Faculty Bibliography

BACKGROUND: Irritable pouch syndrome (IPS) is a functional disease in patients with ileal pouch-anal anastomosis following colectomy for ulcerative colitis (UC). The pathophysiology of IPS is characterized by the presence of visceral hypersensitivity, similar to that seen in irritable bowel syndrome. However, the exact etiology and pathogenesis of IPS are not known. We hypothesized that serotonin-containing enteroendocrine cells or enterochromaffin (EC) cell hyperplasia and alterations in the mucosal immune cells may contribute to the patients' symptoms. The aim of the study was to assess EC cell hyperplasia and alterations in the mucosal immune cells in IPS. METHODS: The Pouchitis Disease Activity Index (PDAI) was used to quantify symptoms and mucosal inflammation in 36 patients with IPS and 25 patients with normal pouches. The histology and immunohistochemistry of pouch mucosal biopsies were assessed by a blinded gastrointestinal pathologist for intraepithelial lymphocytes (IEL), CD3+ T cells, CD25- (interleukin [IL]-2 receptor), tryptase- (mast cells), and serotonin-expressing cells. The numbers of IEL and immune-stained cells were compared between the two groups. RESULTS: Both groups were compatible demographically in terms of age, gender, duration of UC, stage, indication, and duration of the pouch surgery. There were no differences in the number of IEL, CD3+ T cells, CD25+ cells, and mast cells between the IPS and normal control groups. However, there were a significantly larger number of EC cells in the IPS group than that in the control group (54.8 +/- 24.9 vs 36.7 +/- 17.5 per 4 200x epithelial cells, P < 0.005). The number of EC cells appeared to be correlated with the symptom score (r = 0.276, P= 0.032). There were no significant correlations between the PDAI endoscopy and histology scores and the number of EC cells or between the PDAI scores and the number of IEL or other immune-stained cells. CONCLUSIONS: A greater number of EC cells were found in the IPS group than the normal pouch group, and the number of EC cells appeared to be correlated with the clinical symptoms of IPS. EC cell hyperplasia may be a contributing mechanism of visceral hypersensitivity and symptoms in IPS.

BACKGROUND: Although wireless capsule endoscopy (WCE) is widely used in the assessment of small bowel pathology, its application in patients with ileal pouches has not been evaluated. Persistent anemia has been observed in patients with ileal pouches, for which identification of etiology can be challenging. AIM: To assess the utility of WCE in ileal pouch patients with persistent anemia in conjunction with other diagnostic modalities. METHODS: Ulcerative colitis patients with persistent anemia (hemoglobin <10 g/dL) at least 12 months after either ileal pouch-anal anastomosis or continent ileostomy surgery were studied. Esophagogastroduodenoscopy, pouch endoscopy, WCE, and celiac disease serology were studied. The final diagnosis of the etiology of anemia was based on the results from the combined assessment of clinical, endoscopic, histologic, and laboratory data. RESULTS: Seventeen ileal pouch patients (10 females, 7 males) with underlying inflammatory bowel disease were studied with a mean age 42.1+/-15.2 years. Nine patients (52.9%) had active pouchitis and 3 (17.6%) had Crohn's disease (CD). WCE was successfully completed in 16 patients (94.1%). Suspected causes of anemia were identified in 5 patients (29.4%): 2 patients with CD of the pouch and 1 patient with celiac disease, detected by esophagogastroduodenoscopy, pouch endoscopy, small bowel biopsy, and celiac disease serology, and 1 patient with CD of the small bowel and 1 patient with small bowel arterio-venous malformations shown on WCE only. CONCLUSIONS: WCE seemed to be feasible and well tolerated in patients with ileal pouches. WCE provided additional diagnostic information in the pouch patients with anemia.

PURPOSE/OBJECTIVE:Little data exist regarding infliximab use in surgical decision making and postoperative complications in ulcerative colitis. Our goals were to determine the rate of postoperative complications in infliximab-treated ulcerative colitis patients undergoing restorative proctocolectomy and to determine whether three-stage procedures are more often necessary. METHODS:We studied a group of infliximab-treated patients and matched control subjects who underwent two-stage restorative proctocolectomy between 2000 and 2006. Postoperative complications were compared. In addition, the rate of three-stage procedures was compared between all infliximab- and noninfliximab-treated patients. RESULTS:A total of 523 restorative proctocolectomies were performed. In the infliximab group, there were 46 two-stage and 39 three-stage procedures. Covariate-adjusted odds of early complication for the infliximab group was 3.54 times that of controls (P = 0.004; 95 percent confidence interval (CI), 1.51-8.31). The odds of sepsis were 13.8 times greater (P = 0.011; 95 percent CI, 1.82-105) and the odds of late complication were 2.19 times greater (P = 0.08; 95 percent CI, 0.91-5.28) for infliximab. The odds of requirement for three-stage procedures was 2.07 times greater in the infliximab group (P = 0.011; 95 percent CI, 1.18-3.63). CONCLUSIONS:Infliximab increases the risk of postoperative complications after restorative proctocolectomy and has altered the surgical approach to ulcerative colitis. Potential benefits of infliximab should be balanced against these risks.

BACKGROUND & AIMS: There has been an increase in the incidence and severity of Clostridium difficile-associated diarrhea in the U.S. The importance of C difficile infection in patients with ileal pouch-anal anastomosis (IPAA) is unknown. This study was designed to determine risk of acquiring C difficile infection in pouch disorders. METHODS: Consecutive ulcerative colitis patients (n = 115) with IPAA undergoing pouch endoscopy were enrolled from May 2005-March 2006. Fecal specimens of pouch aspirate were collected during pouch endoscopy and analyzed for C difficile toxin A and B by enzyme-linked immunosorbent assay. Nineteen clinical, endoscopic, and histologic variables were assessed with stepwise selection methods. Two multivariate logistic regression models were constructed. RESULTS: Twenty-one patients (18.3%) were positive for C difficile infection. Adjusting for other factors in the model, men were 5.12 (95% confidence interval, 1.38-20.46) times more likely to have C difficile infection than women. Compared with patients with pancolitis, those with preoperative left-sided colitis were 8.4 (95% confidence interval, 1.25-56.4) times more likely to have C difficile infection. Six of 6 patients with C difficile infection (3 with refractory pouchitis, 2 with Crohn's disease, and 1 with irritable pouch syndrome) with repeat clinical, endoscopic, and laboratory evaluation after anti-C difficile therapy experienced clinical remission and disappearance of C difficile toxin from stools, with 4 showing decreased mucosal inflammation. CONCLUSIONS: C difficile infection involving IPAA is common, characteristically occurring with or without previous receipt of antibiotics. Treatment of C difficile infection in patients with IPAA might improve the clinical outcome.

BACKGROUND: Crohn's disease (CD) of the pouch is one of the leading causes of pouch failure in patients with restorative proctocolectomy. Risk factors for pouch failure in these patients are yet to be identified. The aim of the study was to assess risk factors associated with pouch failure in patients with CD of the pouch. METHODS: All patients with a confirmed diagnosis of CD of the pouch in the Pouchitis Clinic between 2002 and 2007 were evaluated. Patients with familial adenomatous polyposis, normal pouches, pouchitis, cuffitis, surgical complications, and other diseased pouch conditions were excluded. Pouch failure was defined as the requirement for a permanent diversion or pouch resection. Demographic and clinical factors were studied with univariable and multivariable analyses. RESULTS: A total of 137 patients with CD of the pouch were included. Twenty-two patients (16%) developed pouch failure a median of 6 years after ileostomy takedown. Four of 50 patients (8.0%) with inflammatory CD, 4 of 30 (13.3%) with fibrostenotic CD, and 14 of 57 (24.6%) with fistulizing CD had pouch failure. A Kaplan-Meier plot for time to pouch failure by CD phenotype showed a trend toward association (P = 0.054) in patients with fistulizing CD. Adjusting for age, smoking status, and the use of immunomodulators or biologics, fistulizing CD was not found to be significantly associated with a higher hazard for pouch failure. Younger age, being an ex-smoker, and the use of immunomodulators or biologics were found to increase the hazard of pouch failure. CONCLUSIONS: Younger age, being an ex-smoker, and the requirement for immunomodulators or biologics were associated with pouch failure. The identification of these risk factors may help delineate the natural history of CD of the pouch and shed light on proper clinical management and prognosis.

BACKGROUND: Pouchitis is the most common long-term complication of in patients with restorative proctocolectomy and ileal pouch-anal anastomosis. Patients often develop antibiotic-dependent form of pouchitis requiring long-term antibiotic therapy for remission maintenance. Rifaximin, an oral, non-systemic, broad-spectrum antibiotic with a favorable safety profile, may be a promising candidate agent for maintenance therapy. This historical cohort open-label study investigated the efficacy and tolerability of rifaximin in maintaining symptomatic and endoscopic remission in patients with antibiotic-dependent pouchitis. METHODS: Adult patients with antibiotic-dependent pouchitis received a 2-week course of various antibiotics for induction of remission. Patients in remission then began maintenance therapy with rifaximin 200 mg/day (to 1800 mg/day) for up to 24 months. Pouchitis Disease Activity Index symptom scores were assessed every 1-3 months to evaluate efficacy. RESULTS: Fifty-one patients began maintenance therapy with rifaximin (median dose 200 mg/day); 33 (65%) maintained remission through 3 months (primary endpoint). Of these 33 patients, 26 (79%) successfully continued maintenance for 6 months after beginning maintenance, 19 (58%) successfully continued for 12 months, and two (6%) successfully continued for 24 months. Only one patient reported an adverse event (transient facial rash). CONCLUSION: Patients' response to rifaximin as a maintenance therapy appears to be favorable in this open-labeled trial of antibiotic-dependent pouchitis. Randomized, placebo-controlled trials with a longer follow-up are warranted.

BACKGROUND: Although tissue eosinophilia in mucosal biopsy specimens from the ileal pouch in patients treated with restorative proctocolectomy is frequently seen, its clinical significance has not been investigated. The aim of this study was to assess whether tissue eosinophilia was associated with disease status of ileal pouches. METHODS: Hematoxylin and eosin slides of pouch and afferent limb biopsy specimens from 106 patients randomly selected from the Pouchitis Database were evaluated by 2 gastrointestinal pathologists. Of 106 patients, 81 had corresponding mucosal biopsy specimens of the afferent limb that were available for review. Tissue eosinophil infiltration was evaluated in a semiquantitative fashion with scores ranging from 0-3. Univariate and multivariate analyses were performed to assess the association between eosinophil scores and demographic, clinical, endoscopic, and histologic features. RESULTS: Multivariate analyses showed that tissue eosinophilia of the pouch and afferent limb was not associated with chronic inflammatory conditions of the pouch and the presence of concurrent autoimmune-mediated disorders. Tissue eosinophil score of the pouch was significantly higher than that in the corresponding afferent limb in the same patient population (P = 0.043). A high tissue eosinophil score in the afferent limb was associated with non-use nonsteroidal antiinflammatory drug use (odds ratio = 3.5; 95% confidence interval [CI]: 1.2, 10.4) and high endoscopic inflammation scores in the afferent limb (odds ratio = 1.6; 95% CI: 1.1, 2.2). Similar associations were not found in pouch biopsy specimens. CONCLUSIONS: Tissue eosinophilia in the pouch was more prominent than that in the afferent limb in patients with restorative proctocolectomy. Tissue eosinophilia in the pouch and afferent limb appeared to be associated with different risk factors. These findings suggest that luminal factors in different topographical locations of the pouch may contribute to eosinophil-mediated inflammation at these sites.

Both medical and surgical therapies for ulcerative colitis have inherent advantages and disadvantages that must be balanced for patients with moderate to severe disease. Restorative proctocolectomy with ileal pouch-anal anastomosis has become the surgical treatment of choice for the majority of patients with ulcerative colitis who require proctocolectomy. However, adverse sequelae of mechanical, inflammatory, functional, neoplastic, and metabolic conditions related to the pouch can occur postoperatively. Recognition and familiarization of the disease conditions related to the ileal pouch can be challenging for practicing gastroenterologists. Accurate diagnosis and classification of the disease conditions are imperative for proper management and prognosis.

BACKGROUND AND AIM: Postoperative abdominal adhesion formation is a troublesome clinical problem and a common cause of intestinal obstruction, chronic pain and infertility. The aim of this study was to evaluate the effect of small bowel obstruction (SBO) on functional outcome and quality of life (QOL) in patients who experienced ileal pouch-anal anastomosis (IPAA). METHODS: A total of 2418 patients who had undergone IPAA were categorized into three groups: group 1 comprised patients who had no SBO episodes until the last follow-up; group 2 comprised patients who had one or more SBO episodes treated medically; and group 3 comprised patients who had one or more SBO episodes, at least one of which was treated surgically. Functional outcomes and QOL scores for patients in each group were evaluated at 1, 3, 5 and 10 years of follow-up using multivariate analysis. RESULTS: We found that patients who had SBO episodes which were treated medically were more likely to have a higher number of total bowel movements in a day in the first year of follow-up compared to patients without postoperative SBO (P = 0.03), and more seepage during the day at 10 years follow-up compared to patients with no SBO episodes or surgically treated SBO episodes (P = 0.01). The Cleveland Global Quality of Life (CGQL) scores were comparable between the three groups at 1, 3, 5 and 10 years of follow-up. CONCLUSION: Medical management of SBO is associated with an increase in two symptoms, but QOL is comparable with surgical management.

BACKGROUND & AIMS: The effect of orthotopic liver transplantation (OLT) for primary sclerosing cholangitis (PSC) and post-OLT immunosuppression on the disease course of pouchitis is not clear. The aims of this study were to compare the frequency of chronic antibiotic-refractory pouchitis (CARP) in PSC patients with or without OLT and to assess potential risk factors for CARP in these patients. METHODS: Ulcerative colitis patients with PSC and ileal pouch-anal anastomosis (IPAA) with or without OLT identified from our prospectively maintained pouch database were analyzed. CARP was diagnosed based on persistent symptomatic pouchitis after a 4-week single- or dual-antibiotic therapy. RESULTS: A total of 63 PSC/IPAA patients were studied, including 19 patients with OLT and 44 patients without OLT. Fifty patients (79.4%) had CARP. In both univariable and multivariable analyses (adjusting for OLT status), none of the variables studied was associated significantly with CARP (P > .20). All 7 patients (100%) with IPAA-then-OLT were diagnosed as having CARP, of whom 4 developed CARP before OLT, which persisted after OLT, and 3 had CARP after OLT. Of 12 patients with OLT-then-IPAA, 7 (58.3%) developed CARP. The frequency of CARP in OLT-then-IPAA was statistically significantly lower than that in IPAA-then-OLT (58.3% vs 100%; P = .047). CONCLUSIONS: CARP is common in patients with ulcerative colitis and PSC. OLT in these patients may not affect the frequency of CARP in general and appears not to alter the disease course of pre-existing CARP. However, in a subset of patients, OLT might reduce the risk for the development of de novo CARP.