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Background: In patients with ulcerative colitis or familial adenomatous polyposis who develop neoplasia or fail medical therapy and require colectomy, restorative proctocolectomy with IPAA is often indicated. Although often well tolerated, IPAA can be complicated by cuffitis or inflammation of the remaining rectal cuff. Although much has been published on this subject, there is no clear and comprehensive synthesis of the literature regarding cuffitis., Methods: Our systematic literature review analyzes 34 articles to assess the frequency, cause, pathogenesis, diagnosis, classification, complications, and treatment of cuffitis., Results: Cuffitis occurs in an estimated 10.2% to 30.1% of pouch patients. Purported risk factors include rectal cuff length >2 cm, pouch-rectal anastomosis, stapled anastomosis, J-pouch configuration, 2- or 3-stage IPAA, preoperative Clostridium difficile infection, toxic megacolon, fulminant colitis, preoperative biologic use, medically refractory disease, immunomodulator/steroids use within 3 months of surgery, extraintestinal manifestations of IBD, and BMI <18.5 kg/m2 at the time of colectomy. Adverse consequences associated with cuffitis include decreased quality-of-life scores, increased risk for pouchitis, pouch failure, pouch excision, and pouch neoplasia., Conclusions: Given the similarities between pouchitis and cuffitis, diagnosis and treatment of cuffitis should proceed according to the International Ileal Pouch Consortium guidelines. This review found that the majority of the current literature fails to distinguish between classic cuffitis (a form of reminant ulcerative proctitis) and nonclassic cuffitis (resulting from other causes). Further work is needed to distinguish the unique risk factors and endoscopic characteristics associated with each subtype, and further randomized clinical trials should be conducted to strengthen the evidence for treatment options., (Copyright © The ASCRS 2022.)

Background & Aims: Disability in patients with medically refractory ulcerative colitis (UC) after total proctocolectomy (TPC) with ileal pouch anal anastomosis (IPAA) is not well understood. The aim of this study was to compare disability in patients with IPAA vs medically managed UC, and identify predictors of disability., Methods: This was a multicenter cross-sectional study performed at 5 academic institutions in New York City. Patients with medically or surgically treated UC were recruited. Clinical and socioeconomic data were collected, and the Inflammatory Bowel Disease Disability Index (IBD-DI) was administered to eligible patients. Predictors of moderate-severe disability (IBD-DI ≥35) were assessed in univariable and multivariable models., Results: A total of 94 patients with IPAA and 128 patients with medically managed UC completed the IBD-DI. Among patients with IPAA and UC, 35 (37.2%) and 30 (23.4%) had moderate-severe disability, respectively. Patients with IPAA had significantly greater IBD-DI scores compared with patients with medically managed UC (29.8 vs 17.9; P < .001). When stratified by disease activity, patients with active IPAA disease had significantly greater median IBD-DI scores compared with patients with active UC (44.2 vs 30.4; P = .01), and patients with inactive IPAA disease had significantly greater median IBD-DI scores compared with patients with inactive UC (23.1 vs 12.5; P < .001). Moderate-severe disability in patients with IPAA was associated with female sex, active disease, and public insurance., Conclusions: Patients with IPAA have higher disability scores than patients with UC, even after adjustment for disease activity. Female sex and public insurance are predictive of significant disability in patients with IPAA., (Copyright © 2022. Published by Elsevier Inc.)

Pouchitis, Crohn's disease of the pouch, cuffitis, polyps, and extraintestinal manifestations of inflammatory bowel disease are common inflammatory disorders of the ileal pouch. Acute pouchitis is treated with oral antibiotics and chronic pouchitis often requires anti-inflammatory therapy, including the use of biologics. Aetiological factors for secondary pouchitis should be evaluated and managed accordingly. Crohn's disease of the pouch is usually treated with biologics and its stricturing and fistulising complications can be treated with endoscopy or surgery. The underlying cause of cuffitis determines treatment strategies. Endoscopic polypectomy is recommended for large, symptomatic inflammatory polyps and polyps in the cuff. The management principles of extraintestinal manifestations of inflammatory bowel disease in patients with pouches are similar to those in patients without pouches., Competing Interests: Declaration of interests BA reports a research grant from Takeda and personal fees from Janssen, AbbVie, Pfizer, Samsung Biospis, Ferring, Bristol Myers Squibb. CNB reports grants and personal fees from AbbVie, Janssen, Pfizer, and Takeda, personal fees from Amgen, Bristol Myers Squibb, Roche, Sandoz, and Mylan Pharmaceuticals, and speaker fees from Medtronics. DHB reports grants from Medtronic and Takeda. RKC reports personal fees from AbbVie, Janssen, Samsung Bioepis, and Birstol Myers Squibb. FAF reports serving as an advisory board member for Bristol Myers Squibb, Braintree Labs, Gilead, GSK, Iterative Scopes, Janssen, Pfizer, and Sebela; owns stocks and shares in Innovation Pharmaceuticals; and is a member of Data Safety and Monitoring Boards for Lilly and Theravance. SVK reports grants from Gilead Sciences and TechLab. PGK reports personal fees from AbbVie, Janssen, Pfizer, Takeda, and Ferring, and grants from Pfizer and Takeda. JTM reports personal fees from Intuitive Surgical. UN reports grants and personal fees from Takeda, Janssen, and AbbVie, and personal fees from Pfizer. SE-H reports personal fees from AbbVie, Janssen, Takeda, UCB–Ferring, Pfizer, Bristol Myers Squibb, and Prometheus. JPh reports speaker fees from AbbVie. DTR reports personal fees from AbbVie, Abgenomics, Allergan, Arena Pharmaceuticals, Bellatrix Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, CDx Diagnostics, Celgene/Syneos, Check-Cap, Dizal Pharmaceuticals, Galen Pharma/Atlantica, Genentech/Roche, Ichnos Sciences SA, InDex Pharmaceuticals, Iterative Scopes, Janssen, Lilly, Materia Prima, Marrow River Mgmt, Pfizer, Prometheus Laboratories, Reistone, Takeda, and TechLab. WJS reports grants, personal fees, and stock options from Prometheus Biosciences; grants and personal fees from AbbVie, Abivax, Alimentiv, Arena Pharmaceuticals, Boehringer-Ingelheim, Celgene, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Janssen, Lilly, Pfizer, Prometheus Biosciences, Seres Therapeutics, Shire, Surrozen, Takeda, and Theravance Biopharma; personal fees and stock options from Beigene, Gossamer Bio, Shoreline Bioscience, and personal fees from Allergan, AbbVie, Amgen, Applied Molecular Transport, Avexegen Therapeutics, Bausch Health, Beigene, Bellatrix Pharmaceuticals, Boston Pharmaceuticals, Bristol Myers Squibb, Celltrion, Cellularity, Conatus, Cosmo Pharmaceuticals, Escalier Biosciences, Ferring, Forbion, Equillium, Gilead, Glanmark Pharmaceuticals, Immunic, Incyte, Index Pharmaceuticals, Intact Therapeutics, Janssen, Kyowa Kirin Pharmaceutical Research, Kyverna Therapeutics, Landos Biopharma, Miraca Life Sciences, Nivalis Therapeutics, Novartis, Nutrition Science Partners, Oppilan Pharma, Pfizer, Progenity, Protagonist Therapeutics, Provention Bio, Reistone Biopharma, Ritter Pharmaceuticals, Shanghai Pharma Biotherapeutics, Sienna Biopharmaceuticals, Sigmoid Biotechnologies, Sterna Biologicals, Sublimity Therapeutics, Takeda, Thetis Pharmaceuticals, Tract, and UCB. ES reports grants and personal fees from AbbVie, Janssen, and Takeda, grants from AstraZeneca, Pfizer, and Genentech, and personal fees from Seres Health, Protagonist Therapeutics, Celgene, Entera Health, Bristol Myers Squibb, and Evidera. JSe reports speaker fees from Janssen and Takeda. DAS reports personal fees from AbbVie, Takeda, UCB, Jansen, Gilead, Pfizer, and Tract. SV reports consultancy fees and/or speaking fees from AbbVie, Arena Pharmaceuticals, Avaxia, Boehringer Ingelheim, Celgene, Dr Falk Pharma, Ferring, Galapagos, Genentech-Roche, Gilead, Hospira, Janssen, Mundipharma, Merck Sharpe & Dohme, Pfizer, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Takeda, Theravance, and Tillots Pharma AG, and grants from AbbVie, Johnson & Johnson, Pfizer, and Takeda. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Restorative proctocolectomy with ileal pouch-anal anastomosis is an option for most patients with ulcerative colitis or familial adenomatous polyposis who require colectomy. Although the construction of an ileal pouch substantially improves patients' health-related quality of life, the surgery is, directly or indirectly, associated with various structural, inflammatory, and functional adverse sequelae. Furthermore, the surgical procedure does not completely abolish the risk for neoplasia. Patients with ileal pouches often present with extraintestinal, systemic inflammatory conditions. The International Ileal Pouch Consortium was established to create this consensus document on the diagnosis and classification of ileal pouch disorders using available evidence and the panellists' expertise. In a given individual, the condition of the pouch can change over time. Therefore, close monitoring of the activity and progression of the disease is essential to make accurate modifications in the diagnosis and classification in a timely manner., Competing Interests: Declaration of interests BA reports a research grant from Takeda and personal fees from Janssen, AbbVie, Pfizer, Samsung Biospis, Ferring, Bristol Myers Squibb. CNB reports grants and personal fees from AbbVie, Janssen, Pfizer, and Takeda, personal fees from Amgen, Bristol Myers Squibb, Roche, Sandoz, and Mylan Pharmaceuticals, and speaker fees from Medtronics. DHB reports grants from Medtronic and Takeda. RKC reports personal fees from AbbVie, Janssen, Samsung Bioepis, and Birstol Myers Squibb. SVK reports grants from Gilead Sciences and TechLab. PGK reports personal fees from AbbVie, Janssen, Pfizer, Takeda, and Ferring, and grants from Pfizer and Takeda. JTM reports personal fees from Surgical. UN reports grants and personal fees from Takeda, Janssen, and AbbVie, and personal fees from Pfizer. SE-H reports personal fees from Abbvie, Janssen, Takeda, UCB–Ferring, Pfizer, Bristol Myers Squibb, and Prometheus. JP reports speaker fees from AbbVie. DTR reports personal fees from AbbVie, Abgenomics, Allergan, Arena Pharmaceuticals, Bellatrix Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, CDx Diagnostics, Celgene–Syneors, Check-Cap, Dizal Pharmaceuticals GalenPharma–Atlantica, Genentech–Roche, Ichnos Sciences SA, InDex Pharmaceuticals, Iterative Scopes, Janssen, Lilly, Materia Prima, Marrow River Mgmt, Pfizer, Prometheus Laboratories, Reistone, Takeda, and TechLab. WJS reports grants, personal fees, and stock options from Prometheus Biosciences, grants and personal fees from AbbVie, Abivax, Alimentiv, Arena Pharmaceuticals, Boehringer–Ingelheim, Celgene, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Janssen, Lilly, Pfizer, Prometheus Biosciences, Seres Therapeutics, Shire, Surrozen, Takeda, Theravance Biopharma, personal fees and stock options from Beigene, Gossamer Bio, Shoreline Bioscience, and personal fees from Allergan, AbbVie, Amgen, Applied Molecular Transport, Avexegen Therapeutics, Bausch Health, Beigene, Bellatrix Pharmaceuticals, Boston Pharmaceuticals, Bristol Myers Squibb, Celltrion, Cellularity, Conatus, Cosmo Pharmaceuticals, Escalier Biosciences, Ferring, Forbion, Equillium, Gilead, Glanmark Pharmaceuticals, Immunic, Incyte, Index Pharmaceuticals, Intact Therapeutics, Janssen, Kyowa Kirin Pharmaceutical Research, Kyverna Therapeutics, Landos Biopharma, Miraca Life Sciences, Nivalis Therapeutics, Novartis, Nutrition Science Partners, Oppilan Pharma, Pfizer, Progenity, Protagonist Therapeutics, Provention Bio, Reistone Biopharma, Ritter Pharmaceuticals, Shanghai Pharma Biotherapeutics, Sienna Biopharmaceuticals, Sigmoid Biotechnologies, Sterna Biologicals, Sublimity Therapeutics, Takeda, Thetis Pharmaceuticals, Tract, and UCB. ES reports grants and personal fees from AbbVie, Janssen, and Takeda, grants from AstraZeneca, Pfizer, and Genentech, and personal fees from Seres Health, Protagonist Therapeutics, Celgene, Entera Health, Bristol Myers Squibb, Evidera. SV reports consultancy fees from AbbVie, Arena Pharmaceuticals, Avaxia, Boehringer Ingelheim, Celgene, Dr Falk Pharma, Ferring, Galapagos, Genentech-Roche, Gilead, Hospira, Janssen, Mundipharma, Merck Sharpe & Dohme, Pfizer, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Takeda, Theravance, Tillots Pharma AG, and grants from AbbVie, Johnson & Johnson, Pfizer, and Takeda. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: Inflammation, villous atrophy, colonic metaplasia, and dysplasia have been observed within the mucosa of ileal pelvic pouches after restorative proctocolectomy. This study was designed to determine the prevalence of mucosal dysplasia in ileal pouch and any associated risk factors., Methods: Prospectively registered patients having restorative proctocolectomy were recruited. A cross-sectional study was performed using a questionnaire focusing on disease history, functional results, and pouchitis after surgery. Participants underwent screening endoscopic pouch examination using sigmoidoscopy. Mucosal biopsies were taken from six specific locations in the pouch from proximal ileal-pouch (inflow) to ileoanal anastomosis. All biopsies were performed under strict surveillance protocol regardless of patients' symptoms. Biopsies were interpreted by two pathologists unaware of each other's report., Results: A total of 138 patients completed the protocol. Colectomy specimens from restorative proctocolectomy showed chronic ulcerative colitis in 118 (85.6 percent), familial adenomatous polyposis in 10 (7.2 percent), Crohn's colitis in 2 (1.4 percent), and indeterminate colitis in 8 (5.8 percent) patients. Twenty-two patients (18.3 percent) had dysplasia and eight (6.7 percent) had invasive cancer found in colectomy specimens after restorative proctocolectomy. Median interval between proctocolectomy and pouch biopsy was 5.4 years. Inflammatory changes were present in a majority of specimens, but these did not correlate with clinical history of pouchitis. No villous atrophy was identified. Pouch biopsies from only one patient were indefinite for dysplasia. Subsequent biopsies were negative., Conclusions: Clinical and microscopic evidence of ileal-pouch inflammation is common. Ileal-pouch mucosal dysplasia is uncommon, occurring in only 1 of 138 patients. Villous atrophy and colonic metaplasia were not observed in this series. Routine pouch surveillance with biopsies may not be warranted.

The risk of lymphoma in inflammatory bowel disease (IBD) has raised concerns regarding the lymphogenic potential of immunomodulatory therapy. The link between immunosuppressive therapy and lymphoma risk is well established in patients with solid organ transplantations. In this population, it is postulated that lymphocytes infected with the Epstein-Barr virus (EBV) proliferate unchecked due to impaired cell-mediated immunity. A similar phenomenon may occur in IBD patients treated with multiple immunomodulators and biological agents. In this report, we describe a case of EBV-positive non-Hodgkin's lymphoma arising in the ileal pouch of a patient with ulcerative colitis. This patient was maintained on prednisone (>20 mg/day) for 8 months, cyclosporine for 7 months, and 6-mercaptopurine for nearly 2 years prior to a single infusion of infliximab (5 mg/kg). The cumulative effects of more than three agents, simultaneously and/or sequentially, may simulate posttransplantation immunosuppression and pose a significant threat of malignancy. Such patients may warrant more aggressive diagnostic surveillance and evaluation.