Detection of epithelial apoptosis in pelvic ileal pouches for ulcerative colitis and familial adenomatous polyposis

<p>Abstract</p> <p>Background</p> <p>Ileal pouch-anal anastomosis (IPAA) is the surgical procedure of choice for patients with refractory ulcerative colitis (UC) and for familial adenomatous polyposis (FAP) with many rectal polyps. Pouchitis is one of the more frequent complications after IPAA in UC patients; however, it is rare in FAP.</p> <p>Objective</p> <p>Evaluate pro-apoptotic activity in endoscopically and histological normal mucosa of the ileal pouch in patients with UC and FAP.</p> <p>Methods</p> <p>Eighteen patients (nine with UC and nine with FAP) with J pouch after total rectocolectomy were studied. Biopsies were obtained from the mucosa of the pouch and from normal ileum. The specimens were snap-frozen and the expressions of Bax and Bcl-2 were determined by immunoblot of protein extracts and by immunohistochemistry analysis. FADD, Caspase-8, APAF-1 and Caspase-9 were evaluated by immunoprecipitation and immunoblot.</p> <p>Results</p> <p>Patients with UC had significantly higher protein levels of Bax and APAF-1, Caspase-9 than patients with FAP, but were similar to controls. The expressions of Bcl-2 and FADD, Caspase-8 were similar in the groups. Immunohistochemistry for Bax showed less intensity of immunoreactions in FAP than in UC and Controls. Bcl-2 immunostaining was similar among the groups.</p> <p>Conclusion</p> <p>Patients with FAP present lower levels of pro-apoptotic proteins in all methods applied, even in the absence of clinical and endoscopic pouchitis and dysplasia in the histological analysis. These findings may explain a tendency of up-regulation of apoptosis in UC patients, resulting in higher rates of progression to pouchitis in these patients, which could correlate with mucosal atrophy that occurs in inflamed tissue. However, FAP patients had low pro-apoptotic activity in the mucosa, and it could explain the tendency to low cell turn over and presence of adenomas in this syndrome.</p

Ulcerative Colitis - Surgery Outcome and Pathophysiological Aspects

Background: Ulcerative Colitis (UC) is a chronic inflammatory bowel disease; the etiology is mainly unknown. Around 30% of the patients are treated by surgery. The aims of this thesis were to evaluate outcome after specific surgical procedures and to investigate possible pathophysiological aspects. Methods: Functional outcome after ileal pouch-anal anastomosis (IPAA) and ileo-rectal anastomosis (IRA) was recorded by Öresland score; different pouch designs (K or J) were compared. Frequency of neoplasia in IPAA:s was evaluated in patients with previous neoplasias. Patients with UC and primary sclerosing cholangitis (PSC) were compared to patients with UC-only regarding outcome of IPAA or IRA. Galectin expression was investigated in full wall specimens from patients with UC. Results: IPAA:s with K-design and stapled anastomosis were associated with better Öresland score than IPAA:s with J-design. The obtained frequency of dysplasia in IPAA:s was 1.8% (95%-CI: 0-5.3%) in patients with previous neoplasia. Patients with UC-PSC operated on with IPAA have similar outcome as patients with UC-only, except for higher incidence of pouchitis. Patients with IRA in the same setting, have worse functional outcome and an increased rate of failure. There was no correlation between galectin expression and inflammatory grade. Conclusions: K-design was associated with best functional outcome; however, the study was non-randomized. The frequency of dysplasia after IPAA is low, even in a selected risk group. IPAA seems superior to IRA in patients with UC-PSC. The role of galectins in the pathogenesis of UC remains to be elucidated