Ulcerative Colitis: Brzezinski A

Seidner DL, Lashner BA, Brzezinski A, Banks PL, Goldblum J, Fiocchi C, Katz J, Lichtenstein GR, Anton PA, Kam LY, Garleb KA, Demichele SJ. · Department of Gastroenterology\A30, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA. · Clin Gastroenterol Hepatol. · Pubmed #15822041 No free full text.

Abstract: BACKGROUND & AIMS: N-3 fatty acids from fish oil, antioxidants, and short-chain fatty acids (SCFAs) produced during the fermentation of soluble fiber may attenuate inflammation associated with ulcerative colitis (UC). We assessed the efficacy of a nutritionally balanced oral supplement enriched with fish oil, fructooligosaccharides, gum arabic, vitamin E, vitamin C, and selenium on disease activity and medication use in adults with mild to moderate UC. METHODS: A total of 121 patients with UC and a disease activity index (DAI) from 3-9 on a 12-point scale were block randomized for extent of disease and smoking status. In addition to their usual diet, patients consumed 18 oz of the oral supplement or a carbohydrate-based placebo formula each day for 6 months. Clinical and histologic responses were assessed at 3 and 6 months or at the final visit. A change in average prednisone use between groups was tested by using a linear mixed-effects model. RESULTS: Eighty-six patients completed the study. Baseline characteristics were not different between groups except for a higher total DAI score in the oral supplement group (7.3 +/- 1.3; n = 36) compared with the placebo group (6.2 +/- 2.0; n = 50) ( P < .05). Both groups showed significant and similar degree of improvement at 6 months in DAI (-2.5 for oral supplement and -2.8 for placebo) and histologic index (-1.9 for oral supplement vs. -2.0 for placebo). Both intent-to-treat and completed patients given oral supplement had a significantly greater rate of decrease in the dose of prednisone required to control clinical symptoms over 6 months as compared with the placebo group ( P < .001). CONCLUSIONS: The improvement in clinical response combined with a decreased requirement for corticosteroids suggest that this enriched oral supplement can be a useful adjuvant therapy in patients with UC.

Shen B, Lashner BA, Bennett AE, Remzi FH, Brzezinski A, Achkar JP, Bast J, Bambrick ML, Fazio VW. · Center for Inflammatory Bowel Disease, Departments of Gastroenterology/Hepatology, Anatomic Pathology, and Colorectal Surgery, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. · Am J Gastroenterol. · Pubmed #15307872 No free full text.

Abstract: BACKGROUND: Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the treatment of choice in the majority of patients with ulcerative colitis (UC) who require surgery. To ease the construction of the IPAA and improve functional outcome by minimizing sphincter related stretch injury, a stapling technique is being commonly used in the pouch-anal anastomosis. Despite its advantages, the procedure normally leaves a 1-2 cm of anal transitional zone or rectal cuff, which is susceptible to recurrence of residual UC or cuffitis. Cuffitis can cause symptoms mimicking pouchitis. AIM: To conduct an open-labeled trial of topical mesalamine in patients with cuffitis. METHODS: We treated 14 consecutive patients with cuffitis by giving mesalamine suppositories 500 mg b.i.d. (mean 3.2 months, range 1-9 months). The Cuffitis Activity Index (adapted from the Pouchitis Disease Activity Index) scores and improvement in symptoms of bloody bowel movements and arthralgias were measured as primary and secondary outcomes. RESULTS: All patients had surgery for medically refractory UC. There were significant reductions in the total Cuffitis Activity Index scores after the therapy (11.93 +/- 3.17 vs 6.21 +/- 3.19, p < 0.001). Symptom (3.24 +/- 1.28 vs 1.79 +/- 1.31), endoscopy (3.14 +/- 1.29 vs 1.00 +/- 1.52), and histology (4.93 +/- 1.77 vs 3.57 +/- 1.39) scores each were significantly reduced (p < 0.05). Ninety-two percent of patients with bloody bowel movements and 70% of patients with arthralgias improved after the therapy. No systemic or topical adverse effects were reported. CONCLUSION: Topical mesalamine appears well tolerated and effective in treating patients with cuffitis, with improvement in symptom as well as endoscopic and histologic inflammation.

Tremaine WJ, Brzezinski A, Katz JA, Wolf DC, Fleming TJ, Mordenti J, Strenkoski-Nix LC, Kurth MC, Anonymous00162. · Mayo Clinic, Rochester, MN 55905, USA. · Aliment Pharmacol Ther. · Pubmed #11876693 links to  free full text

Abstract: BACKGROUND: Mast cells isolated from the colonic mucosa in active ulcerative colitis appear to be partially degranulated, suggesting the release of tryptase. AIM: To investigate the safety and activity of APC 2059, a highly specific tryptase inhibitor, in the treatment of ulcerative colitis. METHODS: This was an open-label, Phase 2, multicentre pilot study in patients with mildly to moderately active ulcerative colitis, with a disease activity index of 6-9 on a 12-point scale. Fifty-six adults received 20 mg APC 2059 subcutaneously twice daily and 53 completed 28 days of treatment. The primary end-point was response, defined as a final disease activity index of < or = 3. Supplementary analyses were also performed. RESULTS: Sixteen (29%) of 56 patients responded. Five (9%) showed complete remission (disease activity index=0). Twenty-seven (49%) improved, with a final disease activity index of < or = 3 or a four-point reduction. Improvement or normalization in each category of the disease activity index was as follows: stool frequency, 64%; bleeding, 64%; endoscopy, 50%; physicians' rating, 63%. There were no significant relationships between outcome and pharmacokinetics. The most common adverse events were related to the injection site (32.1%). CONCLUSIONS: In this pilot study, the tryptase inhibitor APC 2059 was safe and there was evidence of activity in the treatment of ulcerative colitis.

Shen B, Achkar JP, Lashner BA, Ormsby AH, Remzi FH, Brzezinski A, Bevins CL, Bambrick ML, Seidner DL, Fazio VW. · Center for Inflammatory Bowel Disease, Department of Gastroenterology, The Cleveland Clinic Foundation, Ohio 44195, USA. · Inflamm Bowel Dis. · Pubmed #11720319 No free full text.

Abstract: Metronidazole is effective for the treatment of acute pouchitis after ileal pouch-anal anastomosis, but it has not been directly compared with other antibiotics. This randomized clinical trial was designed to compare the effectiveness and side effects of ciprofloxacin and metronidazole for treating acute pouchitis. Acute pouchitis was defined as a score of 7 or higher on the 18-point Pouchitis Disease Activity Index (PDAI) and symptom duration of 4 weeks or less. Sixteen patients were randomized to a 2-week course of ciprofloxacin 1,000 mg/d (n = 7) or metronidazole 20 mg/kg/d (n = 9). Clinical symptoms, endoscopic findings, and histologic features were assessed before and after therapy. Both ciprofloxacin and metronidazole produced a significant reduction in the total PDAI score as well as in the symptom, endoscopy, and histology subscores. Ciprofloxacin lowered the PDAI score from 10.1+/-2.3 to 3.3+/-1.7 (p = 0.0001), whereas metronidazole reduced the PDAI score from 9.7+/-2.3 to 5.8+/-1.7 (p = 0.0002). There was a significantly greater reduction in the ciprofloxacin group than in the metronidazole group in terms of the total PDAI (6.9+/-1.2 versus 3.8+/-1.7; p = 0.002), symptom score (2.4+/-0.9 versus 1.3+/-0.9; p = 0.03), and endoscopic score (3.6+/-1.3 versus 1.9+/-1.5; p = 0.03). None of patients in the ciprofloxacin group experienced adverse effects, whereas three patients in the metronidazole group (33%) developed vomiting, dysgeusia, or transient peripheral neuropathy. Both ciprofloxacin and metronidazole are effective in treating acute pouchitis with significant reduction of the PDAI scores. Ciprofloxacin produces a greater reduction in the PDAI and a greater improvement in symptom and endoscopy scores, and is better tolerated than metronidazole. Ciprofloxacin should be considered as one of the first-line therapies for acute pouchitis.

Shen B, Achkar JP, Lashner BA, Ormsby AH, Remzi FH, Bevins CL, Brzezinski A, Petras RE, Fazio VW. · Department of Gastroenterology, Center for Inflammatory Bowel Disease, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA. · Gastroenterology. · Pubmed #11487535 No free full text.

Abstract: BACKGROUND & AIMS: Pouchitis often is diagnosed based on symptoms alone. In this study, we evaluate whether symptoms correlate with endoscopic and histologic findings in patients with ulcerative colitis and an ileal pouch-anal anastomosis. METHODS: Symptoms, endoscopy, and histology were assessed in 46 patients using Pouchitis Disease Activity Index (PDAI). Patients were classified as either having pouchitis (PDAI score > or =7; N = 22) or as not having pouchitis (PDAI score <7; N = 24). RESULTS: Patients with pouchitis had significantly higher mean total PDAI scores, symptom scores, endoscopy scores, and histology scores. There was a similar magnitude of contribution of each component score to the total PDAI for the pouchitis group. Of note, 25% of patients with symptoms suggestive of pouchitis did not meet the PDAI diagnostic criteria for pouchitis. In both groups, the correlation coefficients between symptom, endoscopy, and histology scores were near zero (range, -0.26 to 0.20; P > 0.05). CONCLUSIONS: The symptom, endoscopy, and histology scores each contribute to the PDAI and appear to be independent of each other. Symptoms alone do not reliably diagnose pouchitis.

Shen B, Remzi FH, Oikonomou IK, Lu H, Lashner BA, Hammel JP, Skugor M, Bennett AE, Brzezinski A, Queener E, Fazio VW. · Pouchitis Clinic, Cleveland Clinic Foundation, Ohio 44195, USA. · Am J Gastroenterol. · Pubmed #19262520 No free full text.

Abstract: OBJECTIVES: Bone mineral density (BMD) can be adversely affected by the chronic nature of inflammatory bowel disease. Ileal pouch-anal anastomosis (IPAA) is the surgical treatment of choice for patients with ulcerative colitis (UC) who require proctocolectomy. There are few data on BMD in UC patients with IPAA. The aim of the study was to assess the prevalence and risk factors associated with low BMD in UC patients after IPAA. METHODS: A total of 327 eligible patients with UC and IPAA from the Pouchitis Clinic were enrolled. Dual-energy X-ray absorptiometry was performed. Patients were classified as having normal or low BMD, based on the criteria by the International Society for Clinical Densitometry. A total of 39 demographic and clinical variables were evaluated with logistic regression models. RESULTS: Of 327 patients with a median of 4 years after IPAA, 105 (32.1%) had low BMD. Fragility fracture was documented in 11 patients (10.5%) in the low BMD group and in 13 of 222 patients (5.9%) in the normal BMD group (P=0.14). In the multivariable analysis, covariate-adjusted factors associated with a low BMD were advanced age (odds ratio (OR) =1.64 per 5 years; 95% CI, 1.44-1.87), low body mass index (OR=0.43 per 5 kg/m(2); 95% CI, 0.30-0.62), and non-use of daily calcium supplement (OR=0.53; 95% CI, 0.29-0.96). Pouch-associated factors were not found to be significantly associated with the bone loss. CONCLUSIONS: Low BMD was common in patients with UC, even after colectomy and IPAA. Low BMD in this patient population was associated with certain risk factors, some of which may be modifiable.

Shen B, Remzi FH, Santisi J, Lashner BA, Brzezinski A, Fazio VW. · Department of Gastroenterology/Hepatology, Center for Inflammatory Bowel Disease, Cleveland Clinic, Cleveland, OH, USA. · J Clin Gastroenterol. · Pubmed #18360292 No free full text.

Abstract: 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.

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.

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.

Shen B, Fazio VW, Remzi FH, Delaney CP, Bennett AE, Achkar JP, Brzezinski A, Khandwala F, Liu W, Bambrick ML, Bast J, Lashner B. · Center for Inflammatory Bowel Disease, Departments of Gastroenterology/Hepatology, The Cleveland Clinic Foundation, Cleveland, Ohio. · Am J Gastroenterol. · Pubmed #15654787 No free full text.

Abstract: BACKGROUND AND AIMS: Ileal pouch-anal anastomosis (IPAA) improves quality of life (QOL) for ulcerative colitis patients who require surgery. Crohn's disease (CD) of the pouch, pouchitis, cuffitis, and irritable pouch syndrome (IPS) have an adverse impact on physical and psychological well-being, which can compromise the gain in QOL after the surgery. Their clinical, endoscopic, and histologic features have not been fully characterized. The aim of this study was to compare demographic, clinical, endoscopic, and histologic features between CD of the pouch, pouchitis, cuffitis, IPS, and normal pouches. METHODS We enrolled 124 patients: normal pouches (N = 26), CD of the pouch (N = 23), pouchitis (N = 22), cuffitis (N = 21), and IPS (N = 32). Symptomatology, endoscopy, histology, and the Cleveland Global QOL and the Irritable Bowel Syndrome-QOL scores were compared among the groups. RESULTS: Univariate analysis of demographic and clinical data showed a possible association between NSAID use and pouchitis, extraintestinal manifestation and cuffitis, and antidepressant use and IPS. There were no differences in the Pouchitis Disease Activity Index symptom scores between the disease groups, with an exception of bleeding, which occurred almost exclusively in cuffitis. Endoscopy was useful in discriminating between CD of the pouch, pouchitis, cuffitis, and normal pouches or IPS. Patients with diseased IPAA had worse QOL scores. CONCLUSIONS: Symptoms largely overlapped among the disease groups of IPAA. Endoscopy is valuable for diagnosis. Inflammatory or noninflammatory sequelae of IPAA adversely affected patients' QOL.

Achkar JP, Al-Haddad M, Lashner B, Remzi FH, Brzezinski A, Shen B, Khandwala F, Fazio V. · Department of Gastroenterology, Cleveland Clinic Foundation, 9500 Euclid Avenue, Desk A30, Cleveland, Ohio 44195, USA. · Clin Gastroenterol Hepatol. · Pubmed #15645406 No free full text.

Abstract: BACKGROUND & AIMS: Pouchitis is the most common complication of ileal pouch anal anastomosis in patients with ulcerative colitis. In some cases the inflammation becomes chronic and requires long-term medical therapy. The clinical course and medical therapy are different between acute pouchitis and chronic pouchitis. The aim of this study was to determine if there are predictors of risk for acute vs. chronic pouchitis. METHODS: Patients with acute pouchitis (N = 40) and patients with chronic pouchitis (N = 40) were matched with a control group who never had pouchitis (N = 40). Data were collected for multiple pre-, peri-, and postoperative factors and follow-up telephone calls were performed. Case-control univariable analyses and multivariate logistic regression were used to measure the association between covariates and pouchitis. Results: Multivariate logistic regression showed that extensive colonic disease (odds ratio [OR], 2.99; P = .045 for acute pouchitis; and OR, 4.61; P = .010 for chronic pouchitis) and extraintestinal manifestations (OR, 2.88; P = .037 for acute pouchitis; and OR, 2.69; P = .047 for chronic pouchitis) were associated with both acute and chronic pouchitis. Postoperative nonsteroidal anti-inflammatory drug (NSAID) use was associated with chronic pouchitis, but less so with acute pouchitis. Patients with fulminant colitis as an indication for surgery had a decreased risk for developing chronic pouchitis (OR, 0.22; P = .036), but no such association was seen for acute pouchitis. CONCLUSIONS: Extensive colonic disease and preoperative extraintestinal manifestations are associated with increased risk for both acute and chronic pouchitis. Fulminant colitis leading to colectomy is protective from development of chronic pouchitis. Postoperative use of NSAIDS is a risk factor for chronic pouchitis and possibly for acute pouchitis, and thus should be discouraged for patients who undergo ileal pouch anal anastomosis.

Shen B, Fazio VW, Remzi FH, Delaney CP, Achkar JP, Bennett A, Khandwala F, Brzezinski A, Doumit J, Liu W, Lashner BA. · Department of Gastroenterology/Hepatology, Center for Inflammatory Bowel Disease, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. · Am J Gastroenterol. · Pubmed #15571580 No free full text.

Abstract: BACKGROUND: Restorative proctocolectomy with ileal pouch-anal anastomosis is the surgical treatment of choice in patients with ulcerative colitis. Strictures can occur at the inlet and outlet of the pouch. Endoscopic balloon dilation has been successfully used in patients with Crohn's strictures at the small intestine and colon. There are no published trials on endoscopic balloon therapy of ileal pouch strictures. AIM: To evaluate outpatient endoscopic balloon dilation of strictures in ileal pouches. METHODS: Patients underwent nonfluoroscopy-guided, nonsedated, outpatient endoscopic dilations with an 8.6-mm upper endoscope and through-the-scope balloons (size: 11-18 mm). Pre- and posttreatment Pouchitis Disease Activity Index symptom scores (range: 0-6), endoscopic stricture scores based on resistance in passing the endoscope (range: 0-4), and Cleveland Global Quality of Life were compared. RESULTS: Nineteen patients with pouch strictures who had concurrent Crohn's disease of the pouch (n = 11), cuffitis (n = 5), and pouchitis (n = 3), including 14 inlet and 14 outlet strictures, were enrolled. The mean number of strictures for each patient was 1.61 +/- 0.78. All strictures were successfully dilated with the through-the-scope balloon, with a mean of 1.74 +/- 1.19 (range: 1-5) sessions for each patient. Nine patients had a second endoscopy at 8 wk and five patients had a third pouch endoscopy at 16 wk after the initial endoscopic dilation. Endoscopic stricture scores immediately (0.30 +/- 0.47), 8 wk (0.40 +/- 0.51), and 16 wk (0.44 +/- 0.76) after the dilation were significantly improved compared to the predilation stricture scores (2.67 +/- 0.78). The symptom scores and quality-of-life (QOL) scores improved at week 8 and 16 following dilation, with a mean follow-up of 6.10 +/- 5.83 months (2-25 months). No complications were experienced with the procedure. One patient with CD who failed endoscopic and medical therapy underwent pouch resection. CONCLUSION: In conjunction with medical therapy, outpatient endoscopic balloon dilation appears safe and effective in treating pouch inlet and outlet strictures, by relieving symptoms, restoring pouch patency, and improving QOL in the majority of patients.

Shen B, Achkar JP, Connor JT, Ormsby AH, Remzi FH, Bevins CL, Brzezinski A, Bambrick ML, Fazio VW, Lashner BA. · Center for Inflammatory Bowel Disease, Cleveland, Ohio, USA. · Dis Colon Rectum. · Pubmed #12794576 No free full text.

Abstract: PURPOSE: Pouchitis is the most common complication of ileal pouch-anal anastomosis for ulcerative colitis. Our previous study suggested that symptoms alone are not reliable for the diagnosis of pouchitis. The most commonly used diagnostic instrument is the 18-point pouchitis disease activity index consisting of three principal component scores: symptom, endoscopy, and histology. Despite its popularity, the pouchitis disease activity index has mainly been a research tool because of costs of endoscopy (especially with histology), complexity in calculation, and time delay in determining histology scores. It is not known whether pouch endoscopy without biopsy can reliably diagnose pouchitis in symptomatic patients. The aim of the present study was to determine whether omitting histologic evaluation from the pouchitis disease activity index significantly affects the sensitivity and specificity of diagnostic criteria for pouchitis. METHODS: Ulcerative colitis patients with an ileal pouch-anal anastomosis and symptoms suggestive of pouchitis were evaluated. Patients with chronic refractory pouchitis and Crohn's disease were excluded. Patients with pouchitis disease activity index scores of seven or more were diagnosed as having pouchitis. Different diagnostic criteria were compared on the basis of the pouchitis disease activity index component scores. Nonparametric receiver-operating-characteristic curves were used to measure proposed pouchitis scores' diagnostic accuracy compared with diagnosis from the pouchitis disease activity index. The receiver-operating-characteristic area under the curve measured how much these diagnostic strategies differed from each other. RESULTS: Fifty-eight consecutive symptomatic patients were enrolled; 32 (55 percent) patients were diagnosed with pouchitis. With the use of the pouchitis disease activity index as a criterion standard, the use of only symptom and endoscopy scores (modified pouchitis disease activity index) produced an area under the curve of 0.995. Establishing a cut-point of five or more for diseased patients resulted in a sensitivity equal to 97 percent and specificity equal to 100 percent. CONCLUSIONS: Diagnosis based on the modified pouchitis disease activity index offers similar sensitivity and specificity when compared with the pouchitis disease activity index for patients with acute or acute relapsing pouchitis. Omission of endoscopic biopsy and histology from the standard pouchitis disease activity index would simplify pouchitis diagnostic criteria, reduce the cost of diagnosis, and avoid delay associated with determining histology score, while providing equivalent sensitivity and specificity.

Shen B, Achkar JP, Lashner BA, Ormsby AH, Brzezinski A, Soffer EE, Remzi FH, Bevins CL, Fazio VW. · Department of Gastroenterology, The Cleveland Clinic Foundation, Ohio 44195, USA. · Am J Gastroenterol. · Pubmed #12003434 No free full text.

Abstract: OBJECTIVE: Pouchitis often is diagnosed based on symptoms alone. However, increased stool frequency, urgency, and abdominal pain could be due to a condition resembling irritable bowel syndrome. This study was designed to assess the etiology of bowel symptoms using the Pouchitis Disease Activity Index (PDAI). METHODS: Symptoms, endoscopy, and histology were assessed in 61 consecutive symptomatic patients with ulcerative colitis after ileal pouch-anal anastomosis. Pouchitis was defined as a PDAI score of > or = 7, cuffitis was defined as endoscopic and histological inflammation of the rectal cuff and no inflammation of the pouch, and irritable pouch syndrome (IPS) was defined as symptoms with a PDAI of <7 and the absence of cuffitis. RESULTS: Thirty-one patients (50.8%) had pouchitis, four (6.5%) had cuffitis, and 26 (42.6%) had IPS. Demographics were similar in the three groups. Increased stool frequency, urgency, and abdominal cramps were the most common symptoms in the three groups. Rectal bleeding was seen only in cuffitis (p < 0.001). No patient in the three groups had fever. Twenty-seven patients (87.1%) with pouchitis responded to a 2-wk course of ciprofloxacin or metronidazole with a reduction in PDAI scores of > or = 3. All four patients with cuffitis responded to topical hydrocortisone or mesalamine with a reduction in the PDAI symptom component score of > or = 1. Twelve patients with IPS (46.2%) responded to antidiarrheal, anticholinergic, and/or antidepressant therapies with a reduction in the PDAI symptom component score of > or = 1, whereas the remaining patients had persistent symptoms despite therapy. CONCLUSIONS: A substantial number of symptomatic patients after ileal pouch-anal anastomosis do not meet the diagnostic criteria for either pouchitis or cuffitis and have been classified as having IPS. There is an overlap of symptoms among patients with pouchitis, cuffitis, and IPS, and endoscopic evaluation can differentiate among these groups. Distinction between these three groups has therapeutic implications.

Shetty K, Rybicki L, Brzezinski A, Carey WD, Lashner BA. · Center for Inflammatory Bowel Disease, Department of Gastroenterology, Cleveland Clinic Foundation, Ohio 44195, USA. · Am J Gastroenterol. · Pubmed #10364038 No free full text.

Abstract: OBJECTIVES: Recent studies have implicated primary sclerosing cholangitis (PSC) as a risk factor for colorectal cancer (CRC) in ulcerative colitis (UC). Our study was designed to define both the risk and the risk factors for CRC or dysplasia in a large UC cohort with PSC. METHODS: Patients with UC and PSC were compared with a random sample of UC controls without PSC. Patients were analyzed from the inception of disease until an outcome or censor. RESULTS: Thirty-three (25%) of 132 UC patients with PSC developed CRC or dysplasia compared with 11 (5.6%) of 196 controls (adjusted relative risk 3.15, 95% confidence interval 1.37-7.27). Possible risk factors were chronic disease activity and lack of folate supplementation. Of 17 CRCs in the PSC group, 76% occurred proximal to the splenic flexure and 35% presented at an advanced stage, compared with one of five (20%) CRCs in controls being proximal and none being advanced. Six (4.5%) PSC patients, and no controls, died of CRC (p < 0.01). CONCLUSIONS: UC patients with PSC are at increased risk of developing CRC or dysplasia. Chronically active disease may be a risk factor, whereas folate could have a protective effect. CRCs associated with PSC are more likely to be proximal, to be diagnosed at a more advanced stage, and to be fatal.