Pouch Inflammation Research Articles

Types, behaviour and therapeutic requirements of inflammatory pouch disorders: Results from the RESERVO study of GETECCU

Background and AimsInflammatory pouch disorders exhibit a heterogeneous clinical spectrum and therapeutic requirements have not been properly studied. MethodsThis retrospective, multicentre study included ulcerative colitis patients with ileal pouch construction and were later diagnosed with an inflammatory pouch disorder between 1995 and 2020. Classifications, behaviour and therapies applied were recorded and compared in the long-term. ResultsOverall, 338 patients were recruited. The most common disorders were pouchitis (n = 258, 76%), Crohn's disease of the pouch (n = 55, 16%) and cuffitis (n = 25, 7%). Pouchitis presented mainly as chronic (65.2%) and recurrent (87%) forms. Crohn's disease manifested as stricturing/penetrating in 53% of cases and perianal disease in 42%. Patients received multiple therapies: 86% antibiotics, 42% steroids, 27% immunosuppressants, 43% biologics and 27% surgery. Compared with pouchitis, Crohn's disease of the pouch was characterised by a later diagnosis (99 vs. 55 months, p < 0.001) and greater needs for immunosuppressants (OR 3.53, 1.79–6.94, p < 0.0001), biologics (OR 5.45, 2.78–10.6, p < 0.0001) and surgeries (OR 2.65, 1.43–4.89, p < 0.001). ConclusionsChronic pouchitis is the most common pouch disorder presentation. These entities have diverse therapeutics requirements, particularly for Crohn's disease of the pouch.

Medical Therapies for Prevention and Treatment of Inflammatory Pouch Disorders - A Systematic Review and Meta-analysis.

Pouchitis and Crohn's like disease of the pouch (CLDP) are common in patients who undergo ileal pouch anal anastomosis for ulcerative colitis (UC). We conducted separate systematic reviews to evaluate the effectiveness of available interventions to prevent and treat pouchitis and CLDP. Through systematic literature reviews, we identified studies that evaluated the effectiveness of probiotics, antibiotics, 5-aminosalicylates, non-systemic 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 CDLP 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, UC and Crohn's disease. Probiotics were effective for primary (RR 0.18; 95% 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. 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.

Ileoanal Pouch-Related Fistulas: A Narrative Review.

Ileoanal pouch-related fistula (IAPRF) is a possible complication after ileal pouch-anal anastomosis that significantly impacts pouch prognosis and the patient's quality of life. This study aimed to perform a comprehensive narrative review to better classify the epidemiology, risk factors, etiology, management, and outcomes of IAPRF, and to propose an algorithm for its systematic classification. Ten studies comprising 664 patients with IAPRF were identified, with a prevalence ranging from 4% to 45%. The reported fistula types were as follows: pouch-vaginal (n = 236, 35.5%), perineal (n = 139, 21%), enterocutaneous (n = 54, 8%), pouch-anal (n = 53, 8%), presacral (n = 18, 2%), and anastomotic (n = 15, 2%). Postsurgical pelvic sepsis occurred in 21%-37.2% of patients. Twenty additional studies regarding fistula classification divided them according to onset time and etiology, defining 5 categories: anastomotic-related, technical aspects of the surgery, Crohn's disease-like pouch inflammation, cryptoglandular, and malignancy. Pouch excision was reported in up to 70% of patients. Fistulas associated with anastomotic complications, technical surgical issues, and cryptoglandular fistulas warrant surgical management. On the other hand, fistulas associated with inflammation are preferentially managed with biologics or small molecules.

Endoscopic Response Reduces the Risk of Subsequent Pouchitis in Patients With Crohn's Disease-Like Pouch Inflammation.

The aim of this study was to report the frequency and impact of endoscopic response and remission on the risk of subsequent pouchitis in patients with Crohn's disease-like pouch inflammation (CDLPI) on therapy. This was a single-center retrospective study of patients older than 18 years with CDLPI on therapy. Among 110 included patients with CDLPI in clinical remission, endoscopic remission was not significantly associated with a reduced risk of subsequent pouchitis when compared with endoscopic response. Endoscopic response, not remission, is sufficient to reduce the risk of subsequent pouchitis in patients with CDLPI.

Are Small Molecules Effective in Treating Inflammatory Pouch Disorders Following Ileal Pouch-Anal Anastomosis for Ulcerative Colitis? Here Is Where We Stand.

Ulcerative colitis (UC) management encompasses conventional and advanced treatments, including biological therapy and small molecules. Surgery, particularly in the form of ileal pouch-anal anastomosis (IPAA), is indicated in cases of refractory/severe disease. IPAA can lead to acute complications (e.g., acute pouchitis) as well as late complications, including chronic inflammatory disorders of the pouch. Chronic pouchitis, including the antibiotic-dependent (CADP) and antibiotic-refractory (CARP) forms, represents a significant and current therapeutic challenge due to the substantial need for evidence regarding viable treatment options. Biological therapies have shown promising results, with infliximab, adalimumab, ustekinumab, and vedolizumab demonstrating some efficacy in chronic pouchitis; however, robust randomized clinical trials are only available for vedolizumab. This narrative review focuses on the evidence concerning small molecules in chronic pouchitis, specifically Janus kinase (JAK) inhibitors and sphingosine-1-phosphate receptor (S1P-R) modulators. According to the preliminary studies and reports, Tofacitinib shows a potential effectiveness in CARP. Upadacitinib presents variable outcomes from the case series, necessitating further evaluation. Filgotinib and ozanimod demonstrate anecdotal efficacy. This review underscores the need for high-quality studies and real-world registries to develop robust guidelines for advanced therapies in post-IPAA inflammatory disorders, supported by vigilant clinical monitoring and ongoing education from international IBD specialist societies.

Endoscopic Normalization and Transition of J-Pouch Phenotypes Over Time in Patients With Inflammatory Bowel Disease.

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. 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. 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). 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.

Characteristics of Neutrophil Migration and Function in Acute Inflammation Induced by Zymosan and Carrageenan in the Mice Air Pouch Model.

Deciphering the complex and redundant process of acute inflammation remains challenging. The failure of numerous clinical trials assessing anti-inflammation agents which had promising preclinical effects inevitably questions the validity of current animal models of inflammation. This study aimed to better understand the process of immune inflammatory response and to select more suitable models to evaluate the effect of potential anti-inflammatory drugs. Zymosan and λ-carrageenan are the most used representatives of particulate and soluble irritants that trigger acute inflammation in the air pouch inflammation model. When zymosan was used, the number of exudate cells first increased at 4h-8h, followed by a drop at 12h-24h. While, the changes in number of leukocytes in peripheral blood and proportion of neutrophils in bone marrow have the opposite trend. Meanwhile, neutrophils released neutrophil extracellular traps (NETs) to clean zymosan particles. In contrast, the cell migration response to carrageenan increased during 4h to 24h, no obvious NETs were observed, and the number of leukocytes in peripheral blood increased and the proportion of neutrophils in bone marrow decreased slightly. This study indicated that although both zymosan and carrageenan are sterile irritants, the characteristics of the inflammatory response induced by each other were different. In the acute phase of inflammation, zymosan-stimulated neutrophils were mobilized, recruited, and engulfed, and then died by NETs. Carrageenan stimulated the production of cytokines/chemokines by neutrophils or macrophages, but did not lead to an obvious death by releasing NETs.

Endoscopic assessment of the J pouch in ulcerative colitis: A narrative review.

Patients with ulcerative colitis sometimes need a total colectomy with ileal pouch-anal anastomosis due to medically refractory disease or colitis-associated neoplasia. Up to 50% of patients with ulcerative colitis postoperatively develop pouchitis and the rate of chronic inflammatory pouch conditions requiring pouch excision or diverting ileostomy is reported to be 10%. In order to diagnose and monitor pouchitis, pouchoscopy is essential to assess endoscopic inflammatory findings of the J pouch and to survey neoplasia development, particularly in the remnant distal rectum. However, endoscopic protocols for the evaluation of the pouch may not be standardized worldwide and the reliability of existing disease activity indices for pouchitis has been questioned due to the lack of validation. Recently, reliable endoscopic scoring systems based on an observation of the anatomical location of the J pouch were reported and a significant association between the distribution pattern of endoscopic inflammation (i.e., endoscopic phenotype) and pouch outcomes was also uncovered. In this review, we discuss how to survey the J pouch using pouchoscopy, endoscopic indices for pouchitis disease activity, endoscopic phenotypes and classification, and the pathological mechanisms of pouchitis phenotype in patients with ulcerative colitis.

Piper longum L. ameliorates gout through the MAPK/PI3K-AKT pathway

Ethnopharmacological relevanceGout, a painful joint disease with a prevalence ranging from 0.86% to 2.2% in China over the past decade. Traditional medicine has long utilized the medicinal and edible Piper longum L. (PL) fruit spikes for treating gout and other joint conditions like rheumatoid arthritis. However, the exact mechanisms behind its effectiveness remain unclear. Aim of the studyThis study aimed to investigate the potential of alcoholic extracts from PL fruit spikes as a safe and effective treatment for gout. We used a combined network pharmacology and experimental validation approach to evaluate the mechanisms behind the anti-gout properties of PL. Materials and methodsUPLC-Q/TOF-MS analysis determined the major components of PL. Subsequently, network pharmacology analysis predicted potential molecular targets and related signaling pathways for the anti-gout activity of PL. Molecular docking simulations further explored the interactions between PL compounds and proteins and characterized the properties of potential bioactive secondary metabolites. Mouse models of air pouch inflammation and hyperuricemia were further established, and the anti-gout mechanism of PL was confirmed by examining the expression of proteins related to the MAPK and PI3K-AKT pathways in the tissue. ResultsOur analysis revealed 220 bioactive secondary metabolites within PL extracts. Network pharmacology and molecular docking results indicated that these metabolites primarily combat gout by modulating the PI3K-AKT and MAPK signaling pathways. In vivo experiments have also proven that PL at a dose of 100 mg/kg can optimally reduce acute inflammation of gout and kidney damage caused by high uric acid. The anti-gout mechanism involves the PI3K-AKT/MAPK signaling pathway and its downstream NF-κB pathway. ConclusionThis study provides compelling evidence for PL's therapeutic potential in gout management by modulating key inflammatory pathways. The findings offer a strong foundation for future clinical exploration of PL as a gout treatment option.

P304 Endoscopic cuffitis is associated with severe inflammatory pouch phenotypes

Abstract Background Ulcerative colitis (UC) patients who undergo ileal pouch-anal anastomosis (IPAA) without mucosectomy may develop inflammation of the rectal cuff (cuffitis). Studies have suggested that cuffitis is associated with clinical pouch inflammation (pouchitis), but it remains unclear if cuffitis is associated with specific endoscopic phenotypes of pre-pouch inflammation (ileitis), pouch body inflammation, and diffuse pouch inflammation. Therefore, this aim of this study is to identify if endoscopic cuffitis is a predictor of more severe pouch phenotypes, which may warrant earlier or more aggressive treatment. Methods In this cohort study, charts were reviewed of patients who underwent IPAA at a tertiary care center from 01/2010 to 12/2021. Inclusion criteria for this study were a diagnosis of UC and ≥18 years old at time of colectomy. Exclusion criteria were lack of endoscopic evaluations after the peri-operative period (defined as 6 months following ileostomy closure) and diagnoses other than UC requiring IPAA. Patients were divided into cohorts based on whether they had cuffitis identified on ≥1 endoscopy following IPAA, which was confirmed by two researchers. Outcomes for this study included pre-pouch ileitis, pouch body inflammation, and diffuse inflammation (inflammation of the pouch body, inlet, and pre-pouch ileum). A multivariate logistic regression was used to test for association between cuffitis and each outcome while controlling for potentially confounding variables suggested to be significant on univariate analyses. Results A total of 363 patients were included in this study with an overall median follow-up time of 2.4 (IQR 1.2-3.8) years after ileostomy closure. 149 (41.0%) patients had cuffitis on ≥1 endoscopy following IPAA. 65 (17.9%) patients developed pre-pouch ileitis (Table 1), which was significantly associated with cuffitis (aOR = 3.85; 95% CI 2.15-6.91; p &amp;lt; 0.0001) and age (aOR = 0.98, 95% CI = 0.96-1.00, p = 0.0254). Pouch body inflammation occurred in 201 (55.4%) patients and was associated with cuffitis (aOR = 2.69, 95% CI = 1.69-4.29, p &amp;lt; 0.0001), PSC (aOR = 6.60, 95% CI = 1.85-23.49, p = 0.0036), extraintestinal manifestations (EIMs) other than PSC (aOR = 2.35, 95% CI = 1.45-3.79, p = 0.0005), and age (aOR = 0.98, 95% CI = 0.97-1.00, p = 0.0359). Finally, diffuse inflammation occurred in 20 (5.5%) patients and was associated with cuffitis (aOR = 6.24, 95% CI = 2.04-19.08, p = 0.0013). Conclusion Endoscopic cuffitis is associated with the development of severe inflammatory pouch phenotypes. Future studies are needed to investigate whether treatment of cuffitis reduces this risk and whether the incidence of cuffitis is rising similar to pouchitis in the post-biologic era.

Effectiveness and safety of azathioprine for inflammatory pouch disorders: results from the RESERVO study of GETECCU.

The usefulness of thiopurines has been poorly explored in pouchitis and other pouch disorders. To evaluate the effectiveness and safety of azathioprine as maintenance therapy in inflammatory pouch disorders. This was a retrospective and multicentre study. We included patients diagnosed with inflammatory pouch disorders treated with azathioprine in monotherapy. Effectiveness was evaluated at 1 year and in the long term based on normalization of stool frequency, absence of pain, faecal urgency or fistula discharge (clinical remission), or any improvement in these symptoms (clinical response). Endoscopic response was evaluated using the Pouchitis Disease Activity Index (PDAI). In all, 63 patients were included [54% males; median age, 49 (28-77) years]. The therapy was used to treat pouchitis (n = 37) or Crohn's disease of the pouch (n = 26). The rate of clinical response, remission and non-response at 12 months were 52%, 30% and 18%, respectively. After a median follow-up of 23 months (interquartile range 11-55), 19 patients (30%) were in clinical remission, and 45 (66%) stopped therapy. Endoscopic changes were evaluated in 19 cases. PDAI score decreased from 3 (range 2-4) to 1 (range 0-3). In all, 21 patients (33%) presented adverse events and 16 (25%) needed to stop therapy. Azathioprine may be effective in the long term for the treatment of inflammatory pouch disorders and could be included as a therapeutic option.

Echinodorus macrophyllus: Acute toxicological evaluation of hydroxycinnamoyl derivatives from SF1 subfractions

Ethnopharmacological relevanceEchinodorus macrophyllus (Kunth.) Micheli (Alismataceae), known as chapéu-de-couro in Brazil, is popularly used to treat inflammatory diseases. We have previously demonstrated a significant reduction in the acute inflammation for the aqueous extract of E. macrophyllus (AEEm) and its ethanolic fraction (Fr20) and described that hydroxycinnamoyl derivatives present in SF1 (Fr20 subfraction) showed higher anti-inflammatory properties by mechanisms that include a reduction of TNF-α, IL-1β, CKCL1/KC, LTB4, and PGE2 levels in exudate. Aim of the studyThis work describes the acute toxicological effect of SF1 subfraction on SW mice treated orally for five days in the air pouch model by evaluating the hematological and biochemical determinations on the blood samples; the relative organ weight and its histopathological analysis; the liver genotoxicity assessment and the activity of liver enzymes from xenobiotic metabolism. Materials and methodsFr20 was earlier fractionated on the Sephadex LH-20 column, yielding mainly four subfractions, including SF1. The SF1 toxicity was evaluated in mice challenged with carrageenan on the air pouch inflammation model and orally treated for five days. The body weight was monitored daily, and the organs were weighed after the euthanasia. Hematological and biochemical determinations were carried out using specific commercial kits and following the protocols provided by the manufacturers. The organs were fixed, sectioned, processed for hematoxylin and eosin staining, and analyzed by light microscopy. Genotoxicity assessment was performed by the alkaline single-cell gel electrophoresis. Livers were processed for ethoxyresorufin-O-deethylase (EROD) and Glutathione S-transferase (GST) assays. ResultsSF1 exhibited low toxicity, as no significant discrepancy was observed in the relative weight of the body organs of mice. Moreover, the daily treatment with SF1 did not alter the number and percentage of red blood cells or hemoglobin concentration in the blood. The treatment with SF1 did not affect the creatinine concentration, but the 25 mg/kg dose reduced the plasma urea level and uric acid, suggesting its use in treating acute renal failure. The parameters analyzed did not present biochemical alterations indicative of liver disease. Regarding serum triglyceride and cholesterol levels, a significant decrease was detected in both parameters in mice treated with SF1. In addition, the histopathological analysis showed that inflammatory focus in the livers seemed more relevant in the control groups than in those treated. There were no significant changes in the renal or splenic tissues of animals treated with SF1. Treatment with SF1 also does not have a genotoxic effect on liver cells. ConclusionTreatment with SF1 showed no toxicity in mice at doses equivalent to those recommended for humans, which provides evidence of the safety of the therapeutic use of this subfraction.

Pouchitis Is Associated with Paneth Cell Dysfunction and Ameliorated by Exogenous Lysosome in a Rat Model Undergoing Ileal Pouch Anal Anastomosis.

Pouchitis is a common complication of restorative proctocolectomy and ileal pouch anal anastomosis (IPAA) for ulcerative colitis (UC), significantly affecting the postoperative quality of life. Paneth cells play an important role in the maintenance of gut homeostasis. This study aimed to investigate the role of Paneth cells in the pathogenesis of pouchitis. Endoscopic biopsies from the pouch body and terminal ileum of UC patients undergoing IPAA with or without pouchitis were obtained to analyze Paneth cell function. Acute pouchitis was induced with 5% dextran sulfate sodium (DSS) for seven consecutive days in a rat model of IPAA. The Paneth cell morphology was examined by immunofluorescence and electron microscopy. The effect of exogenous lysozyme supplementation on pouchitis was also investigated. The fecal microbiota profile after DSS and lysozyme treatment was determined by 16s rRNA ITS2 sequence analysis. Abnormal mucosal lysozyme expression was observed in patients with pouchitis. The rat model of pouchitis showed increased pouch inflammation, increased CD3+ and CD45+ T cell infiltration, and decreased tight junction proteins, including ZO-1 and Occludin. There is a significant deficiency of Paneth cell-derived lysozyme granules in the rat model of pouchitis. Supplementation with exogenous lysozyme significantly ameliorated pouchitis, lowering the levels of inflammatory cytokines such as TNF-α and IL-6 in the pouch tissue. 16s rRNA analysis revealed a higher Lachnospiraceae level after lysosome treatment. Paneth cell dysfunction is prominent in patients and rat models of pouchitis and may be one of its causes. The decrease in Lachnospiraceae, a characteristic of dysbiosis in pouchitis, could be reserved by lysosome treatment. Lysozyme supplementation shows promise as a novel treatment strategy for pouchitis.

S902 Assessing the Impact of Interval Duration Between Ileal Pouch Creation and Loop Ileostomy Closure on the Development of Subsequent Inflammatory Pouch Conditions in Patients with Ulcerative Colitis

S902 Assessing the Impact of Interval Duration Between Ileal Pouch Creation and Loop Ileostomy Closure on the Development of Subsequent Inflammatory Pouch Conditions in Patients with Ulcerative Colitis

Predictors of pouch failure: A tertiary care inflammatory bowel disease centre experience.

Rates of pouch failure after total proctocolectomy with ileal pouch-anal anastomosis (IPAA) range from 5% to 18%. There is little consistency across studies regarding the factors associated with failure, and most include patients who underwent IPAA in the pre-biologic era. Our aim was to analyse a cohort of patients who underwent IPAA in the biologic era at a large-volume inflammatory bowel disease institution to better determine preoperative, perioperative and postoperative factors associated with pouch failure. A retrospective cohort analysis was performed with data from an institutional review board approved prospective database with ulcerative colitis or unclassified inflammatory bowel disease patients who underwent total proctocolectomy with IPAA at Mount Sinai Hospital between 2008 and 2017. Preoperative, perioperative and postoperative data were collected and univariate and multivariate analyses were performed to identify factors associated with increased risk of pouch failure. Out of 664 patients included in the study, pouch failure occurred in 41 (6.2%) patients, a median of 23.3 months after final surgical stage. Of these, 17 (41.4%) underwent pouch excision and 24 (58.5%) had diverting ileostomies. The most common indications for pouch failure were Crohn's disease like pouch inflammation (CDLPI) (n = 17, 41.5%), chronic pouchitis (n = 6, 14.6%), chronic cuffitis (n = 5, 12.2%) and anastomotic stricture (n = 4, 9.8%). On multivariate analysis, pre-colectomy biologic use (hazard ratio [HR] 2.25, 95% CI 1.09-4.67), CDLPI (HR 3.18, 95% CI 1.49-6.76) and pouch revision (HR 2.59, 95% CI 1.26-5.32) were significantly associated with pouch failure. Pouch failure was significantly associated with CDLPI, preoperative biologic use and pouch revision; however, reassuringly it was not associated with postoperative complications.

Preoperative Use of Multiple Advanced Therapies Is Not Associated With Endoscopic Inflammatory Pouch Diseases.

Patients with an ileal pouch-anal anastomosis (IPAA) can experience pouch inflammation postoperatively. The use of antitumor necrosis factor (anti-TNF) biologics may be associated with pouch inflammation, but limited data exist on the impact of multiple advanced therapies on development of subsequent pouch inflammation. The aim of this study was to assess for an association between preoperative use of multiple advanced therapies and risk of endoscopically detected inflammatory pouch diseases (EIPDs). We performed a retrospective analysis of ulcerative colitis (UC) and indeterminate colitis (IBDU) patients who underwent an IPAA at a quaternary care center from January 2015 to December 2019. Patients were grouped based on number and type of preoperative drug exposures. The primary outcome was EIPD within 5 years of IPAA. Two hundred ninety-eight patients were included in this analysis. Most of these patients had UC (95.0%) and demonstrated pancolonic disease distribution (86.1%). The majority of patients were male (57.4%) and underwent surgery for medically refractory disease (79.2%). The overall median age at surgery was 38.6 years. Preoperatively, 68 patients were biologic/small molecule-naïve, 125 received anti-TNF agents only, and 105 received non-anti-TNF agents only or multiple classes. Ninety-one patients developed EIPD. There was no significant association between type (P = .38) or number (P = .58) of exposures and EIPD, but older individuals had a lower risk of EIPD (P = .001; hazard ratio, 0.972; 95% confidence interval, 0.956-0.989). Development of EIPD was not associated with number or type of preoperative advanced therapies.

Evaluation and management of ileal pouch-anal anastamosis (IPAA) complications in pregnancy, and the impacts of an IPAA on fertility.

Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) remains the preferred surgical option for medically refractory ulcerative colitis. Management of individuals with an IPAA prior to and during pregnancy presents challenges that can have serious consequences. Infertility, mechanical obstructive and inflammatory pouch complications are frequently encountered in pregnant women with an IPAA. Mechanical obstructions occur due to a variety of underlying aetiologies, including stricturing disease, adhesions and pouch twists. Conservative management of such obstructions often results in resolution of symptoms without a need for endoscopic or surgical intervention, although endoscopic decompression may be attempted in isolation or as a bridge to definitive surgical intervention. Parenteral nutrition, and early delivery, may also be necessary. Faecal calprotectin and intestinal ultrasound, both of which are accurate in pregnancy, are useful in the setting of suspected inflammatory pouch complications, in some circumstances allowing for avoidance of pouchoscopy. Penicillin-based antimicrobials can be considered first line in pregnancy for the management of pouchitis and pre-pouch ileitis, and biologics can be safely instituted in the setting of refractory disease or suspected Crohn's disease-like inflammation of the pouch or pre-pouch ileum. Pragmatism, clear patient communication and multidisciplinary discussion are essential in approaching pregnant women with complications of an IPAA, particularly given the lack of definitive evidence to guide therapeutic decisions.

Curable leakage in stapled IPAA has little effect on the long-term pouch function.

This study aimed to evaluate the frequency and grade of anastomotic leakage (AL) in stapled ileal pouch-anal anastomosis (IPAA) and its long-term impact on the pouch functions. A longitudinal cohort study was conducted on UC patients who underwent stapled IPAA at Yokohama City University Medical Center between 2007 and 2018. The diagnosis and grading of AL were performed in accordance with the recommendations of the International Study Group of Rectal Cancer. We assessed the functional pouch rate, late complication, pouch survival rate, bowel function (bowel movements per day, soiling, spotting, difficulty in distinguishing feces from flatus) and pouch inflammation (pouchitis disease activity index; PDAI) in the long-term period. Two hundred seventy-six patients were analyzed. Twenty-three (8.3%; grade B/C; 13/10) patients were diagnosed with AL, but a functional pouch was achieved in all the twenty-three patients. Anastomotic stricture was significantly more common in patients with AL (AL group) than in patients without AL (non-AL group; AL/non-AL: 13.0/3.2%, p = 0.020). There were no differences in other late complications. Furthermore, the pouch survival rate did not differ between the AL and non-AL groups (100.0/97.9%/10years, p = 0.494). There were no differences between the groups in bowel movements per day, spotting, soling, difficulty in distinguishing feces from flatus, or PDAI postoperatively. Curable AL may not affect late complications (except anastomotic stricture), pouch survival, the bowel function, or pouch inflammation over the long term. Perioperative management to prevent the severity of AL is as important as preventing its occurrence.

Treatment of Chronic Inflammatory Pouch Conditions With Tofacitinib: A Case Series From 2 Tertiary IBD Centers in the United States.

This case series showed that tofacitinib was effective and safe for some of patients with chronic pouchitis or Crohn’s disease–like pouch inflammation. Further research is warranted to better understand the long-term efficacy and safety of tofacitinib for chronic inflammatory pouch conditions.

P910 Emerging role of IL-33/ST2 and Gut Microbiota axis in the inflammatory process of ulcerative colitis patients with ileal pouch-anal anastomosis

Abstract Background IL-33/ST2 axis and gut microbiota are important factors in the pathogenesis of IBD with a potential reciprocal influence. IL-33/ST2 axis controls the mucosal healing process during intestinal inflammation. Pouchitis, after restorative proctocolectomy with ileal pouch-anal anastomosis, is the most common complication. We aimed to explore the potential correlation between mucosal cytokines and gut microbiota in the inflammatory process of pouchitis. Methods 23 patients with ileal pouch-anal anastomosis were enrolled. 13 showed pouchitis and 10 a normal pouch. Mucosal samples were collected from the afferent ileal loop and from the pouch. Multiplex analysis for cytokines was performed. ELISA, western blot and IHC were run to assess IL-33/ST2 axis. Microbiota was analyzed by 16S ribosomal RNA gene amplicon pyrosequencing. Pouchitis Disease Activity Index and Pouchitis Histological Score were calculated. Multivariate analyses were run to generate transcriptional interaction networks and identify biomarkers for patients with inflamed pouches. Results IL-1Ra, IL-6, IL-8, IL-17, IP-10, MCP-1, MIP-1a, MIP-1b were increased in the inflamed pouch vs. normal pouch. No differences were registered in samples from the afferent ileal loop. In pouchitis, IL-7 resulted reduced in the inflamed pouch vs. the ileal loop. In normal pouch, no differences were recorded. In pouchitis, IL-33 and ST2 protein levels were significantly reduced in the pouch vs. the ileal loop and resulted decreased vs. normal pouch. Full-length, bioactive IL33, ST2L and sST2 were expressed in all experimental groups; the cleaved, less active form of IL33 was increased only in pouchitis. IL-33 and ST2 stainings were less intense within the inflamed and ulcerated mucosa of pouchitis compared to the normal pouch and in close proximity to areas of re-epithelialization. Microbiota analysis showed a decreased biodiversity in pouchitis vs. normal pouch (both at pouch and ileal loop level). Lower levels of Verrucomicrobia and increased abundance of Actinobacteria were recorded in inflamed pouch vs normal pouch. In pouchitis, the ileal loop and the pouch showed decreased levels of Akkermansia muciniphila and augmented abundance of Collinsella vs. samples from the normal pouch. In pouchitis, multivariate analyses evidenced a significant inverse correlation between Collinsella e Collinsella aereofaciens abundance and ST2 levels. Conclusion Pouchitis and normal pouch are characterized by divergent inflammatory molecular pathways and microbial populations with a specific pattern between the pouch and afferent ileal loop. Our results suggest a potential role for IL-33/ST2 and gut microbiota axis in driving the gut mucosal wound healing in patients with ileal pouch-anal anastomosis.