Ulcerative Colitis: Present D

Nilubol N, Scherl E, Bub DS, Gorfine SR, Marion J, Harris MT, Kornbluth A, Lichtiger S, Rubin P, George J, Chapman M, Harpaz N, Present D, Bauer JJ. · Department of Surgery, The Mount Sinai Hospital, New York, New York, USA. · Dis Colon Rectum. · Pubmed #17429711 No free full text.

Abstract: PURPOSE: Inflammation, villous atrophy, colonic metaplasia, and dysplasia have been observed within the mucosa of ileal pelvic pouches after restorative proctocolectomy. This study was designed to determine the prevalence of mucosal dysplasia in ileal pouch and any associated risk factors. METHODS: Prospectively registered patients having restorative proctocolectomy were recruited. A cross-sectional study was performed using a questionnaire focusing on disease history, functional results, and pouchitis after surgery. Participants underwent screening endoscopic pouch examination using sigmoidoscopy. Mucosal biopsies were taken from six specific locations in the pouch from proximal ileal-pouch (inflow) to ileoanal anastomosis. All biopsies were performed under strict surveillance protocol regardless of patients' symptoms. Biopsies were interpreted by two pathologists unaware of each other's report. RESULTS: A total of 138 patients completed the protocol. Colectomy specimens from restorative proctocolectomy showed chronic ulcerative colitis in 118 (85.6 percent), familial adenomatous polyposis in 10 (7.2 percent), Crohn's colitis in 2 (1.4 percent), and indeterminate colitis in 8 (5.8 percent) patients. Twenty-two patients (18.3 percent) had dysplasia and eight (6.7 percent) had invasive cancer found in colectomy specimens after restorative proctocolectomy. Median interval between proctocolectomy and pouch biopsy was 5.4 years. Inflammatory changes were present in a majority of specimens, but these did not correlate with clinical history of pouchitis. No villous atrophy was identified. Pouch biopsies from only one patient were indefinite for dysplasia. Subsequent biopsies were negative. CONCLUSIONS: Clinical and microscopic evidence of ileal-pouch inflammation is common. Ileal-pouch mucosal dysplasia is uncommon, occurring in only 1 of 138 patients. Villous atrophy and colonic metaplasia were not observed in this series. Routine pouch surveillance with biopsies may not be warranted.

Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, Travers S, Rachmilewitz D, Hanauer SB, Lichtenstein GR, de Villiers WJ, Present D, Sands BE, Colombel JF. · University Hospital Gasthuisberg, Leuven, Belgium. · N Engl J Med. · Pubmed #16339095 links to  free full text

Abstract: BACKGROUND: Infliximab, a chimeric monoclonal antibody directed against tumor necrosis factor alpha, is an established treatment for Crohn's disease but not ulcerative colitis. METHODS: Two randomized, double-blind, placebo-controlled studies--the Active Ulcerative Colitis Trials 1 and 2 (ACT 1 and ACT 2, respectively)--evaluated the efficacy of infliximab for induction and maintenance therapy in adults with ulcerative colitis. In each study, 364 patients with moderate-to-severe active ulcerative colitis despite treatment with concurrent medications received placebo or infliximab (5 mg or 10 mg per kilogram of body weight) intravenously at weeks 0, 2, and 6 and then every eight weeks through week 46 (in ACT 1) or week 22 (in ACT 2). Patients were followed for 54 weeks in ACT 1 and 30 weeks in ACT 2. RESULTS: In ACT 1, 69 percent of patients who received 5 mg of infliximab and 61 percent of those who received 10 mg had a clinical response at week 8, as compared with 37 percent of those who received placebo (P<0.001 for both comparisons with placebo). A response was defined as a decrease in the Mayo score of at least 3 points and at least 30 percent, with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or an absolute rectal-bleeding subscore of 0 or 1. In ACT 2, 64 percent of patients who received 5 mg of infliximab and 69 percent of those who received 10 mg had a clinical response at week 8, as compared with 29 percent of those who received placebo (P<0.001 for both comparisons with placebo). In both studies, patients who received infliximab were more likely to have a clinical response at week 30 (P< or =0.002 for all comparisons). In ACT 1, more patients who received 5 mg or 10 mg of infliximab had a clinical response at week 54 (45 percent and 44 percent, respectively) than did those who received placebo (20 percent, P<0.001 for both comparisons). CONCLUSIONS: Patients with moderate-to-severe active ulcerative colitis treated with infliximab at weeks 0, 2, and 6 and every eight weeks thereafter were more likely to have a clinical response at weeks 8, 30, and 54 than were those receiving placebo. (ClinicalTrials.gov numbers, NCT00036439 and NCT00096655.)