Ischemic Bowel/Endoscopy/IBD

Educational Objectives

The goal of this program is to improve the management of ischemic bowel disorders and inflammatory bowel disease (IBD), and the practice of small bowel endoscopy. After hearing and assimilating this program, the clinician will be better able to:

1.   List the risk factors and comorbidities associated with ischemic bowel disorders.

2.    Compare the characteristics of reversible and irreversible bowel ischemia and the symptoms and patient presentation of each.

3.    Explain the mechanisms of bowel injury involved in acute mesenteric ischemia.

4.    Summarize the new techniques of small bowel endoscopy, including capsule endoscopy and balloon-assisted enter­oscopy.

5.    Discuss nonbiologic therapies for IBD presented as abstracts at Digestive Diseases Week.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning committe to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of inter­est. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a pro­prietary business or commercial interest. For this program, the following has been disclosed: Dr. Gerson is on the Speakers’ Bureau and receives honoraria from Given Imaging and Fujinon. Dr. Rubin is a consultant for Procter and Gamble Pharmaceuti­cals, Salix Pharmaceuticals., Prometheus Pharmaceuticals, Abbott Immunology, UCB Pharma, Given Imaging, Shire, and Mil­lenium Pharma; he receives grant support from Procter and Gamble Pharmaceuticals, Salix Pharmaceuticals, and Prometheus Pharmaceuticals, and is on the Speakers’ Bureaus of Abbott Immunology and UCB Pharma. Dr. Brandt and the planning com­mittee reported nothing to disclose.

Acknowledgements

Dr. Brandt was recorded at the 18th Annual GI Symposium, sponsored by the University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Department of Medicine, Division of Gastroenterology/Hepatology, and held November 1, 2008, in New Brunswick, NJ.  Dr. Gerson was recorded at the 32nd Annual New York Course, Gastrointestinal Endoscopy: Breaking New Ground, jointly sponsored by the Albert Einstein College of Medicine and New York Society for Gastrointestinal Endoscopy, and held December 17-20, 2008, in New York, NY. Dr. Rubin was recorded at the 44th Annual Gastroenterology Update, sponsored by the Cleveland Clinic Digestive Disease Institute, and held September 11-12, 2008, in Cleveland, OH.  The Audio-Digest Founda­tion thanks the speakers and the sponsors for their cooperation in the production of this program.

Critical Approach to the Diagnosis and Management of Ischemic Bowel Disorders

Lawrence J. Brandt, MD, Professor of Medicine and Surgery, Albert Einstein College of Medicine, and Chief, Division of Gastroenterology, Montefiore Medical Center, Bronx, NY

Risk factors: old age; female sex; irritable bowel syndrome (IBS; increases risk 3- to 4-fold); chronic obstructive pulmo­nary disease; constipation and drugs that treat it; coagulation disorders; various medications; most common cause un­known, but probably slow phenomenon in microvessels

Anatomic location: segmental disease; any part of colon; site defined by most proximal area involved; right colon  —  20% of cases; disease involving any part of bowel in continuity with right colon; most common pattern involvement of cecum to hepatic flexure, but may wrap around to descending colon; transverse colon  —  transverse to sigmoid colon most com­mon site; left colon  —  most common site (35% of all cases); descending to sigmoid colon most frequently seen; other sites  —sigmoid only; pancolonic involvement

Comorbidities: thrombophilia  —  eg, factor V Leiden; found in 72% of patients in Cretan study, in about one-third of pa­tients in US study; protein C deficiency  —  especially in women on oral contraceptives or hormone replacement therapy

Reversible disease: most cases; colopathy  —  nonulcerative form of disease consisting of intramural hemorrhage and edema that withdraws into wall of bowel; overlying mucosa does not ulcerate; colitis  —  mucosa ulcerates to give transient isch­emic colitis; reversible strictures caused by edema and hemorrhage compromising lumen

Irreversible disease: gangrene; permanent stricture; persistent colitis, usually in elderly patient; fulminant universal colitis that looks and presents like toxic ulcerative colitis (UC); colitis can  —  look like carcinoma; be associated with carcinoma or with protein-losing colopathy; cause recurrent sepsis in patient with previous case of rectal bleeding or bloody diarrhea

Characteristics of reversible disease: bowel damaged by reperfusion; colonic blood flow back to normal by time pa­tient presents; angiography not necessary; presentation  —rectal bleeding; bloody diarrhea; mild abdominal pain; hallmarks  —  submucosal hemorrhage and edema that give appearance of “thumbprinting” along column of barium; colonoscope shows subepithelial hemorrhages with appearance of red or reddish-purple hillocks; resolution  —  these usually heal within 72 hr, and entire bowel usually healed within 2 wk; healing may take £6 mo in some patients, but symptoms gone in 2 wk; if symptoms last longer, patient may have irreversible disease and go on to perforation, late gangrene, or stricture formation

Mechanisms of bowel injury: colonic blood flow decreased whenever intracolonic pressure increased, eg, use of barium, insufflation with air or CO2; this predisposes colon to ischemic injury; if colon inflated with air, pressure decreases to baseline in 30 min, but blood flow during insufflation only 60% of baseline for »20 min; with CO2 insufflation, pressure back to baseline in 5 to 6 min, and blood flow during insufflation >100% (160%) because of vasodilation by CO2

Irreversible ischemia: consider in patient with severe pain, signs of peritonitis, isolated right colon involvement, or symptoms >2 wk; in cecum, pneumatosis cystoides linearis seen only in gangrene or reversible infections of colon in patients with AIDS; inflammatory bowel disease (IBD)  —  do not diagnose IBD in patient >50 yr of age with new onset of symptoms; in older patient, segmental colitis more likely ischemic or infectious than IBD; must rule out infection and ischemic disease; IBD markers  —  patients with recurrent or chronic bowel ischemia have increase in markers used for IBD (also seen in other diseases); antineutrophil cytoplasmic antibody (pANCA) seen in 88% of cases of chronic ischemia, while anti-carbonyl reductase (Cbr)1 seen in 56% of cases of recurrent ischemia; other causes of ischemia  —anything that obstructs colon, eg, carcinoma, fecal impaction, diverticulitis with stricture; mechanism probably in­creased pressure

Right-sided colitis: right colon in distribution of superior mesenteric artery (SMA), so colitis may be accompanied or fol­lowed by acute mesenteric ischemia (AMI); atypical presentation, ie, abdominal pain more common than bright red blood per rectum; outcome 3 to 4 times more unfavorable than other colon ischemias; 5 times more likely to require surgery; mortality twice as high; angiography indicated

Acute mesenteric ischemia: most common cause SMA emboli; high mortality rate (40% best; closer to 80%-100% if aggressive investigation not done in acute phase); patients ill, with severe abdominal pain and few findings on phys­ical examination (PE); diagnostic studies  —  plain film and computed tomography (CT) of abdomen to rule out other causes

Dog experiment: balloon used to occlude flow in SMA; arterial pressure drops »50% then starts to rise due to vasocon­striction; if occlusion removed, flow returns to normal; if occlusion persists for more than several hours, flow does not return to normal because vasoconstriction has become irreversible; intra-arterial papaverine maximizes collateral flow and prevents vasoconstriction, allowing return to normal flow when occlusion removed

Vasoconstriction: caused by local obstruction or systemic problem that diminishes blood flow, eg, hypotension; when va­soconstriction becomes irreversible, peritonitis and acute abdomen occur, and mortality 80% to 100%

Nonocclusive AMI: defined by vasoconstriction; when accompanied by embolic or thrombotic disease, diagnosis made by angiography, and early treatment leads to patient survival; consider diagnosis in every patient with severe abdominal pain and scant findings on PE; obtain plain film or CT of abdomen to rule out other causes; if no other cause found, im­age vasculature; normal film does not exclude ischemic disease; abnormal film in patient with ischemic disease means late disease; treatment  —  correct circulating blood volume; do not use vasopressors (worsen vasoconstriction); angiog­raphy reduces mortality to »40% (do not do in presence of hypotension or hypovolemia); papaverine infusion and sur­gery

Focal segmental ischemia: collateralization reduces injury; presentation  —  acute enteritis resembling appendicitis; chronic enteritis that resembles Crohn’s disease but does not involve terminal ileum; stricture with bacterial overgrowth and diar­rhea or obstruction

Thrombotic disease: usually superimposed on atherosclerotic narrowing; patients do not commonly have chronic mes­enteric ischemia or intestinal angina; diagnosis  —  vascular imaging helps determine whether problem acute or chronic and whether papaverine will help; management  —  angiography or surgery for arterial reconstruction and possibly re­section; CT angiography provides noninvasive management

Mesenteric venous thrombosis: acute form looks like arterial disease; in subacute form, diffuse pain comes and goes; chronic form asymptomatic at time of thrombosis, and progresses to portal hypertension; clinical diagnosis difficult because of absence of specific signs and symptoms; diagnose by imaging; treat by anticoagulation, thrombectomy, and resection

Intestinal angina: chronic disorder characterized by progressive postprandial abdominal pain; patients afraid to eat, have weight loss; most studies negative; angiography reveals occlusion of ³2 vessels; diagnose clinically, not from an­giogram

New Frontiers in Small Bowel Endoscopy

Lauren B. Gerson, MD, Associate Professor of Medicine, and Director, Esophageal and Small Bowel Disorders Center, Stanford University School of Medicine, Palo Alto, CA

Capsule Endoscopy

Technical aspects: 2 commonly used devices (Given PillCam and Olympus Endo Capsule) work on different technology, and produce different image quality; study found differences not statistically significant; read capsules at 15 frames/sec; readers may not agree on findings

Field of view: not yet 360° (156° in latest PillCam); ampullary area in proximal duodenum poorly seen (visible in »10% of cases; push enteroscopy better for this area)

Interpretation of images: red spots  —  probably due to trauma or other causes; lack “spidery look” of true angiodysplastic lesions; false positive for double-balloon; bulges  —  focus on area to see if bulge resolves after few images or persists and is submucosal immunoplastic structure; normal lymphatic structures  —  may be misread as lesions of Crohn’s disease; bowel preparation  —  may enhance diagnostic yield; timing  —  2005 study of 65 patients with acute obscure hemorrhage found that yield higher (91%) when capsule endoscopy performed within 15 days of event, compared to >15 days (34%)

Balloon-Assisted Enteroscopy

Double-balloon enteroscopy (DBE): enteroscope with balloon on tip and overtube with another balloon; apparatus placed into duodenum (avoid area of ampulla); overtube balloon inflated, and DBE advanced

Outcome data: Japanese study  —  majority of patients did not have obscure bleeding, so diagnostic yield high (76%); per­formed total enteroscopy in majority of patients; US data  —multicenter study published 2006; lower yields; no total en­teroscopies achieved (more difficult due to obesity, previous intestinal surgery, and adhesions; German studies found total enteroscopy not necessary, once lesion reached)

Rebleeding rate: older data show »40% of arteriovenous malformations (AVMs) stop bleeding without therapy; 16 pub­lished studies  —  1400 patients; 2600 DBE examinations; mean yield »67%; treatment success 54%; rate of total enter­oscopy »30%; in Japan, yield primarily ulcers and tumors, while in European and US literature, yield contained more angiodysplastic lesions

Decision analysis: computer model looked at options for patients with obscure bleeding; included supportive care (trans­fusions), push enteroscopy, intraoperative enteroscopy, angiography, empiric oral DBE, or capsule endoscopy followed by DBE; results  —  initial DBE cost-effective; using capsule before DBE delays treatment and increases cost; advan­tages of capsule include ability to see entire small bowel and reduced risk for complications

Long-term outcomes: patients with angiodysplastic lesions and normal examinations most likely to rebleed; 20% to 30% of patients still have anemia after follow-up period

Single-balloon enteroscopy (SBE): principles similar to those of DBE; 2 studies in literature (from Japan) SBE does not go as deep as DBE, but procedure easier

New technique: spiral enteroscopy; (Endo-Ease Advancement System by Spirus Medical); faster entry into small bowel (»30 min) than DBE or SBE; data limited

Comments on procedures: average time  —  for DBE 96 min; for SBE, range 60 to 80 min; DBE provides greatest depth of insertion

Complications: DBE, SBE, have same types of complications as regular endoscopy, including aspiration pneumonia, ab­dominal cramping, perforation, and pancreatitis; speaker’s study had 1% complication rate; highest perforation rate with diagnostic retrograde examinations, mainly in patients with altered anatomy, eg, ileoanal anastomoses; to date, no major complications reported for spiral enteroscopy

Algorithm: obscure bleeding  —  perform second-look endoscopy, particularly if previous colonoscopy or upper endoscopy unsatisfactory; massive bleeding  —  consider empiric deep enteroscopy or angiography; no massive bleeding  —  capsule endoscopy; if negative, rate of rebleeding low, observation indicated; if lesion found, consider further evaluation

Nonbiologic Therapy of Inflammatory Bowel Disease

David T. Rubin, MD, Associate Professor of Medicine, Co-Director, Inflammatory Bowel Disease Center, and Program Director Fellowship in Gastroenterology, Hepatology, and Nutrition, Section of Gastroenterology, University of Chicago Medical Center, Chicago, IL

Format: review of abstracts from Digestive Diseases Week

Crohn’s disease: dose response to tobacco smoking  —  even light smokers had more aggressive disease and more surgeries; second-hand smoke  —  also associated with worse disease and more surgeries; azathioprine vs mesalamine for prevention of relapse after surgery  —  patients already had endoscopic recurrence; primary end point therapeutic failure or discontinuation due to lack of effi­cacy or intolerable side effects; secondary end point endoscopic improvement; at 1 yr, azathioprine had higher failure rate, but not statistically significant; however endoscopic improvement better with azathioprine; VSL3 (probiotic) to prevent endoscopic recurrence  —  patients had ileocolonic resection with primary anastomosis; VSL3 compared to placebo; colonoscopy at 90 days and 1 yr showed no significant benefit; steroids  —  30 days and 1 yr after steroid therapy; no difference from previous studies, ie, one-third to two-thirds have early response, and at 1 yr, one-third steroid dependent and one-third require surgery; children or pa­tients with shorter duration of disease more responsive to steroids

Encore Registry: European registry for outcomes in patients with IBD; includes patients on infliximab; risk for serious infection as­sociated with older age, disease severity, and being on steroids; no risk associated with exposure to immune modulators

Lymphoproliferative disorders in patients with IBD: of 20,000 patients and 50,000 yr of follow-up, 19 patients with lymphoma (1 Hodgkin, 18 non-Hodgkin); of patients with non-Hodgkin, 13 on azathioprine, 9 of these positive for Ep­stein-Barr virus, and 10 satisfied criteria for post-transplant lymphoproliferative disorder

Diet and UC: European multicenter cohort  —  >200,000 patients; 126 new cases of UC in 4-yr follow-up; intake of linoleic acid associated with increased risk of developing UC; United Kingdom prospective cohort study  —  25,000 patients; 22 cases of UC; found that dietary omega-3 fatty acids protected against development of UC

Imipramine for UC: often used as adjuvant therapy; study showed improvement in symptom severity as well as mood; in­terpreted as anti-inflammatory activity, but could also be anticholinergic effect (fewer bowel movements)

Steroid delivery: loading of autologous red blood cells with dexamethasone followed by reinfusion into patient; more di­rect delivery may decrease systemic toxicity and lengthens steroid-free follow-up

VSL3 in children with active UC: adjunctive therapy in patients taking mesalamine and steroids; association with higher remission rate and lower relapse rate at 1 yr

Delayed-release phosphatidyl choline for UC: patients with UC have low phosphatidyl choline levels; found some benefit but not across all measurements

Suggested Reading

Baichi MM et al: Capsule endoscopy for obscure GI bleeding: therapeutic yield of follow-up procedures. Dig Dis Sci, 52:1370, 2007; Boley SJ et al: Mesenteric venous thrombosis. Surg Clin North Am. 72:183, 1992; Boley SJ, et al: History of mesenteric isch­emia. The evolution of a diagnosis and management. Surg Clin North Am, 77:275, 1997; Brandt LJ, Boley SJ: AGA technical re­view on intestinal ischemia. American Gastrointestinal Association. Gastroenterology. 118:954, 2000; Brandt LJ, Boley SJ: Colonic ischemia. Surg Clin North Am. 72:203, 1992; Ersoy O et al: Capability of capsule endoscopy in detecting small bowel ul­cers. Dig Dis Sci 54:136, 2009; for small intestinal bleeding. Dig Dis Sci, 52:1914, 2007; Gore RM et al: Imaging in intestinal isch­emic disorders. Radiol Clin North Am, 46:845, 2008; Herbert GS, Steele SR: Acute and chronic mesenteric ischemia. Surg Clin North Am, 87:1115, 2007; Hsu CM et al: The outcome assessment of double-balloon enteroscopy for diagnosing and managing pa­tients with obscure gastrointestinal bleeding. Dig Dis Sci. 52:162, 2007; Kurland B et al:. Diagnostic tests for intestinal ischemia. Surg Clin North Am,72:85, 1992; Levy AD: Mesenteric ischemia. Radiol Clin North Am, 45:593, 2007; Maiden L et al: A blinded pilot comparison of capsule endoscopy and small bowel histology in unresponsive celiac disease. Dig Dis Sci, 54:1280, 2009; Mit­sudo S, Brandt LJ: Pathology of intestinal ischemia. Surg Clin North Am,72:43, 1992; Ross A et al: Double balloon enteroscopy detects small bowel mass lesions missed by capsule endoscopy. Dig Dis Sci. 53:2140, 2008; Sachdev MS, Ismail MK: Capsule en­doscopy: a review. South Med J, 101:407, 2008; Suzuki T et al: Clinical utility of double-balloon enteroscopy for small intestinal bleeding. Dig Dis Sci, 52:1914, 2007; Umphrey H et al: Differential diagnosis of small bowel ischemia. Radiol Clin North Am. 46:943,2008.