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Background: Ulcerative colitis patients who undergo ileal pouch-anal anastomosis (IPAA) without mucosectomy may develop inflammation of the rectal cuff (cuffitis). Treatment of cuffitis typically includes mesalamine suppositories or corticosteroids, but refractory cuffitis may necessitate advanced therapies or procedural interventions. This review aims to summarize the existing literature regarding treatments options for cuffitis., Methods: A broad search strategy was created by a medical librarian to capture cuffitis in IPAA patients. A total of 1877 citations were identified, and 957 studies remained after removal of 920 duplicates. Two reviewers screened all 957 abstracts and 294 full-text articles to determine if they were eligible for inclusion in this review., Results: Twenty-three studies met the inclusion criteria. Medical interventions were investigated in 16 studies with mesalamine and corticosteroid regimens being the most common, followed by ustekinumab, vedolizumab, hyperbaric oxygen, tofacitinib, risankizumab, and infliximab. Studies investigating mesalamine and corticosteroid use generally had larger samples (ranging 4-120 patients) and showed symptomatic improvement in 52-100% of patients and decreases of 1.14-1.8 points in endoscopic disease activity indices. In contrast, advanced therapy studies had small samples (ranging 1-21 patients) and variable responses. Seven studies explored endoscopic and surgical approaches including secondary mucosectomy, cuff resection, needle-knife therapy, and balloon dilation for concomitant outlet strictures. These techniques generally resulted in symptomatic resolution but were limited by small samples (ranging 3-40 patients)., Conclusion: Studies evaluating therapies used to treat cuffitis suggest benefit from conventional mesalamine or corticosteroid-based therapies, whereas data regarding advanced therapies and interventional procedures are inconsistent given small sample sizes., Competing Interests: Declarations. Conflict of interest: JCP received grant funding from the Crohn’s and Colitis Foundation through the Student Research Fellowship Award. KF received a grant from the Crohn’s and Colitis Foundation and from Pfizer and has served on a GI fellows steering committee for Janssen. BC reports personal fees from AbbVie, Bristol Myers Squibb, Takeda, Lilly, and Target RWE and grants and personal fees from Pfizer. TQ reports consulting and advisory board service for AbbVie, Bristol Myers Squibb, Celgene, Janssen, and Prometheus. ED, MS, BL, TH, and AII have no disclosures to report., (© 2025. The Author(s).)

Gastrointestinal immune-related adverse events (GI irAEs) are common manifestations of immune checkpoint inhibitor (ICI) toxicity. We present a comprehensive systematic review of the incidence, management, and clinical course of irAEs across the entire GI system, including the luminal GI tract, liver, and pancreas. MEDLINE, Embase, Web of Science Core Collection, and Cochrane Library were used to conduct this review. All studies pertaining to GI irAEs were included. Both abstracts and full manuscripts were eligible if they included human subjects and were written in the English language. Articles not available in English, animal studies, or research not specific to GI toxicity of immunotherapy were excluded. We excluded certain article types depending on whether stronger evidence was available in the literature for a specific toxicity, for example, if prospective studies were available on a topic, retrospective studies and case reports were excluded. We extracted a final 166 articles for our review and followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for data reporting. Risk of bias tools were not used to evaluate the extracted studies given the narrative nature of this manuscript, but each study was critically appraised by the manuscript writer. We detail the incidence, presentation, evaluation, management, and outcomes of the various GI toxicities that may arise with ICI therapy. Specifically, we discuss the characteristics of upper GI toxicity (esophagitis and gastroenteritis), lower GI toxicity (colitis), hepatobiliary inflammation, pancreatitis, and rarer forms of GI toxicity. We hope this review serves as a useful and accessible clinical tool that helps physicians familiarize themselves with the nuances of gastrointestinal/hepatic/pancreatic ICI toxicity diagnosis and management., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Recurrent Clostridioides difficile infection (rCDI) often occurs after standard-of-care antibiotics. VOWST oral spores (VOS, previously SER-109), an FDA-approved orally administered microbiome therapeutic, is indicated to prevent rCDI following antibiotics for rCDI., Objective, Design, and Patients: To evaluate safety and efficacy of VOS from two phase 3 trials, (randomized, placebo-controlled [ECOSPOR III: NCT03183128] and open-label, single arm [ECOSPOR IV: NCT03183141]) of 349 adults with rCDI and prevalent comorbidities., Methods: VOS or placebo [ECOSPOR III only] (4 capsules once daily for 3 days). Integrated analysis of treatment-emergent adverse events (TEAEs) collected through week 8; serious TEAEs and TEAEs of special interest collected through week 24; and rates of rCDI (toxin-positive diarrhea requiring treatment) evaluated through weeks 8 and 24., Results: TEAEs were mostly mild or moderate and gastrointestinal. Most common treatment-related TEAEs were flatulence, abdominal pain and distension, fatigue, and diarrhea. There were 11 deaths (3.2%) and 48 patients (13.8%) with serious TEAEs, none treatment-related. The rCDI rate through week 8 was 9.5% (95% CI 6.6-13.0) and remained low through 24 weeks (15.2%; 95% CI 11.6-19.4). Safety and rCDI rates were consistent across subgroups including age, renal impairment/failure, diabetes, and immunocompromise/immunosuppression., Conclusions: VOS was well tolerated and rates of rCDI remained low through week 24 including in those with comorbidities. These data support the potential benefit of VOS following antibiotics to prevent recurrence in high-risk patients., Trial Registration: ClinicalTrials.gov identifier, NCT03183128 and NCT03183141., (© 2024. The Author(s).)

Background: Patients with inflammatory bowel disease (IBD) are at higher risk for severe COVID-19 infection. However, most studies are single-center, and nationwide data in the United States are lacking. This study aimed to investigate hospital-related outcomes and predictors of these outcomes in patients with IBD and COVID-19 infection., Methods: The National Inpatient Sample and National Readmission database were queried for all the patient hospitalizations with IBD with concurrent COVID-19 in the study group and non-COVID-19 related hospitalizations in the control group. For patients under 18 years, elective and trauma-related hospitalizations were excluded. Primary outcomes included mortality, septic shock, mechanical ventilation, and intensive care utilization. Secondary outcomes included length of stay and total hospitalization costs., Results: From this query, 8865 adult patients with IBD and COVID-19 were identified. These patients were relatively older (62.8 vs 57.7 years, P < .01), and the majority were females (52.1% with COVID-19 vs 55.2% without COVID-19). Patients with IBD and COVID-19 had higher mortality (12.24% vs 2.55%; P < .01), increased incidence of septic shock (7.9% vs 4.4%; P < .01), mechanical ventilation (11.5% vs 3.7%; P < .01), and intensive care utilization (12% vs 4.6%; P < .01). These patients also had higher mean length of stay (8.28 days vs 5.47 days; P < .01) and total hospitalization costs ($21 390 vs $16 468; P < .01) than those without COVID-19 infection., Conclusions: Patients with IBD and COVID-19 have worse outcomes, with a higher incidence of severe COVID-19 disease, leading to higher mortality rates, longer lengths of stay, and increased total hospitalization costs. Encouraging preventive health measures and treating promptly with advanced COVID-19 therapies may improve outcomes and decrease the healthcare burden., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Although comorbidities are risk factors for recurrent Clostridioides difficile infection (rCDI), many clinical trials exclude patients with medical conditions such as malignancy or immunosuppression. In a phase 3, double-blind, placebo-controlled, randomized trial (ECOSPOR III), fecal microbiota spores, live (VOWST, Seres Therapeutics; hereafter "VOS," formerly SER-109), an oral microbiota therapeutic, significantly reduced the risk of rCDI at week 8. We evaluated the efficacy of VOS compared with placebo in patients with comorbidities and other risk factors for rCDI., Methods: Adults with rCDI were randomized to receive VOS or placebo (4 capsules daily for 3 days) following standard-of-care antibiotics. In this post hoc analysis, the rate of rCDI through week 8 was assessed in VOS-treated participants compared with placebo for subgroups including (i) Charlson comorbidity index (CCI) score category (0, 1-2, 3-4, ≥5); (ii) baseline creatinine clearance (<30, 30-50, >50 to 80, or >80 mL/minute); (iii) number of CDI episodes, inclusive of the qualifying episode (3 and ≥4); (iv) exposure to non-CDI-targeted antibiotics after dosing; and (v) acid-suppressing medication use at baseline., Results: Of 281 participants screened, 182 were randomized (59.9% female; mean age, 65.5 years). Comorbidities were common with a mean overall baseline age-adjusted CCI score of 4.1 (4.1 in the VOS arm and 4.2 in the placebo arm). Across all subgroups analyzed, VOS-treated participants had a lower relative risk of recurrence compared with placebo., Conclusions: In this post hoc analysis, VOS reduced the risk of rCDI compared with placebo, regardless of baseline characteristics, concomitant medications, or comorbidities., Competing Interests: Potential conflicts of interest. E. H. reports receiving institutional grants from Seres and Tend/MicrobiomeX during the conduct of the study; travel support and honoraria from GI Health Foundation; and personal fees from Gilead Sciences, Kowa Pharmaceuticals America, AGA, and UpToDate, unrelated to the submitted work. T. J. L. reports receiving grants per case funding for clinical trials from Finch Therapeutics, Summit PLC, Rebiotix/Ferring, Vedanta Biosciences, Crestone, Adiso/Artugen, Seres Therapeutics, and MGB Biopharma; payment for an advisory meeting with Summit and Seres Therapeutics after completing the clinical trial work; participation on a data and safety monitoring or advisory board for Vedanta Biosciences; and consulting fees from MGB Biopharma. M. S. reports receiving grants as a primary or secondary investigator for clinical trials from Adaptive Phage Therapeutics, BioTest AG, Novozyme, Pfizer, Janssen Research and Development, Genentech Inc, Diasorin Molecular, Shire, Kinevant, Regeneron Pharmaceuticals, Finch, OpGen, Summit Therapeutics, Epigenomics, Merck and Co, Prenosis, Leonard-Meron Biosciences, AstraZeneca, Contrafect, Qiagen Sciences, and Crestone, outside the submitted work; consulting fees from OpGen and Applied Biocode (paid to institution); travel support from Seres; patent application for diagnosing increased risk of methicillin-resistant Staphylococcus aureus (#61/779,307); participation on advisory boards for Prenosis and Venatorx (contracted through institution); board membership for the Michigan Infectious Diseases Society; and receipt of equipment to conduct investigator-initiated research from OpGen. C. O. reports payment for serving on speaker's bureaus for Ferring, AbbVie, BMS, Pfizer, and Salix and having research collaborations with Rebiotix, Seres Therapeutics, AbbVie, Salix, Intercept, Exact Sciences, Janssen, and Vedanta, outside the submitted work. C. L. reports receiving grants from Rebiotix, Seres, Merck, and Summit Therapeutics and serving on the advisory board at Rebiotix, outside the submitted work. A. Deshpande is a consultant for Merck and has received research funding from the Clorox Company and Seres Therapeutics. D. P. reports receiving research grants from Seres Therapeutics, Vedanta, Finch, Takeda, Applied Molecular Transport, and Rise Therapeutics; consultant fees for Seres Therapeutics, Vedanta, Immunic Therapeutics, AbbVie, Otsuka, Ferring, Rise Therapeutics, Boehringer Ingelheim Pharmaceuticals, Phathom Pharmaceuticals, Rebiotix Therapeutics, et al Scientific, Eli Lily, Live biotherapeutics products, Ohealio Medical, and Summit (all paid to institution except for Boehringer Ingelheim); institutional payment for lectures or presentations from Scholars in Medicine; and travel support from GI Reconnect. P. F. reports consultant fees from Merck and Co, Seres Therapeutics, Takeda Pharmaceuticals, Ferring Pharmaceuticals, Sanofi Pharmaceuticals, Regeneron Pharmaceuticals, and Summit Therapeutics; payment or honoraria for serving on speaker’s bureaus for Seres Therapeutics and Ferring Pharmaceuticals; and participation on consulting/advisory boards for Seres Therapeutics, Ferring/Rebiotix, Sanofi, and Takeda Pharmaceuticals. C. K. reports grants or contracts from the Centers for Disease Control and Prevention, consulting fees from Rebiotix/Ferring; travel support as President of the American Society for Microbiology; and serving on scientific advisory boards for Seres Therapeutics and Rebiotix/Ferring. C. S. B. reports a Veterans Affairs–funded Merit Review Grant. C. S. B., L. K., B. L., and B. M. were study investigators. E. E. L. W., B. R. H., A. De, A. M., D. A. L., and L. v. M. all report being shareholders at Seres Therapeutics during the conduct of the study or receiving personal fees from Seres Therapeutics during the conduct of the study and outside the submitted work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Studies report favorable efficacy and safety profiles of ustekinumab (UST) and vedolizumab (VDZ) in Crohn's disease (CD), but effectiveness and safety data in elderly patients with CD is lacking. We retrospectively analyzed 78 elderly patients (39 each UST and VDZ) and found that patients on UST and VDZ experienced similar rates of clinical response, remission and mucosal healing despite high proportion of prior biologic exposure. Both UST and VDZ appear to be effective and safe in this at-risk CD population. Further large studies are needed to validate our findings., (© 2023. Indian Society of Gastroenterology.)

Importance: A safe and effective treatment for recurrent Clostridioides difficile infection (CDI) is urgently needed. Antibiotics kill toxin-producing bacteria but do not repair the disrupted microbiome, which promotes spore germination and infection recurrence., Objectives: To evaluate the safety and rate of CDI recurrence after administration of investigational microbiome therapeutic SER-109 through 24 weeks., Design, Setting, and Participants: This phase 3, single-arm, open-label trial (ECOSPOR IV) was conducted at 72 US and Canadian outpatient sites from October 2017 to April 2022. Adults aged 18 years or older with recurrent CDI were enrolled in 2 cohorts: (1) rollover patients from the ECOSPOR III trial who had CDI recurrence diagnosed by toxin enzyme immunoassay (EIA) and (2) patients with at least 1 CDI recurrence (diagnosed by polymerase chain reaction [PCR] or toxin EIA), inclusive of their acute infection at study entry., Interventions: SER-109 given orally as 4 capsules daily for 3 days following symptom resolution after antibiotic treatment for CDI., Main Outcomes and Measures: The main outcomes were safety, measured as the rate of treatment-emergent adverse events (TEAEs) in all patients receiving any amount of SER-109, and cumulative rates of recurrent CDI (toxin-positive diarrhea requiring treatment) through week 24 in the intent-to-treat population., Results: Of 351 patients screened, 263 were enrolled (180 [68.4%] female; mean [SD] age, 64.0 [15.7] years); 29 were in cohort 1 and 234 in cohort 2. Seventy-seven patients (29.3%) were enrolled with their first CDI recurrence. Overall, 141 patients (53.6%) had TEAEs, which were mostly mild to moderate and gastrointestinal. There were 8 deaths (3.0%) and 33 patients (12.5%) with serious TEAEs; none were considered treatment related by the investigators. Overall, 23 patients (8.7%; 95% CI, 5.6%-12.8%) had recurrent CDI at week 8 (4 of 29 [13.8%; 95% CI, 3.9%-31.7%] in cohort 1 and 19 of 234 [8.1%; 95% CI, 5.0%-12.4%] in cohort 2), and recurrent CDI rates remained low through 24 weeks (36 patients [13.7%; 95% CI, 9.8%-18.4%]). At week 8, recurrent CDI rates in patients with a first recurrence were similarly low (5 of 77 [6.5%; 95% CI, 2.1%-14.5%]) as in patients with 2 or more recurrences (18 of 186 [9.7%; 95% CI, 5.8%-14.9%]). Analyses by select baseline characteristics showed consistently low recurrent CDI rates in patients younger than 65 years vs 65 years or older (5 of 126 [4.0%; 95% CI, 1.3%-9.0%] vs 18 of 137 [13.1%; 95% CI, 8.0%-20.0%]) and patients enrolled based on positive PCR results (3 of 69 [4.3%; 95% CI, 0.9%-12.2%]) vs those with positive toxin EIA results (20 of 192 [10.4%; 95% CI, 6.5%-15.6%])., Conclusions and Relevance: In this trial, oral SER-109 was well tolerated in a patient population with recurrent CDI and prevalent comorbidities. The rate of recurrent CDI was low regardless of the number of prior recurrences, demographics, or diagnostic approach, supporting the beneficial impact of SER-109 for patients with CDI., Trial Registration: ClinicalTrials.gov identifier: NCT03183141.

Background: Postoperative recurrence [POR] of Crohn's disease following ileocolonic resection is common. The impact of immediate postoperative intra-abdominal septic complications [IASC] on endoscopic and surgical recurrence has not been elucidated., Aims: To evaluate if IASC is associated with an increased risk for endoscopic and surgical POR., Methods: This was a retrospective study of adult Crohn's disease patients undergoing ileocolonic resection with primary anastomosis between 2009 and 2020. IASC was defined as anastomotic leak or intra-abdominal abscess within 90 days of the date of surgery. Multivariable logistic and Cox proportional hazard modelling were performed to assess the impact of IASC on endoscopic POR [modified Rutgeerts' score ≥ i2b] at index postoperative ileocolonoscopy and long-term surgical recurrence., Results: In 535 Crohn's disease patients [median age 35 years, 22.1% active smokers, 35.7% one or more prior resection] had an ileocolonic resection with primary anastomosis. A minority of patients [N = 47; 8.8%] developed postoperative IASC. In total, 422 [78.9%] patients had one or more postoperative ileocolonoscopies, of whom 163 [38.6%] developed endoscopic POR. After adjusting for other risk factors for postoperative recurrence, postoperative IASC was associated with significantly greater odds (adjusted odds ratio [aOR]: 2.45 [1.23-4.97]; p = 0.01) and decreased time (adjusted hazards ratio [aHR]: 1.60 [1.04-2.45]; p = 0.03] to endoscopic POR. Furthermore, IASC was associated with increased risk (aOR: 2.3 [1.04-4.87] p = 0.03) and decreased survival-free time [aHR: 2.53 [1.31-4.87]; p = 0.006] for surgical recurrence., Conclusion: IASC is associated with an increased risk for endoscopic and surgical POR of Crohn's disease. Preoperative optimization to prevent IASC, in addition to postoperative biological prophylaxis, may help reduce the risk for endoscopic and surgical POR., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background & Aims: Postoperative Crohn's disease (CD) surveillance relies on endoscopic monitoring. The role of cross-sectional imaging is less clear. We evaluated the concordance of cross-sectional enterography with endoscopic recurrence and the predictive ability of radiography for future CD postoperative recurrence., Methods: We performed a multi-institution retrospective cohort study of postoperative adult patients with CD who underwent ileocolonoscopy and cross-sectional enterography within 90 days of each other following ileocecal resection. Imaging studies were interpreted by blinded, expert CD radiologists. Patients were categorized by presence of endoscopic postoperative recurrence (E+) (modified Rutgeerts' score ≥i2b) or radiographic disease activity (R+) and grouped by concordance status., Results: A total of 216 patients with CD with paired ileocolonoscopy and imaging were included. A majority (54.2%) exhibited concordance (34.7% E+/R+; 19.4% E-/R-) between studies. The plurality (41.7%; n = 90) were E-/R+ discordant. Imaging was highly sensitive (89.3%), with low specificity (31.8%), in detecting endoscopic postoperative recurrence. Intestinal wall thickening, luminal narrowing, mural hyper-enhancement, and length of disease on imaging were associated with endoscopic recurrence (all P &lt; .01). Radiographic disease severity was associated with increasing Rutgeerts' score (P &lt; .001). E-/R+ patients experienced more rapid subsequent endoscopic recurrence (hazard ratio, 4.16; P = .033) and increased rates of subsequent endoscopic (43.8% vs 22.7%) and surgical recurrence (20% vs 9.5%) than E-/R- patients (median follow-up, 4.5 years)., Conclusions: Cross-sectional imaging is highly sensitive, but poorly specific, in detecting endoscopic disease activity and postoperative recurrence. Advanced radiographic disease correlates with endoscopic severity. Patients with radiographic activity in the absence of endoscopic recurrence may be at increased risk for future recurrence, and closer monitoring should be considered., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Introduction: The efficacy and safety profile of ustekinumab (UST) in Crohn's disease (CD) is favorable; however, data in elderly patients are lacking. We aimed to assess the safety and efficacy of UST in elderly CD., Methods: We performed a retrospective cohort study of CD patients classified as elderly (age ≥ 65 years at UST initiation) or nonelderly (<65 years) treated at a large, tertiary referral center. Outcomes assessed were clinical (measured by physician global assessment [PGA]) and steroid-free response, remission, adverse events, and postsurgical complications were compared by age category. Multivariable regression modeling and survival analysis was also performed., Results: In total, 117 patients (elderly n = 39, nonelderly n = 78) were included in the study. Elderly patients had predominantly moderate disease (87.2%), while nonelderly had a higher proportion of severe disease activity (44.9%) (p = 0.001), though no differences in baseline endoscopic activity, prior biologic use, or steroid or immunomodulator use at baseline existed (p > 0.05 all). While nearly 90% patients in both groups experienced clinical response to UST, compared to nonelderly, elderly patients were less likely to achieve complete clinical remission (28.2% vs. 52.6%, p = 0.01). On regression modeling, age was not associated with clinical outcomes (p > 0.05 all). Mucosal healing was achieved in 26% elderly and 30% nonelderly patients (p = 0.74). There were no significant differences in infusion reactions (2.6% vs. 6.4%, p = 0.77), infection (5.2% vs. 7.7%, p = 0.7), or postsurgical complications (p = 0.99) by age category., Conclusion: UST is safe and effective in elderly CD. Although limited by sample size and retrospective design, such real-world data can inform biologic positioning in this IBD population., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

There are conflicting data assessing the impact of isolated post-operative anastomotic inflammation on future disease progression. The aim of this study was to determine the relative risk of severe disease progression in post-operative Crohn's disease (CD) patients with isolated anastomotic disease., Methods: Retrospective cohort study of adult CD patients undergoing ileocolonic resection between 2009 and 2020. Patients with a post-operative ileocolonoscopy ≤18 months from surgery and ≥1 subsequent ileocolonoscopy were included. Disease activity was assessed using the modified Rutgeerts' score (RS). Primary outcome was severe endoscopic progression, defined as i3 or i4 disease, on immediate subsequent ileocolonoscopy and during entire post-operative follow-up. Secondary outcome was surgical recurrence., Results: One hundred and ninety-nine CD patients had an ileocolonoscopy ≤18 months from surgery, index RS of i0-i2b and ≥1 subsequent ileocolonoscopy. At index ileocolonoscopy, 34.7% had i0 disease, 16.1% i1, 24.6% i2a and 24.6% i2b. On multivariable logistic regression, i2b disease was associated with severe endoscopic progression compared to i0 or i1 (aOR 5.53; P < 0.001) and i2a disease patients (aOR 2.63; P = 0.03). However, i2a disease did not confer increased risk compared to i0 or i1 disease (P = 0.09). Furthermore, i2b patients experienced severe endoscopic progression significantly earlier than i0 or i1 disease (aHR 4.68; P < 0.001), whereas i2a disease did not differ from i0 or i1 disease (P = 0.25). Surgical recurrence was not associated with index RS i0-i2b (P = 0.86)., Conclusion: Post-operative ileal disease recurrence, not isolated anastomotic inflammation, confers increased risk for severe endoscopic disease progression. Location of CD recurrence may impact optimal management strategies., (© 2022 John Wiley & Sons Ltd.)

Background: Current therapies for recurrent Clostridioides difficile infection do not address the disrupted microbiome, which supports C. difficile spore germination into toxin-producing bacteria. SER-109 is an investigational microbiome therapeutic composed of purified Firmicutes spores for the treatment of recurrent C. difficile infection., Methods: We conducted a phase 3, double-blind, randomized, placebo-controlled trial in which patients who had had three or more episodes of C. difficile infection (inclusive of the qualifying acute episode) received SER-109 or placebo (four capsules daily for 3 days) after standard-of-care antibiotic treatment. The primary efficacy objective was to show superiority of SER-109 as compared with placebo in reducing the risk of C. difficile infection recurrence up to 8 weeks after treatment. Diagnosis by toxin testing was performed at trial entry, and randomization was stratified according to age and antibiotic agent received. Analyses of safety, microbiome engraftment, and metabolites were also performed., Results: Among the 281 patients screened, 182 were enrolled. The percentage of patients with recurrence of C. difficile infection was 12% in the SER-109 group and 40% in the placebo group (relative risk, 0.32; 95% confidence interval [CI], 0.18 to 0.58; P<0.001 for a relative risk of <1.0; P<0.001 for a relative risk of <0.833). SER-109 led to less frequent recurrence than placebo in analyses stratified according to age stratum (relative risk, 0.24 [95% CI, 0.07 to 0.78] for patients <65 years of age and 0.36 [95% CI, 0.18 to 0.72] for those ≥65 years) and antibiotic received (relative risk, 0.41 [95% CI, 0.22 to 0.79] with vancomycin and 0.09 [95% CI, 0.01 to 0.63] with fidaxomicin). Most adverse events were mild to moderate and were gastrointestinal in nature, with similar numbers in the two groups. SER-109 dose species were detected as early as week 1 and were associated with bile-acid profiles that are known to inhibit C. difficile spore germination., Conclusions: In patients with symptom resolution of C. difficile infection after treatment with standard-of-care antibiotics, oral administration of SER-109 was superior to placebo in reducing the risk of recurrent infection. The observed safety profile of SER-109 was similar to that of placebo. (Funded by Seres Therapeutics; ECOSPOR III ClinicalTrials.gov number, NCT03183128.)., (Copyright © 2022 Massachusetts Medical Society.)

The burden of inflammatory bowel disease (IBD) is increasing globally and imposes a high morbidity in patients with IBD. Advances have been made in medical management of IBD with the advent of novel therapies such as the biologics and small molecule drugs (SMDs). However, response to these medications is limited; with only 40% of patients achieving clinical remission at 1 year with a biologic. Hence, medical management of IBD is a rapidly evolving paradigm in which not only are new medications being developed but understanding how, when and in whom to use them is evolving. Dual targeted therapy (DTT), which is the combination of biologics and/or SMDs is an attractive concept as it is theoretically a potent and multidimensional anti-inflammatory treatment strategy. In this review, we present the published literature on the use of DTT and highlight its utility in clinical practice. The majority of studies on DTT are case reports and case series on the combination of dual biologic therapy. From the limited evidence available in patients with IBD, dual biologic therapy may be a safe option for patients with refractory IBD who have failed multiple biologic therapies and to manage extraintestinal manifestation of IBD. There are a handful of reports of combination therapy with a biologic and a SMD in patients with IBD. Further studies and randomized control trials are required to comprehensivretain hereely evaluate the safety and efficacy of DTT in IBD., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Gastrointestinal (GI) symptoms are seen in patients with COVID-19. The prevalence could be as high as 50%, but most studies show ranges from 16% to 33%. Presenting with GI symptoms increases the risk of testing positive for SARs-CoV-2. Approximately 50% of patients with COVID-19 have detectable virus in their stool. Having GI symptoms has been associated with more severe disease. Management of GI symptoms is mainly supportive. Healthcare providers should be aware of the GI manifestations of COVID-19 and perform SARS-CoV-2 testing for patients presenting with digestive changes, especially in those with respiratory symptoms., (Copyright © 2021 The Cleveland Clinic Foundation. All Rights Reserved.)

Small bowel transplant is an acceptable procedure for intractable Crohn's disease (CD). Some case reports and small series describe the apparent recurrence of CD in the transplanted bowel. This commentary discusses evidence in favor of and against this alleged recurrence and argues that a molecular characterization is needed to prove or disprove that inflammation emerging in the transplanted bowel is a true recurrence of the original CD., (© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Current treatment guidelines for immune-mediated colitis (IMC) recommend 4 to 6 weeks of steroids as first-line therapy, followed by selective immunosuppressive therapy (SIT) (infliximab or vedolizumab) in patients who do not respond to steroids. We assessed the effect of early SIT introduction and number of SIT infusions on clinical outcomes., Methods: We performed a retrospective review of patients with IMC who received SIT at The University of Texas MD Anderson Cancer Center between January and December 2018. Logistic regression analyses were used to assess associations between clinical outcomes and features of IMC., Results: Of the 1459 patients who received immune checkpoint inhibitors, 179 developed IMC of any grade; 84 of these 179 patients received SIT. Of the 84 patients who received SIT, 79% were males, and the mean age was 60 years (standard deviation, 14). Compared with patients who received SIT > 10 days after IMC onset, patients who received early SIT (≤10 days) required fewer hospitalizations (P = 0.03), experienced steroid taper failure less frequently (P = 0.03), had fewer steroid tapering attempts (P < 0.01), had a shorter course of steroid treatment (P = 0.09), and had a shorter duration of symptoms (P < 0.01). Patients who received one or two infusions of SIT achieved histologic remission less frequently (P = 0.09) and had higher fecal calprotectin levels after SIT (P = 0.01) compared with patients who received three or more infusions. Risk factors for IMC recurrence after weaning off steroids included: 1) needing multiple hospitalizations, 2) experiencing steroid taper failure after SIT, 3) receiving infliximab rather than vedolizumab, 4) receiving fewer than three infusions of SIT, 5) having higher fecal calprotectin levels after SIT, and 6) receiving a longer course of steroids, hospitalization and IMC symptoms. Unsuccessful weaning from steroids after SIT was associated with high IMC grades; multiple hospitalizations; steroid-resistant IMC; long interval from IMC to SIT initiation; and long duration of steroids, IMC symptoms, and hospitalization., Conclusion: SIT should be introduced early in the disease course of IMC instead of waiting until failure of steroid therapy or steroid taper. Patients who received three or more infusions of SIT had more favorable clinical outcomes.

Background: The frequency of cytomegalovirus (CMV) colitis in steroid-refractory inflammatory bowel disease has been reported to range from 15.8% to 34.0%. Infected patients are more likely to become hospitalized, have longer lengths of stay, and higher mortality rates. Current data are limited to small scale studies and showed conflicting result regarding the role of antiviral therapy., Aims: (1) To investigate the role of antiviral treatment in ulcerative colitis (UC) patients with CMV infection. (2) To investigate the role of viremia in the outcomes of these patients., Materials and Methods: The Cleveland Clinic pathology database identified 1478 patients who had colon biopsy and were tested for CMV during 1990 to 2013. After inclusion and exclusion, 41 UC patients were selected. Among them, 24 (58.5%) received treatment, 17 (41.5%) did not. A total of 14 demographic data and 4 clinical outcomes (surgery free survival, hospitalization, rehospitalization, and mortality) were compared between treated and nontreated patients. The same outcomes were also compared in patients who received treatment based on their viremia status., Results: All demographic variables are similar between those treated and nontreated groups. Antiviral therapy significantly improved the surgery free survival within 30 days, and lasted 70 months (P<0.01). In contrast, hospitalization, rehospitalization, and mortality were comparable (P>0.05). No significant difference was observed in any of the clinical outcomes based on viremia status., Conclusions: Our small scale study demonstrates that antiviral treatment for colonic CMV infection significantly improves the surgery free survival short-term and long-term in patients with UC.

The presence of concomitant primary sclerosing cholangitis (PSC) with inflammatory bowel disease (IBD) represents a distinct disease phenotype that carries a higher risk of colorectal cancer (CRC) than the average IBD patient. Given that liver transplantation (LT) is the only treatment that offers a survival benefit in PSC patients with hepatic dysfunction, management decisions in IBD patients' post-LT for PSC are frequently encountered. One such consideration is the risk of CRC in this immunosuppressed cohort. With most studies showing an increased risk of CRC post-LT in these IBD patients, a closer look at the associated risk factors of CRC and the adopted surveillance strategies in this subset of patients is warranted. Low-dose ursodeoxycholic acid has shown a potential chemopreventive effect in PSC-IBD patients pre-LT; however, a favorable effect remains to be seen in post-LT group. Also, further studies are necessary to assess the benefit of 5 aminosalicylate therapy. Annual surveillance colonoscopy in the post-LT period is recommended for PSC-IBD patients subset given their high risk for CRC., (© 2018 Crohn’s & Colitis Foundation of America. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Gastric and duodenal Crohn's disease [CD]-associated strictures are rare. Evidence on endoscopic balloon dilation [EBD] of upper gastrointestinal [GI] CD strictures is limited, in particular in respect to serial dilations., Methods: Prospective short- and long-term outcome data as well as complication rates on a cohort of upper GI CD-associated stricture dilations [stomach and duodenum] were collected from 1999 to 2015. Factors linked with clinical and technical success, long-term efficacy and complication rates were investigated., Results: A total of 35 CD patients with symptomatic CD-associated upper GI strictures [20% gastric, 67% duodenal, 11% both; mean age at diagnosis 25 years; mean CD duration to stricture 79.9 months; median post-dilation follow-up 22.1 months] underwent a total of 96 pneumatic dilations [33 gastric and 63 duodenal]. The median maximal dilation diameter was 15 mm. Technical success was achieved in 93% and clinical success in 87%, with a complication rate of 4% per procedure. The mean time to re-dilation was 2.2 months and mean time to stricture-related surgery after first dilation was 2.8 months. There was no difference in short-term efficacy, safety, or long-term outcome between the first and any later dilation procedure in the same patient., Conclusions: Pneumatic dilation of upper GI CD-associated strictures has a high rate of short-term technical and clinical success, with moderate long-term efficacy and acceptable complication rates. Serial dilations do not change the efficacy and could be a feasible option to delay or prevent surgical intervention., (Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com)

Opinion Statement: Inflammatory bowel disease (IBD) is comprised of complex clinical and pathological conditions. It runs a chronic course, and proper management requires constant monitoring of disease activity. Recent evidence suggests that subjective patient scores have a poor correlation with disease activity. Endoscopy remains the gold standard for diagnosing and monitoring disease activity. As healthcare is moving towards less costly and less invasive treatments, the need for biomarkers in the management of IBD is evident. Over the last decade, several biomarkers have been found, which may correct the discrepancy between subjective patient scores and the need for endoscopy.

Objectives: We aimed to identify the frequency and costs of, and the disease predictors and inpatient process issues that may predispose to, 30-day readmission for an inflammatory bowel disease (IBD) patient., Methods: IBD patients admitted to an inpatient gastroenterology service were followed for a time-to-readmission analysis assessing factors associated with readmission within 30 days., Results: Index admissions were more costly among those readmitted than among those not readmitted. Patients admitted with evidence of increased inflammation, infection, or obstruction or for dehydration or pain control had a higher risk of readmission. Patients treated with opioid analgesia during index admission were no less likely to be readmitted, and there was a 2.2-fold increase in readmissions when patients were discharged with no opioid analgesia. Scheduling variability and outpatient follow-up compliance were associated with readmission., Conclusions: Predicting readmission is complex. A predictive model developed to be used at discharge yielded an area under the curve of 0.757.

Background: Intensifying infliximab therapy is often practiced in Crohn's disease (CD) patients losing response to the drug but there are no data if halving the interval is superior to doubling the dose. We aimed to assess the efficacy of infliximab dose intensification by interval-halving compared with dose-doubling., Methods: A multicenter retrospective study of CD patients losing response to infliximab was undertaken. The clinical outcome of patients whose infusion intervals were halved (5 mg/kg/4 weeks) was compared with patients treated by dose-doubling (10 mg/kg/8 weeks)., Results: In all, 168 patients were included from 18 centers in Europe, USA, and Israel. Of these, 112 were intensified by dose-doubling and 56 received interval-halving strategy. Early response to dose-escalation was experienced by 86/112 (77%) patients in the dose-doubling group compared with 37/56 patients (66%) in the interval-halving group (odds ratio [OR] 1.7, 95% confidence interval [CI] 0.8-3.4, P = 0.14). Sustained clinical response at 12 months postescalation was maintained in 50% of patients in the dose-doubling group compared with 39% in the interval-halving group (OR 1.5, 95% CI 0.8-2.9, P = 0.2). On multivariate analysis, predictors of long-term response to escalation were a nonsmoking status, CD diagnosis between 16-40 years of age, and normal C-reactive protein (CRP)., Conclusions: Dose intensification leads to a sustained regained response in 47% of CD patients who lost response to standard infliximab dose, but halving the infusion intervals is probably not superior to dose-doubling. Given the costs and patient inconvenience incurred by an additional infusion visit, the dose-doubling strategy may be preferable to the interval-halving strategy., (Copyright © 2012 Crohn's & Colitis Foundation of America, Inc.)

Chronic inflammatory diseases, depending upon the duration and severity, are frequently associated with an increased risk of developing cancer. A classic paradigm is the enhanced risk of colorectal cancer (CRC) in patients with inflammatory bowel disease (IBD). Carcinogenesis is a multifactorial process that involves accumulation of genetic defects, protein modification, and cell-matrix interaction. In this review, we discuss aspects of chronic inflammation in IBD that influence the development of CRC and highlight the key molecular mediators involved in this process. Also, we identify potential targets that could facilitate earlier detection of dysplasia. The targeted manipulation of specific molecules or pathways could provide opportunities for the development of therapeutic and chemopreventive interventions, which may prove effective in arresting the progression of colitis-associated cancer (CAC), with clinical implications.

The advent of biological therapy has revolutionized inflammatory bowel disease (IBD) care. Nonetheless, not all patients require biological therapy. Selection of patients depends on clinical characteristics, previous response to other medical therapy, and comorbid conditions. Availability, reimbursement guidelines, and patient preferences guide the choice of first-line biological therapy for luminal Crohn's disease (CD). Infliximab (IFX) has the most extensive clinical trial data, but other biological agents (adalimumab (ADA), certolizumab pegol (CZP), and natalizumab (NAT)) appear to have similar benefits in CD. Steroid-refractory, steroid-dependent, or complex fistulizing CD are indications for starting biological therapy, after surgical drainage of any sepsis. For fistulizing CD, the efficacy of IFX for inducing fistula closure is best documented. Unique risks of NAT account for its labeling as a second-line biological agent in some countries. Patients who respond to induction therapy benefit from systematic re-treatment. The combination of IFX with azathioprine is better than monotherapy for induction of remission and mucosal healing up to 1 year in patients who are naïve to both agents. Whether this applies to other agents remains unknown. IFX is also effective for treatment-refractory, moderate, or severely active ulcerative colitis. Patients who have a diminished or loss of response to anti-tumor necrosis factor (TNF) therapy may respond to dose adjustment of the same agent or switching to another agent. Careful consideration should be given to the reasons for loss of response. There are insufficient data to make recommendations on when to stop anti-TNF therapy. Preliminary evidence suggests that a substantial proportion of patients in clinical remission for >1 year, without signs of active inflammation can remain in remission after stopping treatment.

For many years, cancer surveillance colonoscopy in ulcerative colitis patients has involved obtaining at least 30 biopsies of flat and abnormal-appearing mucosa. With the advent of better imaging techniques, biopsies can be better targeted to abnormal-appearing mucosa, thereby increasing the sensitivity of testing. Use of chromoendoscopy, narrow-band imaging, autofluorescence, or confocal endomicroscopy to target biopsies is likely to improve detection of dysplasia and identification of patients at high risk for developing cancer.

Background & Aims: The practice of dosing mesalamines in divided doses for the treatment of ulcerative colitis (UC) began with sulfasalazine and was driven by sulfapyridine toxicity. This convention and the assumption that dosing multiple times a day is necessary to treat UC had not been challenged until recently. This study was conducted to determine the efficacy and safety of once-daily dosing of delayed-release mesalamine (Asacol 400-mg tablets) compared with twice-daily dosing for maintaining remission in UC patients., Methods: A multicenter, randomized, investigator-blinded, 12-month, active-control trial was conducted to assess the noninferiority of delayed-release mesalamine 1.6-2.4 g/day administered once daily compared with twice daily in patients with mild-to-moderate UC currently in clinical remission. The primary end point was maintenance of clinical remission at month 6., Results: A total of 1023 patients were randomized and dosed. The primary objective of noninferiority was met. At month 6, 90.5% of patients receiving once-daily dosing had maintained clinical remission, compared with 91.8% of patients receiving twice-daily dosing (95% confidence interval for twice daily - once daily, -2.3 to 4.9). At month 12, 85.4% of patients receiving once-daily dosing had maintained clinical remission, compared with 85.4% of patients receiving twice-daily dosing (95% confidence interval for twice daily - once daily, -4.6 to 4.7). Both regimens had low rates of withdrawals as a result of adverse events and serious adverse events., Conclusions: Once-daily dosing of delayed-release mesalamine at doses of 1.6-2.4 g/day was shown to be as effective as twice-daily dosing for maintenance of clinical remission in patients with UC., (2010 AGA Institute. Published by Elsevier Inc. All rights reserved.)

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.

Aim: There is limited information on the nutrition impact of antitumor necrosis factor-alpha treatment in adult Crohn's disease (CD). This study was performed to examine the effect of a 6-month course of infliximab on enterocyte function, nutrient status, metabolism, and body composition in these patients., Methods: Seven CD patients were assessed for disease activity, enterocyte function, and body composition prior to, after 6 weeks, and after 6 months of infliximab treatment. Measurements included (1) disease activity: Inflammatory Bowel Disease Questionnaire, Harvey Bradshaw Index, and C-reactive protein; (2) enterocyte function: folate, homocysteine, vitamin B(12), citrulline, vitamin D, beta-carotene, d-xylose absorption; (3) Prognostic Inflammatory and Nutritional Index (PINI); and (4) body composition and metabolism: body mass index (BMI), fat and lean body mass, resting energy expenditure (RRE), and respiratory quotient., Results: Most patients had improvement in disease activity with infliximab. PINI decreased in all patients (-3.35, P = .04). Plasma folate concentration significantly increased. There was an increase in BMI, fat mass, and lean body mass. The respiratory quotient increased in most patients. Changes in citrulline level and REE were inconsistent., Conclusions: Crohn's disease patients have improvements in an index that measures both inflammation and nutrition (PINI) with infliximab therapy. Increases in plasma folate suggest improvement in enterocyte function and/or increased oral intake. The increase in respiratory quotient suggests decreased lipolysis and the lack of a starvation state. It was unclear whether weight gain was predominantly fat or lean muscle mass. These finding also support the use of PINI in Crohn's patients as an overall marker of inflammation and nutrition, and as a measure of response to infliximab therapy.

Background & Aims: Thiazolidinedione ligands for the gamma subtype of peroxisome proliferator-activated receptors (PPARgamma), widely used to treat type 2 diabetes mellitus, have been proposed as novel therapies for ulcerative colitis (UC)., Methods: This multicenter, randomized, double-blind, placebo-controlled clinical trial compared the efficacy of rosiglitazone (Avandia; GlaxoSmithKline, Philadelphia, PA) 4 mg orally twice daily vs placebo twice daily for 12 weeks in 105 patients with mild to moderately active UC. Disease activity was measured with the Mayo score. The primary end point was clinical response (>/=2-point reduction) at week 12. Clinical remission (Mayo score

When patients with inflammatory bowel disease (IBD) are admitted to the hospital with a flare of acute severe colitis, the possibility of a concurrent cytomegalovirus (CMV) infection causing or worsening the colitis is often considered. IBD patients are usually immunosuppressed, and therefore presumably at increased risk for active CMV infection and disease. Multiple techniques are used to diagnose CMV infection, including endoscopy, histology, serology, viral culture, CMV antigen testing, and CMV DNA testing. Immunohistochemistry (IHC) performed on colon biopsy specimens with monoclonal antibodies directed against CMV immediate early antigen is considered by most to be the current gold standard for diagnosis. The prevalence of CMV infection in acute severe colitis appears to be 21-34%, and the prevalence of CMV infection in the steroid refractory subgroup of these patients is 33-36%. After antiviral therapy, colitis remission rates in IBD patients with CMV infection range from 67% to 100%, though CMV histological infection or the presence of circulating virus alone is not always associated with steroid resistance, and may not require antiviral therapy.

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.

Collagenous colitis is characterised by watery diarrhoea, normal colonic mucosa on endoscopy, diffuse colitis with surface epithelial injury, and a distinctive thickening of the subepithelial collagen table on histology. Some patients can develop medically refractory collagenous colitis, in which case they may require surgical intervention. This is the first report of collagenous pouchitis in a collagenous colitis patient with proctocolectomy and ileal pouch-anal anastomosis. A patient with medically refractory collagenous colitis who underwent a total proctocolectomy and ileal pouch-anal anastomosis was sequentially evaluated with an endoscopy and histology of the colon, distal small intestine, and ileal pouch. A 58-year-old female had a 10-year history of collagenous colitis before having a total proctocolectomy and ileal pouch-anal anastomosis for medically refractory disease. The histologic features of collagenous colitis were present in all colon and rectum biopsy or resection specimens, but were absent in the distal ileum specimen. The post-operative course was complicated by persistent increase of stool frequency, abdominal cramps, and incontinence. A pouch endoscopy was performed 3 years after ileal pouch-anal anastomosis which showed the histologic features of collagenous colitis in the ileal pouch, collagenous pouchitis, while the pre-pouch neo-terminal ileum had no pathologic changes. After antibiotic therapy, the histologic changes of collagenous pouchitis resolved. This is the first reported case of collagenous pouchitis. Since the abnormal collagen table and its associated features were only present in the pouch and absent in the neo-terminal ileum, and the patient had histologic improvement after antibiotic therapy, it would suggest that faecal stasis and bacterial load may play a role in the pathogenesis.

Ileal pouch-anal anastomosis (IPAA) after total proctocolectomy is the surgical treatment of choice for ulcerative colitis (UC) patients with medically refractory disease or dysplasia. IPAA significantly improves quality of life in UC patients who require surgery. However, certain inflammatory and noninflammatory diseases can develop after the surgery, including pouchitis, Crohn's disease (CD) of the pouch, cuffitis, and irritable pouch syndrome. The cause and pathogenesis of these disease conditions of IPAA are largely unknown. Accurate diagnosis and classification are important for appropriate management.

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.