Colon, Rectum & Anus, Part III

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Vol 41 | 6 | 2015

S E L E C T E D R E A DI NG S i n G E N E R A L S U RG E RY

Colon, Rectum & Anus, Part III

Vol 41 | 6 | 2015

Crohn Colitis

Ulcerative Colitis

page 15

page 17

Clostridium Difficile Infection page 24

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SE L EC T ED R E A DI NGS in GE N E R A L SU RGE RY

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A MER IC A N COLL EGE OF SURGEONS

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AMERICAN COLLEGE OF SURGEONS  |  DIVISION OF EDUCATION Blended Surgical Education and Training for Life

Ischemic Colitis page 30

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Editor in chief

Editorial and business offices

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Lewis Flint, MD, FACS

ACS-SRGS

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ACS steering committee L. D. Britt, MD, MPH, FACS, chair Ajit K. Sachdeva, MD, FACS, FRCSC Patrice Gabler Blair, MPH

Editorial board Nita Ahuja, MD, FACS, The Johns Hopkins Medical Institutions, Baltimore, MD L. D. Britt, MD, MPH, FACS, Eastern Virginia Medical School, Norfolk, VA Ara Darzi, MD, FACS, FRCS(Eng), KBE, FMedSci, Imperial College of London, London, UK Karen Deveney, MD, FACS, Oregon Health and Science University, Portland, OR Michael B. Edye, MD, FACS, University of Western Sydney, Seven Hills, Australia Jean C. Emond, MD, FACS, Columbia University Medical Center/New YorkPresbyterian Hospital, New York, NY John Ferrara, MD, FACS, Virginia Tech Carilion School of Medicine, Roanoke, VA Donald E. Fry, MD, FACS, Michael Pine & Associates, Chicago, IL Amy L. Halverson, MD, FACS, Northwestern Memorial Hospital, Chicago, IL Tyler G. Hughes, MD, FACS, Memorial Hospital, McPherson, KS Roger Keith, MD, FACS, University of Saskatchewan, Saskatoon, Canada Solly Mizrahi, MD, FACS, Soroka Medical Center, Beer Sheva, Israel Chandrajit Premanand Raut, MD, MSc, FACS, Brigham and Women’s Hospital, Boston, MA Raul J. Rosenthal, MD, FACS, Cleveland Clinic Florida, Weston, FL Ajit K. Sachdeva, MD, FACS, FRCSC, American College of Surgeons, Chicago, IL Eduardo de Santibañes, MD, PhD, FACS, Instituto Universitario del Hospital Italiano de Buenos Aires, Buenos Aires, Argentina Murray Shames, MD, FACS, University of South Florida, Tampa, FL Nathaniel J. Soper, MD, FACS, Northwestern Memorial Hospital, Chicago, IL Steven Steinberg, MD, FACS, The Ohio State University Hospitals, Columbus, OH Christopher B. Weldon, MD, PhD, FACS, Children’s Hospital Boston, Boston, MA Steven D. Wexner, MD, PhD(Hon), FACS, FRCS, FRCS(Ed), Cleveland Clinic Florida, Weston, FL

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The American College of Surgeons is a scientific and educational organization of surgeons that was founded in 1913 to raise the standards of surgical practice and improve the quality of care for surgical patients. The College is dedicated to the ethical and competent practice of surgery. Its achievements have significantly influenced the course of scientific surgery in America and have established it as an important advocate for all surgical patients. The College has more than 80,000 members and is the largest organization of surgeons in the world.

ACS disclosure policy In accordance with ACCME accreditation criteria, ACS must ensure that anyone in a position to control the content of SRGS has disclosed all relevant financial relationships with any commercial interest. Members of the SRGS editorial board and those providing editorial assistance are required to disclose all financial relationships. All reported conflicts are managed by a designated official to ensure bias-free content. However, if you perceive a bias, please contact us at [email protected]. The following relationships were disclosed in 2015: Nita Ahuja, MD, FACS, has disclosed a commercial interest in Astea and Celgene; Ara Darzi, MD, FACS, FRCS(Eng), KBE, FMedSci has disclosed a commercial interest in G.E. Healthymagination; Donald E. Fry, MD, FACS, had disclosed a commercial interest in CareFusion, Ethicon, IrriMax Corporation, and Merck; Raul J. Rosenthal, MD, FACS, has disclosed a commercial interest in Covidien, Ethicon, and STORZ; Murray Shames, MD, FACS, has disclosed a commercial interest in Cook, Gore, and Medtronic; Steven D. Wexner, MD, PhD(Hon), FACS, FRCS, FRCS(Ed), has disclosed a commercial interest in Asana Medical, CareFusion, Covidien, CRH Medical, Edwards LifeSciences, EZ Surgical, GI View Ltd., Incontinence Devices, Inc., Intuitive Surgical, KARL STORZ EndoscopyAmerica, Inc., LifeBond, Mederi Therapeutics, Medtronic, NeatStitch, Novadaq, novoGI, Precision Therapeutics, Renew Medical, and Unique Surgical Innovations, LLC.

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Continuing medical education

Statement of purpose

Accreditation The American College of Surgeons is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

Selected Readings in General Surgery (SRGS) is a topic oriented, in-depth review of the field of general surgery presented eight times annually as an educational offering of the Division of Education of the American College of Surgeons. The mission of the Division of Education is to improve the quality of surgical care through lifelong learning, based on educational programs and products designed to enhance the competence or performance of practicing surgeons, surgery residents, and members of the surgical team. The intent of the publication is to analyze relevant medical literature to give the surgeon the knowledge necessary to practice state-of-the-art surgery. To accomplish this goal, the editor selects 100–125 pertinent articles from the literature for each issue. Each article is reviewed and an overview is written that places the content of these articles in the perspective of the best, day-to-day, clinical practice. In addition to the overview, 12–18 fulltext articles are reprinted in each issue.

CME credit The American College of Surgeons designates this enduring material for a maximum of 10 AMA PRA Category 1 Credits.™* Physicians should claim only the credit commensurate with the extent of their participation in the activity. *Of the AMA PRA Category 1 Credits™ listed above, a maximum of 10 credits meet the requirements for Self-Assessment. Learning objectives This activity is designed for general surgeons, surgical residents, and allied professionals. Regular reading of SRGS should enable learners to: • Maintain an excellent knowledge base in all areas of general surgery • Develop comparative and critical literature reading skills • Apply newly acquired knowledge to surgical practice • Prepare effectively for recertification exams Additional information at www.facs.org/publications/srgs/cme

Maintenance of certification The American Board of Surgery (ABS) recognizes SRGS as a resource for surgeons enrolled in its Maintenance of Certification (MOC) program. Successful completion of the SRGS program fulfills MOC Part 2 requirements that focus on lifelong learning and self-assessment. ACS in cooperation with ABS has created a process wherein ACS members can directly submit their ACS CME transcript to the ABS for MOC purposes. For more information, go to www.facs.org, click Member Login and enter your ACS user name and password. Then, go to My Profile, My CME, and click on “Send Credit to ABS.” For information on ABS’s MOC requirements, go to http://absurgery.org and click on “Maintenance of Certification (MOC)” or e-mail [email protected].

medical evidence evaluation, surgical education, outcomes research, standard setting, and performance improvement. SRGS is a unique resource because the overview and selected full-text articles provide the reader with the most valuable and pertinent content illuminated with informed opinion and critique. Unnecessary material is eliminated. SRGS does not present itself as infallible and the editorin-chief takes responsibility for the content that appears in each issue. The editor-in-chief and the editorial board recognize that there is no such thing as the “average” surgical patient, and that the information in the literature must be interpreted in the light of the clinical presentation of each individual patient.

Copyright Material printed in SRGS is covered by copyright law. The overview and CME tests are copyrights of the American College of Surgeons. Permission has been obtained from individual journal publishers to reprint articles that appear in SRGS. Copying all or portions of this journal for distribution to a group practice, residency program, university, hospital, or colleague is strictly prohibited.

The overview is compiled with the assistance of an 18-member, international board of editors who are experts in the various focus areas that comprise the specialty of surgery. In addition, the editorial board has representation and expertise in such important fields as

© 2015 American College of Surgeons All rights reserved

2015 SRGS Publishing Schedule Title

Volume/Issue

Publication Date

Biliary Tract & Pancreas, Part II

V41N1

Published

Small Intestine

V41N2

Published

Endocrine Surgery

V41N3

Published

Colon, Rectum & Anus, Part I

V41N4

Published

Colon, Rectum & Anus, Part II

V41N5

Published

Colon, Rectum & Anus, Part III

V41N6

Published

Hernia

V41N7

October

Rural Surgery

V41N8

December

Visit www.facs.org/publications/srgs/issues/upcoming for a list of previously published topics and next year’s topics.

Questions about ACS CME can be e-mailed to [email protected] or call 866-918-4799.

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Vol 41 | 6 | 2015

Table of Contents Literature Overview

COLON, REC TUM & ANUS, PART III VOLUME 41 | 6 | 2015



Editor in Chief: Lewis Flint, MD, FACS Associate Editor: Michael McGee, MD, FACS

CME Pretest.................................................. iv

Clostridium Difficile Colitis...................... 24

Introduction................................................... 1

Evolving Aspects of Clostridium Difficile Bacteriology & Infection

Hirschsprung Disease................................ 2

Preventing Clostridium Difficile Infection

The Etiology of Hirschsprung Disease

Management Therapies for Clostridium Difficile Colitis

Diagnosing & Treating Hirschsprung Disease

Therapies for CDAD in Special Circumstances

Enterocolitis

Probiotic Therapy for CDAD

Total Colonic Aganglionosis

Fecal Transplantation Therapy for CDAD

Surgical Management of Hirschsprung Disease

Surgical Therapy for CDAD

Diagnosing Clostridium Difficile Colitis

Long-Term Bowel Function in Patients Treated Surgically for Hirschsprung Disease

Ischemic Colitis.......................................... 30 Inflammatory Bowel Disease Involving the Colon..................................... 5 Cancer Risk in Patients with Inflammatory Disease of the Colon

Epidemiology & Pathogenesis of Colon Ischemia Ischemic Colitis as a Complication of Vascular Surgical Procedures Diagnosis of Ischemic Colitis

Diagnosing Inflammatory Bowel Disease Medical Management of Inflammatory Bowel Disease General Aspects of Colonic Crohn Disease

Diagnosis of Ischemic Colitis Associated with Vascular Surgical Procedures Nonoperative Management of Ischemic Colitis Surgical Management of Ischemic Colitis

Surgical Management of Crohn Disease Management of Perianal Crohn Disease

Conclusion................................................... 34

General Aspects of Ulcerative Colitis Surgical Management of Ulcerative Colitis

References................................................... 35

Laparascopic Proctocolectomy with Ileal Pouch-Anal Anastomosis

CME Posttest............................................. 39

Techniques & Outcomes of Laparoscopic Total Proctocolectomy

Recommended Reading........................ 44

Laparascopic Proctocolectomy in Patients with Severe Colitis Laparascopic Surgical Management of Ulcerative Colitis in Children Diagnosis & Management of Pouchitis

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CME Pretest

COLON, REC TUM & ANUS, PART III VOLUME 41 | 6 | 2015

To earn CME credit, completing the pretest is a mandatory requirement. The pretest should be completed BEFORE reading the overview and taking the posttest. Both tests must be completed online at www.facs.org/publications/srgs/cme.

1. What percentage of patients will require a

4. Long-segment Hirschsprung disease and

permanent colostomy during long-term followup after operation for Hirschsprung disease?

total colonic aganglionosis are conditions associated with mutations of which gene?

a) 50%

a) p53

b) 90%

b) BRAF

c) 10%

c) K-RAS

d) 30%

d) RET

e) 24%

e) APC

2. Rectal mucosal biopsy for diagnosing

5. Which of the following conditions is

Hirschsprung disease is performed 3-4 cm proximal to the dentate line. This location is chosen because?

associated with an increased risk of Hirschsprung disease-related enterocolitis?

a) The rectal mucosa at the dentate line is hypoganglionic

b) Familial medullary thyroid carcinoma

b) The columnar epithelium in this location is hypoplastic

d) Turcot syndrome

a) Familial adenomatous polyposis c) Gardner syndrome

c) Squamous epithelium extends 1–2 cm proximal to the dentate line

6. Approximately how many new cases of

d) Ganglion cell overgrowth is common near the dentate line e) Transitional epithelium is commonly found near the dentate line 3. With follow-up of 20 years or more,

what percent of patients complain of persistent fecal soiling following operation for Hirschsprung disease?

e) Down syndrome

inflammatory bowel disease are recorded annually in the United States? a) 500 b) 1 million c) 350,000 d) 100,000 e) 600,000

a) 3% b) 29% c) 55% d) 90% e) 12%

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Pretest |

7. All of the following statements regarding

COLON, REC TUM & ANUS, PAR T III

10. Which of the following is true regarding

the epidemiology of inflammatory bowel disease are true except which one? a) Fewer cases of inflammatory bowel disease are diagnosed in Hispanics b) More patients with inflammatory bowel disease reside in Northern sections of Europe and North America

the relationship of chronic inflammation to the risk of colorectal cancer in patients with inflammatory bowel disease? a) Adenomatous polyps always precede the development of colorectal cancer in patients with inflammatory bowel disease

c) Risk for inflammatory bowel disease increases with increased fruit and grain intake

b) The chronic inflammation associated with inflammatory bowel disease is characterized by the downregulation of oxidative stress

d) The incidence of Crohn disease is bimodal, with one peak in early adulthood and the second in the 50–60 age range

c) The development of primary sclerosing cholangitis reduces colorectal cancer risk in patients with inflammatory bowel disease

e) “Westernization” of low-incidence areas is associated with an increasing incidence of inflammatory bowel disease

d) Intake of antiinflammatory medications does not alter the risk of colorectal cancer in patients with inflammatory bowel disease e) Colonic mucosal cells in areas of inflammation display genetic characteristics similar to those displayed by colon cancer cells

8. Which of the following geographic

areas has an increasing incidence of inflammatory bowel disease?

11. A 26-year-old man presents with a history

a) Australia

of crampy abdominal pain, diarrhea that is occasionally bloody, and weight loss. All of the following would be useful to confirm the diagnosis of Crohn disease except which one?

b) Sweden c) Great Britain d) France e) United States

a) Finding of granulomata in biopsies of inflamed colonic mucosa b) Finding evidence of small bowel disease in the ileo-colonic junction area on CT enterography

9. All of the following statements

regarding the natural history of Crohn disease are true except which one?

c) Negative serum test for amoebic infection d) Discovery of a fistula-in-ano on physical examination

a) Crohn’s disease diagnosed after age 50 is most likely to present with stricture and/or fistula formation

e) History of recent fluoroquinolone use

b) Fistula-in-ano develops in 30% of patients with Crohn disease

12. All of the following techniques are used

c) Over a 20-year disease history, the risk of perianal disease development in patients with Crohn disease is 50%

effectively for detecting colon mucosal dysplasia in patients with inflammatory bowel disease except which one?

d) Overall mortality risk for patients with Crohn disease is identical to the risk in the general population

a) CT colonography

e) Cumulative risk of a diverting ostomy in patients with Crohn disease is 80% over 20 years

c) Colonoscopy with biopsy targeted with indigo carmine mucosal spraying

b) Colonoscopy with multiple non-targeted biopsies

d) Colonoscopy with biopsy targeted with endo-microscopy e) Colonoscopy with biopsy targeted with methylene blue mucosal spraying

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13. What is a dysplastic colon lesion that

17. Which of the following characteristics

cannot be completely excised at the time of colonoscopic surveillance in patients with inflammatory bowel disease called?

enables C. difficile organisms to secrete toxins A and B at an increased rate?

a) FAS-1 lesion

b) Increased bacterial membrane permeability

b) Dysplasia associated lesion or mass (DALM)

c) Increased secretion of binary toxin

c) Residual polypoid growth

d) tcdC gene deletion

d) Adenomatous degenerated lesion

e) Increased resistance of spores to refrigeration

a) Enhanced anaerobic growth rate

e) Indefinite for dysplasia lesion 18. Which of the following risk factors is most 14. Each of the following agents is accepted for

treating Crohn disease except which one? a) 5-aminosalicylate compounds

common in patients with C. difficile colitis? a) Age less than 50

b) Cyclosporine

b) Broad spectrum antibiotic therapy within the month prior to colitis development

c) Azathioprine

c) Diabetes mellitus

d) Ciprofloxacin

d) History of aortic-coronary bypass within the past year

e) Infliximab

e) Female gender

15. Following total proctocolectomy with

19. Which of the following is effective for

ileal pouch-anal anastomosis, longterm normal continence is observed in what percentage of patients?

preventing the spread of C. difficile infection? a) Prophylactic vancomycin enemas

a) 20%

b) Prophylactic oral metronidazole

b) 13%

c) Oral cephalexin prophylaxis

c) 1%

d) Soap and water hand hygiene

d) 34%

e) Vaccination with C. difficile vaccine

e) 90% 20. A 74-year-old man develops bloody diarrhea 16. Which of the following is an accepted first-line

operative procedure for ulcerative colitis? a) Sigmoid colectomy with primary anastomosis b) Right hemicolectomy c) Ileocecal resection with primary anastomosis d) Proctectomy with diverting stoma e) Total proctocolectomy with ileostomy

two days following successful open repair of a ruptured abdominal aortic aneurysm. Which of the following would be a useful method of diagnosing the etiology of the diarrhea? a) Stool culture b) Serial hematocrit determinations c) Colonoscopy d) Serial white blood cell counts e) Plain abdominal radiograph © 2015 American College of Surgeons

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Vol 41 | 6 | 2015

Introduction

COLON, REC TUM & ANUS, PART III VOLUME 41 | 6 | 2015

W

elcome to the third and final issue of our series dealing with surgical diseases of the colon, rectum, and anus. We will open with Hirschsprung disease, and then continue our discussion of inflammatory diseases involving the colon, which we began in the previous issue. Additionally, we will explore two diseases that are diagnosed with increasing frequency: Clostridium difficile colitis and ischemic colitis. As in past issues, I owe a large debt of gratitude to Michael McGee, MD, FACS, of the Department of Surgery at Northwestern University Feinberg School of Medicine for his assistance in article selection for this series.

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Vol 41 | 6 | 2015

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COLON, REC TUM & ANUS, PAR T III

Hirschsprung Disease Hirschsprung disease is the most common congenital motility disorder involving the distal intestine, and is the result of the absence of neural ganglion cells in a segment of colon of variable length. A review article on Hirschsprung disease by Langer1 in Current Opinion in Pediatrics, 2013, noted that Hirschsprung disease is diagnosed in 1 out of 5,000 live births. The most common clinical presentation is one of distal colon obstruction, but the disease can present in older children as chronic constipation or recurrent colitis.

The Etiology of Hirschsprung Disease Hirschsprung disease stems from the absence of ganglion cells in the myenteric and submucosal plexuses. Usually, the distal colon is involved, but total colon aganglionosis—with or without aganglionosis of the distal ileum— can present in 5%–10% of patients. Langer noted that cells from the neural crest migrate from proximal to distal colon during the first 13 weeks of gestation and these cells mature and become functioning ganglion cells after they arrive in the distal colon. Two main theories have been offered as explanations for the failure of ganglion cells to become functional in the distal colon of patients with Hirschsprung disease: the first theory is that the ganglion cells never reach the distal colon because they become mature, functioning cells earlier than they should, with localization in a proximal rather than distal colon segment; the second theory is that the ganglion cells do reach the distal colon, but they do not mature. Evidence for both etiologies can be found in individual patients, suggesting that the disease has multiple etiologic mechanisms. Langer noted that the heterogeneous nature of Hirschsprung disease is supported by the observation of several genetic alterations in patients with the disease; for example, alterations of the RET proto-oncogene are seen in patients with familial Hirschsprung disease and in patients with long-segment disease. Other genes that may be involved are the Endothelin-3 and EndothelinB genes: it is known that these genes can suppress the maturation of neural crest cells, and patients with these genetic mutations may also have other disorders of neural crest cells, such as pigmentation abnormalities and sensorineural hearing loss. 2

Additional research that helped to clarify the roles of mutations of the RET proto-oncogene in Hirschsprung disease was reported in an article by Moore and Zaahl2 in the Journal of Pediatric Surgery, 2014. This article is supplied as a full-text reprint accompanying some formats of SRGS. The article describes a study that analyzed mutations of the RET gene system in excised colon tissue from patients with Hirschsprung disease. The authors noted that alterations occurred in the SNP1 and SNP2 RET intronic locations. SNP1 mutations were associated with short-segment disease, while SNP2 intron abnormalities were associated with long-segment disease and total colon aganglionosis (TCA). The authors concluded that diverse genetic alterations are likely in patients with Hirschsprung disease, and that these alterations determine the type of Hirschsprung disease that presents in individual patients.

Diagnosing & Treating Hirschsprung Disease Langer1 noted that the majority of patients with Hirschsprung disease present with neonatal colonic obstruction characterized by feeding intolerance, abdominal distention, bilious vomiting, and delayed passage of meconium. Patients may also present with cecal or appendiceal perforation. A water-soluble contrast enema is indicated when plain film imaging confirms the clinical picture of distal bowel obstruction; the author stressed that using this type of enema is important because it may definitively treat conditions such as meconium ileus or meconium plug syndrome that may have similar clinical pictures. Most patients will have a transition zone noted on imaging that confirms the diagnosis, but up to 10% of patients may not have a visible transition zone; a suction biopsy of the rectum is indicated to provide histologic evidence of the absence of enteric ganglion cells. Langer also noted that Hirschsprung disease may present in older children as chronic constipation; the diagnosis may be suggested if there is a history of failure to pass meconium in the first 48 hours of life, if the constipation is refractory to diet therapy, if the patient is dependent on enemas, and if growth patterns are abnormal. Imaging may be helpful in diagnosing Hirschsprung disease in older children or adults: visualizing a dilated, feces-filled colon on plain abdominal radiograph and/or

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Vol 41 | 6 | 2015

Hirschsprung Disease |

barium enema is strongly suggestive. Anal manometry is also useful and associated with an accuracy exceeding 90% for diagnosing Hirschsprung disease.3 This said, it is important to note that while abnormal anal manometry may suggest the diagnosis, the diagnosis will need to be confirmed with a full-thickness rectal biopsy (rather than a suction biopsy) because of the thickness of the rectal wall in these older children. As the understanding of the basic biology of Hirschsprung disease increases, research may open new treatment pathways. An example of one such pathway was described in an article by El-Nachef and Grikscheit4 in the European Journal of Pediatrics, 2014. The authors reviewed the status of research into transplantation of mature enteric nervous system cells into the intestine; they noted that these cells can be harvested from both rodent and human intestine, and that since the cells are not embryonic stem cells, many of the ethical challenges of stem cell transplantation are not encountered in this work. The authors cited data from several animal studies that confirm successful engraftment of harvested cells in the walls of the colon—the cells were shown to be viable and were located in the normal positions within the colon wall. While the contribution of the implanted cells in colonic motility has been confirmed, the authors stressed that the function of the enteric nervous system is complex, and that additional research will be necessary to confirm the full functionality of these implanted cells.

Enterocolitis Two complications of Hirschsprung disease, enterocolitis and total colon aganglionosis, may adversely impact outcomes in patients treated for this disease. Langer noted that approximately 10% of children will have enterocolitis as the presenting symptom: this condition is characterized by fever, abdominal distention, and diarrhea, and may be life-threatening. The diagnosis of Hirschsprung disease as a cause of the colitis is supported by a history of failure to pass meconium and intermittent symptoms of obstruction. In an article by Kapur5 in Seminars in Pediatric Surgeries, 2009, it was noted that enterocolitis may complicate Hirschsprung disease before or after operative management. Full-thickness necrosis of the colon may occur in severe cases; rectal biopsy will supply histopathologic evidence of inflammation and necrosis. American College of Surgeons  www.facs.org/publications/srgs 

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COLON, REC TUM & ANUS, PAR T III

The diagnosis, management, and outcomes of management of enterocolitis complicating Hirschsprung disease is the topic of a single-center retrospective case review by Menezes and Puri6 in Pediatric Surgery International, 2006. The authors reported medical record review data on 74 patients with enterocolitis. Thirty patients had enterocolitis as the presenting sign of Hirschsprung disease in the neonatal period. Enterocolitis occurred as a postoperative complication in 42% of patients. Most of the patients had left-colon disease, but nearly 25% of patients had long-segment disease. Enterocolitis was more common in patients with Down syndrome. Anal sphincter division to relieve obstruction was necessary in 35% of patients. After successful treatment of enterocolitis, definitive operation was performed. Fifty-eight patients were available for longterm follow-up. Three patients died of complications of enterocolitis. Thirty-five of the 58 patients had abnormal bowel function, including recurrent enterocolitis in eight patients. The authors concluded that Down syndrome is a risk factor for enterocolitis and that patients successfully treated for enterocolitis who underwent definitive surgery for Hirschsprung disease had a high rate of bowel dysfunction and recurrent enterocolitis. Data from an article by Estevao-Costa and coauthors7 in the Journal of Pediatric Surgery, 2006, suggest that intestinal neuronal dysplasia contributes to the development of postoperative enterocolitis. The authors reported data from two small groups of patients. In one group, only the aganglionic segment of the colon was removed during a pull-through operation. In the second group, the zone of intestinal neuronal dysplasia was removed as well. The authors observed postoperative enterocolitis in 56% of the patients who had only the aganglionic colon removed, while 8% of the patients who also had the zone of intestinal neuronal dysplasia removed developed enterocolitis. The authors concluded that documenting the dysplastic neuron area with intraoperative frozen section examination and removing that segment may serve to protect patients against postoperative enterocolitis. Treating enterocolitis requires supportive critical care and antibiotic therapy. Recent data have indicated that colonic lavage may be useful for patients with severe postoperative enterocolitis.8 A randomized trial of probiotic therapy for Hirschsprung disease-associated enterocolitis was reported by Wang and coauthors9 in

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Hirschsprung Disease |

COLON, REC TUM & ANUS, PAR T III

the International Journal of Colorectal Disease, 2015. The authors enrolled 60 children: the treatment group was given probiotics including lactobacillus, Bifidobacterium, and enterococcus organisms after the surgical treatment of Hirschsprung disease. At three months postoperatively, the analysis showed that probiotic-treated children had a significantly reduced incidence of enterocolitis, and that those patients in the treated group who did develop enterocolitis had significantly less severe disease. Contrasting data were presented in an article by ElSawaf and coauthors10 in the Journal of Pediatric Surgery, 2013. The article described a prospective, randomized trial that included 62 patients. After resection of the involved colon segment, the treatment group received a readily available probiotic capsule containing Bifidobacterium, lactobacillus, and streptococcus organisms. The primary endpoint was frequency of postoperative enterocolitis, and the analysis showed that there was not a significant difference in the incidence of enterocolitis in the comparison groups. The authors concluded that additional study is necessary before probiotic therapy can be supported as a means of reducing the risk of postoperative enterocolitis.

Total Colonic Aganglionosis Total colonic aganglionosis is most often treated with diverting enterostomy in the small bowel proximal to the zone of aganglionosis, followed by a pull-through operation with anastomosis of the normally innervated ileum to the anal canal. A single-center retrospective experience with the management of patients with total colon aganglionosis is by Cheung and coauthors11 in the Journal of Pediatric Surgery, 2009. The authors reported data from seven patients found to have total colon aganglionosis, but who had normal innervation within the first 15 cm of the terminal ileum. Three patients had conventional pull-through procedures. In a follow-up period averaging more than 13 years, all patients were continent, and four patients were treated with a one-stage laparoscopic pullthrough operation. In a short follow-up period averaging three years, patients had an average of five bowel movements per day, but most of the patients were too young to reliably evaluate continence. The authors concluded that conventional open pull-through and laparoscopic pull-through procedures are feasible for treating patients with total colon aganglionosis. 4

Surgical Management of Hirschsprung Disease Langer1 noted that there are three surgical procedures used for the definitive surgical management of Hirschsprung disease: the Swenson procedure is a full-thickness resection of the involved colonic segment with anastomosis of normally innervated colon to the anal sphincter; the Soave procedure includes a transanal removal of the mucosa of the rectal segment with pull-through of normally innervated colon through the demucosalized rectal sheath with anastomosis at the level of the anal sphincter; the Duhamel procedure involves a side-to-side anastomosis of normally innervated colon to the retained pelvic segment of the aganglionic rectum. The Soave and the Duhamel procedures were developed to minimize the risk of urinary and sexual dysfunction that might result from injury to the pelvic nerves, and the Duhamel procedure is also useful for long-segment Hirschsprung disease. For patients with total colon aganglionosis, a total proctocolectomy with ileal pouch anal anastomosis may be indicated. The transanal pull-through operation (Swenson or Soave) is currently the most common approach for the management of Hirschsprung disease. This can be done either with a total transanal approach, or with laparoscopic or open intraabdominal mobilization of the colon and rectum. Comparisons of the two approaches are discussed in two articles: Kim and coauthors12 presented a multicenter study in the Journal of Pediatric Surgery, 2010, that compared the two approaches. The authors reported data from five pediatric centers with a group of 281 patients. Eighty-nine of the patients had a transabdominal component to their operation and the remaining patients had a total transanal approach. The goal of the study was to evaluate long-term continence, since damage to the anal sphincter during the total transanal approach due to retraction and stretching might contribute to late problems with continence. Follow-up was obtained by questionnaires completed by parents; patients who were at least six months postoperative and older than 3 years were included. The data disclosed no difference in continence when the two groups were compared. Confirmatory evidence was provided in a single-center study by Stensrud and coauthors12 in the Journal of Pediatric Surgery, 2010. These authors reported data from a group of 52 children followed over intervals of 3–10 years af-

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ter operation. The authors found that nearly half of the children who underwent either a transabdominal assisted or total transanal pull-through procedure complained of fecal soiling at long-term follow-up. Constipation was reported by 10%–15% of patients. The authors concluded that continence and constipation were observed in similar proportions of patients undergoing each type of operation. An article that reviewed data from a single-center experience with the Swenson operation is by Levitt and coauthors13 in the Journal of Pediatric Surgery, 2013. This article is supplied as a full-text reprint accompanying some formats of SRGS. The authors reported long-term outcomes of urinary and sexual function following transanal procedures in a group of 67 patients: a complete transanal procedure was performed in 27 patients, transanal pull-through plus laparoscopy was done in five patients, and the remaining patients had a transanal pull-through plus open laparotomy procedure. At a median follow-up of 17 months, urinary continence was present in 100% of patients and 88% of male patients were observed to have spontaneous penile erections. Constipation requiring occasional laxatives was observed in 32% of patients. Another article reporting outcomes of surgical therapy of Hirschsprung disease was by de la Torre and Langer15 in Seminars in Pediatric Surgery, 2010. The authors discussed various issues related to management of patients with Hirschsprung disease, such as timing of the pullthrough operation, use of colostomy, technical features of the anal-rectal dissection, features of postoperative care, and the management of postoperative stricture. Readers are encouraged to review this article in detail.

Long-Term Bowel Function in Patients Treated Surgically for Hirschsprung Disease A paper by Mills and coauthors in the Journal of Pediatric Surgery, 2008, analyzed long-term quality of life and continence, as well as the incidence of significant constipation, in a group of patients who underwent operation for Hirschsprung disease at a single Canadian center. Fifty-one children and their families participated in the questionnaire survey; patient age ranged from 5 to 21. The data disclosed that nearly half of the patients experienced problems with continence. By the time patients reached 14

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their teenage years, continence problems were observed in only 20% of patients. In the patient group with symptoms of incontinence, however, quality of life was significantly impacted: patients who experienced continence problems had substantially lower quality-of-life scores. The authors concluded that continence abnormalities affect a relatively small group of patients, but that the adverse impact on quality of life in this patient group is significant. Another study evaluating quality of life in adults who underwent operation for Hirschsprung disease in infancy was presented by Gunnarsdottir and coauthors15 in the Journal of Pediatric Gastroenterology and Nutrition, 2010. The authors reported data from a quality-of-life questionnaire survey of 42 patients. The median age of patients was 23 and the interval between operation and the survey was, on average, more than 6 years. Overall, 29% of patients reported fecal soiling and 12% reported constipation. Quality-of-life scores for men were not significantly different from the general population, but the women’s scores were significantly worse than the general population. The authors concluded that long-term outcomes after treatment of Hirschsprung disease are satisfactory in the majority of patients, that there is a relatively small proportion of patients with reductions in overall qualityof-life scores, and that female patients are more likely to have significant reductions in quality of life.

Inflammatory Bowel Disease Involving the Colon Inflammatory bowel disease (IBD) affects nearly 1.5 million patients in the United States and nearly twice that number in Europe. Ulcerative colitis is a disease localized almost entirely to the colon (terminal ileum involvement is documented in some patients); the disease has few extraintestinal manifestations, but some of these, such as episcleritis and large joint arthropathy, respond favorably to colectomy. More than two-thirds of patients with Crohn disease have involvement of the small intestine and cecal area, while the remaining one-third has colonic

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disease. Extraintestinal manifestations of Crohn disease are common, and perianal and perineal Crohn disease are sources of significant disability that impair quality of life. This section of the overview reviews articles focusing on the clinical aspects of IBD involving the colon, rectum, and anus. A recent review of the epidemiology of IBD is by Cosnes and coauthors16 in Gastroenterology, 2011. The authors reviewed available data from the literature and confirmed earlier observations that the incidence of IBD is high, but stable, in Europe and North America, while case frequency is increasing in Asia, India, Japan, and Australia. The authors cited data from studies of migrant populations that confirm that migrating to high-incidence areas during childhood increases IBD risk; this observation supports the significant causal relationship between IBD and environmental factors. The authors also noted that up to 80% of patients with Crohn disease will require one or more operative procedures during their lifetimes, and up to 30% of patients with ulcerative colitis will require an operation. The one-third of patients who have Crohn disease isolated to the colon has the lowest risk of operation for patients with Crohn disease; data reviewed by the authors suggests that Crohn colitis is frequently quiescent, especially in patients with a long history of the condition. Cosnes and colleagues also reviewed the natural history of Crohn disease and ulcerative colitis and noted that the early manifestations of Crohn disease are primarily inflammatory; patients diagnosed with Crohn disease later in life tend to develop fistulas and strictures, and in the course of this disease, repeated flare-ups occur. With each of these flare-ups, there is an increased risk for surgical intervention. Perianal disease (primarily fistula formation) develops in up to 30% of patients in the early stages of Crohn disease, and the cumulative risk for perianal fistula development over the course of 20 years approaches 50%. Patients with Crohn disease also have a risk of operation, permanent stoma creation that approaches 80% over the course of 20 years, and an overall mortality risk that is significantly higher than the predicted mortality risk for the general population. A review article by Loftus17 in Gastroenterology, 2004, provided data on the epidemiology of IBD involving the colon. The author opened the review by defining terms

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that are frequently used in the field of descriptive epidemiology: incidence of disease is the case frequency that occurs in a country or region over time, and incidence is usually expressed as cases per 100,000 person-years; prevalence is the case frequency expressed as numbers of cases per 100,000 persons. Loftus noted that the incidence of ulcerative colitis, gathered from a number of epidemiology studies cited in the review, is in the range of 2.2–14.6 cases per 100,000 person-years. For Crohn disease, the range is 3.1–14.3 cases per 100,000 person-years. Prevalence of ulcerative colitis is in the range of 37–246 per 100,000 person-years; for Crohn disease, prevalence is 26–199 per 100,000 person-years. These numbers imply that, at any given time, 746,000 cases of ulcerative colitis exist in the United States, along with 630,000 cases of Crohn disease. In any given year, nearly 100,000 new cases of IBD are diagnosed. IBD is more common in the northern areas of Europe and case density is higher in the northern regions of North America. Loftus noted that IBD incidence and prevalence have stabilized in Europe and North America, but that its incidence and prevalence are rising in developing countries. Several factors contribute to this rise, including the increasing ability to diagnose IBD and the increasing consciousness of the disease among physicians in developing countries. This pattern also supports the basic understandings of IBD as a spectrum of diseases having genetic and environmental etiologies. With the “westernization” of developing countries, the environmental factors that contribute to the development of IBD become more prominent. Loftus cited data suggesting that IBD is most likely to be diagnosed in late childhood or early adulthood, and that case frequencies in Caucasians and African-Americans are nearly equal, while case frequencies are increasing among Hispanics and Asians. Additionally, two sets of data analyses confirmed the incidence, prevalence, age, and gender distribution of IBD: Herrinton and coauthors18 analyzed data from a California health care system, and Kappelman and coauthors19 analyzed data drawn from a national database of insurance claims. These two large database analyses confirmed the north-south gradient of incidence and prevalence as well as the bimodal incidence of Crohn disease (first peak in early adulthood and second peak in the 50–60 year age range); comparatively, ulcerative colitis shows a rising frequency of diagnosis in late childhood, with a continuing rise throughout adulthood.

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Loftus17 also reviewed risk factors for IBD. The most consistent data are available for cigarette smoking, which increases the risk for Crohn disease, but has a protective effect for ulcerative colitis. Less clear are data linking appendectomy and oral contraceptive use to IBD risk. Valuable data on disease incidence and mortality risk came from epidemiologic studies of specific geographic regions. One source of these data is the Rochester Epidemiology Project (REP). An article that reviewed the incidence and prevalence of IBD in according to data from this source is by Loftus and coauthors20 in Inflammatory Bowel Diseases, 2007. This article used data gathered over the 60-year interval from 1940 to 2000. The data disclosed that IBD diagnoses increased steadily from 1940 to 1970 and has been stable since 1970. The data predicted that there would be approximately 400 people with IBD in Olmsted County, Minnesota in 2001. An actual count showed that there were 460 people with either ulcerative colitis or Crohn disease. Another analysis of data from Olmsted County sought to establish the mortality risk for patients with IBD. This analysis was reported in an article by Jess and coauthors21 in Gut, 2006. As mentioned earlier, the reviewed data demonstrated that the risk of death in patients with Crohn disease was significantly higher than the predicted mortality risk for the general population; an increased risk of gastrointestinal malignancy contributed to the increased mortality risk. The data also support the observation of an increased frequency of smoking (and therefore, lung disease) in patients with Crohn disease. Fewer patients with ulcerative colitis died compared with the predicted number; specifically, cardiovascular disease was less frequent than expected in patients with ulcerative colitis. A final article reporting data on the natural history of IBD is by Langholz22 in Therapeutic Advances in Gastroenterology, 2010. Langholz noted that for patients with Crohn disease, relapse after operation was more likely to occur in patients diagnosed at a young age and in patients who require operation soon after disease diagnosis. The observations regarding the epidemiology and natural history of inflammatory diseases of the colon reviewed by Cosnes and coauthors16 are largely confirmed in the review by Langholz.

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Cancer Risk in Patients with Inflammatory Disease of the Colon An article that reviewed the epidemiology, biology, and clinical aspects of malignancies associated with IBD is by Beaugerie and Itzkowitz23 in the New England Journal of Medicine, 2015. This article is supplied as a full-text reference accompanying some formats of SRGS. The authors opened the review with data on the health burden of IBD, and acknowledged that overall life span is reduced in patients with Crohn colitis and ulcerative colitis. The magnitude of this reduction is related to the duration of the disease, and one of the reasons that life span is reduced is the increased risk of malignant disease of the colon in these patients. Beaugerie and Itzkowitz wrote that lifestyle factors may contribute to the increased cancer risk observed in patients with IBD of the colon. For example, smokers are overrepresented in patients with Crohn colitis compared with the general population. The authors also cited data supporting the conclusion that cancer risk is associated not only with the duration of disease, but with the severity of inflammation; the data disclosed that patients whose colonic inflammation is controlled with medical therapy have a cancer risk that is similar to the general population. Beaugerie and Itzkowitz noted that genetic alterations resulting from ongoing inflammation activate carcinogenic genes and inactivate tumor suppressor genes. In addition, the altered microbial population in chronically inflamed colons may contribute to cell damage that predisposes the colonic region to malignant change. Two additional factors that may contribute to increased cancer risk with IBD are the formation of dysplastic polyps that may accompany chronic inflammation, and the fact that the formation of strictures, as well as ongoing perianal inflammation, may make colonoscopic surveillance difficult. Evidence reviewed Beaugerie and Itzkowitz confirmed that the polyp-to-cancer progression in the development of sporadic colorectal cancer is also present in cancers that develop in patients with IBD involving the colon; an illustration of the polyp-cancer sequence was presented in this article and is reproduced as Figure 1.

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Figure 1

Polyp-cancer sequence for patients with sporadic colorectal cancer and for patients with inflammatory bowel disease-related dysplasia. Reproduced from Beaugerie and Itzkowitz23 with permission.

Polyps that develop in patients with inflammatory colon disease tend to be flatter, with less distinct borders than those observed in patients who do not have IBD. This has led to the use of white-light endoscopy and chromoendoscopy techniques that make these polyps easier to detect on colonoscopy. A discussion of the appearance and histopathology of lesions that are precursors of colorectal cancer is the focus of an article by Harpaz and Polydorides24 in the Archives of Pathology and Laboratory Medicine, 2010. The authors noted that dysplastic lesions are classified as high-grade dysplasia, low-grade dysplasia, or indefinite for dysplasia. They also emphasized that accurate histologic interpretation is possible in almost all instances if the pathologist(s) involved are experienced 8

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and seek consultation in cases of uncertainty. In areas of very intense inflammation, interpretation is the most difficult; re-biopsy might be necessary. Macroscopic classification of suspected dysplastic lesions groups lesions according to whether they are raised or flat: a raised dysplastic lesion that can be completely excised at the time of colonoscopy indicates that the patient can be safely followed with endoscopic surveillance, while a lesion that cannot be completely excised at the time of colonoscopy is classified as a dysplasia-associated lesion or mass (DALM). Incomplete excision occurs because of indistinct lesion borders, large lesion size, or the presence of a raised lesion in an area of flat dysplasia. The presence of DALM lesions is an indication for colectomy

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because there is a high risk of malignancy in the index lesion or in a synchronous lesion elsewhere in the colon. Flat lesions may be discovered with non-targeted biopsies. Newer endoscopic techniques that use chromoendoscopy (mucosal spraying with methylene blue or indigo carmine) or endo-microscopy improve the localization of dysplastic lesions for biopsy; flat dysplastic lesions with either highor low-grade dysplasia are treated with colectomy. Data reviewed in the article by Beaugerie and Itzkowitz23 confirm that most clinical practice guidelines support the use of colonoscopic surveillance for dysplastic lesions that can be excised completely, with colon resection recommended for patients with confirmed malignant lesions and dysplastic lesions that cannot be completely removed endoscopically. The authors mentioned that cancer prevention could theoretically be accomplished by controlling the inflammation with medications; available data on the effectiveness of this approach have not consistently been positive and, for this reason, antiinflammatory drug treatment is not currently recommended solely for cancer prevention. Another summary of reasons for an increased risk of colorectal cancer in patients with IBD was presented in an article by Ullman and Itzkowitz25 in Gastroenterology, 2011. The authors noted that available data support the conclusion that, compared with the general population, patients with ulcerative colitis and Crohn disease have a three- to five-fold increased risk of developing colorectal cancer—with the exception of patients with isolated ulcerative proctitis, who do not seem to be at an increased risk. In fact, risk of colorectal cancer varies according to the type of IBD; consequently, the overall increased cancer risk can be altered by modern approaches to disease detection and treatment. For example, an analysis of the colorectal cancer risk in patients in Olmsted County, Minnesota, reported in an article by Jess and coauthors,26 disclosed a risk for colorectal cancer in patients with ulcerative colitis who participated in an active endoscopic surveillance program that was nearly identical to the general population (for patients with Crohn disease, the overall cancer risk is twice that of the general population). The authors emphasized that colorectal cancer risk is highest in patients with extensive involvement of the colon or who have sustained colitis that is resistant to treatment.

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Additional data cited in the Ullman and Itzkowitz25 article confirm that cancer risk is further increased in patients who have sclerosing cholangitis along with IBD. This concept is supported by data, albeit indirectly, that treatment with medications that reduce inflammation reduces colon cancer risk in patients with IBD; similar reductions were noted in patients with familial adenomatous polyposis who took nonsteroidal antiinflammatory agents. Ullman and Itzkowitz observed that the colonic mucosal cells located within areas of inflamed tissue have the genetic characteristics found in cells of adenomatous polyps and colorectal cancers (microsatellite instability, DNA methylation disorders) before overt neoplasia develops—the adenomatous polyp that is the precursor of colorectal cancer is a discrete focus of cancer development. In contrast, the precursor lesions of colorectal cancer in patients with IBD are multiple, polypoid, or flat, with varying degrees of dysplasia. The component of the chronic inflammatory process that perpetuates the carcinogenic stimulus is probably ongoing oxidative stress. Clinical programs for the management of cancer risk in patients with IBD are described in an article by Ullman and coauthors27 in Inflammatory Bowel Disease, 2009. Also, the article by Beaugerie and Itzkowitz23 includes a useful algorithm for the management of patients with IBD of the colon who are at increased risk for malignancy; this illustration is included as Figure 2. Ullman and coauthors27 noted that the goals of endoscopic surveillance in patients with IBD are to reduce the incidence and mortality of colorectal cancer in these patient groups and to minimize the use of colectomy in patients without a definite diagnosis of dysplasia. The conceptual basis of endoscopic surveillance is founded on several principles based on clinical observations: the first of these is that there is an increased risk of colorectal cancer in some groups of patients with IBD; furthermore, the documented fact that adenomatous polyps do not always precede colorectal cancer in the presence of chronic IBD provides additional support for surveillance, and the documented fact that dysplasia diagnosed in one part of the colon is predictive of cancer elsewhere in the colon provides support for programs designed to detect dysplasia through endoscopic surveillance.

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Figure 2

Management algorithm for patients with risk for inflammatory bowel disease-related colorectal cancer. Reproduced from Beaugerie and Itzkowitz23 with permission.

The other two important principles behind endoscopic surveillance are that dysplastic lesions progress to cancer more rapidly than adenomatous polyps, and that there is a “field effect” of inflammation-induced genetic damage that places the entire colonic mucosa at risk. Ullman and colleagues noted that the risk of colorectal cancer in patients with colitis is 2% at 10 years, 8% at 20 years, and 18% at 30 years. Surveillance is recommended to begin after 8 years of disease. The risk of cancer, as mentioned previously, rises with increased colonic involvement and inflammation severity. Patients who undergo adequate surveillance biopsies and are found not to have dysplasia can have repeat colonoscopy in 1–2 years. Patients with dysplastic lesions that are completely removed should have repeat colonoscopy in 3–6 months. The authors stressed that there are no conclusive data supporting the value of endoscopic surveillance. It is known, however,

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that cancers resected in patients who undergo endoscopic surveillance have significantly earlier stage tumors than patients treated without surveillance. Beaugerie and Itzkowitz25 noted the risk of cancer development in chronic perineal and perianal fistulas that may complicate Crohn disease. Risk factors for typical anal cancers are similar to those documented for patients without IBD (men who have sex with men, HIV positive patients, and female patients with cervical cancer). The surgical management of dysplasia and cancers in patients with inflammatory disease of the colon was reviewed in an article by Connelly and Koltun28 in Expert Reviews in Gastroenterology and Hepatology, 2013. The authors noted that the most effective surgical procedure for patients with known malignancy or patients at high risk for malignancy associated with IBD is total proctocolectomy with ileal pouch-anal anastomosis or diverting ileostomy: this procedure offers the best likelihood of

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removing both the tumor and the associated dysplastic lesions and synchronous malignant lesions. Connelly and Koltun emphasized that some patients may not be candidates for this approach because of increased operative risk or reluctance to have a diverting stoma. Ileal pouch-anal anastomosis is also associated with fecal incontinence, urinary dysfunction, and sexual function problems. Other surgical approaches, such as segmental colectomy and total abdominal colectomy with ileal-rectal anastomosis, may be offered to patients who have associated conditions that increase operative risk, but postoperative endoscopic surveillance will be necessary. Depending on disease severity and patient risk, a one-, two-, or three-stage approach to total proctocolectomy with ileoanal reconstruction may be chosen. Connelly and Koltun provide a useful illustration of these approaches; this is reproduced as Figure 3.

Figure 3

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An article by Kiran and coauthors29 in Annals of Surgery, 2012, attempted to identify clinical characteristics of patients who might be candidates for segmental colectomy. The authors analyzed outcomes data in 50 patients. The data analysis showed that a diagnosis of high-grade dysplasia had predictive accuracy of 73% for the presence of additional high-grade dysplastic lesions or cancer in the resected specimen; the presence of low-grade dysplasia had a predictive value of 36% for detection of high-grade dysplasia in the resected specimen; multifocal dysplasia, or dysplasia remote from the site of a cancer, was observed in 40% of resected specimens. Similar to Connelly and Koltun’s28 findings, Kiran and coauthors30 recommended that patients who are acceptable operative risks should undergo total proctocolectomy, and confirmed that lesser procedures can be offered to high-risk patients, or patients with low-grade dysplasia, if endoscopic surveillance is employed consistently.

Illustration of staged approaches for total proctocolectomy with ileoanal anastomosis. Reproduced from Connelly and Koltun28 with permission.

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Connelly and Koltun28 provide clear algorithms for managing dysplasia and malignancy in patients with ulcerative colitis and Crohn disease; these are reproduced as Figure 4 and Figure 5.

Diagnosing Inflammatory Bowel Disease Practice guidelines for the clinical, laboratory, and imaging diagnosis of ulcerative colitis and Crohn disease have been promulgated by the American College of Gastroenterology and published in an article by Kornbluth and Sachar31 in the American Journal of Gastroenterology, 2010. The authors noted that the clinical triad of bloody diarrhea, fecal urgency, and tenesmus should raise suspicion for ulcerative colitis, especially in young patients, while

Figure 4

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patients with Crohn disease often present with a history of intermittent abdominal pain, diarrhea, and weight loss. Fever and leucocytosis can be present in both diseases. The most common conditions that need to be excluded in these patients are infectious diarrhea syndromes, which may be caused by E. coli, amoebic infection, or C. difficile (in patients recently treated with antibiotics or recently hospitalized). Stool examination for infectious causes and serum testing for amoeba infection may be helpful. The next step recommended by the guidelines is sigmoidoscopy because 95% of patients presenting with newonset ulcerative colitis will have inflammation primarily in the rectum. Endoscopy with biopsy will disclose the typical mucosal inflammatory changes of ulcerative colitis. Crohn disease can also present with bloody diarrhea.

Algorithm for management of dysplasia complicating ulcerative colitis. Reproduced from Connelly and Koltun28 with permission.

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Figure 5

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Management algorithm for dysplasia complicating Crohn disease. Reproduced from Connelly and Koltun28 with permission.

Biopsy of the inflamed mucosa may show granulomata, and this finding supports a diagnosis of Crohn disease, but granulomata can also be present in patients with infectious diarrhea. A small bowel imaging study will sometimes assist in the diagnosis of Crohn disease if small bowel involvement accompanies colitis. Enterography using CT and/or MRI provides the most accurate assessment of the extent of disease in patients with Crohn colitis. Patients with Crohn disease often have signs and symptoms of extracolonic manifestations of the disease: cutaneous lesions and ocular symptoms are frequent, and perianal fistula and abscess are also common. Crohn disease patients may also present with signs of inflammatory disease, or with stricturing and fistulas that are enteral-enteral or enteralcutaneous, in addition to perianal fistulas. Endoscopy is the most accurate means of evaluating strictures and enteric fistulas.

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The guidelines noted that biomarkers, such as perinuclear antineutrophil cytoplasmic protein (pANCA) and antibodies to S. cerevisiae (ASCA), are frequently demonstrated in patients with ulcerative colitis and Crohn disease. A positive pANCA test associated with a positive S. cerevisiae antibody assay has a positive predictive value of 75% for the diagnosis of ulcerative colitis. A negative pANCA test associated with a positive ASCA antibody assay has a 60% positive predictive value for Crohn disease. Other markers indicative of increased inflammation are C-reactive protein and erythrocyte sedimentation rate; however, these markers are nonspecific. Biomarkers that are useful in the diagnosis of Crohn disease were reported in an article by Van Assche and coauthors32 in the Journal of Crohn’s and Colitis, 2010. This article also contains the consensus guidelines for diagnosis of Crohn disease developed by the European Crohn’s and Colitis Organization. Van Assche and coauthors recomVol 41 | 6 | 2015

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mended the use of two fecal markers, calprotectin and lactoferrin, as means of supporting a diagnosis of Crohn disease in patients with acute onset of colitis. The authors noted that Crohn colitis often presents clinically with abdominal pain, diarrhea, and weight loss. Still, there is significant heterogeneity of clinical presentation, and confirmatory markers may be helpful in differentiating Crohn colitis from ulcerative colitis. Additional information on using biomarkers to diagnose IBD is found in an article by Lewis33 in Gastroenterology, 2011. Lewis noted that calprotectin levels in stool samples are closely related to the intensity of inflammation. Depending on the level selected (50 or 100 micrograms), the sensitivity and specificity for the diagnosis of IBD exceeds 90%, and may approach 96% in adult patients. The sensitivity level is good in children with IBD, but the specificity is less than 76%. Increased lactoferrin levels in stool samples have a sensitivity and specificity of 80% for the diagnosis of IBD; S100A12 is a protein that can be detected in stool samples, and elevated levels have a sensitivity and specificity exceeding 92% for the diagnosis of IBD in children. Lewis added that pANCA and ASCA tests are nonspecific and cannot accurately identify whether patients have ulcerative colitis or Crohn disease. He also cited interesting data demonstrating that nearly 50% of patients without clearcut evidence of IBD, but who have positive tests, develop some form of IBD over long-term follow-up. The practice guidelines from the American College of Gastroenterology31 also recommend imaging studies in selected patients where clinical and endoscopic assessments are inconclusive, or where there is a need to determine whether multiple areas of the intestinal tract are involved. The effectiveness of MR enterography for diagnosis and disease progression monitoring in patients with Crohn disease is the focus of an article by Ordas and coauthors34 in Gastroenterology, 2014. The authors reported data from a prospective, multi-institution trial involving 48 patients. Using MR enterography and ileocolonoscopy, they evaluated the ability of MR enterography to document mucosal healing and to accurately predict endoscopic confirmation of disease remission. The data analysis showed that MR enterography had an accuracy of 90% for documenting ulcer healing and predicted endoscopic evidence of remission with an 83% accuracy. The authors concluded

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that MR enterography was an effective means to monitor disease progression and determine ulcer healing in patients with Crohn disease. In an editorial that accompanied this article, Novak and Panaccione35 emphasized the fact that MR enterography has potential value, but that widespread adoption is hampered by the fact that availability of the technology and expert radiologists is inconsistent. Novak and Panaccione also urged caution because this report was not a randomized prospective trial and is, therefore, subject to multiple sources of bias. They concluded that additional confirmatory evidence is needed. A recent update on the status of imaging for diagnosis of IBD is by Fletcher and coauthors36 in Gastroenterology, 2011. The authors noted that imaging technologies developed over the last decade can now accurately quantify inflammation in intestinal mucosa, the intestinal wall, and in the mesentery and soft tissues adjacent to the intestine. The information from imaging can supplement findings on clinical examination, laboratory studies, and endoscopic evaluations. Specifically, imaging studies can evaluate stenosing and fistulizing disease in Crohn colitis when endoscopy and biomarkers fail to quantify the intensity and extent of inflammation. The most reliable imaging assessments are obtained with CT and MR enterography. The authors noted that enterally administered contrast agents given before the imaging sequence begins are chemically formulated to provide images that assess inflammation in the mucosa, the bowel wall, mesentery, and adjacent tissues: intravenous contrast for CT imaging is administered 50 seconds before the imaging sequence begins. Segmental inflammation and bowel wall thickening (>3 mm thickness) documented in more than one bowel segment are pathognomonic of Crohn disease. Thickening of perienteric fat and engorgement of vasa recta (comb sign) correlate with blood levels of inflammatory markers such as C-reactive protein. The authors emphasized that imaging studies can also diagnose extraenteric manifestations of IBD, such as sclerosing cholangitis, as well as side effects of therapy for IBD, such as avascular necrosis of bone secondary to steroid use. CT and MR enterography demonstrate strictures as areas of segmental narrowing of the intestine and fistulas as tracts containing gas and/or fluid. The sensitivity for CT and MR enterography are equivalent and exceed 95% in data reviewed and cited in this article. Fletcher and coauthors pointed out that

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capsule endoscopy is not as sensitive or specific for establishing a diagnosis of IBD when compared to CT and MR enterography. Data cited in the article also indicate that capsule endoscopy is not cost-effective as a diagnostic test; however, this type of evaluation has value in assessing mucosal healing in areas not visualized endoscopically and might be useful for monitoring purposes during clinical trials of therapeutic agents. Other imaging technologies such as enteral ultrasonography, positron emission tomography, and fluoroscopy may be useful in selected patients—fluoroscopy is particularly valuable in patients who cannot undergo CT or MR imaging.

Medical Management of Inflammatory Bowel Disease The practice guidelines described in the article by Kornbluth and Sachar31 summarize medical therapy for patients with ulcerative colitis. Localized distal colitis that can be monitored with endoscopy can be treated with oral or topical 5-aminosalicylate drugs, such as mesalamine. Maintenance of remission, once remission is accomplished, can be achieved with mesalamine suppositories. Topical steroid enemas are also helpful for patients who do not promptly respond to 5-aminosalicylate therapy. Patients with extensive colonic involvement can be treated with oral therapy using 5-aminosalicylate drugs and/or oral steroids. Azathioprine and 6-mercaptopurine intravenous therapy may be useful as a means of maintaining remission without steroid drugs. Severe colitis may require inpatient therapy with systemic steroids supplemented in selected patients with cyclosporine. For patients resistant to systemic therapy or patients with severe inflammation resulting in systemic toxicity, surgical intervention is indicated. An evidence-based review of medical therapy for IBD is provided in an article by Talley and coauthors37 in the American Journal of Gastroenterology, 2011. The authors noted that 5-aminosalicylate therapy is not recommended for either treating acute flare-ups or maintaining the remission of Crohn disease. They also stressed that antiTNF antibody therapy (infliximab) promotes healing in fistulizing Crohn disease and is valuable in preventing fistula disease relapse. Infliximab is also useful for treating

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patients with ulcerative colitis. Anti a4 integrin antibody therapy is useful for treating acute Crohn disease flareups and for remission maintenance. The authors added that, while antibiotic therapy has been shown to produce statistically significant benefit for treatment of patients with Crohn disease, there is not sufficient evidence to determine a specific antibiotic selection; therefore, antibiotics are not recommended for the routine management of patients with Crohn disease. This said, antibiotic therapy may be useful for reducing drainage from fistulas caused by Crohn disease.

General Aspects of Colonic Crohn Disease The colon is the only bowel segment involved with Crohn disease in up to one-third of patients. As stated previously, Crohn disease can present with inflammatory symptoms including diarrhea, abdominal pain, urgency, anemia, and weight loss. The disease can also present with complications of transmural granulomatous and ulcerative inflammation, leading to intestinal perforation, abdominal abscess, stricturing, and fistula formation. Perianal disease is a disabling form of Crohn disease that may cause perianal, perirectal, and perineal inflammation, abscess formation, and multiple sites of fistula in ano. Crohn disease patients may also develop “metastatic” foci of granulomatous disease that can result in cutaneous abscesses in multiple extracolonic sites. General descriptions of the natural history and clinical outcomes of Crohn disease are topics addressed in two selected articles selected: the first of these is by Duricova and coauthors38 in Inflammatory Bowel Disease, 2010. The authors conducted a systematic review of the available literature. Nine studies were acceptable for inclusion. The data confirmed a statistically significant increase in mortality risk in Crohn disease patients compared with the general population. As noted in earlier discussions, there is also a significant increase in mortality risk from gastrointestinal malignancy (colorectal and small intestine). Because cigarette smoking is a major risk factor for development of Crohn disease, mortality risk is also increased for chronic obstructive pulmonary disease and lung cancer.

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The second article reviewed is by Peyrin-Biroulet and coauthors39 in Inflammatory Bowel Disease, 2011. These authors conducted a systematic review of the literature to determine the risks for extraintestinal diseases in patients with Crohn disease. The data disclose that a significant increased risk exists for ocular diseases, deep venous thrombosis and pulmonary embolus, osteopenia with fracture, and demyelinating disease. The evidence suggests that patients who present with indications for surgical management of complications of Crohn disease will have significant potential for multisystem disease involvement.

Surgical Management of Crohn Colitis Indications for colectomy for Crohn disease include intestinal perforation with abscess, colonic stricture with obstructive symptoms, and colorectal cancer. In contrast to ulcerative colitis, segmental colectomy can be used more often because of localized disease. A further contrast with ulcerative colitis is that recurrent disease necessitating multiple operations is common. One concern regarding the use of segmental colectomy has been the risk of disease recurrence. An article comparing rates of overall recurrence and stoma-free recurrence in patients who underwent segmental colectomy vs. total abdominal colectomy for Crohn colitis not complicated by malignancy or elevated cancer risk is by Kiran and coauthors40 in Annals of Surgery, 2011. This article is supplied as a full-text reprint accompanying some formats of SRGS. The authors analyzed data from a prospectively maintained database involving 108 patients. Subtotal colectomy was used in 59 patients and the remainder had segmental colectomy. The data analysis showed that the presence of perianal sepsis and more than one medical comorbid condition predicted reduced stomafree survival. Of interest is the fact that stoma-free survival was not affected by the use of segmental colectomy. As expected, patients who underwent segmental colectomy had reduced recurrence-free survival. Also, quality-of-life assessments were similar in both groups of patients. The authors concluded that segmental colectomy was a suitable alternative for patients with Crohn disease localized to a single segment of colon.

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Additional data on outcomes of surgical treatment of colonic Crohn disease was presented by Holubar and coauthors41 in Expert Reviews in Clinical Immunology, 2010. The authors noted that segmental colectomy using laparoscopic techniques has been associated with reductions in hospital length of stay and recovery time that are similar to the surgical approaches used for ulcerative colitis. Laparoscopic fecal diversion may also be indicated for fistulizing anal-rectal complications of Crohn disease. Holubar and coauthors cited an article by da Luz-Moreira and coauthors42 in the Journal of Gastrointestinal Surgery, 2007. The article provided data from a group of 27 patients undergoing laparoscopic segmental colectomy for complications of Crohn disease matched for age, gender, and surgical risk scores with patients undergoing open colectomy. The authors noted that complications and perioperative blood loss were similar when the groups were compared. Both recovery time and hospital length of stay were shorter for patients having laparoscopic operation. Of note is that the conversion to open operation rate was 26% related to the frequency with which inflammatory masses and intraabdominal abscesses were encountered. Holubar and colleagues cited a case series study43 from their institution that included more than 90 patients. Patients were frequently on multiple medications, including steroids and biologic agents. Disease involvement of the colon was extensive, as indicated by the fact that nearly half the patients underwent total proctocolectomy with ileal pouch-anal anastomosis. The overall complication rate was 34%, and the most common serious complication was intestinal obstruction. Anastomotic leak occurred in 4% of patients. Reoperation was relatively common (more than 5%) and perianal disease was the most common factor associated with the need for secondary operation—this is expected because of the need to drain perianal abscesses and place setons in this patient group. There was no operative mortality and the conversion rate to an open procedure was 16%. A meta-analysis by Tan and coauthors44 in Diseases of the Colon and Rectum, 2007, confirmed the short-term benefits of the laparoscopic approach for patients with Crohn disease, especially in the areas of shortened hospital stay and recovery time. The presented data also suggested that complication rates are lower for patients undergoing laparoscopic procedures. Unfortunately, prospective

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data are scarce and no randomized studies are available. Although suggestive, the data did not provide strong evidence of reduced complication risk with the laparoscopic approach. Crohn disease patients are at risk for the formation of entero-enteric fistulas and for recurrent disease; these two complications are discussed at this time. Laparoscopic management of entero-enteric fistula is addressed in an article by Melton and coauthors45 in the Journal of Gastrointestinal Surgery, 2009. These authors reported a retrospective case series involving 104 patients. The authors noted that patients were frequently anemic, presented with hypoalbuminemia, and frequently had undergone prior abdominal operation. The authors also reported that preoperative diagnosis of entero-enteric fistula was possible in only 70% of patients, despite the use of state-of-the-art imaging; discovery of the fistula intraoperatively was common. The authors cited data that concomitant enteric-vesicle fistula may be encountered in up to 30% of patients. Because of the complexity of disease and the presence of disease in multiple sites, multiple segmental intestinal resections were necessary. The authors reported that laparoscopic approaches may be successful in carefully selected patients. They also emphasized that primary closure of the colonic site of the fistula might be appropriate if Crohn disease of the colon is excluded. If colonic Crohn disease is present, the authors recommended segmental colonic resection with primary anastomosis with the use of a protective stoma that is placed, if possible, proximal to all sites of resection. Surgical management of recurrent Crohn disease was the focus of an article by Pinto and coauthors46 in Colorectal Disease, 2011. The authors reported a single institution retrospective study. Outcomes in 80 patients undergoing primary laparoscopic surgery for Crohn disease were compared with outcomes in 50 patients undergoing laparoscopic surgery for recurrent Crohn disease. Colonic resections were done in 21 primary patients and 6 patients with recurrent disease. The conversion rate to open operation was 36% for patients with recurrent disease. This is not surprising, given the high risk of complex anatomy and extensive adhesions. The authors stressed that overall complications, the need for reoperation, anastomotic leaks, and intestinal obstructions were not encountered more often in patients with recurrent disease than in pa-

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tients operated on primarily. The authors concluded that laparoscopic colon resection is feasible and safe for patients with recurrent disease if careful patient selection is used.

Management of Perianal Crohn Disease Surgical management of perianal Crohn’ disease is used for specific indications such as abscess formation; drainage, seton placement, and diverting colostomy in the face of extensive perianal disease may also be indicated. Occasional patients with extensive, recurrent perianal disease will be candidates for proctectomy. As mentioned previously, available literature supports the effectiveness of biologic agents such as infliximab to assist in healing of perianal disease. Complete excision of perianal fistulas is discouraged because of the prolonged healing that results in a long-standing open perineal wound. The use of proctectomy for complex perianal Crohn disease is the focus of an article by Figg and Church47 in Diseases of the Colon and Rectum, 2009. The authors reported data from experience with 19 patients with extensive perineal involvement. The clinical manifestations included painless fissures, waxy perineal edema, and rectal involvement with Crohn disease in 25% of patients. In this last group, proctectomy was necessary. Biopsy of perineal lesions disclosed granulomata in all patients with perineal involvement. Successful healing with judicious drainage procedures and fecal diversion was 32%, compared with healing rates of more than 60% for patients who had anal fistulas without perineal involvement. The authors stressed that recent experience with infliximab therapy indicates that this agent is associated with healing success in a significant number of patients.

General Aspects of Ulcerative Colitis Practice parameters for the surgical management of ulcerative colitis were promulgated by the American Society of Colon and Rectal Surgeons and published in 2014.48 The practice parameters document is available free from the society website at www.fascrs.org. The practice parameters document noted that current medical therapies for ulcerative colitis are safe and effective; over long-term– follow-up, surgical intervention will be needed in up to 30% of patients. The document emphasized the fact that

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surgical procedures for ulcerative colitis should remove all tissue that would be at risk for development of recurrent disease or for malignant change; removal of at-risk tissue is achieved through total proctocolectomy with diverting ileostomy, or the use of ileal pouch-anal anastomosis in order to maintain intestinal continuity. Patients who require operation for ulcerative colitis are, in general, patients with acute fulminating colitis, patients resistant to nonoperative therapy, and patients at increased risk for colorectal cancer. As mentioned previously, if total abdominal colectomy with ileal-rectal anastomosis is used, endoscopic surveillance is necessary postoperatively. Also, while anal and rectal mucosectomy prior to ileal pouchanal anastomosis has been used to ensure removal of all mucosa, the addition of this step requires a perineal stage of the operative procedure. Medical management of ulcerative colitis includes the use of 5-amino salicylic acid, immunosuppressants such as cyclosporin and methotrexate, monoclonal antibodies to tumor necrosis factor, and corticosteroids. The practice parameters document stressed the importance of offering patients the full spectrum of medical therapy options prior to recommending operation. Patients with severe colitis that does not respond to 3–5 days of medical therapy can be considered for “rescue therapy,” which consists of adding monoclonal antibody therapy and/or immunosuppressive therapy (prior to recommending operation). The practice parameters document recommends a treatment interval of 5–7 days to determine the effectiveness of medical therapy or “rescue therapy” because of data (cited in the document) confirming significantly increased risk of mortality and morbidity with longer waiting periods. There has been an interest in treating ulcerative colitis with fecal transplantation because of the recognition that the microbiologic profile of the colon is altered in patients with this disease. An article reporting a randomized, prospective trial of fecal transplantation is by Moayyedi and coauthors49 in Gastroenterology, 2015. The authors reported a trial involving 75 patients randomized to receive fecal transplantation via enema or placebo (water enema). All patients were screened with sigmoidoscopy and confirmed not to have infectious diarrhea at the time of enrollment. Remission occurred in 24% of patients who received fecal transplantation and in 5% of patients receiving placebo at seven days after enrollment. Of interest was the ob-

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servation that most responders received fecal material from a single donor. There were no serious adverse events observed in either group. The authors concluded that fecal transplantation is potentially beneficial in treating patients with ulcerative colitis. In an editorial that accompanies the article, Grinspan and Kelly50 emphasized the fact that the transplanted fecal material was delivered by enema, and that other studies that delivered fecal material via a duodenal tube have not shown effectiveness. Grinspan and Kelly also noted that the trial was stopped early because of failure to reach the primary endpoint and statistical significance was achieved only with the addition of data gathered after the trial was stopped. Grinspan and Kelly stressed the fact that fecal transplantation is not nearly as effective for ulcerative colitis as it is for C. difficile colitis, and that the donor-specific effect observed in this study is interesting, but is also a limitation to the widespread adoption of this approach.

Surgical Management of Ulcerative Colitis The practice parameters document48 recommends that urgent surgery be performed for patients with colon perforation or severe fulminant colitis. The document noted that elective operation for ulcerative colitis is most often needed in patients who are refractory to medical therapy or in patients with significantly decreased quality of life, usually because of extraintestinal manifestations of ulcerative colitis, such as episcleritis, erythema nodosum, and large joint arthropathy. These conditions often improve after colectomy, whereas hepatic and hematologic abnormalities associated with ulcerative colitis frequently do not improve after colectomy. Long-term outcomes of total proctocolectomy and ileal pouch anal anastomosis are discussed in an article by Fazio and coauthors51 in Annals of Surgery, 2013. This article is supplied as a full-text reprint accompanying some formats of SRGS. The authors reported data on 3,707 patients who underwent primary or redo ileal pouch anal anastomosis at a single institution over a 25-year interval. Ulcerative colitis was the diagnosis leading to operation in 80% of patients. The data analysis showed that outcomes were excellent, with a mortality rate of 0.1%. Early (and mostly minor) complications were observed

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in 33% of patients. Serious complications such as pelvic sepsis, pouch fistula, and anastomotic leak were observed in 12% of patients. Late complications occurred in 29% of patients, and the most frequent serious complication was small intestinal obstruction, which was observed in 12% of patients. Pouchitis requiring antibiotic therapy occurred in 35% of patients; late failure of the pouch, which required either redo operation or fecal diversion, was observed in 5.3% of patients. The authors noted that quality of life assessed in patients with at least 10 years of follow-up was rated as excellent by 93% of patients operated on for ulcerative colitis. A classic article that reported outcomes data for ileal pouch anal anastomosis is by Meagher and coauthors52 in the British Journal of Surgery, 1998. These authors reported outcomes data on more than 1,300 patients followed for a mean of more than six years. Ten-year outcomes data were available for a significant proportion of this patient group. Perioperative mortality was extremely low—three patients died. The authors noted that increasing experience was associated with a decline in the rate of pelvic sepsis from 7% to 3%. Frequent daytime and nighttime incontinence occurred in 7% and 12% of patients, respectively. Approximately 90% of patients had normal continence. The mean number of stools per 24 hours was six, with only one of these occurring at night. Pouch failure occurred in 2% of patients within one year and 9% of patients within 10 years. When pouch failure occurred within the first two years postoperatively, pouchitis was the cause; long-term failure was most likely due to Crohn disease or fistula formation. The authors concluded that ileal pouch-anal anastomosis is safe and highly effective. Twenty-year–follow-up data from this same group of authors were included in an article by Hahnloser and coauthors53 in the British Journal of Surgery, 2007. The authors’ updated experience totals nearly 1,900 patients, with 20-year follow-up available for the majority of these patients. The authors noted that daily stool frequency increased over time, but remained fewer than seven stools within a 24-hour period. Episodes of incontinence also increased slowly with time, but the proportion of patients complaining of incontinence averaged 11% during the day and 21% during the night at 20 years. The authors also observed that the introduction of techniques like doublestapled anastomosis and laparoscopic-assisted operations

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had expanded availability of the procedure to patients at increased operative risk and to obese patients. More than 90% of patients had functioning pouches at 20 years of follow-up, and pelvic sepsis was the most common cause of pouch failure. Hahnloser and coauthors reported that 92% of patients indicated that quality of life was “normal,” and concluded that these data confirm the safety and effectiveness of the ileal pouch-anal reconstruction for patients with ulcerative colitis. As mentioned previously, pouchitis is the most common long-term complication of the surgical management of ulcerative colitis. The outcomes reported in the article by Meagher and coauthors52 indicate that the cumulative risk of at least one episode of pouchitis is 48% at 10 years postoperatively. Nearly all episodes of pouchitis respond to antibiotic therapy, even though the exact cause of pouchitis is unknown. An analysis comparing costs of medical care in patients who have undergone total proctocolectomy with ileal pouch-anal anastomosis with patients treated medically for ulcerative colitis is the focus of an article by Holubar and coauthors54 in Diseases of the Colon and Rectum, 2009. The authors queried a database of epidemiologic data on patients with ulcerative colitis residing in a single geographic area. The costs of care for these patients over the two years before operation were compared with costs incurred in the two years after operation (the cost data were obtained from an administrative database). The total cost for operation ranged from $35,000 to $50,000, depending on the operation performed. Total proctocolectomy with ileal pouch-anal anastomosis was the more costly procedure compared with total proctocolectomy with Brooke ileostomy. The authors noticed a statistically significant reduction of total medical costs in the two years after operation; this cost reduction ranged from $9,000 to $12,000. The authors concluded that successful operation reduces the costs of care for patients with ulcerative colitis, and noted that other data available in the literature have not documented reduced costs of care for patients operated on for ulcerative colitis. In the two studies they cited, cost of admission for surgery was 47% higher than an admission for medical therapy; the second study did not identify a cost difference when patients treated surgically were compared with patients treated medically. All reports agreed, however, that patients treated medi-

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cally required multiple hospitalizations and received more transfusions and experienced more steroid therapy-related complications. Also, weight loss was greater in patients treated medically. Ultimately, the available data support the operative management of patients with prolonged or medically refractory ulcerative colitis as cost-effective.

Laparoscopic Proctocolectomy with Ileal Pouch-Anal Anastomosis Laparoscopic proctocolectomy with either Brooke ileostomy or ileal pouch-anal anastomosis is the preferred approach for elective operative management of patients with ulcerative colitis. Data relevant to operative mortality, morbidity, and quality of outcomes are reviewed here. The utility and cost-effectiveness of laparoscopic approaches for managing ulcerative colitis and Crohn disease are discussed in an article by Polle and coauthors55 in Nature Clinical Practice Gastroenterology and Hepatology, 2007. Comparative data on the use of laparoscopic approaches to total colectomy and ileal pouch-anal anastomosis for patients with ulcerative colitis have confirmed that the operation is feasible and safe. A small midline or Pfannenstiel incision is required for removal of the specimen. Some surgeons prefer to use this incision for completion of the double-stapled ileal pouch-anal anastomosis. The anastomosis can be completed with a total laparoscopic approach, with the specimen removed via a small incision. There are also reports of specimen removal via one of the large port sites used for the laparoscope and instruments. Comparison of mortality, morbidity, recovery time, long-term outcomes, and quality of life indicate that there is no difference between laparoscopic and conventional open approaches. Cosmesis and body-image studies have reported mixed results: in one study, there were no differences noted in sexual function, level of satisfaction with body image, or cosmesis;56 in the second study,57 cosmesis and body image scores were significantly better for patients undergoing laparoscopic proctocolectomy for ulcerative colitis. More data on the use of laparoscopic techniques for IBD were reviewed in an article by Rosenthal and coauthors58 in Digestive Diseases, 2009. In this review, the authors confirmed the value of laparoscopic ileocolectomy

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for the treatment of Crohn disease involving this area of the gastrointestinal tract. Most of the case series comparing laparoscopic techniques with open approaches with total proctocolectomy and ileal pouch-anal anastomosis show no definite superiority of the laparoscopic approach on any outcomes variable. The authors stressed, however, that case series reported recently by surgeons practicing in referral centers caring for large numbers of patients with ulcerative colitis have begun to show improved hospital lengths of stay and faster recovery times for patients operated on laparoscopically; these recent case series are cited in the article. The authors believe that laparoscopic proctocolectomy will lead to significant patient benefit via faster recovery times as clinical experience increases.

Techniques & Outcomes of Laparoscopic Total Proctocolectomy An article supplying clear illustrations of one technique of total proctocolectomy with ileal pouch-anal anastomosis is by Boller and Larson59 in the Journal of Gastrointestinal Surgery, 2007. A report providing data on outcomes for open vs. laparoscopic total proctocolectomy with ileal pouch-anal anastomosis is by Maartense and coauthors60 in Annals of Surgery, 2004. Maartense and coauthors described a randomized prospective trial comparing laparoscopic-assisted total proctocolectomy with ileal pouch-anal anastomosis in 28 patients, with open operation in 27 patients; the authors stressed that all patients were young and low-risk. The primary endpoint of the study was postoperative quality of life at 3 months. Secondary endpoints included length of hospital stay, duration of operation, perioperative narcotic use, and cost of care for hospitalization (including the operation). The authors found there were no significant differences in hospital stay, narcotic use, or postoperative quality of life at three months. Compared with open operations, laparoscopic operations were longer in duration and overall costs of care for laparoscopic patients were higher. Maartense and coauthors reported that it is their practice to leave a pouch drain in place for five days postoperatively; during this interval, the patient remains hospitalized. The authors further emphasized that temporary diverting ileostomy was performed selectively. Approximately 30% of each group had a temporary ileostomy. It is noteworthy that the ileal-anal anastomosis

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was constructed via a Pfannenstiel incision in these patients; cosmesis and patient satisfaction with body image were not assessed. In the discussion following Maartense and coauthors’ article, several discussants noted that the mandatory five-day hospitalization, combined with the time necessary for the patient to adjust to caring for the ileostomy, obscures any advantage for the laparoscopic approach in terms of shortened hospital stay and faster recovery. Readers are encouraged to remember that patient acceptance and adjustment to a newly formed stoma is also influenced by patient education: assistance for patients, surgeons, and other caregivers with patient education to facilitate stoma adjustment can be found in the “Patient Education” section of the American College of Surgeons website at www.facs.org/patienteducation. Additional data on outcomes for laparoscopic proctocolectomy with ileal pouch-anal anastomosis were included in a report by Larson and coauthors61 in Annals of Surgery, 2006. The authors reported a consecutive case series of 100 patients undergoing either laparoscopic total proctocolectomy with ileal pouch-anal anastomosis or hand-assisted laparoscopic total proctocolectomy. The authors compared these patients with a group of patients undergoing open operation matched for gender, age, and surgical risk factors; outcomes were compared using an “intent to treat” approach. Laparoscopic operations were performed using a four-port technique. Specimen removal was via a lower midline incision, Pfannenstiel incision, or laparoscopic hand-assist port site. The choice of anastomosis via either an open or a laparoscopic-stapled technique was determined by surgeon preference; conversion from laparoscopic to open procedures occurred in 6% of patients. Overall, operative morbidity, including the need for early reoperation, was no different in the groups. The authors found that duration of operation was significantly longer for the laparoscopic approach; however, hospital lengths of stay, time to resumption of feeding, and recovery times were shorter for the laparoscopic group. Narcotic use was also less in the laparoscopic patients. The authors concluded that the laparoscopic approach to total proctocolectomy and ileal pouch-anal anastomosis is safe, feasible, and associated with patient benefit in terms of faster recovery time and a shortened hospital stay.

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A meta-analysis of available data that compared outcomes of laparoscopic proctocolectomy with open proctocolectomy was reported by Tan and coauthors62 in Colorectal Disease, 2006. The authors found 10 studies that met their criteria for inclusion; all were case series or comparisons with matched patients who underwent open operation. The authors’ analysis supports the conclusion that hospital lengths of stay, narcotic use, and recovery time all favor the laparoscopic approach. The main limitation for this meta-analysis is that prospective data were not available and the authors did not provide an assessment of quality for the included studies. A report that used data from the National Surgical Quality Improvement Program (NSQIP) database to compare major and minor complication rates for open and laparoscopic proctocolectomy is by Fleming and coauthors63 in Diseases of the Colon and Rectum, 2011. Risk adjusted outcomes data were available on 676 patients. The authors’ analysis disclosed a 35% reduction of major complications and a 44% reduction in minor complications in patients undergoing the laparoscopic procedure. An editorial by Mutch64 in Diseases of the Colon and Rectum, 2011, offers a cautionary note on the interpretation of this NSQIP data; Mutch commented that the available clinical series reports cite patient benefits for the laparoscopic approach in the areas of cosmesis, length of hospital stay, and narcotic use, and he stressed that these areas were also noted as benefits in a recent Cochrane review (cited in the editorial) that analyzed data from more than 600 patients. While the strengths of the NSQIP database are sample size and the quality of the data points gathered for risk adjustment, all sources of potential bias were not controlled for in the database. For example, information on patient body habitus, prior abdominal surgery, experience of the surgeon, surgeon preference for the procedure, and individual surgeon skill set are not known. For these reasons, data such as what is presented in the report by Fleming and coauthors63 need to be interpreted with caution. Long-term outcomes data from a prospective patient series of laparoscopic and open proctocolectomy were presented in an article by Fichera and coauthors65 in the Journal of Gastrointestinal Surgery, 2009. These authors presented data from 76 patients who underwent laparo-

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scopic operation and 106 patients who underwent open operation. The authors used a small Pfannenstiel incision to remove the specimen as well as to divide the anal-rectal stump and construct the anastomosis. Operative blood loss was less in the laparoscopic group. Bowel function and oral intake both returned earlier in the patients having laparoscopic procedures. Complication rates were similar in the two groups with the exception of incisional hernia, which was observed less frequently in the laparoscopic group. The authors stressed that the relatively short followup probably underestimates the actual risk of incisional hernia. Normal continence was observed in nearly 84% of patients at more than two years of follow-up; this rate was equivalent for both procedures. Total proctocolectomy with permanent end ileostomy may be the preferred operation for selected patients. Indications for permanent ileostomy include obesity, elderly patients with suboptimal anal sphincter function or a history of fecal incontinence, and patients with rectal cancer complicating ulcerative colitis. An article describing a case series experience with this approach is by Holubar and coauthors66 in Inflammatory Bowel Disease, 2009. The authors described a case series of 44 patients who had total proctocolectomy with permanent end ileostomy. Conversion to open operation was done in 4% of patients. There were no perioperative deaths and overall serious morbidity rate was 9%. The authors concluded that laparoscopic approaches are feasible and safe in patients requiring permanent end ileostomy.

Laparoscopic Proctocolectomy in Patients with Severe Colitis Patients who undergo total proctocolectomy for treatment of severe ulcerative colitis have higher complication risks because of malnutrition, steroid use, and the use of biologic agents at the time the operation is performed. The association of infliximab use with perioperative complications is the focus of an article by Selvasekar and coauthors67 in the Journal of the American College of Surgeons, 2007. This retrospective analysis of a single-center case series compared 47 patients who received infliximab during the preoperative period to 254 patients who did not receive the drug. Of interest is that most patients receiving infliximab were simultaneously receiving corticosteroid

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therapy, immunomodulating drugs, and/or 5 aminosalicylic acid. Half of the patients received infliximab within 60 days of operation. The authors found that infectious complications (superficial and deep wound infections and organ space infections) and pouch-specific complications (pouch failure and anastomotic leak) were significantly increased in patients who had received infliximab. On multivariate analysis, infliximab therapy was associated with a 3.5-fold increase in risk of complications. Contrasting data are offered in an article by Coquet-Reinier and coauthors68 in Surgical Endoscopy, 2010. The authors reported a single-center case series involving 13 patients who received infliximab. The patients were matched for age, gender, and type of operative procedure with patients who had not received infliximab. The mean interval between infliximab therapy and operation was 44 days. Half of the infliximab group was also receiving corticosteroids and/or immunomodulating drugs. The authors found no significant differences in infectious and pouch-specific complications when the infliximab group and the noninfliximab group were compared. In this study, sample size was small and complications were unusual in both groups of patients. The authors also routinely used diverting ileostomy in their patients. Patients with severe refractory colitis are more likely to have anemia requiring transfusion, a history of weight loss, concomitant corticosteroid use, and prior exposure to immunomodulating drugs and biologic agents. It is important to document the value (or lack thereof) of total laparoscopic approaches in this high-risk group; as might be anticipated, staged operations are used more often in these patients. Data on the use of laparoscopic total proctocolectomy in patients with severe colitis are found in three articles that will be reviewed at this time. The first article reviewed is by Holubar and coauthors69 in Diseases of the Colon and Rectum, 2009. The authors treated 50 patients over a six-year interval at a single center. All patients had severe refractory colitis as defined by a standard colitis severity scoring system. At the initial operation, patients underwent laparoscopic subtotal colectomy with diverting ileostomy. At the second procedure, laparoscopic completion proctocolectomy with ileal pouch-anal anastomosis was performed; a protecting temporary ileostomy was used in this second operation. The authors’ data showed that conversion rates were low (6%) and major complications occurred in 4% of pa-

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tients. There was no perioperative mortality. The authors concluded that this approach was safe and effective for patients with severe colitis. The second article compared outcomes for a threestage laparoscopic approach in patients with severe colitis with experience from the same center using open operation.70 The authors found that patients undergoing laparoscopic procedures had shorter hospital lengths of stay and less narcotic requirements than patients undergoing open operations; complication rates were equivalent. Of importance is that patients having laparoscopic procedures had ileal pouch anal anastomosis and ileostomy closure significantly earlier than patients undergoing open procedures. The final article analyzed the value of two-stage vs. three-stage procedures, and is by Pandey and coauthors71 in Diseases of the Colon and Rectum, 2011. The authors reported data on 68 patients undergoing a two-stage operation (laparoscopic total abdominal colectomy followed by ileal pouch-anal anastomosis without diverting ileostomy), and 50 patients undergoing a three-stage operation (laparoscopic total abdominal colectomy followed by ileal pouch anal anastomosis followed by ileostomy closure). Overall, patients undergoing the two-stage procedure were lower risk than the three-stage groups, as judged by steroid use, weight loss, and use of immunomodulators and biologic agents. However, despite their overall lowerrisk status, patients undergoing the two-stage procedure had a higher rate of intraabdominal abscess. The authors concluded that the three-stage procedure had significant advantages for patients with severe colitis, even if risk factors were higher.

Laparoscopic Surgical Management of Ulcerative Colitis in Children Two articles presented data on the use of laparoscopic procedures to manage ulcerative colitis in children. The first article is by Flores and coauthors72 in Pediatric Surgery International, 2010. The authors reported data from 32 consecutive patients treated in a single center. The authors noted that their early experience was with laparoscopic subtotal colectomy and ileocolonic anastomosis. Subsequently, they evolved to a protocol using elective

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total proctocolectomy and ileal pouch-anal anastomosis. Rectal-anal excision was done by everting the colon through the anus, and anastomosis was completed extracorporeally. Data on the frequency of use of diverting ileostomy were not presented. The authors documented advantages for the laparoscopic approach in terms of less narcotic use and faster recovery times. The second article is by Mattioli and coauthors73 in Pediatric Surgery International, 2011; in this report, the authors presented data on 12 patients undergoing laparoscopic proctocolectomy with ileal pouch-anal anastomosis. Protective ileostomy was used in all patients. There was no mortality, and overall complication rates were within acceptable ranges. The authors noted postoperative intestinal obstruction in 16% of patients. Ileostomy closure was accomplished in 10 out of 12 patients. “Normal” fecal continence was observed in 80% of patients in a follow-up averaging 15 months.

Diagnosis & Management of Pouchitis As mentioned earlier, pouchitis is a significant complication after operation for ulcerative colitis. The cumulative risk approaches 50% for developing pouchitis during a 10year interval after total proctocolectomy and ileal pouchanal anastomosis. Although most instances of pouchitis are easily managed, severe pouchitis is a common cause of pouch failure in the first two years after operation. In this section of the overview, we will discuss a recent Cochrane Collaboration systematic literature review on the diagnosis and management of pouchitis. The Cochrane review is by Holubar and coauthors,74 who noted that, while pouchitis can occur after operation for ulcerative colitis or familial adenomatous polyposis, the condition is more common after operation for ulcerative colitis. The overall frequency of pouchitis is 30% after construction of an ileal pouch-anal anastomosis or a continent ileostomy. The cause of the condition is unknown, but frequency and severity data support the interpretation that pouchitis is a symptom of the immune system disorder that accompanies IBD. Clinical symptoms of pouchitis include increased stool volume, rectal bleeding, abdominal cramping pain, fecal urgency, and tenesmus. The diagnosis is confirmed by findings of

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pouch inflammation on endoscopy that are confirmed by histologic examination of pouch biopsies. Pouchitis scoring scales are available that enable clinical discrimination of mild, moderate, and severe pouchitis. Symptoms lasting less than four weeks are termed acute pouchitis, while symptoms persisting for more than four weeks are termed chronic pouchitis. The authors included an analysis of 10 available randomized prospective trials, and concluded that ciprofloxacin is the most effective treatment for acute pouchitis; metronidazole and budesonide are also effective, but less so than ciprofloxacin. Probiotics have been used for acute pouchitis, chronic pouchitis, and as preventive therapy for pouchitis, but superiority over placebo or no therapy has not been shown. For prevention of pouchitis and for chronic pouchitis the authors concluded that the probiotic bacteria VSL#3 is effective therapy. According to the manufacturer’s website, www. vsl3.com, VSL#3 is a probiotic medical food consisting of fixed amounts of several live freeze-dried lactic acid bacteria.

Clostridium Difficile Colitis The clinical burden imposed by Clostridium difficile-associated diarrhea (CDAD) is growing. Originally described as a form of health care-related diarrhea found mainly in nursing home patients and a few hospitalized patients, the disease is now becoming more common, with cases appearing in critically ill patients and spontaneous cases arising in the community setting. Changes in the resistance characteristics of the causative organism are the most important factors leading to this increase in colitis cases. This resistance pattern change has probably occurred because of selection of more resistant strains due to environmental pressure from excessive or inappropriate use of broad spectrum antibiotics. As the number of diagnosed cases increase, the mortality rate of affected patients is also rising. This concerning observation likely is a consequence of the increasing virulence of the causative organism, increasing toxicity of the Clostridium difficile (C. difficile) toxins, and greater patient risk due to advanc-

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ing patient age and greater numbers of comorbid factors in vulnerable patient groups. For example, severe pancolitis that progresses to toxic megacolon, colonic necrosis, and colon perforation are challenging complications that require surgical management. In this section of the overview we will discuss current understandings of the basic biology and epidemiology of CDAD, as well as the medical and surgical management of patients with this disease.

Evolving Aspects of Clostridium Difficile Bacteriology & Infection An article by Hookman and Barkin75 in Digestive Diseases and Sciences, 2007, discusses the epidemiology of C. difficile colitis, as well as the evolving biologic characteristics of the C. difficile organism that have changed the face of this challenging clinical problem. The authors opened the discussion by citing data from a comparative microbiologic study of organisms recovered from outbreaks of diarrheal disease in health care facilities in six states from 2000 to 2003. The genetic characteristics and toxin production patterns of organisms recovered were compared with organism characteristics from a database of more than 6,000 organisms from cases recorded before 2000. The data analysis disclosed that organisms recovered from the recent interval were more likely to secrete the binary toxin CDT. The more recently recovered organisms were also more likely to have a deletion in the pathogenicity gene locus tcdC that could enable the organism to secrete toxins A and B more vigorously than previously recovered organisms could. The data further confirmed that the organisms were more likely to be resistant to fourthgeneration fluoroquinolone drugs, such as gatifloxacin. Hookman and Barkin also cited data from an analysis of more than 1,700 cases of CDAD from outbreaks in 12 Canadian hospitals. This study confirmed that the incidence of diarrhea cases was 22 per 1,000 admissions, with a cause-specific mortality of 6.9%. When cases were matched for age and medical risk with patients who were not infected, the study found that infected patients were four times more likely to have received fluoroquinolone antibiotics during the month preceding onset of diarrhea and were three times more likely to have received cephalosporin antibiotics during the same interval. The recovered organisms were resistant to fluoroquinolones in

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more than 80% of infected patients, secreted the CDT binary toxin, and had the tcdC gene locus deletion in nearly 85% of instances. Taken together, these data lent support to the suspicion that the evolution of resistance patterns and toxin production capabilities are being driven by antibiotic use, and that CDAD is becoming a more frequent, more powerful, and more lethal infection. Epidemiologic data cited by Hookman and Barkin emphasized the importance of specific antibiotics in the production of resistant organisms. They noted that initial resistance in the late 1980s and 1990s was driven by the use of clindamycin and cephalosporin. More recently, fluoroquinolone use has been associated with the development of resistance. Data from one study conducted in a long-term care facility documented the emergence of resistant strains of C. difficile after a formulary change from levofloxacin to Gatifloxacin; immediately after the emergence of resistant strains, an outbreak of symptomatic diarrhea occurred, and this outbreak resolved after stopping the use of gatifloxacin. The authors noted that studies of the effect of fluoroquinolones on colonic bacterial flora have demonstrated a profound bacteriocidal effect on anaerobic organisms with the use of Gatifloxacin, and postulated that this change in the microbiologic environment contributes to the production of conditions conducive to the development of clinical diarrhea and the emergence of resistant organisms. In another report, Hookman and Barkin76 reviewed data suggesting excessive use of proton pump inhibitors is also likely to be a risk factor for the development of resistant C. difficile infection—this factor probably also functions through disruption of the normal intestinal microflora environment. The authors stressed that infections caused by antibiotic-resistant organisms have migrated to the community. Increasingly, methicillinresistant staphylococcus infection is being diagnosed in previously healthy community patients with no recent exposure to the inpatient environment. The authors cited a report from the Centers for Disease Control and Prevention that documented the occurrence of drug-resistant C. difficile diarrhea in healthy peripartum patients without a history of prolonged inpatient health care exposure. Hookman and Barkin also noted that discharge diagnoses of C. difficile infection are increasing: in the year

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2001 alone, diagnosis frequency increased by 26%. Cost estimates in the United States attributable to C. difficile infection were estimated to exceed $1.1B in 2001. With an estimated 3 million diagnoses in 2005, the costs have certainly escalated beyond this point. Cellular damage leading to symptomatic infection occurs because of the actions of the toxins produced by the infecting organisms. Data cited by Hookman and Barkin75 confirmed that toxins A and B gain entry to colonic mucosal cells by initiating phosphorylation of Rho proteins. Once inside the cell, an intense inflammatory response is stimulated with elaboration of neuroimmune mediators. Recruitment of mast cells occurs with elaboration of leukotrienes. The authors also cited data documenting the ability of toxin B to incite widespread colonocyte apoptosis. Colonocyte apoptosis produces colonic mucosal ulceration and the development of pseudomembranes. The recently described CDT toxin is genetically programmed to adhere to cell membranes and penetrate the cell. Once inside the cell, the toxin disrupts the actin filament—this causes cell death. The authors noted additional data confirming the similarity of the CDT toxin to the binary toxin associated with gas gangrene from C. perfringens infection. The 2009 article by Hookman and Barkin76 discussed the contribution of colonocyte immune responses to the pathophysiology of CDAD. The authors cited data that the toxins produced by these organisms incite an exaggerated cellular immune response that accelerates cell damage, and noted that the innate immune system plays an important role in defending colon mucosal cells; they also referenced data supporting the view that defensins, an important cellular defense system of the innate immune system, are able to defend against toxin B, but not toxin A.

Preventing Clostridium Difficile Infection C. difficile spores spread by both adhering to the hands and clothing of health care workers and to surfaces within health care facilities. The numbers of contaminating spores are increasing in concert with the number of infections. Spores can also be deposited on surfaces and on the hands and clothing of caregivers by asymptomatic carriers of infection. These carriers are known to shed C.

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difficile spores in fecal material intermittently. Identifying asymptomatic carriers is difficult and data are lacking that confirm the effectiveness of stool screening for spores. Hookman and Barkin76 referenced data pertinent to CDAD prevention and noted that occult infection screenings are most likely to be effective when conducted in health care facilities known to be at an increased risk for diarrhea outbreaks, such as long-term care facilities and rehabilitation facilities. Once a patient with asymptomatic or symptomatic infection is identified, isolation of the patient is indicated. Caregivers should assiduously use barrier precautions when contacting a patient known to be infected. Hand hygiene with soap and water is also known to be effective; patients with symptomatic or asymptomatic infections rapidly colonize multiple skin surface sites, and careful hygiene with soap and water baths is indicated to manage these areas. Similarly, since spores are more likely to adhere to moist surfaces, washing these surfaces with sodium hypochlorite bleach and drying is an effective cleaning maneuver.

Diagnosing Clostridium Difficile Colitis Hookman and Barkin stressed that clinically significant infection and colitis is most often manifested by diarrhea and leucocytosis. Abdominal distention is also commonly seen. Abdominal tenderness, fever, and signs of multiplesystem organ failure, when present, support the diagnosis of fulminant colitis. Clinically important infection can occur without diarrhea. The authors emphasized that C. difficile infection should be in the differential diagnosis of hospitalized patients with unexplained leukocytosis, and they cited data confirming the presence of positive C. difficile diagnostic tests in more than 50% of patients with unexplained leucocytosis without diarrhea. Risk factors for colitis include advanced age, comorbid disease, preexisting IBD, conditions associated with prolonged hospitalization, malnutrition (as evidenced by hypoalbuminemia), and immune compromise. Patients with comorbid conditions that increase C. difficile infection risk may have clinical evidence indicating the clear need for antibiotic therapy; however, this treatment, although appropriate, may be complicated by the development of C. difficile infection. A concomitant infection is the most common associated diagnosis in patients who

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are discharged with a CDAD diagnosis. Similarly, CDAD may complicate the use of perioperative antibiotic prophylaxis in patients at risk for CDAD. Organ transplant patients who are immune suppressed are also vulnerable to CDAD; this infection’s frequency is increasing, particularly in heart transplant patients. Patients undergoing complex operations, such as total joint replacement and major gastrointestinal surgery, are likewise vulnerable. An article dealing with the emergence of CDAD as a complication of colon resection is by Lesperance and coauthors77 in the American Journal of Surgery, 2011. The authors queried a large clinical database (the National Inpatient Sample) and found that the risk, overall, of CDAD in hospitalized patients was 1%. The risk in patients undergoing segmental colectomy was 1.4%. In the two-year interval studied, the authors noted a consistent increase in the number of CDAD diagnoses and speculated that preoperative bowel preparation may alter the colonic flora, thus permitting C. difficile to invade colonic cells and become symptomatic. They also noted that probiotic therapy may have potential as a preventive measure in vulnerable patients, and cited data from one prospective randomized study that demonstrated a dosedependent decrease in C. difficile colonization in patients treated with increasing doses of Lactobacillus. Reliable data confirming the preventive value of probiotic therapy in surgery patients are currently not available. Hookman and Barkin76 emphasized that patients with overt diarrhea may develop symptoms and signs of protein-losing enteropathy. Peripheral edema may develop as uncompensated albumin loss produces or aggravates preexisting hypoalbuminemia. Other conditions producing peripheral edema, such as congestive cardiac failure, may be mistakenly diagnosed, and the correct diagnosis of CDAD will be delayed. Laboratory testing to confirm a CDAD diagnosis can be accomplished using tests for C. difficile toxins or a culture of stool to document the presence of the organism. Hookman and Barkin noted that enzyme immunoassay tests, real-time PCR testing, and cytotoxin assays are all available. Most clinical laboratories use enzyme immunoassay testing for cytotoxin. Three stool samples should be tested and cytotoxin assay results are usually available

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within four hours. These tests are, however, subject to significant rates of false negative testing, especially if testing single stool samples, or if stool samples are refrigerated for an interval before testing. Prompt testing of three stool samples using the available enzyme immunoassay tests should provide acceptable sensitivity and specificity with a short turn-around time based on data reported by Hookman and Barkin. Endoscopic diagnosis can also be accomplished with flexible sigmoidoscopy or colonoscopy; however, there is a small but significant risk of perforation for endoscopy done during an acute episode of colitis. Endoscopic diagnosis is confirmed by documenting the presence of mucosal ulcerations and/or pseudomembranes: pseudomembranes are raised yellow or off-white plaques scattered randomly on the colonic mucosal surface. Other findings include bowel wall edema, mucosal erythema and friability, and inflammation. The authors stressed that endoscopy is not indicated in patients with typical clinical findings and a positive enzyme immunoassay for CDAD toxins. Imaging may be useful for providing supporting evidence for a CDAD diagnosis and for identifying patients at risk for fulminant colitis. Plain abdominal radiographs may show colonic dilation and, on occasion, small bowel dilation. CT imaging may disclose colonic dilation and colon wall edema. The presence of free intraperitoneal fluid is predictive of severe disease; this finding is an indication for considering surgical intervention. One of the main goals of the diagnostic process is the early detection of fulminant colitis, because progression to fulminant colitis raises the risk of multisystem organ failure and mortality. Fulminant colitis is the topic of an article by Adams and Mercer78 in Current Opinion in Critical Care, 2007. Data reviewed in this article confirm the value of endoscopy, CT imaging, and rapid enzyme immunoassay testing for toxins. The authors stressed that early diagnosis is critical when documenting fulminant colitis; patients who develop fulminant disease associated with multisystem organ failure have a mortality risk approaching 90%. Early total colectomy with diverting ileostomy has been associated with a reduced mortality risk. Adams and Mercer emphasized that operation may be necessary based on partial diagnostic information.

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Management Therapies for Clostridium Difficile Colitis Therapy for mild to moderate diarrhea from C. difficile is usually successful. The first-line therapeutic interventions include discontinuing (if possible) any antibiotic that might be associated with the development of colitis and instituting oral therapy with metronidazole. The articles by Hookman and Barkin75,76 and the review by Adams and Mercer78 describe the available therapeutic options, which are summarized in this section of the overview. Adams and Mercer78 reviewed data supporting various treatment strategies for patients suspected of having fulminant colitis. They noted that oral metronidazole is the first-line treatment of choice. Second-line therapy uses vancomycin delivered via enema or intravenously. The oral or enteral routes for CDAD management are preferred because intravenous metronidazole is not detectable in the colonic lumen after intravenous injection. The authors noted that vancomycin therapy, while efficacious, is associated with a risk of producing resistant strains of Enterococcus sp. Third-line drugs include bacitracin, teicoplanin, and fusidic acid, but teicoplanin and fusidic acid are not available in the United States. Clearance of infecting organisms and diarrhea relief are usually observed within 72 hours after administering treatment, and complete resolution of symptoms is observed in 95% of patients over the course of 10 days. If symptoms do not improve within 72 hours, surgical intervention should be considered because treatment failure is likely. Hookman and Barkin76 and Adams and Mercer78 advise against the use of adjunctive therapies, such as motility-reducing drugs; Adams and Mercer stressed that these drugs may permit longer exposure of the colonic mucosa to bacterial toxins, resulting in more severe colitis. The use of motility-reducing drugs in CDAD is the focus of a systematic literature review by Koo and coauthors79 in Clinical Infectious Disease, 2009. The authors were able to identify 20 reports that provided data on 55 patients. One of the reports was a retrospective series; the remaining articles were case reports. The authors’ review confirmed the high mortality for patients who progressed to fulminant colitis associated with multisystem organ failure. They noted that all adverse outcomes reported for patients receiving motility-reducing drugs occurred when the drugs were given without proper antimicrobial therapy adminVol 41 | 6 | 2015

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istered concomitantly. Koo and coauthors concluded that the reported data do not support adverse outcomes of treating CDAD with motility-reducing drugs, as long as the diagnosis is not in doubt and appropriate antibiotic therapy is administered concurrently. An editorial commentary on this article is by Gerd80 ing in Clinical Infectious Disease, 2009. The author noted that antimotility agents, even if there is no specific attributable adverse effect of the drug being administered, may obscure a valuable change in the clinical picture, namely, the reduction or cessation of diarrhea. Reduction or cessation of diarrhea is one of the most valuable clinical indices of effectiveness of CDAD therapy. If this sign is masked by use of motility-reducing drugs, therapeutic failure may not be detected in a timely fashion. Gerding added that production of ileus with these drugs can retard delivery of metronidazole or vancomycin to the colon and reduce the therapeutic effectiveness of these drugs. The author concluded that the weight of the evidence does not support use of motility-reducing drugs in any patients group except, perhaps, patients with mild disease. Even in patients with mild disease, motility reducing drugs should be used with caution.

Therapies for CDAD in Special Circumstances Hookman and Barkin76 reviewed three therapeutic approaches that may be useful for managing patients with recurrent CDAD or patients who may not be able to tolerate antibiotic therapy. These approaches include therapy with intravenous immunoglobulin, probiotic therapy, and fecal transplantation protocols. Hookman and Barkin cited data from a single study of patients with severe, refractory, or recurrent CDAD. Fourteen patients received one or more doses of intravenous immunoglobulin. Nine patients recovered in the course of 10 days of therapy. Two patients required urgent colectomy and one patient developed pulmonary edema after receiving immunoglobulin infusion. The authors concluded that immunoglobulin therapy may be helpful in the management of recalcitrant or recurrent CDAD. Contrasting data are presented in an article by Abougergi and coauthors81 in the Journal of Hospital Medicine, 2010. These authors reported retrospective medical re-

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cord data from 21 patients (from a total cohort of 1,230 patients) who were treated with intravenous immunoglobulin for refractory, recurrent, or severe CDAD. The authors noted that the conceptual basis for the use of immunoglobulin is from observations that passive immunity produced by the delivery of IgG antibodies to C. difficile toxin B can result in neutralization of the toxin. In their patient series, overall mortality was 57%. Mortality was closely related to overall health status and disease severity, as reflected by the APACHE II score; in fact, only one patient with an APACHE II score higher than 22 survived treatment. The authors believe that immunoglobulin treatment should probably be used early for recurrent and recalcitrant disease and in patients with good overall risk status. Other immune therapy approaches include the use of monoclonal antibodies and vaccination; however, Hookman and Barkin76 noted that consistent benefit has not been demonstrated for either of these therapies.

Probiotic Therapy for CDAD Because CDAD is believed to occur, at least in part, because of the disruption of normal colonic bacterial flora, reestablishment of normal flora with probiotic therapy has theoretic appeal. Hookman and Barkin cited data from one systematic review of the literature that found four studies of sufficient quality for inclusion. Only one study found a statistically significant benefit for probiotic therapy for CDAD. One additional recent randomized prospective trial showed statistically significant benefit in terms of recurrence prevention in patients with CDAD when treated with a combination of appropriate antibiotics (high-dose vancomycin) and S. boulardii. The authors concluded that probiotic therapy may benefit carefully selected patients with recurrent CDAD.

Fecal Transplantation Therapy for CDAD Another approach to restoring the colonic microflora is fecal transplantation. An article that presented data on the effectiveness of fecal transplantation administered as a duodenal infusion is by van Nood and coauthors82 in the New England Journal of Medicine, 2013. This report presented data from an open-label randomized prospective

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trial comparing fecal transplantation administered via a nasoduodenal tube following conventional vancomycin therapy and bowel lavage with vancomycin therapy with or without bowel lavage. The authors noted that the study was stopped after an interim analysis showed that 81% of patients treated with fecal transplantation resolved their recurrent CDAD after the first infusion and the remaining patients resolved after a second infusion. Resolution occurred in 31% of patients receiving vancomycin therapy and in 23% of patients receiving vancomycin plus bowel lavage. Stool cultures performed after fecal transplantation confirmed the development of a normal colonic bacterial pattern in treated patients. Mild abdominal cramping was noted in most fecal transplantation patients on the day of the infusion. The authors noted that the patients enrolled in the study all had recurrent CDAD and were enrolled relatively late in the clinical course, indicating the reluctance of patients and treating physicians to choose early fecal transplantation therapy. The authors concluded that fecal transplantation was safe and effective in patients with recurrent CDAD.

Surgical Therapy for CDAD Patients with fulminant CDAD and associated critical illness have traditionally been managed with open subtotal colectomy and diverting ileostomy. Reported mortality rates ranging from 40% to 65% have been typical in published clinical series. Mortality risk factors for following subtotal colectomy with diverting ileostomy in patients with fulminant CDAD is the focus of an article by Lee and coauthors83 in Annals of Surgery, 2014. This article reported data obtained from the ACS NSQIP database over a five-year interval. Subtotal colectomy was performed in 335 patients with a CDAD diagnosis. The authors noted that CDAD is increasing in frequency in both the inpatient and community settings. Colectomy may be required in up to 8% of patients, and this patient group is frequently critically ill with multiple comorbid conditions. The reported analysis noted that the 30-day mortality was 33%. Factors strongly associated with mortality risk was age >80, preoperative shock, presence of chronic renal disease requiring dialysis, chronic obstructive pulmonary disease, and a heavily contaminated surgical incision (possibly due to intraoperative fecal spillage).

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Signs of sepsis-associated coagulopathy (thrombocytopenia) were also significantly associated with mortality risk. The authors noted that recovery times were prolonged in surviving patients with the mean hospital length of stay being more than three weeks, and concluded that the clustering of mortality in older patients and in patients with severe comorbid conditions strongly supports the need for early diagnosis and a low threshold for recommending operation in high-risk patients. Adams and Mercer78 presented data from two series evaluating surgical therapy for fulminant C. difficile colitis; in both analyses reviewed, subtotal colectomy with ileostomy was the preferred procedure. In one clinical series, the overall mortality was 57% after subtotal colectomy with ileostomy. Increased mortality risk was associated with advanced age, malignant disease, immunosuppression, and signs of multisystem organ failure. Most patients operated on had been admitted to intensive care before operation. The second series discussed patients who underwent subtotal colectomy with ileostomy; these patients were compared with severity-matched patients who were not operated on before death. Patients managed surgically had an 80% reduction in mortality risk. This observation adds additional support for early diagnosis and the recommendation of operative therapy in patients with signs of fulminant CDAD. Hookman and Barkin76 also discussed surgical therapy for severe CDAD. From the data reviewed, the authors concluded that the most consistently successful approach is subtotal colectomy and ileostomy. The authors also reported that progression of disease can occur rapidly, and suggested that surgical intervention may be most successful if performed within 48 hours of intensive care unit admission; the best results were obtained in patients not requiring ventilator support or vasopressor therapy, and overall mortality ranged, in the data reviewed, from 36% to 60%. An alternative approach that is less invasive and potentially less physiologically stressful than open laparotomy with subtotal colectomy consists of creating a temporary loop ileostomy laparoscopically, followed by intraoperative lavage of the colon with 8 liters of PEG 3350 electrolyte solution, and then postoperative retrograde vancomycin enemas at a dose of 500 mg every

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8 hours for 10 days. Experience with this approach is described in an article by Neal and coauthors84 in Annals of Surgery, 2011. This article is supplied as a full-text reprint accompanying some formats of SRGS. A group of 34 patients with severe CDAD was treated with this new technique, and an historical control group of 34 patients treated with subtotal colectomy was used for comparison of outcomes. Mortality was 21% in the lavage group vs. 47% in the colectomy group. The colon was retained in 24 out of 27 survivors of lavage therapy. With six months of follow-up, more than half of the surviving patients had undergone ileostomy reversal. This article was presented to the plenary session of the annual meeting of the American Surgical Association in 2011. In the discussion that followed the presentation, several interesting and illuminating questions were asked. For example, one discussant noted the inclusion of patients who were chosen for treatment based only on CT imaging evidence of severe colitis; the question was raised if there were any patients included that did not have fulminant CDAD. The author responded that all patients had CDAD diagnosed by culture or toxin assay, but that the results of these tests were sometimes not available when the decision for operation was made. Another question was raised regarding the potential for the retained colon to contribute to ongoing systemic inflammatory response syndrome and organ failure; the author responded that ongoing organ failure was observed in a few patients and colectomy was done in three patients. In most patients, however, there was evidence of reversal of organ failure within the first two days after ileostomy and use of colonic lavage and vancomycin. The authors concluded that this approach has potential for the effective management of severe CDAD.

Ischemic Colitis Colon ischemia is the most common form of intestinal ischemic disease. Colon ischemia can occur as a complication of surgical procedures, particularly open cardiac operations, as well as open and endovascular procedures for abdominal aortic disease. The incidence of ischemic colitis is apparently increasing, and the number of dis-

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eases associated with or complicated by colon ischemia is also increasing. This observation has prompted investigators to question whether all conditions presenting with colonoscopic evidence of ischemic colitis are actually associated with reduced colon blood flow. An article that reviewed evidence relevant to this question is by Carlson and Madoff 85 in Diseases of the Colon and Rectum, 2011. This article is provided as a full-text reprint accompanying some formats of SRGS. The authors hypothesized that ischemic colitis is a group of diseases, not a single clinical entity. They further noted that in the more than 50 years since the original description of ischemic colitis, several myths regarding the anatomic and physiologic features of ischemic colitis have been perpetuated. For example, classic surgical teaching has maintained that the colon is very sensitive to reductions in blood flow, but the authors cited data from experimental studies showing that the changes in the mucosa of the colon that are typical in ischemic colitis could not be produced in dogs unless all of the feeding blood vessels were occluded. Another myth discussed by the authors is that hypovolemic shock can produce ischemia of the colon. Additional data reviewed in the article confirm that hypovolemia sufficient to reduce mesenteric blood flow by 75% did not produce the tissue changes typical of colon ischemia unless one of the two main feeding arteries of the canine colon was occluded at the same time. Additional data cited in the article showed that increased intraluminal pressure did not produce ischemic changes until pressures >60 mm Hg were applied. The authors stressed that pressures this high are never encountered in clinical settings. Carson and Madoff acknowledged that colon ischemia is a known complication of abdominal vascular reconstructive procedures, but emphasized that the complication is seen in less than 5% of procedures in which the aorta is occluded above the origin of the inferior mesenteric artery, or above the origins of both the inferior and superior mesenteric arteries for more than 30 minutes. Carson and Madoff also emphasized the paucity of evidence supporting the long-held view that a period of global hypoperfusion is required for clinical evidence of ischemic colitis. In addition, they noted that there is no evidence to support an increased risk of colon ischemia

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in “watershed” areas such as the splenic flexure and the rectosigmoid junction. In fact, data from a large singlecenter experience with more than 300 cases of ischemic colitis cited by the authors showed that only 3% of cases were isolated to the rectosigmoid junction. Data from a large autopsy series confirmed that the splenic flexure is involved in 25% of patients diagnosed with ischemic colitis at autopsy, but this location was the only involved area in half of these cases. Based on the data reviewed, Carson and Madoff concluded that ischemic colitis is not commonly caused by reductions in blood flow and is really a spectrum of diseases rather than a single entity. The authors suggested that unless a true ischemic etiology can be confirmed, “ischemic” colitis would be more appropriately termed “acute idiopathic colitis.”

Epidemiology & Pathogenesis of Colon Ischemia A review article dealing with general aspects of colon ischemia was presented by Feuerstadt and Brandt86 in Current Gastroenterology Reports, 2010. The authors opened their report with a brief review of the pathophysiology of colon ischemia. They emphasized that an anatomic vascular occlusive lesion is rarely identified in cases of colon ischemia; this suggests that a process involving the small vessels and the microcirculation of the colon is possibly important in producing ischemic colitis. The clustering of colon ischemia in elderly patients suggests an age-related dysfunction of the small vessels. The authors noted that small vessel dysfunction occurs in association with inflammatory states, and that patients with sepsis and multiple organ failure, Crohn colitis, infectious colitis, and ulcerative colitis are at an increased risk for colon ischemia. The most common infectious forms of colitis that produce colon ischemia are E. coli colitis and cytomegalovirus colitis occurring in patients with HIV infection. Recently, thrombophilic conditions such as Factor V Leiden deficiency, presence of anti-phospholipid antibody, and activated protein C resistance, have emerged as important contributors to the problem of colonic ischemia. These disorders primarily involve the venous circulation; thus, colon ischemia can have an arterial as well as a

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venous etiology. Feuerstadt and Brandt cited data confirming that a variety of drugs, including cocaine and digoxin, can cause colon ischemia. The relationship of at least one variant of irritable bowel syndrome (IBS) to ischemic colitis came to light when an increased risk of colon ischemia was confirmed in patients taking one of the 5-hydroxytryptamine-3 receptor antagonists, alosetron. This observation eventually led to studies documenting that patients with IBS have nearly a four-fold increased risk of colonic ischemia. The authors also emphasized that constipation and drugs that cause constipation may lead to shunting of blood away from the mucosa of the colon toward the serosal surface. The majority of colon ischemia cases involve the left colon, while approximately 25% of cases of colon ischemia involve the right colon. This said, the authors cited data confirming that all areas of the colon may be sites of colon ischemia; watershed areas near the splenic flexure (Griffith’s point) and the sigmoid colon (Sudeck’s point) are thought to be areas where collateral circulation is limited. Data also associated right colon ischemia with an increased need for surgical intervention and an increased mortality risk compared with cases involving other colonic regions. Additional information about clinical features of ischemic colitis was presented in an article by Montoro and coauthors87 in the Scandinavian Journal of Gastroenterology, 2011. The authors reported an analysis of data gathered during a prospective, multicenter study of patients with a definite or highly probable diagnosis of colon ischemia. More than 350 patients had criteria for inclusion. An unfavorable outcome was defined as mortality or the need for operation; this outcome was observed in 13% of patients. Most patients had transient ischemic colitis or reversible colopathy. Eighteen percent of patients had signs of chronic ischemia (stricture). The analysis confirmed worse outcomes in patients with right colon ischemia and in patients with signs of peritonitis, systemic hypotension, anemia, and metabolic acidosis. Montoro and colleagues examined clinical factors that were predictive of the need for operation. These included abdominal pain without hematochezia, nonbloody diarrhea, peritoneal signs, and endoscopic or imaging evidence of colon gangrene. Not surprisingly, gangrenous colitis was associated with a high risk for surgical intervention

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Ischemic Colitis |

COLON, REC TUM & ANUS, PAR T III

and a mortality rate of 31%. All patients with fulminant pan-colitis underwent surgery and the mortality rate for this group of nine patients was 100%. The authors noted that the clinical presentation of ischemic colitis is variable, with the “classic” clinical presentation (abdominal pain, urge to defecate, and bloody diarrhea) being present in less than half the patients. The authors stressed that early colonoscopy (within the first 24–48 hours) was very helpful in suggesting the diagnosis, but endoscopic findings were not a sensitive predictor of the need for operation. They recommended that a high index of clinical suspicion for colon ischemia in hospitalized patients with unexplained abdominal pain will facilitate early endoscopy, and further emphasized that more than 80% of patients with colon ischemia will recover with supportive care alone. Of interest is the fact that the authors identified recent use of nonsteroidal antiinflammatory agents in 31% of patients with documented colonic ischemia. They also speculated that the use of these drugs may be a marker for a patient group at risk for colon ischemia. The possibility also exists that nonsteroidal antiinflammatory drugs may adversely affect the colonic microcirculation. Additional data relating to clinical factors that predict the need for operation in patients with colon ischemia appear in an article by Paterno and coauthors88 in the American Journal of Surgery, 2010. These authors provided data from a single-center case series of 253 patients. Most of the patients presented to the emergency department with abdominal pain and rectal bleeding; most had multiple comorbid diseases, along with evidence of medium and small vessel vasculopathy; evidence of bowel infarction was present on admission in 4.7% of patients, and these patients were operated on with a perioperative mortality of more than 40%. Thirty-six patients (15%) required delayed surgical intervention: factors predictive of the need for delayed operation were abdominal pain in the absence of rectal bleeding (suggestive of right colon ischemia), use of the antiplatelet agent clopidogrel, and the presence of free intraperitoneal fluid on CT imaging. The authors speculated that free intraperitoneal fluid suggests the presence of transmural ischemia of the colon. An analysis of risk factors for mortality from colonic ischemia is by Reissfelder and coauthors89 in Surgery, 2011. The authors reported an analysis of data from 177 patients seen in a six-year interval from a single center.

32

They confirmed the high risk of mortality in patients with right colon ischemia. Additional factors associated with mortality included ASA score of III or IV, presence of congestive cardiac failure, presence of acute or chronic renal failure, and elevated plasma lactate levels.

Ischemic Colitis as a Complication of Vascular Surgical Procedures Feuerstadt and Brandt86 noted that colon ischemia occurs in 7% of patients undergoing abdominal aortic surgery and can be demonstrated in up to 60% of patients after operation for ruptured abdominal aneurysm. Factors increasing risk of colon ischemia include prolonged cross-clamp time, hypotension, hypoxemia, and acidosis. Failure to restore flow in a patent inferior mesenteric artery can predispose patients to colon ischemia. The authors noted that tonometric measurement of colonic pH has been useful for predicting which patients will develop symptomatic colon ischemia postoperatively.

Diagnosis of Ischemic Colitis Sporadic cases of colon ischemia usually involve the left colon, and the most common clinical presentation is abdominal pain followed by bloody diarrhea. Montoro and coauthors87 stressed the variable clinical presentation and noted that the most life-threatening forms of colonic ischemia (right colon ischemia and transmural necrosis) often do not present with abdominal pain followed by bloody diarrhea. The authors presented a table of common clinical findings observed in patients enrolled in their prospective multicenter study of colonic ischemia. Because of the variability of the clinical presentation, Montoro and associates emphasized the importance of early colonoscopy—there were no complications of colonoscopy performed within the first 48 hours after the initial physical examination. Colonoscopic visualization and biopsy was a highly reliable diagnostic tool. Biopsy confirmation of threatened transmural ischemia was observed in 8% of patients who had endoscopy within the first 48 hours. Also, absence of signs of transmural ischemia was a reliable indicator that operation would not be needed.

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Ischemic Colitis |

Feuerstadt and Brandt86 suggested a more selective approach to colonoscopy. They recommended initial screening CT imaging with colonoscopy performed if colonic wall thickening is observed on CT images. Using this approach, they were able to obtain accurate diagnostic biopsies in most patients who required subsequent operation. They noted that the observation of the “single stripe sign” (an erythematous mucosal stripe along the long axis of the colonic lumen) was an accurate clue identifying an area for obtaining biopsies diagnostic of colon ischemia. Feuerstadt and Brandt stressed that the presence of the “single stripe sign” is predictive of a milder form of ischemic colitis.

Diagnosis of Ischemic Colitis Associated with Vascular Surgical Procedures Steele,90 in an article in Surgical Clinics of North America, 2007, cited data that the most common postoperative signs of colon ischemia are abdominal pain and bloody diarrhea; metabolic acidosis can also be present. The author also cited data from a large clinical series that diagnosis delays are common, even when symptoms are present. The mean interval between symptom onset and diagnosis approached six days in the study cited, and the author recommended more intensive effort to arrive at an early diagnosis. Additional data encouraged reductions in diagnostic delay with the use of plasma markers, such as D-lactate. Steele next reviewed data on using endoscopy to diagnose postoperative colonic ischemia. Available data do not support the use of routine endoscopy, and endoscopy did not result in reduced diagnostic delay in most patients. Furthermore, the use of endoscopy in the early postoperative period was associated with increased patient discomfort and increased cost, and the majority of the “routine” examinations were negative. Steele recommended early CT imaging and endoscopy for patients who have colon wall thickening or free intraperitoneal fluid evident on CT images.

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Nonoperative Management of Ischemic Colitis Feuerstadt and Brandt86 emphasized the importance of excluding the presence of threatened transmural ischemia using clinical examination, CT imaging, and selective endoscopy. Once the absence of transmural ischemia is confirmed, patients are treated with supportive care, including optimization of associated illnesses, intravenous fluids, and bowel rest. The authors noted that the use of antibiotics for treatment of patients with mild colonic ischemia not requiring operation is supported by some clinicians based on experimental data showing improved survival with antibiotic therapy; however, they stressed that high-quality data supporting this practice are not available.

Surgical Management of Ischemic Colitis The cornerstone of surgical management of colonic ischemia is resection of the ischemic segment and fecal diversion. Second-look operations within 24–48 hours are often indicated because the viability of the remaining colon is frequently in doubt. One important aspect of managing intestinal ischemia after vascular procedures is the reimplantation of the inferior mesenteric artery. Steele90 noted that available data do not support a single approach to selecting patients for inferior mesenteric artery reimplantation, and also cited data suggesting routine reimplantation of all patent inferior mesenteric arteries using the Carrel patch technique; this cited report did not mention any instances of colonic ischemia in patients with reimplanted patent inferior mesenteric arteries. Other reports cited by Steele support the use of reimplantation when evidence of reduced colonic blood flow is documented intraoperatively or when inferior mesenteric artery stump pressure suggests patency and significant flow.

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Conclusion

COLON, REC TUM & ANUS, PART III VOLUME 41 | 6 | 2015

T

his issue completes our three-part offering dealing with surgical diseases of the colon, rectum, and anus. In the next issue, we will discuss the diagnosis and surgical management of hernia; editorial assistance for that issue will be supplied by Robert Fitzgibbons Jr., MD, FACS.



As always, I hope you will find these issues helpful in your practice.



Thanks for reading SRGS!



Lewis Flint, MD, FACS Editor in Chief

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Vol 41 | 6 | 2015

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American College of Surgeons  www.facs.org/publications/srgs 

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Vol 41 | 6 | 2015

35

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24. Harpaz N, Polydorides AD. Colorectal dysplasia in chronic

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36

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Vol 41 | 6 | 2015

References

49. Moayyedi P, Surette MG, Kim PT, et al. Fecal Microbiota

| COLON, REC TUM & ANUS, PAR T III

61. Larson DW, Cima RR, Dozois EJ, et al. Safety, feasibility,

Transplantation Induces Remission in Patients With Active

and short-term outcomes of laparoscopic ileal-pouch-anal

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Pemberton JH, Cima RR. Minimally invasive subtotal

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on recovery and subsequent completion restorative proctectomy. Dis Colon Rectum. 2009;52(1):4-10. 71. Pandey S, Luther G, Umanskiy K, et al. Minimally invasive

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72. Flores P, Bailez MM, Cuenca E, Fraire C. Comparative anal-

84. Neal MD, Alverdy JC, Hall DE, Simmons RL, Zuckerbraun

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86. Feuerstadt P, Brandt LJ. Colon ischemia: recent insights and advances. Curr Gastroenterol Rep. 2010;12(5):383-390. 87. Montoro MA, Brandt LJ, Santolaria S, et al. Clinical patterns and outcomes of ischaemic colitis: results of the Work-

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89. Reissfelder C, Sweiti H, Antolovic D, et al. Ischemic colitis: who will survive? Surgery. 2011;149(4):585-592.

77. Lesperance K, Causey MW, Spencer M, Steele SR. The morbidity of Clostridium difficile infection after elective colonic

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resection-results from a national population database. Am J Surg. 2011;201(2):141-148. 78. Adams SD, Mercer DW. Fulminant Clostridium difficile colitis. Curr Opin Crit Care. 2007;13(4):450-455. 79. Koo HL, Koo DC, Musher DM, DuPont HL. Antimotility agents for the treatment of Clostridium difficile diarrhea and colitis. Clin Infect Dis. 2009;48(5):598-605. 80. Gerding DN. Antimotility agents for the treatment of Clostridium difficile infection: is the juice worth the squeeze? Clin Infect Dis. 2009;48(5):606-608. 81. Abougergi MS, Broor A, Cui W, Jaar BG. Intravenous immunoglobulin for the treatment of severe Clostridium difficile colitis: an observational study and review of the literature. J Hosp Med. 2010;5(1):E1-9. 82. van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013;368(5):407-415. 83. Lee DY, Chung EL, Guend H, Whelan RL, Wedderburn RV, Rose KM. Predictors of mortality after emergency colectomy for Clostridium difficile colitis: an analysis of ACS-NSQIP. Ann Surg. 2014;259(1):148-156.

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CME Posttest

COLON, REC TUM & ANUS, PART III VOLUME 41 | 6 | 2015

To earn CME credit, the posttest should be completed AFTER taking the pretest and reading the overview. Both tests must be completed online at www.facs.org/publications/srgs/cme.

1. The Endothelin-3 and Endothelin-B genes affect

4. Which of the following results in a lower quality

neural crest cells of patients with Hirschsprung disease in which of the following ways?

of life over long-term follow-up in patients successfully treated for Hirschsprung disease?

a) The genes prevent migration of neural crest cells

a) Growth abnormalities

b) The genes cause apoptosis of neural crest cells

b) Constipation

c) The genes suppress maturation of neural crest cells

c) Recurrent enterocolitis

d) The genes stimulate an inflammatory state in the myenteric plexus

e) Fecal incontinence

e) The genes prevent development of ganglion cells

d) Rectal bleeding

5. Population-level estimates suggest

2. Imaging for diagnosis of Hirschsprung

disease depends on the documentation of a “transition zone,” which indicates the point at which the colon segment with hypoganglionosis ends and normally innervated colon begins. This transition zone is absent in which percentage of patients? a) 10% b) 3.5%

that the total number of patients with inflammatory bowel disease in the United States is which of the following? a) 500,000 b) 1.5 million c) 3 million d) 200,000 e) 4.25 million 6. Which of the following is a risk

c) 1%

factor for Crohn colitis?

d) 17%

a) Hispanic ethnicity

e) 36%

b) Age >60 years c) Cigarette smoking

3. Data from the report by Levitt and

coauthors indicate that chronic constipation occurs in which percentage of patients following a successful Swenson pull-through procedure for Hirschsprung disease?

d) Family history of chronic constipation e) Marijuana use

a) 5% b) 60% c) 14% d) 32% e) 23%

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Posttest | COLON,

REC TUM & ANUS, PAR T III

7. Which of the following patient groups

11. The article by Ordas and coauthors provides

with inflammatory bowel diseaseassociated dysplasia is eligible for followup with colonoscopic surveillance?

data supporting which of the following accuracy rates for MR enterography documentation of ulcer healing in patients with Crohn colitis?

a) Patients with flat dysplastic lesions

a) 21%

b) Patients with dysplastic lesions that have indistinct borders

b) 11%

c) Patients with high-grade dysplasia

d) 90%

c) 83%

d) Patients with raised dysplastic lesions that can be completely excised at the time of colonoscopy

e) 99% 12. The report by Peyrin-Biroulet and coauthors

e) Patients with friable dysplastic lesions

confirms that patients with Crohn disease have increased risks of each of the following conditions except which one?

8. Which of the following types of

inflammatory colon disease is not associated with increased cancer risk?

a) Ocular diseases b) Deep venous thrombosis

a) Crohn colitis with stricture

c) Pulmonary embolus

b) Crohn colitis with intermittent bleeding

d) Osteopenia with fracture

c) Ulcerative proctitis

e) Glioblastoma

d) Ulcerative colitis presenting in childhood e) Ulcerative colitis in women

13. The report by Fazio and coauthors

9. The article by Ullman and coauthors

recommends that colonoscopic surveillance begin at which point in time after a diagnosis of inflammatory colon disease?

confirms an early complication rate for total proctocolectomy with ileal pouch-anal anastomosis of which of the following percentages? a) 0.1%

a) Immediately after diagnosis

b) 33%

b) Within the first year after diagnosis

c) 12%

c) Five years after diagnosis

d) 29%

d) Eight years after diagnosis

e) 6%

e) Whenever colonic bleeding is detected

14. Twenty-year–follow-up data from patients

10. Which of the following is a fecal marker

b) Calprotectin

who have undergone total proctocolectomy with ileal pouch-anal anastomosis indicate that daytime incontinence occurs in which percentage of patients?

c) Antibodies to S. cerevisiae

a) 11%

d) C-reactive protein

b) 21%

e) Interleukin-10

c) 7%

for a diagnosis of Crohn colitis? a) Perinuclear antineutrophil cytoplasmic protein

d) 34% e) 51%

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Vol 41 | 6 | 2015

Posttest |

15. Data reported in the Cochrane

COLON, REC TUM & ANUS, PAR T III

19. Data reported by Lee and coauthors

Collaboration review by Holubar and coauthors confirms that the most effective antibiotic treatment for postoperative pouchitis is which of the following?

indicate that colectomy may be required in which percentage of patients with severe C. difficile colitis?

a) Cephalexin

b) 14%

b) Vancomycin

c) 29%

c) Neomycin-erythromycin base

d) 8%

d) Ciprofloxacin

e) 37%

a) 0.5%

e) Fluoroquinolones 20. Mortality for total abdominal colectomy 16. Which of the following antimicrobial drugs

has been associated with increased resistance of C. difficile to antibiotic therapy? a) Cefoxitin b) Penicillin c) Gatifloxacin

with ileostomy for severe C. difficile colitis is reported to be 33%–50%. The mortality reported for laparoscopic ileostomy with colonic lavage and vancomycin enemas in the article by Neal and coauthors is which of the following? a) 47%

d) Vancomycin

b) 33%

e) Metronidazole

c) 21%

17. Risk factors for C. difficile infection include

all of the following except which one? a) Preexisting inflammatory bowel disease

d) 66% e) 3% The following four questions are required by the American College of Surgeons for accreditation purposes. You must complete these four questions before submitting your answers.

b) Malnutrition c) Immunosuppression d) Age >80 years e) African-American ethnicity

21. This issue met the stated learning objectives. 18. Testing for C. difficile toxins should be

a) Strongly agree

done on how many stool samples?

b) Agree

a) One

c) Neutral

b) Three

d) Disagree

c) Two

e) Strongly disagree

d) Four e) Five

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Vol 41 | 6 | 2015

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Posttest | COLON,

REC TUM & ANUS, PAR T III

22. The content was relevant to my educational

needs and practice environment. a) Strongly agree b) Agree c) Neutral d) Disagree e) Strongly disagree 23. There are potential barriers to

incorporating what I have learned from this issue into my practice. a) Strongly agree b) Agree c) Neutral d) Disagree e) Strongly disagree 24. The content was fair, objective, and unbiased. a) Strongly agree b) Agree c) Neutral d) Disagree e) Strongly disagree

© 2015 American College of Surgeons

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Purchase a previously published issue Back issues of SRGS, published in 2014, 2013, and 2012, are available for sale at a discount to current subscribers. For pricing and an order form: www.facs.org/publications/srgs/issues/related 2015 topic list is available: www.facs.org/publications/srgs/issues/upcoming

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Recommended Reading

COLON, REC TUM & ANUS, PART III VOLUME 41 | 6 | 2015

The SRGS Recommended Reading List is a carefully selected summary of current, classic, and seminal articles for further study. All of the articles below are cited in the order they appear in the literature review; they also appear in the reference list (0-0). Full-text reprints of these articles are included in certain formats of SRGS. SRGS has obtained permission from journal publishers to reprint these articles. Copying and distributing these reprints is a violation of our licensing agreement with these publishers and is strictly prohibited.

1. Tissue specific somatic mutations and aganglionosis in Hirschsprung’s disease...(0–0)

5. Ileal pouch anal anastomosis: analysis of outcome and quality of life in 3707 patients...(0–0)

Moore SW, Zaahl MG

Fazio VW, Kiran RP, Remzi FH, et al.

This article provides useful data on the role of genetic abnormalities in Hirschsprung disease.

This article reviews a very large single-center experience with ileal pouch-anal reconstruction for patients undergoing total proctocolectomy.

2. Transanal, full-thickness, Swenson-like approach for Hirschsprung disease…(0–0) Levitt MA, Hamrick MC, Eradi B, Bischoff A, Hall J, Pena A This article provides data on long-term outcomes of the Swenson procedure for Hirschsprung disease. 3. Cancers complicating inflammatory bowel disease…(0–0) Beaugerie L, Itzkowitz SH This is a comprehensive review article on the topic of malignancy developing in patients with inflammatory bowel disease. 4. Dysplasia associated with Crohn’s colitis: segmental colectomy or more extended resection?...(0–0)

6. Diverting loop ileostomy and colonic lavage: an alternative to total abdominal colectomy for the treatment of severe, complicated Clostridium difficile associated disease…(0–0) Neal MD, Alverdy JC, Hall DE, Simmons RL, Zuckerbraun BS Neal and coauthors provide data supporting a potentially useful alternative approach for managing severe C. difficile colitis. 7. Is “ischemic” colitis ischemic?...(0–0) Carlson RM, Madoff RD This article provides perspective on a list of important questions relevant to our understanding of ischemic colitis

Kiran RP, Nisar PJ, Goldblum JR, et al. Kiran and colleagues provide valuable data that will help guide the management of patients who are at risk for malignancy complicating inflammatory bowel disease.

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Vol 41 | 6 | 2015

The American College of Surgeons offers a variety of surgical patient education products for your colon and rectal practice.

Colonoscopy Brochure

Ostomy Home Skills Kit

Colectomy Brochure

There is a value to membership—member discounts apply. Order online at www.surgicalpatienteducation.org or call 312-202-5263.

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