. Segnan N, Armaroli P, Bonelli L, et al. Once-only sigmoidoscopy in colorectal cancer screening: follow-up findings of the Italian randomized controlled trial—SCORE. J Natl Cancer Inst. 2011;103(17):1310–1322. U.S. Preventive Services Task Force. Screening for colorectal cancer: U.S. Preventive Services Task Force Recommendation statement. Ann Intern Med. 2008;149(9):627–637. Zauber AG, Winawer SJ, O’Brien MJ, et  al. Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths. N Engl J Med. 2012;366(8):687–696.

Molecular Genetics of Colorectal Cancer

56

James M. Church

INTRODUCTION Cancer is a disorder of cellular growth and differentiation that is due to a loss of function of regulatory pathways and feedback loops. Colorectal cancer is an excellent example of this mechanism because access via colonoscopy to the spectrum of premalignant lesions in the colon and rectum allows demonstration and study of the process. Sporadic colorectal cancer arises from pre-existing benign lesions that begin small and gradually enlarge as they transition histologically and biologically toward cancer via an adenoma-carcinoma or a serrated polyp-carcinoma sequence. In 1988, Bert Vogelstein published a sequence of genetic abnormalities that appeared to correlate with the histologic adenoma to carcinoma sequence. Subsequent research has confirmed Vogelstein’s observations and has expanded knowledge and understanding of the genetics of colorectal carcinogenesis. It is now known that at least three different genetic mechanisms lead to colorectal cancer, producing cancers of different biology. Understanding the molecular genetics of colorectal neoplasia is important. Fostering an understanding of the molecular genetics of colorectal neoplasia is the purpose of this chapter. 

GROWTH CONTROL Normal cell growth is regulated tightly by multiple redundant systems that are conserved from one species to another. Multiple dysfunctional genetic events need to accumulate in an epithelium before clinical effects of growth deregulation are noticeable. Each colorectal cancer is genetically unique and has accumulated mutations in an average of 90 different genes. Only a small number of these mutations are driver mutations, which are responsible for the carcinogenesis. Most are “passenger” mutations. Normal cell growth is a balance between proteins that stimulate (coded for by proto-oncogenes) and proteins that inhibit (coded for by tumor suppressor genes). When that balance is disturbed, carcinogenesis can occur. Tumor suppressor genes and proto-oncogenes are organized into various signal transduction pathways that react to extracellular signals and transmit them to the cell nucleus, where an appropriate response is generated. Four main signal transduction pathways are involved in colorectal adenocarcinoma: wnt/wingless, epidermal growth factor (EGF), transforming growth factor (TGF)-β, and p53-mediated cell cycle arrest/apoptosis and DNA repair. All must be inactivated or overstimulated for cancer to develop. Overstimulation occurs by mutation or DNA hypomethylation. Inactivation of tumor suppressor genes happens through mutations, chromosomal instability (loss of heterozygosity), and DNA hypermethylation. Mutations are permanent structural changes in genes. These changes may have no effect on gene function (coding of their protein; called polymorphisms), or they may be deleterious, with an impact on function. Mutations may be inherited (the cause of hereditary colorectal cancer) or acquired. They may be acquired as a result of lifestyle or

environmental factors (e.g., smoking and drinking alcohol), chance, or defects in DNA repair. Because each cell has two copies of each gene, both copies of a tumor suppressor gene must be inactivated for gene expression to be lost. The time taken to inactivate both copies from environmental or lifestyle causes is one reason why carcinogenesis in the colon takes so long to occur. When one copy is lost as a result of inheritance of a mutation, the time for inactivation is reduced. Chromosomal instability is reflected in loss of heterozygosity— that is, chromosomal events by which chromosomal instability allows chromosomal deletion or rearrangements, including nondisjunction, duplication, or translocation. The function of the genes on the re­arranged chromosomes may be lost. Mutations in APC can promote chromosomal instability, the most common molecular mechanism in colorectal cancer (70% of cancers are a result of chromosomal instability) and a characteristic of hereditary cancers in FAP, MYH-associated polyposis, and polymerase proofreading polyposis (Table 56-1). Hypermethylation inactivates genes by abrogating expression. The gene is structurally normal, but the addition of extra methyl groups to CpG base pairs in the gene promoter stops expression and production of the protein. DNA methylation is a normal phenomenon and a way in which gene expression is controlled to suit the changing needs of organ function. Hypomethylation, leading to unstable DNA, was one of the early causes of colorectal carcinogenesis described by Vogelstein. However, it is promoter hypermethylation that plays a key role in the production of colorectal cancer via the histologic precursor of serrated polyps. About 15% to 18% of sporadic colorectal cancers arise in this way. They are known as CpG island methylation phenotype (CIMP) cancers. 

DNA REPAIR Each time a cell divides, the DNA is replicated. The fidelity of replication is extremely important to preservation of a normal cell line and is protected by a series of DNA repair mechanisms. Loss of DNA repair results in mutations as the unrepaired DNA is transmitted into daughter cells, potentially affecting hundreds of genes. Three types of DNA repair are involved in colorectal carcinogenesis: mismatch repair, base excision repair, and polymerase proofreading. Defective DNA mismatch repair is seen as a dominantly inherited phenomenon in Lynch syndrome and as a sporadic cause of microsatellite instability in 15% to 18% of colorectal cancers. Microsatellite instability results from unrepaired mismatches in DNA microsatellites, a cause of mutations in multiple genes. 

CLINICAL SIGNIFICANCE The molecular profile of any colorectal cancer is relevant to clinical care because the cancer biology is set by the mechanisms of carcinogenesis. Chromosomal instability causes aneuploid cancers that 273

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Molecular Genetics of Colorectal Cancer

TABLE 56-1:   Mechanisms of Colorectal Carcinogenesis % Sporadic Colorectal Cancers

Mechanism

Cause of the Mechanism

Initiating Mutation

Drivers

Chromosomal instability

APC mutation

APC

APC, KRAS, SMAD4, TP53 mutations; loss of heterozygosity

60% colon, 90% rectum

Chromosomal instability

Defective DNA polymerase proofreading

POLD1, POLE

APC

1000 adenomas

APC (codon 1309)

Colorectal, gastric, small intestinal neoplasia; desmoid disease; benign and malignant tumors of thyroid, skin, bone, brain, liver, and pancreas

Classical FAP

100-1000 adenomas

APC

Same

Attenuated FAP

10-100 adenomas

APC (5′ and 3′ mutations)

Same

MAP

Any adenomas

MYH

Same

PPAP

>5 adenomas

POLD1 POLE

Young age of onset, microsatellite stable colorectal cancer; endometrial cancer (POLE)

Juvenile polyposis

>5 juvenile polyps

SMAD4 BMPR1A ENG

Gastric and colorectal hamartomas and cancer

Peutz-Jeghers

Peutz-Jegher polyps/small bowel > colorectum

STK11

Oral/cutaneous pigmentation, cancers of the breast, pancreas, stomach, ovary, testis, and small intestine

Hereditary mixed polyposis

>5 adenomas, serrated polyps, and hamartomas (the hamartoma is important)

GREM1 expression

SPS

Unknown >20 serrated polyps of any size anywhere; any serrated polyps and a family history of SPS >5 serrated polyps proximal to the sigmoid, 2 of which are >10 mm

FAP, Familial adenomatous polyposis; MAP, MYH-associated polyposis; PPAP, polymerase proofreading-associated polyposis; SPS, serrated polyposis.

that the genotype can be used to plan surgery, but surgery should always be determined by the colonic polyposis phenotype. 

Colorectal Cancer in Familial Adenomatous Polyposis In all patients with FAP who are untreated, a microsatellite stable, chromosomal unstable colorectal cancer will develop at an average age of 40 years. The age range is wide, although cancer in teenagers is rare. The cancer risk is proportional to the severity of the polyposis, with cancer in attenuated FAP occurring much later than with profuse FAP. Surveillance and prophylactic surgery aim to prevent cancer. Surveillance begins at diagnosis or at puberty. Patients who are part of a family with established FAP undergo genetic testing, and yearly colonoscopic surveillance is targeted to mutation carriers. If no mutation is detectable, all at-risk relatives are screened with flexible sigmoidoscopy until adenomas are found (and colonoscopy starts) or until they reach their mid twenties, when surveillance schedules can be eased. Prophylactic surgery is performed if the colorectal polyps are symptomatic, profuse, or unstable (i.e., increase in size to >1 cm, display severe dysplasia, or increase in number). Children with mild polyposis can be followed up yearly, and elective surgery can be performed when physical and emotional maturity is reached and the time is right from a financial and psychological point of view. It is critical to remember that FAP cannot be cured by surgery, many patients with FAP are asymptomatic and young, and the prophylactic operation should not worsen quality of life. 

Surgical Options for the Large Bowel The two main surgical options for the large bowel are colectomy and ileorectal anastomosis (IRA) and proctocolectomy and ileal pouch– anal anastomosis (IPAA). The respective indications, advantages, and disadvantages of each option are shown in Table 57-2. IPAA can be stapled or hand sewn after an anal mucosectomy. A stapled IPAA offers better bowel function but leaves anal transitional zone (ATZ) epithelium, in which cancer may develop. A hand-sewn anastomosis is more difficult to perform and to survey. If adenomas are present in the ATZ at index surgery, then there is no choice but to perform a mucosectomy. However, postoperative surveillance is critical for all patients because anastomotic cancers have been reported after both stapled and hand-sewn IPAA. Laparoscopic technique offers major advantages for young, active, asymptomatic patients with FAP. However, laparoscopic pouches are tricky. Making the pouch reach to the anus can be an issue, especially when desmoid disease is present. Desmoid disease prevents IPAA in about 15% of patients presenting for a proctectomy and IPAA after an initial IRA. 

Extracolonic Manifestations Hereditary colorectal cancer syndromes are associated with multiple extracolonic manifestations because of the effect of the germline mutation on other organs. Those associated with polyposis are mentioned in Table 57-1.

COLON

277

TABLE 57-2:  Two Main Options for Prophylactic Treatment of the Large Bowel in Familial Adenomatous Polyposis Option

Indications

Colectomy and ileorectal anastomosis

20 rectal polyps; >1000 colon polyps; curable ileal pouch–anal rectal cancer; good anal anastomosis function

Contraindications

Advantages

Disadvantages

Relatively normal bowel function; no pelvic dissection (no impact on sexual function or fecundity); less complex and complicated surgery; no stoma

Rectal mucosa at risk for progressive neoplasia and cancer

Advanced rectal cancer; Maintains per anal defecation; Range of function from weak anal sphincters minimizes cancer risk good to bad; risk of pouch and anal transition zone neoplasia; temporary ileostomy; risk of complications (including pelvic nerve damage and reduced fecundity)

Colorectal cancer is the most common cause of death in persons with FAP, followed by desmoid disease and ampullary carcinoma. Desmoid disease is discussed in Chapter 58. 

Ampullary Cancer and Duodenal Adenomas Almost all patients with FAP have duodenal adenomas, and duodenal/ampullary cancer will develop in about 10% if they are not treated. Duodenal surveillance begins at age 20 years and continues according to the findings at the prior examination. Duodenal adenomatosis is scored according to adenoma number, size, and histology of the adenomas, expressed as a Spigelman grade. Grade I is the mildest form of duodenal polyposis and is usually followed by repeat esophagogastroduodenoscopy in 3 to 5 years. Grade II requires follow-up in 3 years, grade III in 1 year, and grade IV, which is associated with a 36% incidence of cancer, is an indication to consider prophylactic surgery. Treatment of duodenal adenomas is endoscopic or surgical. An endoscopic or transduodenal polypectomy is associated with a high rate of recurrence. The lowest recurrence rates follow pancreas-preserving duodenectomy, which is the operation of choice for stage IV duodenal polyposis. Although a pancreas-preserving duodenectomy results in significant morbidity, the morbidity is less than for a Whipple procedure, which should be reserved for patients with cancer. No effective agent exists for chemoprevention of duodenal adenomas, although celecoxib has shown a weak effect. The stomach may exhibit three manifestations of FAP. Fundic gland polyps are found in more than 90% of patients. These polyps are hyperplastic, although low-grade dysplasia can be found in 40%. Gastric adenomas are found in 10% of patients with FAP, usually in the antrum. These adenomas may be precursors of gastric cancer. Gastric cancer is rare in Western countries but much more common in Asia. Esophagogastroduodenoscopy (EGD) screening and removal of gastric adenomas is part of upper gastrointestinal surveillance. 

Thyroid Cancer FAP is associated with a high risk of papillary thyroid cancer, which is more common in women than in men. Screening with ultrasound is effective in achieving early diagnosis, and nodules larger than 1 cm in diameter are biopsied by fine-needle aspiration. Screening begins at diagnosis and continues yearly. When cancer is diagnosed, a thyroidectomy should be performed. 

Adrenal Masses Adrenal tumors are often seen in patients with FAP who are having computed tomography scans for other reasons. These tumors are generally benign, nonfunctional adenomas and are not treated. Adrenal tumors greater than 5 cm may need to be resected. 

Brain Tumors FAP is associated with an increased risk of brain tumors, in particular astrocytoma and glioblastoma. This combination has been referred to as Turcot syndrome, although this term includes patients with Lynch syndrome in whom a medulloblastoma develops. 

Hepatoblastoma A hepatoblastoma is a rare tumor that affects boys with FAP from infancy to age 6 years. Screening is controversial because it means that genetic testing is performed in infancy. Liver ultrasound and serum alpha fetoprotein can lead to early diagnosis, but even without screening the tumor is rarely fatal. 

Gardner-Type Manifestations A set of extraintestinal manifestations associated with FAP was identified by Utah genetics professor Eldon Gardner and came to bear his name. These manifestations include desmoid tumors, osteomas, dental anomalies (extra teeth), and epidermoid cysts. This association is useful because the presence of some of these manifestations predicts a high risk of desmoid tumors. None needs to be treated unless symptomatic. 

Congenital Hypertrophy of the Retinal Pigmented Epithelium CHRPE can be defined as the presence of four or more hyper- or hypopigmented spots involving both eyes. The spots have no functional effect, and CHRPE is most significant as a marker of disease. Alert ophthalmologists may diagnose FAP. 

278

Polyposis Syndromes

Surveillance Surveillance is key to preventing cancer and relies on good compliance on the part of the patient and hard work from a registry or clinical coordinator on the part of the registry. The large bowel is surveyed yearly, unless the presence of advanced neoplasia requires more frequent examinations. The upper gastrointestinal tract is checked regularly, with a frequency dependent on findings of the previous examination. Severe duodenal polyposis is associated with an increased risk of small intestinal polyps, and capsule endoscopy is indicated. Thyroid screening is performed yearly. The IRA Yearly proctoscopy is performed with a flexible scope after two enemas. No sedation is required. The anastomosis should be checked, along with the terminal ileum for 15 cm. Small ulcers are common and do not mean that Crohn disease is present. Polyp size, number, and location should be noted. Polyps measuring less than 5 mm can be counted but not treated, as long as the patient is compliant with screening. Larger polyps should be removed. Flat red velvety areas should be biopsied, especially in scarred rectums. The other side of the rectal valves should be checked.  The IPAA Yearly pouchoscopy is performed with a flexible scope after two enemas. The anus may be stenotic and tender, especially after a hand-sewn anastomosis. In this case a pediatric gastroscope may be used, along with Xylocaine jelly as a lubricant. The scope should be passed into the afferent ileum, and one must be aware of the difference between lymphoid follicles and adenomas: if in doubt, a biopsy should be performed. The top of the pouch and then the pouch itself should be checked. Ulcers are normal and do not necessarily mean that Crohn disease is present. Particular attention should be directed to the ATZ and anus. Retroversion of the scope may be possible and may detect ATZ polyps more easily. Polyps larger than 5 mm should be removed. If the ATZ has extensive polyposis, polypectomy or a mucosal strip and pouch advancement may need to be performed after induction of general anesthesia. 

Oligopolyposis/Attenuated Familial Adenomatous Polyposis The presence of fewer than 100 synchronous adenomas is termed oligopolyposis or attenuated polyposis. This condition occurs in persons with FAP in the setting of a 5′ or 3′ mutation. Polyps are generally more right sided, and cancer develops later than with classic FAP. Sometimes the polyps are hard to see, and chromoendoscopy of the right colon has been recommended. Genetic testing is less productive of a germline mutation in patients with attenuated polyposis, and the differentials of MYHassociated polyposis (MAP), polymerase proofreading-associated polyposis (PPAP), and even Lynch syndrome are relevant. Table 57-3 is an amalgam of data from two recent studies and shows that oligopolyposis can be explained genetically in APC mutation–negative patients. Whereas mutations at either end of the gene have a mild polyposis phenotype, they are associated with severe duodenal polyposis (5′) and symptomatic desmoid disease (3′). EGD screening is therefore critical, and surgery in patients with a 3′ mutation must be performed in the context of a high desmoid risk, which means that when the polyp size and histologic features indicate surgery, a laparoscopic IRA or an open pouch is favored. 

TABLE 57-3:   Genotypes of Patients with Oligopolyposis: Number of Adenomas Genotype

1 relative

Extracolonic manifestations (Gardner syndrome)

None

1

>1

Genotype

5′ of codon 400

Codon 400 to 1399

3′ of codon 1399

Female

4-6 points: low risk (5%) 6-8 points: medium risk (21%) 8-10 points: high risk (40%) 10-12 points: very high risk (>80%)

281

282

Desmoid Disease

patients and their disease, easier documentation of the disease progress, and rationalization of treatment (Table 58-2). This staging system correlates with survival. Most patients with desmoid disease have multiple tumors or multiple plaques. In any patient, the staging system is applied to the worst manifestation. 

MANAGEMENT Setting Expectations Although some desmoids completely disappear, this outcome is not a realistic expectation in most patients. Acceptable outcomes are stabilization of previously growing tumors, shrinkage, or even just resolution of symptoms. Medical treatment may soften tumors without affecting their dimensions, but this softening may be enough to relieve a bowel or ureteric obstruction. Overall, about 12% of desmoid tumors resolve, about 7% grow relentlessly and are fatal, and 80% show variable or stable growth. Most patients live with their desmoids. A pattern of decreasing symptoms with age is noticeable, along with a definite beneficial effect of pregnancy. 

A Philosophy of Care Because desmoid disease is not curable and no predictably effective treatment is available, the management strategy is to use the least toxic approach that has a realistic chance of working. Close followup, with scans every 3 to 6 months, allows new agents to be added or substituted as necessary. Because repeated CT scans over time can build up a significant radiation dose, magnetic resonance imaging scans should be used in young patients. 

Extra-abdominal Desmoid Tumors Extra-abdominal desmoids can occur anywhere and sometimes are found in unusual sites such as the jaw, back, neck, and chest wall. When they are found in children, treatment depends on the rate of growth and symptoms. Asymptomatic tumors and those that are growing slowly can be observed, although if they can be easily resected, this option is reasonable. Large or rapidly growing tumors tend to be symptomatic and should be treated either with chemotherapy or surgery—­ whichever seems to be less morbid and more likely to be effective. The presence of extra-abdominal desmoid tumors in patients with FAP is an indicator of risk for intra-abdominal tumors after elective colectomy. 

The earlier they are resected, the smaller the defect. The defect can be closed with mesh. Sometimes portions of small intestine have adhered to abdominal wall desmoids, and at times a segment of intestine needs to be removed with the desmoid (Fig. 58-1). Histologic margins are not always clearly definable, and there is no evidence that an R1 margin leads to a higher risk of recurrence. Resection with a gross margin of 1 cm is adequate. Abdominal wall desmoids can be treated with medications, chemotherapy, brachytherapy, external beam radiotherapy, or cryotherapy. However, when they can be excised without difficulty, what is the point in using these other modalities? Occasionally an abdominal wall tumor is continuous with a mesenteric desmoid (“transabdominal”). In this difficult situation, surgery should be avoided. 

Intra-abdominal Desmoid Disease Intra-abdominal desmoid disease is the most difficult problem in patients with FAP. The disease tends to occur on or within the small bowel mesentery or retroperitoneum, where it can be seen as a hard white plaque or tumor that tethers and distorts the adjacent tissues, including mesenteric vessels, bowel, and ureter. Desmoid disease often surrounds the superior mesenteric artery, making resection impossible without depriving large amounts of small intestine of its blood supply. Workup An abdominal CT scan or magnetic resonance imaging will show a desmoid tumor and may even show whorls in the small bowel mesentery indicative of desmoid reaction (plaques). The appearance is typical, and in a patient with FAP, a biopsy is not needed. Desmoid disease often occurs in multiple places within the abdomen, and small desmoids may also be seen in the abdominal wall. One should check for hydroureter and stage the desmoid (the initial stage relies on history for estimation of the growth rate). In a person with multiple desmoids, the tumor with the worst stage represents the patient.  Medical Treatment As a means of general support, nutrition should be optimized. If the patient has nutritional deficits, intravenous nutrition may be needed. One should ensure that the gastrointestinal tract is free of threatening lesions.   

Stage I: No treatment or sulindac, 150 to 200 mg twice a day with food.

Abdominal Wall Tumors Abdominal wall desmoids usually can be resected without sequelae other than the creation of a defect in the abdominal wall.

TABLE 58-2:   Desmoid Staging System Stage

Size

Growth

Symptoms

I

1 cm, and/or 3 or more adenomas polyposis colorectal cancer–related cancers: found upon a single endoscopic endometrial, ovarian, gastric, small bowel, examination ureter, renal pelvis, pancreas, biliary tract, brain, sebaceous adenomas/adenocarcinomas

BOX 59-1:   Revised Bethesda Guidelines Colorectal cancer diagnosed before age 50 years Presence of synchronous or metachronous colorectal cancer or Lynch syndrome–associated tumors* Microsatellite instability high–type histologic features: tumorinfiltrating lymphocytes, Crohn-like reaction, mucinous tumor, signet cell differentiation, medullary growth pattern in tumor from a patient younger than 60 years Patient with colorectal cancer and a first-degree relative with colorectal cancer or a Lynch syndrome–associated tumor* before age 50 years Patient with colorectal cancer and two first- or second-degree ­relatives with colorectal cancer or a Lynch syndrome–­ associated tumor* at any age *Lynch syndrome–associated tumors include tumors of the colorectum, endometrium, stomach, ovary, pancreas, ureter, renal pelvis, biliary tract, brain, small bowel, and sebaceous glands, along with keratoacanthomas.

A

cells, mucinous components, and a lack of dirty necrosis. Some of these histologic factors have been incorporated into the revised Bethesda criteria (Box 59-1) as a tool to identify which patients should undergo testing for the presence of MSI (Figs. 59-1, 59-2, and 59-3.) 

DIAGNOSING LYNCH SYNDROME The first step in managing Lynch syndrome in a family is to diagnose it. Several strategies can be used to select patients for genetic testing, including clinical criteria, prediction models, and tumor testing.

B Clinical Criteria Amsterdam I criteria (see Table 59-1) require three relatives affected with colorectal cancer, with two being first degree to the other one, in at least two consecutive generations, with one relative younger than 50 years and polyposis excluded. Amsterdam II criteria are more inclusive than Amsterdam I criteria because they include any Lynch-related cancers as qualifying events. Amsterdam II criteria are highly sensitive (85%) but poorly specific (20%). However, the shrinking size of families and the attenuation of phenotype caused by increasingly widespread colonoscopic screening is decreasing the sensitivity of family-based criteria. Therefore, we have adopted “Amsterdam-like” criteria, in which high-risk adenomas count as a qualifying lesion (see Table 59-1). The revised Bethesda guidelines include details of the cancers, as well as family history and age at diagnosis, and are aimed at identifying tumors suitable for MSI testing (see Box 59-1). 

Models In an effort to improve the predictive accuracy of clinical criteria, several clinical computational prediction models have recently been

FIGURE 59-1  A, Poorly differentiated (medullary) adenocarcinoma

composed of irregular, solid sheets of large eosinophilic cells containing small glandlike spaces. B, Signet-ring adenocarcinoma.

developed and validated to determine a person’s risk for Lynch syndrome. These models include MMRpro, MMRpredict, and PREMM. They include factors such as age, gender, location of tumor, and the presence of multiple tumors or endometrial cancer, and they are available for use as Internet-based programs. Although they seem to outperform traditional clinical criteria, they do not replace a comprehensive family history and clinical acumen. 

Tumor Testing For patients who have a cancer or a large adenoma, tumor testing for MMR deficiency is a more accurate and cost-effective way of identifying potential patients with Lynch syndrome than are clinical criteria or prediction models alone. MMR deficiency is evaluated by MSI or by immunohistochemistry for expression of MMR proteins. About 90% of Lynch syndrome CRCs will be MSI-H and lack MMR protein expression. Lack of expression of a specific protein

COLON

can direct germline testing for mutations to a specific gene. If MSH2 is mutated, both MSH2 and MSH6 are lost; if MSH6 is mutated, only MSH6 is lost. If MLH1 is mutated, both MLH1 and PMS2 expression are lost, but if PMS2 is mutated, then only PMS2 is lost. Depending on the findings of immunohistochemistry, the appropriate gene(s)

FIGURE 59-2  Crohn-like lymphoid aggregation within a germinal

center in the stroma inferior to the tumor.

287

is/are sequenced. About 15% to 18% of all colorectal cancers are MSI-H, and approximately 85% of these are attributable to acquired methylation of the MLH1 promoter not associated with Lynch syndrome. Therefore, if MLH1 expression is lost, results should be taken within the context of age and family history. Most tumors with methylation of MLH1 will have mutations in BRAF, whereas these are almost never found in Lynch tumors. Therefore, testing for BRAF mutations and MLH1 methylation can differentiate most tumors with absent MLH1 expression into Lynch syndrome and not Lynch syndrome. Although tumor testing is the best way to identify patients for genetic testing, selection criteria for testing are debated. Limiting tumor testing by age or clinical criteria would lead to a significant number of Lynch syndrome cases being missed, and thus there is a move toward testing of all resected CRCs. In 2009, the Evaluation of Genomic Applications in Practice and Prevention Working Group recommended that samples of all newly diagnosed CRC undergo MSI and/or immunohistochemistry for MMR protein expression. These guidelines are endorsed by the Collaborative Group of the Americas on Inherited Colorectal Cancer. Recently, the National Comprehensive Cancer Network recommended universal screening of all colorectal cancers for persons younger than 70 years and for those older than 70 years who meet revised Bethesda guidelines. The Cleveland Clinic approach to universal tumor testing is summarized in Figure 59-4. Ideally, tumor testing is performed using the colonoscopic biopsy specimen taken at the time of diagnosis, before surgery. This testing allows preoperative identification of Lynch syndrome and affords an opportunity for patient education and a more informed choice regarding surgical strategy. 

GENETIC COUNSELING AND TESTING

FIGURE 59-3 Tumor-infiltrating lymphocytes. (Courtesy Tom C.

Smyrk, MD, Associate Professor of Pathology, University of Nebraska College of Medicine.)

Identification of a specific mutation as the underlying cause of Lynch syndrome benefits the patient in terms of personalized risk assessment and facilitates testing of at-risk family members. Indications for referral to a genetic counselor are listed in Box 59-2. For patients with a diagnosis of cancer, genetic counseling and testing should be initiated at the time of diagnosis. Working with the clinician, the genetic counselor uses tumor test results to guide which gene should be sequenced. Germline genetic testing is most commonly conducted with a blood sample but also may be conducted with material from a buccal swab. When tumor testing is not available to

Initial screen: DNA testing for MSI or IHC for MMR proteins

BRAF testing

Test for MSI

MSS

No further evaluation

MLH1 MLH1 methylation

MSI-H

MMR IHC

MMR protein loss

BRAF WT and MLH1 not methylated Genetic counseling Germline testing for specific MMR mutation

MSH2, MSH6, PMS2

FIGURE 59-4  Universal testing of colorectal cancers for Lynch syndrome. IHC, Immunohistochemistry; MMR, mismatch repair; MSI-H, microsatellite instability high; MSS, microsatellite stable; WT, wild type. (From Kalady MF, Heald B. Diagnostic Approach to Hereditary Colorectal Cancer Syndromes. Clin Colon Rect Cancer Surg 2015;28:205-214.)

288

Hereditary Nonpolyposis C ­ olorectal Cancer and Lynch Syndrome

BOX 59-2:   Indications for Referral to Genetic Counseling and Testing for Lynch Syndrome Family meets Amsterdam I or II or Amsterdam-like criteria Colorectal or endometrial cancer before age 50 years Patient/family satisfies revised Bethesda guidelines First-degree relative of a known patient with Lynch syndrome >5% chance of mutation by computed prediction models Molecular and genetic tumor testing consistent with Lynch syndrome

TABLE 59-2:   Lifetime Colorectal Cancer Risk by Age 70 Years in Persons with Lynch Syndrome by Gene Gene

Colorectal Cancer Risk, %

MLH1/MSH2

Male

27-74

Female

22-53

MSH6

TABLE 59-3:   Lifetime Extracolonic Cancer Risk by Age 70 Years in Persons with Lynch Syndrome Cancer

Risk in General Population, %

Endometrial

2.7

Risk in Lynch Syndrome, %

MLH1/MSH2

14-54

MSH6

17-71

PMS2

15

Gastric