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d i s c u s s i o n
Ulcerative Colitis
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Related narratives: Ulcerative Colitis,
Total Colectomy and J-Pouch, Ulcerative colitis is an inflammatory process limited to the mucosa of the colon. Its etiology is poorly understood. An autoimmune mechanism is suspected to play a role, but no inciting antigen or target cell has been identified. There appears to be dysfunctional immunoregulation within the intestinal wall, leading to the abnormal production of cytokines (interleukin 1 rectptor antagonist), correlating with the severity of disease. There also appears to be a genetic component, with about 10% of patients having affected family members. The pericentromeric region of chromosome 16 and defective DNA repair genes have been implicated. The onset of ulcerative colitis can be insidious with diarrhea and hematochesia which must be differentiated from other etiologies, most commonly infectious, ischemic and radiation induced colitis. Ulcerative colitis always involves the rectum. If the rectum is spared on colonoscopy, Crohn's colitis must be suspected. The disease is variable in its extent and manifestations. Disease extending proximally beyone the hepatic flexure is defined as total or unversal vs. partial. Medical treatment of chronic ulcerative colitis relies on anti-inflammatory derivatives of 5-ASA, the earliest being azulfadine, and newer agents such as mesalamine. For acute exacerbations, severe or intractable disease, immunomodulators are used. These include steroids, tacrolimus, 6-mercaptopurine, methotrexate, cyclosporine and mycophenate. Acute exacerbations usually respond to medical therapy. In about 15% of patients, unresponsive fulminant colitis, massive bleeding, perforation, obstruction from stricture or carcinoma and toxic megacolon may require emergency surgery. About 25% of patients with chronic ulcerative colitis develop extraintestinal complications. The most common of these are arthritis and ankylosing spondylitis. Others include uveitis, pyoderma gangrenosum and sclerosing cholangitis. The relationship of these manifestations to the primary disease is unclear. Arthritis responds to total colectomy, as do about 50% of the dermatological manifestations. Ankylosing spondylitis and sclerosing cholangitis are not improved by colectomy. Younger patients tend to have more fulminant disease and systemic complications, and children with ulcerative colitis have growth retardation that is proportional to the severity of disease. Colectomy in such cases often results in dramatic resumption of growth. Late sequellae of ulcerative colitis include stricture and carcinoma. Stricture may be a consequence of scarring from repeated bouts of ulceration, but differentiating a benign stricture from a carcinoma may be difficult. Carcinoma in ulcerative colitis tends to be more aggressive and multicentric than sporadic colorectal cancer and is often diagnosed at a more advanced stage. The biological mechanism also seems to differ from the sequential mutation of multiple genes leading to adenomatous polyps and invasive carcinoma seen in sporadic cancer. Carcinoma developing on a background of ulcerative colitis arises in flat fields of dysplastic tissue which is often normal-appearing on colonoscopy. There is early genomic instability (DNA aneuploidy, microsatellite instability) in these tumors. Abnormalities of the APC tumor repressor gene is rarely seen in UC-related carcinoma in contrast to sporadic, p53 mutation appears earlier, and K-ras mutation may be less common. While the risk of developing carcinoma in ulcerative colitis (and equally in Crohn's colitis) is several times that of the general population and is related to the duration of the disease, other factors such as extent, activity and effectiveness of medical therapy have been harder to define precisely despite multiple studies. The presence of sclerosing cholangitis in 5% of patients with ulcerative colitis adds to the risk of developing carcinoma. Dysplasia in normal-appearing mucosa has been stratified into negative, indefinite, low grade and high grade categories by the bowel disease morphology group. Dysplasia in abnormal mucosa is termed dysplasia-associated lesion or mass (DALM) and is associated with a higher incidence of concomitant or subsequent carcinoma. Increased surveillance in multiple trials has thus far failed to produce a survival advantage for patients with ulcerative colitis related carcinoma. The difficulties of detecting dysplasia and carcinoma in normal-appearing mucosa are highlighted by the finding that detection to a 95% confidence level required as many as 56 biopsies per colonoscopy. The current American College of Gastroenterology guidelines for patients with total ulcerative colitis of eight or more years duration is annual colonoscopy with biopsy every 10 cm, and surgery for high grade dysplasia or DALM. About 50% of patients with ulcerative colitis require surgery in the first 10 years of disease for unresponsiveness, extrecolonic manifestations, inability to tolerate drug side effects (diabetes, cataract, hypertension, osteopenia), dysplasia/carcinoma or emergency. In 15%, emergency surgery is necessary. Massive hemorrhage is rare (10% of emergency colectomies). If emergency rectal-sparing total abdominal colectomy is performed, 12% of patients have persistent hemorrhage from the rectal stump. The most lethal emergency in ulcerative colitis is toxic megacolon. Toxic megacolon (see toxic megacolon) involves extensive deep mucosal ulcerations with destruction of the colonic myenteric plexuses (Auerbach and Meissner), resulting in atonic dilatation of the colon. Emergency medical management with intravenous high-dose steroids may reverse some cases (~10%), but often there are microperforations whose manifestations are masked by the steroids and mortality is high if total abdominal colectomy is not performed early. Acute perforation in the absence of toxic megacolon is rare. Because of these patients' poor condition and concomitant high-dose steroids, emergency surgery itself carries a high morbidity (50%: sepsis, wound infection, abscess, fistula, delayed healing) and mortality (~13%), and expeditious total abdominal colectomy, Hartmann's closure of the rectal stump and Brooke iliostomy is the only safe option. Later completion proctectomy is performed, usually with a pouch procedure and ileoanal anastomosis in patients who are otherwise healthy. Elective surgery for ulcerative colitis most commonly now (80%) consists of sphincter sparing total colectomy, pelvic ilial pouch with ileoanal anastomosis and in some cases diverting loop ileostomy (to reduce the 10% incidence of complications). Several varieties of pouch have been used (J, S, W types). The pouch constitutes a reservoir which allows thickening of the stool and decreased frequency. Patients typically experience up to six semi-formed stools per day. Addition of loperamide and/or fiber helps regulate consistency. The great majority of patients have a good result. Between 10 and 50% of patients develop some degree of inflammation in the pouch, termed pouchitis. Symptoms are watery stool, cramps, urgency, nocturnal leakage, arthralgias, malaise and fever. The etiology is unclear, but may be related to bacterial overgrowth, stasis, ischemia, nutritional or immunological factors. A short course of metronidazole and ciprofloxacin resolves 2/3 of episodes. There is about a 7% pouch failure rate in the first 10 years. References: Rolandelli RH, in Townsend: Sabiston Textbook of Surgery, 16th ed., Copyright © 2001 W. B. Saunders Company, 950-955. Becker JM, Surgical therapy for ulcerative colitis and crohn's disease, Gastroenterology Clinics Volume 28 o Number 2 o June 1999, Copyright © 1999 W. B. Saunders Company, 371-390. Lewis JD et al, Cancer risk in patients with inflammatory bowel disease, Gastroneterology clinics, vol. 28:2, June 1999, WB Saunders, 459-477.
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