Ulcerative Colitis: Lopez R

Shen B, Wu H, Remzi F, Lopez R, Shen L, Fazio V. · Digestive Disease Institute, the Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. · Inflamm Bowel Dis. · Pubmed #18972552 No free full text.

Abstract: BACKGROUND: Inflammatory and noninflammatory complications of ileal pouch-anal anastomosis (IPAA) are common after restorative proctocolectomy of ulcerative colitis (UC). Some of the patients can have upper gastrointestinal pathology. The diagnostic role of esophagogastroduodenoscopy (EGD) in these patients has not been evaluated. The aim was to estimate the prevalence of upper gastrointestinal (GI) diseases detected by EGD and to assess factors associated with the abnormal EGD findings. METHODS: IPAA patients with underlying inflammatory bowel disease undergoing diagnostic EGD were recruited from a subspecialty pouchitis clinic. Diagnostic yield and incidental findings of EGD were evaluated. Twenty-three variables were evaluated including age, gender, UC duration, IPAA duration, the Pouchitis Disease Activity Index scores, pouch type, pre-IPAA diagnosis, and disease category of the pouch. Univariate and multivariate analyses were performed; stepwise selection with 0.35 and 0.10 as entry and exit criteria. RESULTS: Sixty-six patients undergoing EGD were enrolled in the study, of whom 64 (97%) patients had a concomitant pouch endoscopy. Indications for EGD include anemia, upper abdominal pain, weight loss, nausea and vomiting, and persistent diarrhea refractory to antibiotic therapy. Seventeen patients (25.8%) had a conclusive diagnosis and 14 (21.2%) had incidental findings, on EGD. The most common abnormal findings on EGD were Crohn's disease 12%), peptic ulcer disease (3%), gastritis/duodenitis on histology (11%), Candida esophagitis (3%), and arteriovenous malformations (3%). In multivariate analysis, factors associated with a conclusive EGD diagnosis were a high Pouchitis Disease Activity Index endoscopy score of the afferent limb (odds ratio [OR] = 1.8; 95% confidence interval [CI]: 1.09, 2.9; P = 0.02) and pouch types other than original J pouch (OR = 5.9; 95% CI: 1.08, 32.2; P = 0.041). CONCLUSIONS: EGD evaluation can yield valuable diagnostic information in selected symptomatic patients with IPAA.

Shen BO, Jiang ZD, Fazio VW, Remzi FH, Rodriguez L, Bennett AE, Lopez R, Queener E, Dupont HL. · Center for Inflammatory Bowel Disease, Department of Gastroenterology/Hepatology, The Cleveland Clinic Foundation, Cleveland, Ohio, USA. · Clin Gastroenterol Hepatol. · Pubmed #18467184 No free full text.

Abstract: 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.

Shen B, Plesec T, Remzi FH, Kariv R, Lopez R, Queener E, Fazio VW, Goldblum JR. · Pouchitis Clinic, the Cleveland Clinic, Cleveland, Ohio 44195, USA. · Inflamm Bowel Dis. · Pubmed #18286609 links to  free full text

Abstract: 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.

Freeman K, Shao Z, Remzi FH, Lopez R, Fazio VW, Shen B. · Digestive Disease Center, Cleveland Clinic, Cleveland, Ohio 44195, USA. · Clin Gastroenterol Hepatol. · Pubmed #18065274 No free full text.

Abstract: 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.

Shen B, Fazio VW, Remzi FH, Bennett AE, Lavery IC, Lopez R, Brezinski A, Sherman KK, Bambrick ML, Lashner BA. · Center for Inflammatory Bowel Disease, Department of Gastroenterology/Hepatology, Cleveland Clinic, Cleveland, OH 44195, USA. · Dis Colon Rectum. · Pubmed #17665259 No free full text.

Abstract: PURPOSE: Crohn's disease of the pouch can occur in patients with colectomy and ileal pouch-anal anastomosis performed for ulcerative colitis. The clinical features of inflammatory, fibrostenotic, and fistulizing Crohn's disease have not been characterized. METHODS: A total of 73 eligible patients with Crohn's disease of the pouch, who were seen in the Pouchitis Clinic, were enrolled: 25 with inflammatory Crohn's disease, 17 with fibrostenotic Crohn's disease, and 31 with fistulizing Crohn's disease. The clinical phenotypes of Crohn's disease were based on a combined assessment of clinical, endoscopic, radiographic, and histologic features. Clinical symptoms, endoscopic and histologic features, and health-related quality-of-life scores were assessed. RESULTS: Demographic and clinical features, including preoperative and postoperative parameters, were similar between the three phenotypes of Crohn's disease of the pouch. The use of nonsteroidal anti-inflammatory drugs, neuropsychiatric drugs, antidiarrheal agents, and Crohn's disease medicines was not different between the three groups. Predominant symptoms, as expected, were significantly different between the three phenotypes: diarrhea and/or pain in 92 percent of patients with inflammatory Crohn's disease, obstructive symptoms in 64.7 percent of patients with fibrostenotic Crohn's disease, and fistular drainage in 51.6 percent of those with fistulizing Crohn's disease (P < 0.0001). There was no statistical difference in quality-of-life scores between the three phenotypes, adjusted for disease activity. There was no significant correlation between quality-of-life and symptom scores in any of the three groups. Although not statistically significant, patients with fistulizing Crohn's disease (16.1 percent) tended to have an increased risk for pouch failure compared with inflammatory (8 percent) or fibrostenotic (5.9 percent) Crohn's disease. CONCLUSIONS: Predominant symptoms were different in clinical phenotypes of Crohn's disease. Each of the three phenotypes of Crohn's disease similarly affected quality-of-life. Fistulizing Crohn's disease may be associated with a higher risk for pouch failure.

Shen B, Fazio VW, Remzi FH, Bennett AE, Lopez R, Lavery IC, Brzezinski A, Sherman KK, Lashner BA. · Center for Inflammatory Bowel Disease, Department of Gastroenterology/Hepatology-Desk A30, Cleveland Clinic, 9500 Euclid Ave., Cleveland, OH 44195, USA. · Dig Dis Sci. · Pubmed #17410449 No free full text.

Abstract: NSAID use has been shown to exacerbate disease activity of inflammatory bowel disease. The detrimental effect of NSAIDs on the ileal pouch has not been characterized. To study the effect of withdrawal of NSAID use on ileal pouch disorders. The study consisted of a cohort of 17 symptomatic patients seen in the Pouchitis Clinic who had ulcerative colitis and ileal pouch-anal anastomosis with chronic (>6 months) daily use of NSAIDs. The patients were treated by withdrawing NSAID use. The Pouchitis Disease Activity Index (PDAI) consisting of symptom, endoscopy and histology scores, and Cleveland Global Quality of Life, Irritable Bowel Disease Quality of Life, and Short Inflammatory Bowel Disease Questionnaire scores were measured before and after a 4-week intervention. The cohort consisted of 11 patients with chronic refractory pouchitis (65%), 2 with acute pouchitis (12%), 1 with cuffitis (6%), 1 with cuffitis and chronic refractory pouchitis (6%), and 2 with irritable pouch syndrome (12%). The withdrawal of NSAID use alone resulted in a significant reduction in the mean PDAI scores of -3.6 +/- -3.0 (p<0.02) and a significant improvement in mean quality-of-life scores (p<0.05). Patients with pouch disorders who regularly used NSAIDs appeared to benefit from the complete cessation of such agents, suggesting an association between NSAID use and pouch disorders.

Shen B, Fazio VW, Remzi FH, Bennett AE, Lopez R, Brzezinski A, Oikonomou I, Sherman KK, Lashner BA. · Department of Gastroenterology/Hepatology, Center for Inflammatory Bowel Disease, Cleveland Clinic, Cleveland, Ohio 44195, USA. · Dis Colon Rectum. · Pubmed #17279300 No free full text.

Abstract: PURPOSE: Management of chronic refractory pouchitis, a common cause for pouch failure with pouch resection or diversion, is often challenging. The aim of this study was to assess the efficacy and safety of a combination therapy of ciprofloxacin and tinidazole in patients with chronic refractory pouchitis compared with mesalamine therapy. METHODS: Sixteen consecutive ulcerative colitis patients with chronic refractory pouchitis (disease>4 weeks and failure to respond to>4 weeks of single-antibiotic therapy) were treated with a four-week course of ciprofloxacin 1 g/day and tinidazole 15 mg/kg/day. A historic cohort of ten consecutive patients with chronic refractory pouchitis treated with oral (4 g/day), enema (8 g/day), or suppository (1 g/day) mesalamine served as controls. The Pouchitis Disease Activity Index, clinical remission, clinical response, the Cleveland Global Quality of Life, the Irritable Bowel Syndrome-Quality of Life, and the Short Inflammatory Bowel Disease Questionnaires scores were calculated before and after therapy and compared between the two treatment groups. RESULTS: Patients taking ciprofloxacin and tinidazole had a significant reduction in the total Pouchitis Disease Activity Index scores and subscores and a significant improvement in quality-of-life scores (P < 0.002). For patients in the mesalamine group, there was a significant reduction in the total Pouchitis Disease Activity Index scores only. Patients in the antibiotic group had a greater reduction in the total Pouchitis Disease Activity Index scores and a greater improvement in the quality-of-life scores than those in the mesalamine group (P <or= 0.03). The rate of clinical remission and clinical response for the antibiotic group was 87.5 percent and 87.5 percent, respectively, and for the mesalamine group it was 50 percent and 50 percent, respectively (P = 0.069). Two patients in the antibiotic group (peripheral neuropathy and dysgeusia) developed adverse effects. CONCLUSIONS: Combination therapy with ciprofloxacin and tinidazole was generally well tolerated and was effective in treating patients with chronic refractory pouchitis.

Shen B, Fazio VW, Remzi FH, Bennett AE, Brzezinski A, Lopez R, Oikonomou I, Sherman KK, Lashner B. · Department of Gastroenterology/Hepatology, Center for Inflammatory Bowel Disease, Cleveland Clinic, Cleveland, Ohio 44195, USA. · Am J Gastroenterol. · Pubmed #17227523 No free full text.

Abstract: BACKGROUND: Crohn's disease (CD) of the pouch can occur in patients with colectomy and ileal pouch-anal anastomosis (IPAA) originally performed for a preoperative diagnosis of ulcerative colitis. The clinical presentations of CD of the pouch are inflammatory, fibrostenotic, and fistulizing. Risk factors for clinical phenotypes of CD of the pouch have not been characterized. METHODS: A total of 78 eligible patients with CD of the pouch together with 294 nonselected non-CD patients with IPAA seen in the Pouchitis Clinic were enrolled, including 28 with inflammatory CD, 18 with fibrostenotic CD, and 32 with fistulizing CD. The clinical phenotypes of CD were diagnosed based on a combined assessment of clinical, endoscopic, radiographic, and histologic features. Three separate analyses were performed, and for each analysis, the outcome of interest was having one of the phenotypes versus not having it. A stepwise selection multivariable logistic regression analysis was used. RESULTS: In the multivariable analysis, the risk factor for inflammatory CD was higher afferent-limb endoscopy scores (hazard ratio [HR] 1.87 95% confidence interval [CI] 1.54-2.27); the risk factors for fibrostenotic CD were higher afferent-limb (95% CI 1.81-3.48, HR 2.51) and higher cuff (95% CI 1.01-1.84, HR 1.36) endoscopy scores; and for fistulizing CD the risk factors were younger age (95% CI 0.93-0.99, HR 0.96), female gender (95% CI 1.35-6.97, HR 3.07), a preoperative diagnosis of indeterminate colitis (95% CI 1.72-9.34, HR 4.00), and no use of nonsteroidal antiinflammatory drugs (95% CI 1.31-8.25, HR 3.28). CONCLUSIONS: Each of the three phenotypes of CD of the pouch was associated with certain risk factors, suggesting that each of these diseases has a different etiology and disease process. The identification and management of some of the modifiable risk factors may reduce CD-related morbidity.

Oikonomou IK, Fazio VW, Remzi FH, Lopez R, Lashner BA, Shen B. · Department of Gastroenterology, Cleveland Clinic, Cleveland, Ohio 44195, USA. · Dis Colon Rectum. · Pubmed #17115336 No free full text.

Abstract: PURPOSE: Anemia is frequently observed in patients with ileal pouch-anal anastomosis. The identification of the underlying causes can be challenging. This study was designed to define the prevalence and to identify etiologic factors for anemia in this patient population. METHODS: A prospectively maintained database and medical records of patients who had restorative proctocolectomy between 1998 and 2005 were reviewed. All patients with laboratory evaluation at least six months after the surgery were studied. The last reported hemoglobin served as the index value. All patients with anemia (hemoglobin < 13.5 g/dl for males, <12 g/dl for females) were identified. A second group of randomly selected, ileal-pouch patients with normal hemoglobin served as control. Demographic and clinical variables were evaluated. RESULTS: A total of 389 patients (214 males) had documented hemoglobin values. Sixty-seven patients (17 percent; 40 males) had anemia. The prevalence of anemia was 19 and 15 percent in males and females, respectively. The prevalence was 17 percent among patients with underlying ulcerative colitis vs. 26 percent in patients with familial adenomatous polyposis (P = 0.27). The mean hemoglobin in the anemia group was 11.4 (median, 11.7) g/dl. One patient (2 percent) had severe (<7 g/dl), 11 (16 percent) had moderate (7-9.9 g/dl), and 55 (82 percent) had mild (> or =10 g/dl) anemia. One patient (2 percent) had macrocytic, 16 (24 percent) had microcytic, and 49 (74 percent) had normocytic anemia. Sixteen patients (24 percent) had unidentified causes for anemia. Multivariable analysis showed that the presence of malignancy or desmoid tumor and the J-pouch configuration were the only independent risk factors associated with anemia. CONCLUSIONS: Anemia is common in ileal-pouch patients. Malignancy or desmoid tumor and J-pouch configuration are independent risk factors for anemia. One-fourth of the patients with anemia have unclear etiology.

Shen B, Fazio VW, Remzi FH, Brzezinski A, Bennett AE, Lopez R, Hammel JP, Achkar JP, Bevins CL, Lavery IC, Strong SA, Delaney CP, Liu W, Bambrick ML, Sherman KK, Lashner BA. · Department of Gastroenterology/Hepatology, Center for Inflammatory Bowel Disease, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. · Clin Gastroenterol Hepatol. · Pubmed #16431309 No free full text.

Abstract: BACKGROUND & AIMS: Although pouchitis is considered the most common adverse sequela of ileal pouch-anal anastomosis (IPAA), inflammatory and noninflammatory conditions other than pouchitis are increasingly being recognized. The risk factors for these non-pouchitis conditions, including Crohn's disease (CD) of the pouch, cuffitis, and irritable pouch syndrome (IPS), have not been studied. The aim of this study was to assess risk factors for inflammatory and noninflammatory diseases of IPAA in a tertiary care setting. METHODS: The study consisted of 240 consecutive patients who were classified as having healthy pouches (N = 49), pouchitis (N = 61), CD of the pouch (N = 39), cuffitis (N = 41), or IPS (N =50). Demographic and clinical features were assessed to determine risk factors for each of these conditions by using logistic regression analysis. RESULTS: Risk factors remaining in the final logistic regression models were for pouchitis: IPAA indication for dysplasia (odds ratio [OR], 3.89; 95% confidence interval [CI], 1.69-8.98), never having smoked (OR, 5.09; 95% CI, 1.01-25.69), no use of anti-anxiety agents (OR, 5.19; 95% CI, 1.45-18.59), or use of NSAIDs (OR, 3.24; 95% CI, 1.71-6.13); for CD of the pouch: a long duration of IPAA (OR, 1.20; 95% CI, 1.12-1.30) and current smoking (OR, 4.77; 95% CI, 1.39-16.25); for cuffitis: arthralgias (OR, 4.13; 95% CI, 1.91-8.94) and younger age (OR, 1.16; 95% CI, 1.01-1.33); and for IPS: use of antidepressants (OR, 4.17, 95% CI, 1.95-8.92) or anti-anxiety agents (OR, 3.21; 95% CI, 1.34-7.47). CONCLUSIONS: The majority of risk factors for the 4 inflammatory and noninflammatory conditions of IPAA are different, suggesting that each of these diseases has a different etiology and pathogenesis. The identification and modification of these risk factors might help patients and clinicians to make a preoperative decision for IPAA, reduce IPAA-related morbidity, and improve response to treatment.