Differential expression of toll-like receptor 3 and 5 in ileal pouch mucosa of ulcerative colitis patients.

BACKGROUND AND AIMS: The pathogenesis of pouchitis, major complication after restorative proctocolectomy, and ileal J pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC) is still unclear. Changes in intraluminal bacterial colonization and correlated changes of pouch mucosa are thought to play an important role. Toll-like receptors (TLRs) as part of the innate immune system are capable of recognizing bacterial antigens. Their activation can lead to secretion of proinflammatory mediators. In this study, TLR2, 3, 4, and 5 expression profiles in the pouch mucosa of patients with UC and IPAA were analyzed and correlated with pouchitis. MATERIALS AND METHODS: Clinical symptoms, endoscopy, and histology were assessed in 35 patients using the Heidelberg Pouchitis Activity Score to classify patients as either having pouchitis or not. TLR mRNA expression in normal ileal mucosa and pouch mucosa was investigated by performing semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR). The results of RT-PCR were associated with the pouchitis score. RESULTS: In the analysis of all patients, TLR3 expression was decreased significantly whereas TLR5 expression was increased significantly in pouch mucosa compared to normal ileal mucosa (p-values 0.0076 and 0.016, respectively). A more detailed analysis upon dividing the patients into patients with and without pouchitis showed decreased TLR3 expression in the pouch mucosa only of patients without pouchitis (p-value=0.0067). TLR5 expression was increased in the pouch mucosa only of patients with pouchitis (p-value=0.023). No differences in TLR2 and 4 expression were found in either group. CONCLUSION: Differential expression of TLR3 and 5 suggests bacterial involvement in the pathogenesis of pouchitis in patients with UC.

Diagnosing pouchitis: comparative validation of two scoring systems in routine follow-up.

PURPOSE: Pouchitis represents a serious threat to patients with ulcerative colitis after restorative proctocolectomy with ileal pouch-anal anastomosis. The frequency of pouchitis is high, and it implies the risk of pouch failure and the risk of malignant mucosal transformation in the pouch. Early detection and precise classification of the inflammatory process are required for adequate therapy, which might be facilitated using a scoring system. The aim of the present study was to validate two existing scoring systems in routine outpatient practice. METHOD: The Heidelberg Pouchitis Activity Score and the Pouchitis Disease Activity Index developed at the Mayo Clinic were simultaneously prospectively applied in a consecutive series of 103 outpatient consultations of 41 patients at our hospital and comparatively validated against the diagnosis of " pouchitis" or "no pouchitis" concurrently made by a physician and a surgeon. RESULTS: The median score of examinations in which the clinicians' diagnosis was consistent with pouchitis were significantly higher than those of examinations inconsistent with pouchitis in both scoring systems (Heidelberg Pouchitis Activity Score, 17 (interquartile range, 14-21) and 8 (interquartile range, 5-10), respectively, P < 0.001; Pouchitis Disease Activity Index, 7 (interquartile range, 5-8) and 2.5 (interquartile range, 1-4), respectively, P < 0.001). The sensitivity and specificity in the two total scores were 84 and 79.5 percent, respectively (Heidelberg Pouchitis Activity Score), and 60 and 96.2 percent, respectively (Pouchitis Disease Activity Index); in the field clinical manifestations 44 and 73.1 percent, respectively (Heidelberg Pouchitis Activity Score), and 20 and 87.2 percent, respectively (Pouchitis Disease Activity Index); in the field endoscopic manifestations 88 and 83.3 percent, respectively (Heidelberg Pouchitis Activity Score), and 60 and 89.7 percent, respectively (Pouchitis Disease Activity Index); and in the field histologic manifestations 72 and 76.9 percent, respectively (Heidelberg Pouchitis Activity Score), and 44 and 96.2 percent, respectively (Pouchitis Disease Activity Index). Lowering the cutoff point for diagnosis of pouchitis in the Pouchitis Disease Activity Index by 2 points (pouchitis: score >or= 5) would result in an 88 percent sensitivity and a 67 percent specificity. CONCLUSIONS: Specificity and sensitivity of the Heidelberg Pouchitis Activity Score were satisfactory. The cutoff point for diagnosing pouchitis in the Pouchitis Disease Activity Index would have to be lowered to reach an acceptable sensitivity and specificity. The very poor validity of the field clinical manifestations in diagnosing pouchitis emphasizes the need for endoscopic and histologic examination for detection of pouchitis. The issue of whether the diagnosis of pouchitis should be based on endoscopic and histologic features alone, instead of additionally taking clinical features into account, should be addressed in future studies.

Risk factors for ileoanal J pouch-related septic complications in ulcerative colitis and familial adenomatous polyposis.

OBJECTIVE: To analyze the association between pre- and perioperative factors and pouch-related septic complications (PRSC) in ulcerative colitis (UC) and in familial adenomatous polyposis (FAP) after ileal pouch-anal anastomosis (IPAA). SUMMARY BACKGROUND DATA: For patients with UC and FAP, IPAA is the surgical therapy of choice, but in some patients the outcome is compromised by PRSC. METHODS: A total of 706 consecutive patients (494 UC, 212 FAP) were assessed in a study aimed at identifying subgroups of patients who were at high risk for PRSC. The rate of PRSC was analyzed as a time-dependent function (Kaplan-Meier estimation). Patients with UC and FAP were stratified separately according to associated factors (age, sex, surgeon's experience, temporary ileostomy, colectomy before IPAA, anastomotic tension, and several factors specific for UC). RESULTS: In all, 131 (19.2%) patients had PRSC (23.4% UC, 9.4% FAP). In patients with UC, the estimated 1-year PRSC rate was 15.6% and the estimated 3-year PRSC rate was 24.2%. In patients with FAP, the estimated 1-year and 3-year PRSC rates were 9.2%. The difference between the estimated rates of PRSC was significant (P <.001). In the univariate analysis, patients with UC younger than 50 years, with severe proctitis, with preoperative hemoglobin levels less than 10 g/L, or receiving corticoid medication had a significantly higher risk for PRSC (P =.039, P =.037, P =.047, P =.003, respectively). Multivariate analysis showed that patients with UC receiving a systemic prednisolone-equivalent corticoid medication of more than 40 mg/day had a significantly greater risk of developing pouch-related complications than patients with UC receiving 1 to 40 mg/day and patients with UC who were not receiving corticoid medication (RR: 3.78, 2.25, 1, respectively, P <.001). Patients with FAP proved to have a significantly higher risk for PRSC in the univariate and multivariate analyses if anastomotic tension had occurred (RR 3.60, P =.0086). CONCLUSIONS: Pouch-related septic complications occur as late complications and should therefore be considered in regular, specific long-term follow-up examinations. The authors identified significant risk factors for PRSC specific to patients with UC and FAP; these must be considered for each individual surgical strategy.