A Distinct Colon-Derived Breath Metabolome is Associated with Inflammatory Bowel Disease, but not its Complications.

OBJECTIVES: The accuracy of available noninvasive biomarkers for diagnosis, stratification, and prediction of inflammatory bowel disease (IBD) courses is limited. We analyzed volatile organic compounds (VOCs) in the breath of IBD patients and controls for diagnosis and differentiation of IBD as well as their link with disease location, activity, and phenotype. METHODS: A prospective study of diagnostic testing was conducted, recruiting Crohn's disease (CD), ulcerative colitis (UC), other inflammatory gastrointestinal diseases (OGDs), and healthy controls (HCs), as well as subjects with ileal pouch anal anastomosis (IPAA). The breath VOC profile was analyzed using selective ion flow tube-mass spectrometry. RESULTS: One hundred and twenty-four subjects (n=24 CD, n=11 UC, n=6 OGD, n=53 HC, n=30 IPAA) were included. The breath metabolome was significantly different in patients with IBD, CD, or UC compared with OGD and HC (7 out of 22 VOCs), but not between CD and UC. No link between the level of VOCs with complications, disease location, and clinical or radiologic disease activity, as well as lab parameters or type of medication was found. Breath VOCs were markedly different in patients with IPAA compared with any other group (17 out of 22 VOCs) and the presence of pouch inflammation did not alter the VOC levels. CONCLUSIONS: A specific breath metabolome is associated with IBD and markedly changes in patients with IPAA. Analysis of a broader spectrum of VOCs can potentially aid in the development of breath prints to diagnose or differentiate inflammatory bowel disorders.

Impact of Low Immunoglobulin G Levels on Disease Outcomes in Patients with Inflammatory Bowel Diseases.

BACKGROUND: Inflammatory bowel diseases (IBDs) are considered immune-mediated disorders with dysregulated innate and adaptive immunities. Secondary immunogloblin deficiency can occur in IBD and its impact on the disease course of IBD is not clear. AIMS: We sought to determine associations between low IgG/G1 levels and poor clinical outcomes in IBD patients. METHODS: This historic cohort study was performed on IBD patients with obtained IgG/IgG1 levels. The primary outcome was defined as any IBD-related bowel resection surgery and/or hospitalization. Subgroup analyses assessed particular surgical outcomes in Crohn's disease (CD), ulcerative colitis (UC) or indeterminate colitis (IC), and ileal pouch-anal anastomosis (IPAA). The secondary outcomes included IBD drug escalations and C. difficile or cytomegalovirus infections. RESULTS: A total of 136 IBD patients had IgG/G1 levels checked and adequate follow-up, 58 (42.6 %) with normal IgG/G1 levels and 78 (57.4 %) having low levels. A total of 49 patients (62.8 %) with low immunoglobulin levels had IBD-related surgeries or hospitalizations, compared to 33 patients (56.9 %) with normal levels [odds ratio (OR) 1.28, 95 % confidence interval (CI) 0.64-2.56; p = 0.49]. Low IgG/G1 levels were associated with IBD-related surgery in CD in univariate analysis [hazard ratio (HR) 4.42, 95 % CI 1.02-19.23; p = 0.048] and in Kaplan-Meier survival curve analysis (p = 0.03), with a trend toward significance on multivariate analysis (HR 3.07, 95 % CI 0.67-14.31; p = 0.15). IBD patients with low IgG/G1 levels required more small bowel resections (12.8 vs. 1.7 %, p = 0.024) and 5-aminosalicylate initiations (28.2 vs. 13.8 %, p = 0.045). CONCLUSIONS: Our study demonstrated a possible association between low IgG/G1 levels and poor outcomes in CD including surgery. Future implications include using immunoglobulin levels in IBD patients as a prognostic indicator or boosting humoral immunity as a treatment in this subset.

Severe adverse outcomes of endoscopic perforations in patients with and without IBD.

BACKGROUND: Endoscopy-associated perforation (EAP) is a dreaded adverse event with significant morbidity and even mortality. Whether EAP in patients with inflammatory bowel disease (IBD) is associated with worse outcomes is not known. We aimed to assess the frequency of perforations in patients undergoing lower gastrointestinal (GI) endoscopies and compare the risk factors and perforation-associated complications (PAC) in patients with IBD with those without IBD. METHODS: In this case-control study, we identified patients with lower GI EAP from January 2002 to June 2011. PAC was defined as EAP-associated death, colectomy with ileostomy, and bowel resection with/without diverting ostomy. Twenty-nine demographic, clinical, endoscopic, and surgical features were evaluated in univariable and multivariable analyses. RESULTS: A total of 217,334 lower GI endoscopies were performed (IBD, N = 9518 and non-IBD, N = 207,816). Eighty-four patients with EAP were included. The rate of perforation was 18.91 per 10,000 and 2.50 per 10,000 procedures for IBD and non-IBD endoscopy, respectively. PAC occurred in 59 patients (70.2%) with death in 4 (4.8%) and bowel resection with or without ostomy in 55 (65.5%) (total colectomy with ileostomy, n = 3; resection with diversion and secondary anastomosis, n = 28; and resection with primary anastomosis, n = 24). On multivariable analysis, the use of systemic corticosteroids at the time of endoscopy was associated with 13 times greater risk for PAC (13.5 [95% confidence interval, 1.3-1839.7] P = 0.007), whereas IBD was not found to be associated with an increased risk for PAC (0.69 [95% confidence interval, 0.23-2.1] P = 0.52). CONCLUSIONS: Patients with IBD have a higher frequency of EAP than those without IBD. Endoscopists need to be cautious while performing a lower GI endoscopy in patients taking systemic corticosteroids.

Safety and efficacy of endoscopic dilation for primary and anastomotic Crohn's disease strictures.

BACKGROUND: Literature on endoscopic dilation of Crohn's disease (CD) strictures, especially for primary (non-anastomotic) strictures is limited. METHODS: A historical cohort study was performed on patients who underwent endoscopic stricture dilations for CD in our IBD center. Primary endpoint was the efficacy of first endoscopic dilation in preventing the need for surgery in primary strictures compared to anastomotic strictures. Cox proportional hazards models using robust sandwich covariance matrix estimate were used to evaluate the need for surgery and any further endoscopic intervention. RESULTS: In our study cohort (mean age 42.2 ± 13.1 years, 57% females, 16.4% current smokers, and median follow-up 1.8 years), 128 patients underwent a total of 430 endoscopic stricture dilations for 169 strictures (88 primary, 81 secondary). Forty-two patients (32.8%) required surgery in the follow-up period, with a mean interval period between first dilation and surgery of 33 months. There was no difference between primary or anastomotic strictures with respect to the need for surgery (34.1% vs. 29.6%, p=0.53), redilation (59.1% vs. 58%, p=0.89) or total interventions (surgery+redilations, 71.6% vs. 72.8%, p=0.86). Multivariable analysis did not show any significant difference between patients who received and did not receive intralesional steroid injections, biologics or immunomodulators with respect to the need for repeat intervention or surgery. CONCLUSION: Efficacy and safety of endoscopic dilation are similar between primary and anastomotic CD strictures. Intralesional steroid injection or use of biologics did not decrease the need for re-intervention or surgery for either primary or anastomotic strictures.

Frequency and risk factors of renal insufficiency in inflammatory bowel disease inpatients.

BACKGROUND: Renal involvement in patients with inflammatory bowel disease (IBD) has been well documented. However, there was a paucity of data on the frequency of renal insufficiency and its risk factors in this patient population. The aim of the study was to determine the frequency and factors associated with renal insufficiency within IBD inpatients. METHODS: This case-control study was conducted on both Crohn's disease and ulcerative colitis inpatients in our tertiary care center from 2009 to 2010. Patients were identified as having renal insufficiency by the criterion of glomerular filtration rate < 60 mL/min/1.73 m. The glomerular filtration rate was further assessed against normal reference ranges. Risk factors for renal insufficiency were evaluated by univariable and multivariable analyses. RESULTS: A total of 251 eligible patients were included. The frequency of renal insufficiency was 15.9% (95% confidence interval: 11.4-20.5), with 40 patients having a glomerular filtration rate <60 mL/min/1.73 m. Univariable analysis demonstrated several possible risk factors, including older age at admission (42.0 ± 16.2 years versus 57.6 ± 13.3 years, P < 0.001), and a longer median duration of IBD (9.0 years [interquartile range: 3.5-20.0] versus 25.0 years [interquartile range: 15.0-36.0], P < 0.001). The multivariable logistic analysis demonstrated that for every 5-year increase in age at the time of admission, the likelihood of having renal insufficiency increased by 30%. CONCLUSION: Acute or chronic renal sufficiency in IBD inpatients was common, especially in elderly. Acute renal insufficiency can be medically reversed if properly treated. We recommend that renal function be closely monitored in IBD inpatients.

Similar outcomes of IBD inpatients with Clostridium difficile infection detected by ELISA or PCR assay.

BACKGROUND: Clostridium difficile infection (CDI) is known as a risk factor for exacerbation of inflammatory bowel disease (IBD). CDI has been most commonly tested with enzyme-linked immunosorbent assay for toxins, but with a suboptimal sensitivity. Compared with conventional ELISA, the polymerase chain reaction-based assay (PCR) is a highly sensitive detection technique for C. difficile. However, its pure detection of only the DNA of toxin B may lead to over-treatment. AIMS: The purpose of this study was to compare the frequency and clinical outcomes of IBD inpatients with CDI between the PCR and ELISA assays and to assess the factors associated with CDI. METHODS: The retrospective study was performed with the IBD inpatients at Cleveland Clinic from 2009 to 2011, who were tested by either ELISA or PCR or both. Outcomes under comparison included intensive care unit transfer, length of hospital stay, requirement for gastrointestinal surgeries and all cause re-hospitalization. Multivariable analysis was performed to assess the associated factors for the combined cohorts. RESULTS: A total of 255 patients were included, among them 222 had ELISA test, and 103 had PCR test. Thirteen (5.9 %) patients were ELISA positive, versus 14 (13.5 %) patients who were PCR positive (P = 0.02). With comparable demographic and clinical background, clinical outcomes of the ELISA and PCR positive groups showed no significant difference. Instead, the overall percentage of C. difficile positive patients had a much higher rehospitalization rate than C. difficile negative patients (P < 0.01). Multivariable analysis identified comorbidities (P = 0.03), extra-intestinal manifestations (P = 0.03) and PPI use (P < 0.01) as the associated factors for CDI. CONCLUSION: There was a greater percentage of patients tested positive by PCR compared to ELISA. The outcomes of CDI diagnosed by PCR or ELISA, however, appeared comparable. The presence of comorbidities, extra-intestinal manifestations, and the use of PPI were found to be associated with CDI.

Manometric evaluation of evacuatory difficulty (dyschezia) in ileal pouch patients.

BACKGROUND: Dyschezia occurs in patients with ileal pouch-anal anastomosis. There are limited data on the mechanisms of this condition. We hypothesized that paradoxical contractions may contribute to dyschezia in those patients with mechanical or inflammatory pouch conditions. This study was aimed to evaluate the underlying manometric abnormalities in this population. METHODS: In this retrospective analysis, we screened our Pouchitis Registry for patients with dyschezia and underlying inflammatory bowel disease. Patients having undergone anopouch manometry were considered eligible and included. Patients without inflammatory or structural diseases of the pouch (the functional pouch disorder [FPD] group) were compared with those with inflammatory or structural diseases (the inflammatory/structural pouch disorder [ISPD] group). Demographic, clinical, manometric, and laboratory variables were analyzed. RESULTS: A total of 45 patients were included; of which, 21 (46.7%) were female. The median age of patients in the FPD group (n = 10) and ISPD group (n = 35) were 41 (interquartile range =32.5-56) years and 40 (interquartile range = 28-49) years, respectively (P = 0.469). There were no differences in the demographic, clinical, and laboratory variables between the 2 groups, with the exception of the modified Pouch Disease Activity Index. For manometric evaluations, paradoxical contractions and failure of balloon expulsion occurred in 50.0% and 60.0%, respectively, of the FPD group and in 17.1% and 20.0%, respectively, of the ISPD group (P = 0.048 and 0.043, respectively). CONCLUSIONS: In this cohort, manometric evaluation demonstrated that paradoxical contractions occurred more frequently in patients with FPD than in those with inflammatory/structural conditions. This suggests that the underlying physiologic mechanisms of dyschezia in these patients differ.

Risk factors for low bone mass in patients with ulcerative colitis following ileal pouch-anal anastomosis.

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.

Association between immune-associated disorders and adverse outcomes of ileal pouch-anal anastomosis.

OBJECTIVES: Autoimmune disorders (ADs) frequently coexist with inflammatory bowel disease. The aim of the study was to determine whether coexisting AD in patients with ileal pouches increases the risk for chronic antibiotic-refractory pouchitis (CARP) and other inflammatory conditions of the pouch. METHODS: A total of 622 patients seen in our Pouchitis Clinic were enrolled. We compared the prevalence of adverse outcomes of the pouch (including CARP, Crohn's disease of the pouch, and pouch failure) in patients with or without concurrent AD and assessed the factors for these adverse outcomes. RESULTS: There were seven pouch disease categories: normal (N=60), irritable pouch syndrome (N=112), active pouchitis (N=131), CARP (N=67), Crohn's disease (N=131), cuffitis (N=83), surgical complications (N=36), and anismus (N=2). The prevalence of AD in these pouch disease categories was 4.5%, 12.5%, 9.2%, 13.4%, 10.7%, 3.8%, 1.5%, and 0%, respectively. The presence of at least one AD at time of pouch surgery was shown to be associated with a twofold increase in the risk for CARP (hazard ratio=2.29; 95% CI: 1.52, 3.46; P<0.001) and for pouch-associated hospitalization (hazard ratio=2.39; 95% CI: 1.59, 3.58; P<0.001). The presence of AD was not associated with increased risk for irritable pouch syndrome, active pouchitis, Crohn's disease, cuffitis, surgical complications, or pouch failure. Patients with Crohn's disease of the pouch had a 2.42 times higher risk for pouch failure (P=0.042) than these without. Active smoking or a history of smoking was shown to be associated with an increased risk for pouch-associated hospitalization and pouch failure. CONCLUSIONS: AD appears to be associated with an increased risk for CARP, and the presence of the association between these AD and pouch disorders may stimulate further research on the link of these organ systems on an immunological basis.

Use of infliximab within 3 months of ileocolonic resection is associated with adverse postoperative outcomes in Crohn's patients.

BACKGROUND: Few studies have evaluated preoperative infliximab use and postoperative outcomes in Crohn's patients. Our aim was to evaluate 30-day postoperative outcomes for Crohn's patients treated with infliximab within 3 months prior to ileocolonic resection. METHODS: The study is a retrospective evaluation of data for patients undergoing ileocolonic resection after 1998 from a prospective Crohn's disease database. Patient characteristics and 30-day complications were compared for patients treated with infliximab within 3 months before surgery and an infliximab naïve group. The infliximab group was also compared with non-infliximab patients undergoing ileocolonic surgery before 1998. RESULTS: Sixty of 389 Crohn's patients undergoing ileocolonic resection received infliximab. The infliximab and non-infliximab groups had similar characteristics, preoperative risk factors, and surgical procedure. However, steroid use was higher (p < 0.05) in the non-infliximab group while concurrent immunosuppressive use was higher (p < 0.001) in the infliximab group. Multivariate analysis showed infliximab use to be associated with 30-day postoperative readmission (p = 0.045), sepsis (p = 0.027), and intraabdominal abscess (p = 0.005). The presence of diverting stoma (n = 17) in the infliximab group was associated with lower risk of sepsis (0% vs. 27.9%, p = 0.013). Similar results were noted when the infliximab group was compared to the pre-infliximab patients. CONCLUSIONS: Infliximab use within 3 months before surgery is associated with increased postoperative sepsis, abscess, and readmissions in Crohn's patients. Diverting stoma may protect against these complications.

Application of wireless capsule endoscopy for the evaluation of iron deficiency anemia in patients with ileal pouches.

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.

Risk factors for pouch failure in patients with different phenotypes of Crohn's disease of the pouch.

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.

Effect of withdrawal of nonsteroidal anti-inflammatory drug use on ileal pouch disorders.

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.

Combined ciprofloxacin and tinidazole therapy in the treatment of chronic refractory pouchitis.

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

Risk factors for diseases of ileal pouch-anal anastomosis after restorative proctocolectomy for ulcerative colitis.

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.

Risk factors for clinical phenotypes of Crohn's disease of the ileal pouch.

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.

An oral supplement enriched with fish oil, soluble fiber, and antioxidants for corticosteroid sparing in ulcerative colitis: a randomized, controlled trial.

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.

Differentiating risk factors for acute and chronic pouchitis.

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.

Comprehensive evaluation of inflammatory and noninflammatory sequelae of ileal pouch-anal anastomoses.

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.