Ileal lesions in patients with ulcerative colitis after ileo-rectal anastomosis: relationship with colonic metaplasia.

AIM: To assess whether in ulcerative colitis (UC) patients with ileo-rectal anastomosis (IRA), ileal lesions may develop in the neo-terminal-ileum and their possible relation with phenotypic changes towards colonic epithelium. METHODS: A total of 19 patients with IRA under regular follow up were enrolled, including 11 UC and 8 controls (6 Crohn's disease, CD; 1 familial adenomatous polyposis, FAP; 1 colon cancer, colon K). Ileal lesions were identified by ileoscopy with biopsies taken from the ileum (involved and uninvolved) and from the rectal stump. Staining included HE and immunohistochemistry using monoclonal antibodies against colonic epithelial protein CEP (Das-1) and human tropomyosin isoform 5, hTM5 (CG3). Possible relation between development of colonic metaplasia and ileal lesions was investigated. RESULTS: Stenosing adenocarcinoma of the rectal stump was detected in 1 UC patient. The neo-terminal ileum was therefore investigated in 10/11 UC patients. Ileal ulcers were detected in 7/10 UC, associated with colonic metaplasia in 4/7 (57.1%) and Das-1 and CG3 reactivity in 3/4 UC. In controls, recurrence occurred in 4/6 CD, associated with colonic metaplasia in 3/4 and reactivity with Das-1 and CG3 in 2/3. CONCLUSION: Present findings suggest that in UC, ileal lesions associated with changes towards colonic epithelium may develop also after IRA. Changes of the ileal content after colectomy may contribute to the development of colonic metaplasia, leading to ileal lesions both in the pouch and in the neo-terminal ileum after IRA.

Current therapeutic recommendations: infliximab for ulcerative colitis.

Randomized, controlled studies have shown that infliximab, the chimeric anti-tumor necrosis factor alpha (TNF-alpha) antibody, is effective for the treatment of active and fistulizing Crohn's disease. Because infliximab is beneficial in patients with Crohn's disease, in whom other therapies have failed, it has been postulated that infliximab may also be helpful in patients with ulcerative colitis. Many investigators have studied the effectiveness of infliximab in ulcerative colitis, mainly in patients who are refractory to corticosteroids. Unfortunately, these studies have not yielded a conclusive answer to the efficacy of infliximab in inducing remission in patients with severe ulcerative colitis. However, some have reported excellent results and others less effective, with the overall data being inconclusive. The purpose of this review is to summarize the current literature on the use of infliximab in ulcerative colitis, as well as to provide insight into the possible mechanisms of why it may or may not work in these difficult-to-treat patients.

Tropomyosin expression in the ileal pouch: a relationship with the development of pouchitis in ulcerative colitis.

OBJECTIVE: Human tropomyosin isoform 5 (hTM5) is a cytoskeletal protein expressed in normal epithelial cells, predominantly in the colon. An autoimmune response toward hTM5 has been reported in ulcerative colitis (UC). Whether hTM5 expression in the ileum is involved in pouchitis is unknown. We assessed hTM5 expression on ileal epithelial cells at surgery and subsequently on development of pouchitis in UC. METHODS: In a prospective longitudinal study, 28 UC patients undergoing ileal pouch procedures were included. Biopsy samples were taken from the rectum at surgery, as well as from the ileal pouch at surgery and at 6 months. The specimens were stained by immunoperoxidase using the anti-hTM5 monoclonal antibody CG3. Pouchitis was assessed by the Pouchitis Disease Activity Index and hTM5 expression on a scale of 0-3. RESULTS: At surgery, in rectal samples, hTM5 expression was strong in all epithelial cells including the luminal surface, whereas in ileal samples hTM5 was not expressed or focally expressed only in the goblet cells. At 6 months, the ileum was found to have undergone morphological changes, becoming similar to the colon and showing shortening or reduced number of villi. These changes were associated with a diffuse hTM5 staining in the goblet cells and in the nongoblet epithelial cells lining the crypts and the lumen. The hTM5 score was related to the Pouchitis Disease Activity Index at 6 months (r = 0.82; p = 0.01). CONCLUSIONS: Expression of hTM5 shows a different pattern in the ileal pouch in UC after surgery. This event is associated with morphological changes of the ileum toward colonic epithelium, related to the development of pouchitis.