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Introduction: Pouchitis and Crohn's-like disease of the pouch (CLDP) are common in patients who undergo ileal pouch anal anastomosis for ulcerative colitis. We conducted separate systematic reviews to evaluate the effectiveness of available interventions to prevent and treat pouchitis and CLDP., Methods: Through systematic literature reviews, we identified studies that evaluated the effectiveness of probiotics, antibiotics, 5-aminosalicylates, nonsystemic oral corticosteroids, and advanced therapies for prevention and treatment of pouchitis and CLDP for meta-analysis. Primary outcomes were occurrence of pouchitis for pouchitis prevention and clinical response for pouchitis and CLDP treatment. We estimated the relative effectiveness of these interventions using the existing placebo response rates or hypothetical spontaneous improvement rates derived from clinical trials of pouchitis, ulcerative colitis, and Crohn's disease., Results: Probiotics were effective for primary (relative risk [RR] 0.18; 95% confidence interval [CI] 0.05-0.62) and secondary prevention (RR 0.17; 95% CI 0.09-0.34) of pouchitis. Antibiotics were effective for treatment of acute and chronic pouchitis (12 cohorts; RR 1.67; 95% CI 1.34-2.01; response rate 65%; 95% CI 52-75) with ciprofloxacin and metronidazole-based regimens being more effective than rifaximin. Advanced therapies were effective for treatment of chronic antibiotic-refractory pouchitis (31 cohorts; RR 1.71; 95% CI 1.28-2.56; response rate 50%; 95% CI 43-57) and CLDP (10 cohorts; RR 2.49; 95% CI 1.87-3.73; response rate 74%; 95% CI 68-79) without significant difference between classes., Discussion: Multiple medical interventions are effective for prevention and treatment of pouchitis and CLDP. Given the overall low quality of data, further research is needed to confirm these findings., (Copyright © 2024 by The American College of Gastroenterology.)

Background: Patients with inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC) frequently undergo restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for medically refractory disease or colonic dysplasia/neoplasia. Subtotal colectomy with ileosigmoid or ileorectal anastomosis may have improved outcomes but is not well studied. Due to increased risk for colorectal cancer in PSC-IBD, there is hesitancy to perform subtotal colectomy. We aim to describe the frequency of colorectal dysplasia/neoplasia following IPAA vs subtotal colectomy in PSC-IBD patients., Methods: We completed a retrospective study from 1972 to 2022 of patients with PSC-IBD who had undergone total proctocolectomy with IPAA or subtotal colectomy. We abstracted demographics, disease characteristics, and endoscopic surveillance data from the EMR., Results: Of 125 patients (99 IPAA; 26 subtotal), the indication for surgery was rectal sparing medically refractory disease (51% vs 42%), dysplasia (37% vs 30%) and neoplasia (11% vs 26%) in IPAA vs subtotal colectomy patients, respectively. On endoscopic surveillance of IPAA patients, 2 (2%) had low-grade dysplasia (LGD) in the ileal pouch and 2 (2%) had LGD in the rectal cuff after an average of 8.4 years and 12.3 years of follow-up, respectively. One (1%) IPAA patient developed neoplasia of the rectal cuff after 17.8 years of surgical continuity. No subtotal colectomy patients had dysplasia/neoplasia in the residual colon or rectum., Conclusions: In patients with PSC-IBD, there was no dysplasia or neoplasia in those who underwent subtotal colectomy as opposed to the IPAA group. Subtotal colectomy may be considered a viable surgical option in patients with rectal sparing PSC-IBD if adequate endoscopic surveillance is implemented., (© 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.)

Introduction: There is a paucity of data on the real-world effectiveness of therapies in patients with Crohn's disease of the pouch., Methods: This was a prospective multicenter study evaluating the primary outcome of remission at 12 months of therapy for Crohn's disease of the pouch., Results: One hundred thirty-four patients were enrolled. Among the 77 patients with symptoms at baseline, 35 (46.7%) achieved remission at 12 months. Of them, 12 (34.3%) changed therapy. There was no significant association between therapy patterns and remission status., Discussion: Approximately 50% with symptoms at enrollment achieved clinical remission at 12 months, most of whom did so without a change in therapy., (Copyright © 2024 by The American College of Gastroenterology.)

Background: Evidence-based recommendations regarding the influence of diet on inflammatory conditions of the pouch after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) are limited., Methods: We analyzed dietary patterns at enrollment in a prospective registry of patients with 1 of 4 inflammatory conditions of the pouch (acute pouchitis, chronic antibiotic-dependent pouchitis, chronic antibiotic refractory pouchitis, and Crohn's disease of the pouch). We analyzed dietary intake by disease activity at enrollment and then compared dietary patterns among patients who remained in remission throughout the 12-month follow-up to those patients who experienced a disease relapse. We also compared dietary patterns among patients with inflammatory conditions of the pouch to the United States Department of Agriculture (USDA) recommended daily goals., Results: Among 308 patients, there were no differences in dietary patterns among patients with 1 of the 4 disease states at enrollment. Additionally, among the 102 patients in remission at baseline, there were no significant differences noted among patients who went on to experience a disease flare in the 12 months after enrollment compared to those patients who remained in remission. However, patients with inflammatory conditions of the pouch demonstrated decreased intake of several food groups and macronutrients including dairy, fruits, vegetables, whole grains, and fiber when compared to USDA recommendations., Conclusions: In a prospective cohort, we demonstrated no impact of dietary patterns on disease activity. The relative deficiencies in several food groups and macronutrients among patients after IPAA indicate the potential role of targeted nutritional counseling in this population., Competing Interests: E.L.B. has served as a consultant for AbbVie, Bristol-Meyers Squibb, Eli Lilly, and Target RWE. P.D. has served as a consultant or on an advisory board for Janssen, Pfizer, Prometheus Biosciences, Boehringer Ingelheim, AbbVie, Arena Pharmaceuticals, Takeda Pharmaceuticals LLC, Roche Genentech, Bristol Myers Squibb and Scipher Medicine Corporation. He has also received funding under a sponsored research agreement unrelated to the data in the paper from Takeda Pharmaceutical, Arena Pharmaceuticals, Bristol Myers Squibb-Celgene, Janssen, Landos Pharma, Teva Pharma, Iterative scopes, CorEvitas and Boehringer Ingelheim. P.D. holds the position of Associate Editor for Crohn’s & Colitis 360 and has been recused from reviewing or making decisions for the manuscript. P.B.-P. has received honorarium from the Takeda speaker’s bureau. L.R. has served on an advisory board for Janssen. LR holds the position of Associate Editor for Crohn’s & Colitis 360 and has been recused from reviewing or making decisions for the manuscript. M.D. has served as a consultant or has received advisory board fees from Abbvie, Arena, BMS, Eli Lilly, Gilead, Janssen, Pfizer, Prometheus Labs, Takeda. She has received grant support from Janssen, Abbvie. She also has the following relationships: Licenser of software: Takeda; Co-Founder, Equity ownership and board of director for Trellus Health Shannon Chang has served as a consultant for AbbVie, BMS, and Pfizer. R.K.C. has participated in advisory boards for AbbVie, Bristol Myers Squibb, Fresenius Kabi, and has served as a consultant for Fzata, Magellan Health, Pfizer, and Samsung Bioepis. He is on the Data Safety Monitoring Board for Adiso, is a member of the Executive Committee for the IBD Education Group and is Co-Director of the CorEvitas Registry. M.D.L. has served as a consultant for AbbVie, UCB, Takeda, Janssen, Pfizer, Salix, Valeant, Target Pharmasolutions and has received research support from Pfizer and Takeda. H.H.H. has served as a consultant for Alivio, AMAG, BMS, ExeGI Finch, Gilead, Janssen, Lycera, Merck, Otsuka, Pfizer, PureTech, Seres and has received research support from Pfizer and Artizan Biosciences. M.K., P.D.R.H., J.B., and C.A. have no relevant disclosures., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Pouchoscopy provides a critical objective measure in the evaluation of patients with suspected inflammatory conditions of the pouch; however, there remain significant gaps in the reliability of the endoscopic scales used in the assessment of these conditions. 1,2 Reliability and reproducibility in the assessment of patients after ileal pouch-anal anastomosis (IPAA) are critical, as evidenced by recent efforts to improve standardization in the evaluation of patients with pouch-related disorders. 3 ., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background and Aims: SCENIC (International Consensus Statement on Surveillance and Management of Dysplasia in IBD) guidelines recommend that visible dysplasia in patients with longstanding inflammatory bowel disease (IBD) should be endoscopically characterized using a modified Paris classification. This study aimed to determine the interobserver agreement (IOA) of the modified Paris classification and endoscopists' accuracy for pathology prediction of IBD visible lesions., Methods: One hundred deidentified endoscopic still images and 30 videos of IBD visible colorectal lesions were graded by 10 senior and 4 trainee endoscopists from 5 tertiary care centers. Endoscopists were asked to assign 4 classifications for each image: the standard Paris classification, modified Paris classification, pathology prediction, and lesion border. Agreement was measured using Light's kappa coefficient. Consensus of ratings was assessed according to strict majority., Results: The overall Light's kappa for all study endpoints was between .32 and .49. In a subgroup analysis between junior and senior endoscopists, Light's kappa continued to be less than .6 with a slightly higher agreement among juniors. Lesions with the lowest agreement and no consensus were mostly classified as Is, IIa, and mixed Paris classification and sessile and superficial elevated for modified Paris classification. Endoscopist accuracy for prediction of dysplastic, nondysplastic, and serrated pathology was 77%, 56%, and 30%, respectively. There was a strong association (P < .001) between the given morphology classification and the predicted pathology with Ip lesions carrying a much lower expectation of dysplasia than Is/IIc/III and mixed lesions. The agreement for border prediction was .5 for junior and .3 for senior endoscopists., Conclusions: This study demonstrates very low IOA for Paris and modified Paris classifications and low accuracy and IOA for lesion histopathology prediction. Revisions of these classifications are required to create a clinically useful risk stratification tool and enable eventual application of augmented intelligence tools., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. All rights reserved.)

Background: Much of our understanding about the natural history of pouch-related disorders has been generated from selected populations. We designed a geographically diverse, prospective registry to study the disease course among patients with 1 of 4 inflammatory conditions of the pouch. The primary objectives in this study were to demonstrate the feasibility of a prospective pouch registry and to evaluate the predominant treatment patterns for pouch-related disorders., Methods: We used standardized diagnostic criteria to prospectively enroll patients with acute pouchitis, chronic antibiotic-dependent pouchitis (CADP), chronic antibiotic refractory pouchitis (CARP), or Crohn's disease (CD) of the pouch. We obtained detailed clinical and demographic data at the time of enrollment, along with patient-reported outcome (PRO) measures., Results: We enrolled 318 patients (10% acute pouchitis, 27% CADP, 12% CARP, and 51% CD of the pouch). Among all patients, 55% were on a biologic or small molecule therapy. Patients with CD of the pouch were more likely to use several classes of therapy ( P < .001). Among patients with active disease at the time of enrollment, 23% with CARP and 40% with CD of the pouch were in clinical remission at 6 months after enrollment., Conclusions: In a population where most patients had refractory inflammatory conditions of the pouch, we established a framework to evaluate PROs and clinical effectiveness. This infrastructure will be valuable for long-term studies of real-world effectiveness for pouch-related disorders., (© The Author(s) 2022. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Perianal Crohn's disease remains a challenging condition to treat and can have a substantial negative impact on quality of life. It often requires combined surgical and medical interventions. Anti-tumor necrosis factor (anti-TNF) therapy, including infliximab and adalimumab, remain preferred medical therapies for perianal Crohn's disease. Infliximab has been shown to be efficacious in improving fistula closure rates in randomized controlled trials. Clinicians can be faced with a number of questions relating to the optimal use of anti-TNF therapy in perianal Crohn's disease. Specific issues include evaluation for the presence of perianal sepsis, the treatment target of therapy, the ideal time to commence treatment, whether additional medical therapy should be used in conjunction with anti-TNF therapy, and the duration of treatment. This article will discuss key studies which can assist clinicians in addressing these matters when they are considering or have already commenced anti-TNF therapy for the treatment of perianal Crohn's disease. It will also discuss current evidence regarding the use of vedolizumab and ustekinumab in patients who are failing to achieve a response to anti-TNF therapy for perianal Crohn's disease. Lastly, new therapies such as local injection of mesenchymal stem cell therapy will be discussed., Competing Interests: Conflict-of-interest statement: Loftus EV Jr has consulted for AbbVie, Allergan, Amgen, Arena, Boehringer Ingelheim, Bristol-Myers Squibb, Calibr, Celgene, Celltrion Healthcare, Eli Lilly, Genentech, Gilead, Iterative Scopes, Janssen, Ono Pharma, Pfizer, Sun Pharma, Takeda, and UCB; and has received research support from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Genentech, Gilead, Janssen, Receptos, Robarts Clinical Trials, Takeda, Theravance, and UCB. Bruining DH—Medtronics: consulting agreement; Takeda: research support. Raffals L, Ehman EC, Faubion W and Vasudevan A have no disclosures., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Certolizumab pegol (CZP) has been successfully used for the treatment of Crohn disease (CD); however, real-world data regarding the utility of CZP trough levels (CTLs) are lacking. We aimed to correlate CTL with CD outcomes and to determine frequency of CZP antibodies., Methods: Retrospective evaluation of all CD patients on maintenance CZP with CTL obtained between 2016 and 2019. Outcomes included: median CTL, presence of anti-CZP antibodies, biochemical response (BR), clinical response (CR), radiologic response (RR), radiologic healing (RH), and mucosal healing (MH)., Results: Seventy-seven CD patients were included. Median CTL was 18.9 µg/mL (interquartile range, 7.6-35.4). Twenty-three patients (27.3%) had positive antibody levels, with lower median CTL compared to patients with no antibodies (0.0 vs 29.8; P < 0.0001). Median CTL levels were higher in patients with vs without CR (30.4 vs 10.3 µg/mL; P = 0.0015) and RR (29.6 vs 5.8 µg/mL; P = 0.006). CZP dosing at least every 2 weeks was associated with higher odds of achieving MH (odds ratio, 3.2; 95% confidence interval, 1.03-9.97). CTL resulted in change in clinical management in 62.7% of cases and presence of CMZ antibodies was associated with an odds ratio of 5.83 (95% confidence interval, 1.57-21.73) of change in management. Receiver operating characteristic curve and quartile analysis suggested that CTL >19 µg/mL is associated with increased rates of CR and RR., Conclusions: Higher CTL was significantly associated with CR and RR. The rate of CZP antibodies was 27.3%. Our data suggest maintenance CTL of ≥19 µg/mL should be achieved in order to optimize outcomes in clinical practice., (© The Author(s) 2021. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Background: Gaps exist in our understanding of the clinical course of pouch-related disorders., Methods: We evaluated baseline disease activity and longitudinal treatment patterns among patients with inflammatory conditions of the pouch., Results: Among 468 patients with an ileal pouch-anal anastomosis (IPAA), 94 (20%) had acute pouchitis, 96 (21%) had chronic pouchitis, and 192 (41%) had Crohn disease of the pouch. Following an IPAA, 38% of patients were treated with a biologic and 11% underwent inflammatory bowel disease- or bowel-related surgery., Conclusions: Treatment patterns after IPAA indicate that pouch-related disorders have a significant impact on individual patients and the healthcare system., (© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Background and Aims: Inflammation of the pouch after ileal pouch-anal anastomosis (IPAA) can significantly impact quality of life and be difficult to treat. We assessed the effectiveness and safety of vedolizumab in Crohn's disease (CD) of the pouch and chronic antibiotic-dependent or antibiotic-refractory pouchitis., Methods: This was a retrospective, multicenter cohort study at 5 academic referral centers in the United States. Adult patients with endoscopic inflammation of the pouch who received vedolizumab were included. The primary outcome was clinical response at any time point. Secondary outcomes included clinical remission, endoscopic response, and remission. Univariate analysis and multivariate analysis were performed for the effect of the following variables on clinical response: fistula, onset of pouchitis less than 1 year after IPAA, younger than 35 years old, gender, previous tumor necrosis factor inhibitor-alpha use, and BMI >30., Results: Eighty-three patients were treated with vedolizumab for inflammation of the pouch between January 2014 and October 2017. Median follow-up was 1.3 years (interquartile range 0.7-2.1). The proportion of patients that achieved at least a clinical response was 71.1%, with 19.3% achieving clinical remission. Of the 74 patients with a follow-up pouchoscopy, the proportion of patients with endoscopic response and mucosal healing was 54.1% and 17.6%, respectively. Patients who developed pouchitis symptoms less than 1 year after undergoing IPAA were less likely to respond to vedolizumab, even after controlling for other risk factors., Conclusions: Vedolizumab is safe and effective in the management of CD of the pouch and chronic pouchitis. Further studies are needed to compare vedolizumab with other biologic therapies for pouchitis and CD of the pouch., (© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Inflammatory bowel diseases (IBDs) are a group of heterogeneous inflammatory conditions affecting the gastrointestinal tract. Although there is considerable evidence linking the gut microbiota to intestinal inflammation, there is limited knowledge on its potential role in the development of extraintestinal manifestations of IBD., Methods: Four groups of patients were included: IBD-associated arthropathy (IBD-A); IBD without arthropathy (IBD-N); rheumatoid arthritis (RA); and non-IBD, nonarthritis controls. DNA from stool samples was isolated and sequenced using the Illumina platform. Paired-end reads were quality-controlled using SHI7 and processed with SHOGUN. Abundance and diversity analyses were performed using QIIME, and compositional biomarker identification was performed using LEfSe., Results: One hundred eighty patients were included in the analysis. IBD-A was associated with an increased abundance of microbial tyrosine degradation pathways when compared with IBD-N (P = 0.02), whereas IBD-A and RA patients both shared an increased abundance of Clostridiaceae when compared with controls (P = 0.045). We found that history of bowel surgery was a significant source of variability (P = 0.001) among all IBD patients and was associated with decreased alpha diversity and increased abundance of Enterobacteriaceae (P = 0.004)., Conclusions: An increased abundance of gut microbial tyrosine degradation pathways was associated with IBD-A. An increased abundance of Clostridiaceae was shared by both IBD-A and RA patients and suggests a potentially common microbial link for inflammatory arthritis. The increased abundance of Enterobacteriaceae, previously reported in IBD, may be due to the effects of previous bowel surgery and highlights the importance of controlling for this variable in future studies., (© 2018 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Crohn's disease (CD) of the pouch and chronic pouchitis occur in approximately 10% of patients after ileal pouch-anal anastomosis (IPAA) for refractory ulcerative colitis (UC) or UC-related dysplasia. The efficacy of anti-tumor necrosis factor (anti-TNF) agents and vedolizumab have been reported for the treatment of CD of the pouch and chronic pouchitis, but little is known regarding the use of ustekinumab in these settings. Our primary aim was to evaluate the efficacy of ustekinumab for these conditions., Methods: This is a retrospective, multicenter cohort study evaluating the efficacy of ustekinumab in patients with CD of the pouch and chronic pouchitis. Clinical response or remission was judged by the treating physician's assessment at 6 months., Results: Fifty-six patients (47 with CD of the pouch and 9 with chronic pouchitis) were included the study. Of these, 73% had previously been treated with either anti-TNF therapy, vedolizumab, or both after IPAA. Among patients with CD of the pouch and chronic pouchitis, 83% demonstrated clinical response 6 months after induction with ustekinumab. Responders demonstrated significantly less pouch inflammation on endoscopy when compared with nonresponders (29% vs 100%; P = 0.023). Higher mean body mass index at induction (26.3 vs 23.7; P = 0.033) and male sex (83% vs 30%; P = 0.014) were significant predictors of nonresponse to ustekinumab in those with CD of the pouch., Conclusion: In this refractory patient population, ustekinumab appears to be a safe and effective treatment for chronic pouchitis and CD of the pouch in biologic-naïve patients and those with prior anti-TNF or vedolizumab therapy failure. 10.1093/ibd/izx005&#95;video1 izy302.video1 5844889626001., (© 2018 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background/aims: The clinical utility of vedolizumab (VDZ) trough levels (VTLs) in inflammatory bowel disease (IBD) is not well defined. The aims of this study are to determine the median VTLs and frequency of detected antibodies, the correlation of VTLs with C-reactive protein (CRP) and mucosal healing (MH), and the change in clinical management based on VTLs., Methods: A cross-sectional study of IBD patients treated with VDZ with VTLs checked between July 1, 2016, and March 1, 2017, was conducted. Mucosal healing was defined as absence of mucosal ulcers in Crohn's disease (CD) and Mayo endoscopic score ≤1 for ulcerative colitis (UC). Normal CRP was defined as ≤8 mg/L., Results: A total of 171 patients (62% CD, 31% UC, 7% indeterminate colitis) were included. Median VTLs was 15.3 ug/mL (range, 0-60), and 1 patient had detectable antibodies to VDZ. Patients with a normal CRP had a median VTLs of 17.3 ug/mL vs 10.7 ug/mL in high CRP patients (P = 0.046). This was noted in CD (20.3 vs 10.4 ug/mL; P = 0.005) but not in UC patients (14.4 vs 20.8; P = 0.72). Mucosal healing was achieved in 35% of patients (37 of 105); among these, median VTLs was 13.7 ug/mL vs 16.1 ug/mL in patients who did not achieve MH (P = 0.64). Vedolizumab trough levels resulted in a change in clinical management in 73%., Conclusions: Our cohort showed a low rate of immunogenicity to VDZ and an association between VTLs and CRP in CD but not in UC patients. No relationship between VTLs and MH was detected. Vedolizumab trough level measurements altered management in approximately three fourths of patients., (© 2018 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Recent findings suggest that αE expression is enriched on effector T cells and that intestinal αE+ T cells have increased expression of inflammatory cytokines. αE integrin expression is a potential predictive biomarker for response to etrolizumab, a monoclonal antibody against β7 integrin that targets both α4β7 and αEβ7. We evaluated the prevalence and localization of αE+ cells as well as total αE gene expression in healthy and inflammatory bowel disease patients., Methods: αE+ cells were identified in ileal and colonic biopsies by immunohistochemistry and counted using an automated algorithm. Gene expression was assessed by quantitative reverse-transcriptase polymerase chain reaction., Results: In both healthy and inflammatory bowel disease patients, significantly more αE+ cells were present in the epithelium and lamina propria of ileal compared with colonic biopsies. αE gene expression levels were also significantly higher in ileal compared with colonic biopsies. Paired biopsies from the same patient showed moderate correlation of αE expression between the ileum and colon. Inflammation did not affect αE expression, and neither endoscopy nor histology scores correlated with αE gene expression. αE expression was not different between patients based on concomitant medication use except 5-aminosalicylic acid., Conclusion: αE+ cells, which have been shown to have inflammatory potential, are increased in the ileum in comparison with the colon in both Crohn's disease and ulcerative colitis, as well as in healthy subjects. In inflammatory bowel disease patients, αE levels are stable, regardless of inflammatory status or most concomitant medications, which could support its use as a biomarker for etrolizumab.

Tuberculosis involvement of the gastrointestinal tract, peritoneum, and associated viscera is an uncommon but well described entity. While peritoneal tuberculosis and tuberculous enteritis are more common, involvement of the esophagus, stomach, colon, rectum, anus, liver, bile ducts, gallbladder, and pancreas can occur. Diagnosis is challenging as cases often mimic neoplasm or inflammatory bowel disease. In this review we outline the pathogenesis, clinical presentation, diagnostic testing, and treatment strategies pertaining to such cases., (© 2018 The Authors.)

Background: The operation of choice for patients with chronic ulcerative colitis (CUC) is restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA). Pouchitis is the most common complication after IPAA. The incidence of Clostridium difficile infection (CDI) is higher in CUC patients than the general population and can lead to significant disease flares and higher rates of colectomy. We sought to determine the risk of pouchitis in patients with precolectomy CDI and 90-day postoperative IPAA complications., Methods: A retrospective case-control study was conducted on patients with CUC who underwent an IPAA between January 1, 2000 and January 10, 2015. The study cohort was comprised of patients diagnosed with CDI within 90 days before colectomy; patients with CUC without CDI comprised the control cohort. The primary outcome measure was the frequency of pouchitis after IPAA. Secondary outcomes included time to pouchitis, 90-day postoperative pouch morbidity: surgical site infection, hemorrhage, anastomotic leak, fistula formation, pouchitis treatment and response, and pouch failure requiring end-ileostomy or fecal diversion. Univariate and multivariable analysis was used to determine differences between CDI and non-CDI groups., Results: Forty-eight case patients and 154 control patients were included. Patients with preoperative CDI were younger (P = 0.010), had higher rates of medically refractory disease (P = 0.002), and had greater use of biologic therapy (P = 0.046). The rate of pouchitis was 50.0% (n = 24) and 46.8% (n = 72) (P = 0.694) among patients with and without preoperative CDI, respectively. Patients with preoperative CDI who developed pouchitis post-IPAA were more likely to require medical management with an anti-TNFα (P = 0.042) and surgical management with end/diverting ileostomy (P = 0.042). Preoperative CDI was associated with higher rates of postoperative IPAA anastamotic or pouch strictures (P = 0.018). Multivariable analysis revealed primary sclerosing cholangitis (PSC) as the only variable associated with increased risk for pouchitis (OR 10.59; 95% CI, 3.07-51.08; P < 0.001)., Conclusions: Preoperative CDI does not seem to be associated with an increased risk of pouchitis in patients with CUC.

Immune-related Adverse Events (irAEs) are the most significant toxicities associated with the use of checkpoint inhibitors, and result from disinhibition of the host's immune homeostasis. The adverse effects experienced from immunotherapy are significantly different from those of chemotherapy and, to a lesser extent, targeted therapy. Early recognition and diagnosis of these toxicities is often challenging, but is critically important because of the potentially life-threatening nature and associated morbidity. Gastrointestinal, dermatologic, endocrine, and liver toxicities are the most commonly observed. Less commonly, the eyes, pancreas, kidneys, lungs, bone marrow, or nervous system may be affected. Although most irAEs may resolve with supportive care or discontinuation of drug, in severe cases, they may require hospitalization and immune suppressants, such as steroids, and/or may even cause death. The management of immune-related side effects requires a multidisciplinary approach.

Background & Aims: There is debate over whether patients with Crohn's disease who start anti-tumor necrosis factor (TNF) therapy after failed immunomodulator therapy should continue to receive concomitant immunomodulators. We conducted a meta-analysis of subgroups from randomized controlled trials (RCTs) of anti-TNF agents to compare the efficacy and safety of concomitant immunomodulator therapy vs anti-TNF monotherapy., Methods: We performed a systematic review of literature published from 1980 through 2008 and identified 11 RCTs of anti-TNF agents in patients with luminal or fistulizing Crohn's disease. We excluded RCTs of patients who were naive to anti-TNF and immunomodulator therapy. The primary end points were clinical response at weeks 4-14 and 24-30 and remission at weeks 24-30. Secondary end points included infusion site or injection site reactions and selected adverse events. A priori subgroup analyses were performed to evaluate fistula closure and the efficacy and safety of combination therapy with different anti-TNF agents., Results: Overall, combination therapy was no more effective than monotherapy in inducing 6-month remission (odds ratio [OR], 1.02; 95% confidence interval [CI], 0.80-1.31), inducing a response (OR, 1.08; 95% CI, 0.79-1.48), maintaining a response (OR, 1.53; 95% CI, 0.67-3.49), or inducing partial (OR, 1.25; 95% CI, 0.84-1.88) or complete fistula closure (OR, 1.10; 95% CI, 0.68-1.78). In subgroup analyses of individual anti-TNF agents, combination therapy was not more effective than monotherapy in inducing 6-month remission in those treated with infliximab (OR, 1.73; 95% CI, 0.97-3.07), adalimumab (OR, 0.88; 95% CI, 0.58-1.35), or certolizumab (OR, 0.93; 95% CI, 0.65-1.34). Overall, combination therapy was not associated with an increase in adverse events, but inclusion of infliximab was associated with fewer injection site reactions (OR, 0.46; 95% CI, 0.26-0.79.), Conclusions: On the basis of a meta-analysis, continued use of immunomodulator therapy after starting anti-TNF therapy is no more effective than anti-TNF monotherapy in inducing or maintaining response or remission. RCTs are needed to adequately assess the efficacy of continued immunomodulator therapy after anti-TNF therapy is initiated., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

We performed a prospective study of patients with inflammatory bowel diseases to examine variations in treatment among medical centers. In a prospective cohort study of 1659 patients with Crohn's disease and 946 patients with ulcerative colitis seen at 7 high-volume referral centers, we collected data on demographics, disease characteristics, and medical and surgical treatments. We used logistic regression to determine differences in treatment among centers, controlling for potential confounders. We found significant variations among centers in the treatment of Crohn's disease with immunomodulators (odds ratio [OR], 3.34; 95% confidence interval [CI], 2.09-5.32) but not anti-tumor necrosis factor agents (OR, 1.64; 95% CI, 0.97-2.77). There was less variation in the treatment of ulcerative colitis; we found no difference in use of immunomodulators (OR, 1.83; 95% CI, 1.00-3.36) or anti-tumor necrosis factor therapy (OR, 0.81; 95% CI, 0.40-1.65). The development and implementation of evidence-based standards of care for inflammatory bowel disease may help reduce variation and improve outcomes., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Pouchitis is a common complication seen in patients with ulcerative colitis who undergo total proctocolectomy with ileal pouch anal anastomosis. Bacteria seem to play an important role in the development of pouchitis, although this role is not well defined. Because technology has advanced, we are able to apply molecular techniques to describe the structure and function of the pouch microbial community. In recent years, several studies have been performed comparing the pouch microbiota in patients with ulcerative colitis with healthy pouches and pouchitis. Many of these studies have suggested that pouchitis is characterized by dysbiosis and/or decreased microbial diversity. There has not been a clear pattern identifying a pathogenic organism or a group of organisms responsible for pouchitis. This review summarizes recent studies exploring the pouch microbiota in health and disease, the relationship of bacterial metabolites and pouchitis, and the role of antibiotics and probiotics for the treatment and prevention of pouchitis.

Background: Butyrate, which is produced by the human microbiome, is essential for a well-functioning colon. Bacteria that produce butyrate are phylogenetically diverse, which hinders their accurate detection based on conventional phylogenetic markers. As a result, reliable information on this important bacterial group is often lacking in microbiome research., Results: In this study we describe a gene-targeted approach for 454 pyrotag sequencing and quantitative polymerase chain reaction for the final genes in the two primary bacterial butyrate synthesis pathways, butyryl-CoA:acetate CoA-transferase (but) and butyrate kinase (buk). We monitored the establishment and early succession of butyrate-producing communities in four patients with ulcerative colitis who underwent a colectomy with ileal pouch anal anastomosis and compared it with three control samples from healthy colons. All patients established an abundant butyrate-producing community (approximately 5% to 26% of the total community) in the pouch within the 2-month study, but patterns were distinctive among individuals. Only one patient harbored a community profile similar to the healthy controls, in which there was a predominance of but genes that are similar to reference genes from Acidaminococcus sp., Eubacterium sp., Faecalibacterium prausnitzii and Roseburia sp., and an almost complete absence of buk genes. Two patients were greatly enriched in buk genes similar to those of Clostridium butyricum and C. perfringens, whereas a fourth patient displayed abundant communities containing both genes. Most butyrate producers identified in previous studies were detected and the general patterns of taxa found were supported by 16S rRNA gene pyrotag analysis, but the gene-targeted approach provided more detail about the potential butyrate-producing members of the community., Conclusions: The presented approach provides quantitative and genotypic insights into butyrate-producing communities and facilitates a more specific functional characterization of the intestinal microbiome. Furthermore, our analysis refines but and buk reference annotations found in central databases.