Search

Background: The modified pouchitis disease activity index (mPDAI) based on clinical symptoms and endoscopic findings is used to diagnose pouchitis, but validated instruments to monitor pouchitis are still lacking. We recently established an endoscopic classification that described 7 endoscopic phenotypes with different outcomes. We assessed symptoms and compared mPDAIs among phenotypes in inflammatory bowel disease (IBD)., Methods: We retrospectively reviewed pouchoscopies and classified them into 7 main phenotypes: normal ( n  = 25), afferent limb (AL) involvement ( n  = 4), inlet involvement ( n  = 14), diffuse ( n  = 7), focal inflammation of the pouch body ( n  = 25), cuffitis ( n  = 18), and pouch-related fistulas ( n  = 10) with a single phenotype were included. Complete-case analysis was conducted., Results: One hundred and three IBD patients were included. The median mPDAI was 0 (IQR 0-1.0) in patients with a normal pouch. Among inflammatory phenotypes, the highest median mPDAI was 4.0 (IQR 2.25-4.75) in cuffitis, followed by 3.0 (IQR 2.5-4.0) in diffuse inflammation, 2.5 (IQR 1.25-4.0) in inlet involvement, 2.5 (IQR 2.0-3.5) in AL involvement, 2.0 (IQR 1.0-3.0) in focal inflammation, and 1.0 (IQR 0.25-2.0) in the fistula phenotype. Perianal symptoms were frequently observed in pouch-related fistulas (8/10, 80%) and cuffitis (13/15, 87%). Among patients with cuffitis, all had incomplete emptying (6/6, 100%)., Conclusions: We correlated the mPDAI with the endoscopic phenotypes and described the limited utility of symptoms in distinguishing between inflammatory phenotypes. Further studies are warranted to understand which symptoms should be monitored for each phenotype and whether mPDAI can be minimized after pouch normalization., Competing Interests: S.A., J.E.O., N.A.C., V.R., L.R.G., Y.Y., C.T., J.R., K.B.S., R.D.H., K.U., B.D.S., N.H.H., and A.S. have no relevant disclosures. R.D.C. is on the speaker’s bureau from AbbVie and Takeda. He is a consultant/advisor for AbbVie Laboratories, BM/celgene, Eli Lilly, Gilead Sciences, Janssen, Pfizer, Takeda, UCB Pharma. He has received clinical trial support/grants from Abbvie, BMS/Celgene, Boehringer Ingelheim, Crohn’s and Colitis Foundation of America, Genentech, Gilead Sciences, Hollister, Medimmune, Mesoblast Ltd., Osiris Therpeutics, Pfizer, Receptos, RedHill Biopharma, Sanofi-Aventis, Schwarz Pharma, Seres Therapeutics, Takeda Pharma, UCB Pharma. His wife is on the board of directors of Aerpio Therapeutics, Novus Therapeutics, Vital Therapeutics, Inc, and NantKwest. M.A.R. has served as a consultant for Pfizer. S.R.D. has served as a consultant for Pfizer and is on the speaker’s bureau for AbbVie. J.P. has received grant support from AbbVie and Takeda. He has served as a consultant for Veraste,. CVS Caremark and is on the advisory board for Takeda, Janssen and Pfizer. E.B.C. is the founder and chief medical officer of AVnovum Therapeutics. D.T.R. has received grant support from Takeda; and has served as a consultant for Abbvie, Altrubio, Amgen, AvaloTherapeutics, Bristol-Myers Squibb, Buhlmann Diagnostics Corp, Chronicles Health, ClostraBio, Connect BioPharma, Cytoki Pharma, Douglas Pharmaceuticals, EcoR1, Ferring Pharma, Image Analysis Group, Index Pharmaceuticals, Iterative Health, Janssen Pharmaceuticals, Lilly, Odyssey Therapeutics, Pfizer, Prometheus Biosciences, Reistone Biopharma, Samsung Neurologica, Sangamo Therapeutics, Shanghai Pharma Biotherapeutics USA, Takeda, Tissium S.A., and Trellus Health., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Background: Patients with inflammatory bowel disease (IBD) who undergo proctocolectomy with ileal pouch-anal anastomosis may develop pouchitis. We previously proposed a novel endoscopic classification of pouchitis describing 7 phenotypes with differing outcomes. This study assessed phenotype transitions over time., Methods: We classified pouch findings into 7 main phenotypes: (1) normal, (2) afferent limb (AL) involvement, (3) inlet (IL) involvement, (4) diffuse, (5) focal inflammation of the pouch body, (6) cuffitis, and (7) pouch-related fistulas noted more than 6 months after ileostomy takedown. Among 2 endoscopic phenotypes, the phenotype that was first identified was defined as the primary phenotype, and the phenotype observed later was defined as the subsequent phenotype., Results: We retrospectively reviewed 1359 pouchoscopies from 426 patients (90% preoperative diagnosis of ulcerative colitis). The frequency of primary phenotype was 31% for AL involvement, 42% for IL involvement, 28% for diffuse inflammation, 72% for focal inflammation, 45% for cuffitis, 18% for pouch-related fistulas, and 28% for normal pouch. The most common subsequent phenotype was focal inflammation (64.8%), followed by IL involvement (38.6%), cuffitis (37.8%), AL involvement (25.6%), diffuse inflammation (23.8%), normal pouch (22.8%), and pouch-related fistulas (11.9%). Subsequent diffuse inflammation, pouch-related fistulas, and AL or IL stenoses significantly increased the pouch excision risk. Patients who achieved subsequent normal pouch were less likely to have pouch excision than those who did not (8.1% vs 15.7%; P = .15)., Conclusions: Pouch phenotype and the risk of pouch loss can change over time. In patients with pouch inflammation, subsequent pouch normalization is feasible and associated with favorable outcome., (© The Author(s) 2024. 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: Despite significant differences in surgical outcomes between pediatric and adult patients with ulcerative colitis (UC) undergoing colectomy, counseling on pediatric outcomes has largely been guided by data from adults. We compared differences in pouch survival between pediatric and adult patients who underwent total proctocolectomy with ileal pouch-anal anastomosis (IPAA)., Methods: This was a retrospective single-center study of patients with UC treated with IPAA who subsequently underwent pouchoscopy between 1980 and 2019. Data were collected via electronic medical records. We stratified the study population based on age at IPAA. Differences between groups were assessed using t tests and chi-square tests. Kaplan-Meier curves were used to compare survival probabilities. Differences between groups were assessed using a log-rank test., Results: We identified 53 patients with UC who underwent IPAA before 19 years of age and 329 patients with UC who underwent IPAA at or after 19 years of age. Subjects who underwent IPAA as children were more likely to require anti-tumor nerosis factor (TNF) postcolectomy compared with adults (41.5% vs 25.8%; P < .05). Kaplan-Meier estimates revealed that pediatric patients who underwent IPAA in the last 10 years had a 5-year pouch survival probability that was 28% lower than that of those who underwent surgery in the 1990s or 2000s (72% vs 100%; P < .001). Further, children who underwent IPAA and received anti-TNF therapies precolectomy had the most rapid progression to pouch failure when compared with anti-TNF-naive children and with adults who were either exposed or naive precolectomy (P < .05)., Conclusions: There are lower rates of pouch survival for children with UC who underwent IPAA following the uptake of anti-TNF therapy compared with both historical pediatric control subjects and contemporary adults., (© 2022 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aims: Recurrence of Crohn's disease after surgical resection and primary anastomosis is an important clinical challenge. Previous studies have demonstrated the benefit of imidazole antibiotics, but have been limited by adverse events and medication intolerance. We evaluated whether administration of low-dose metronidazole [250 mg three times per day] for 3 months reduces endoscopic postoperative recurrence rates., Methods: We performed a retrospective cohort study of patients with Crohn's disease who underwent ileal resection with a primary anastomosis and subsequently received care at our center. We compared the cases who received low-dose metronidazole for 3 months with control patients who did not receive this therapy. Data collected included demographics, risk factors for recurrence, and medications before and after surgery. The primary end point was the number of patients with ≥i2 [Rutgeerts] endoscopic recurrence by 12 months. Variables found to be predictive in univariate analysis at p < 0.10 were introduced in the Cox model for multivariate analysis., Results: In all, 70 patients with Crohn's disease [35 cases and 35 controls] met inclusion criteria. Risk factors for Crohn's recurrence were similar between groups. The number of patients with ≥i2 endoscopic recurrence within 12 months following ileal resection was significantly lower in the metronidazole group [7 of 35 patients; 20%] compared with the number in the control group [19 of 35 patients; 54.3%] [p = 0.0058]. Eight participants [22.9%] in the metronidazole group experienced adverse events, and 3 of these patients [8.6%] discontinued the therapy., Conclusion: Low-dose metronidazole reduces endoscopic recurrence of Crohn's disease postoperatively and is well tolerated. This intervention should be considered as a therapy option following ileocolonic resection., (Copyright © 2019 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Previous work has demonstrated that anastomotic leak can be caused by collagenolytic bacteria such as Enterococcus faecalis via an effect on wound collagen. In humans, E. faecalis is the organism cultured most commonly from a leaking anastomosis, and is not routinely eliminated by standard oral or intravenous antibiotics. Novel strategies are needed to contain the virulence of this pathogen when present on anastomotic tissues., Methods: Polyphosphorylated polymer ABA-PEG20k-Pi20 was tested in mice for its ability to prevent anastomotic leak caused by collagenolytic E. faecalis. The study design included a distal colonic resection and anastomosis followed by introduction of E. faecalis to anastomotic tissues via enema. Mice were assigned randomly to receive either ABA-PEG20-Pi20 or its unphosphorylated precursor ABA-PEG20k in their drinking water. The development of anastomotic leak was determined after the animals had been killed., Results: Overnight incubation of two different E. faecalis collagenolytic strains with 2 mmol/l of ABA-PEG20k-Pi20 led to near complete inhibition of collagenase production (from 21 000 to 1000 and from 68 000 to 5000 units; P < 0·001; 6 samples per group) without suppressing bacterial growth. In mice drinking 1 per cent ABA-PEG20k-Pi20, the phosphate concentration in the distal colonic mucosa increased twofold and leak rates decreased from eight of 15 to three of 15 animals (P < 0·001). In mice drinking ABA-PEG20k-Pi20, the percentage of collagenolytic colonies among E. faecalis populations present at anastomotic tissue sites was decreased by 6-4800-fold (P = 0·008; 5 animals)., Conclusion: These data indicate that oral intake of ABA-PEG20k-Pi20 may be an effective agent to contain the virulence of E. faecalis and may prevent anastomotic leak caused by this organism. Clinical relevance Progress in understanding the pathogenesis of anastomotic leak continues to point to intestinal bacteria as key causative agents. The presence of pathogens such as Enterococcus faecalis that predominate on anastomotic tissues despite antibiotic use, coupled with their ability to produce collagenase, appears to alter the process of healing that leads to leakage. Further antibiotic administration may seem logical, but carries the unwanted risk of eliminating the normal microbiome, which functions competitively to exclude and suppress the virulence of pathogens such as E. faecalis. Therefore, non-antibiotic strategies that can suppress the production of collagenase by E. faecalis without affecting its growth, or potentially normal beneficial microbiota, may have unique advantages. The findings of this study demonstrate that drinking a phosphate-based polymer can achieve the goal of preventing anastomotic leak by suppressing collagenase production in E. faecalis without affecting its growth., (© 2018 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Background: Ulcerative colitis is frequently treated with total proctocolectomy and ileal pouch-anal anastomosis reconstruction. Causes of pouch failure and criteria for improved patient selection remain poorly understood. We aimed to identify risk factors for pouch failure., Methods: We performed a retrospective chart review of patients in a prospectively maintained database. Consecutive patients undergoing ileal pouch-anal anastomosis for inflammatory bowel disease between 2000 and 2010 at our institution were included. The primary outcome was pouch failure, defined as permanent ostomy diversion or pouch excision., Results: Of 417 total patients, 28 (6.7%) patients developed pouch failure. Pouch failure was associated with female gender, anastomotic leak, Crohn's disease of the pouch and preoperative Clostridium difficile colitis. The use of anti-tumor necrosis factor alpha biologics was not associated with pouch failure. Notably, 14.9% of patients were diagnosed with preoperative C. difficile colitis, a factor independently associated with pouch failure (hazard ratio 3.02; 95% confidence interval, 1.23-7.44; P = 0.016). C. difficile colitis did not contribute to failure by increasing the incidence of anastomotic leak but was associated with a diagnosis of Crohn's disease of the pouch (adjusted hazard ratio 2.27 [1.08-4.79]; P = 0.031). Anastomotic leak (P < 0.001) and pelvic abscess requiring drainage (P = 0.031) were other independent risk factors for pouch failure., Conclusions: In addition to previously known risk factors, history of preoperative C. difficile colitis was associated with pouch failure after reconstruction, suggesting the need for further study into the role of the gut-associated microbiome in pouch outcomes.