Ileal Pouch Research Articles

Long-term mental and physical quality of life outcomes following ileal pouch anal anastomosis surgery.

This study presents the authors' experience over 14 years of performing restorative procto-colectomy with ileal pouch anal anastomosis (IPAA). The aim was to study the long-term quality of life outcomes and analyse the predictors of pouch function as well as physical and mental wellbeing. This is a single-centre retrospective study conducted in a specialised colorectal surgery unit in the UK. The study included patients who underwent two- or three-staged panproctocolectomy with defunctioning ileostomy for ulcerative colitis (UC) or familial adenomatous polyposis between 2004 and 2018. Data were collected from a prospectively, surgeon-maintained database. Pouch function and quality of life scores were obtained via validated questionnaires. A multivariate analysis was utilised to explore predictors of quality of life and pouch function. The study reports 105 patients who underwent IPAA with a covering ileostomy. The majority of operations were performed for UC (97, 92.4%). The median age of patients was 36 years and the male to female ratio was 1:1. Thirty patients (28.5%) suffered early post-IPAA complications, while pouch failure rate was 11.4% (12/105). Late complications were reported at a rate of 45%. On long-term follow-up, the median Pouch Function Score was 7 (IQR 3-14). Both the physical and mental sections of the quality of life score were at a median indistinguishable from the normal population but had different predictors associated with them. Our findings recognise the complex interplay between physical and psychological wellbeing after pouch surgery and advise psychological counselling where appropriate.

Endoscopic Evaluation of the Ileal Pouch.

Structural and inflammatory adverse sequelae are common after restorative proctocolectomy and IPAA. On rare occasions, neoplasia can occur in patients with ileal pouches. Pouchoscopy plays a key role in the diagnosis, differential diagnosis, disease monitoring, assessment of treatment response, surveillance, and delivery of therapy. A systematic review of the literature was performed, and principles and techniques of pouchoscopy were described. PubMed, Google Scholar, and Cochrane databases. Relevant articles on endoscopy in ileal pouches published between January 2000 and May 2023 were included based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Diagnostic, surveillance, and therapeutic endoscopy in ileal pouch disorders were included. Accurate characterization of the ileal pouch in healthy or diseased states. The main anatomic structures of a J- or S-pouch are the stoma closure site, prepouch ileum, inlet, tip of the "J," pouch body, anastomosis, cuff, and anal transition zone. Each anatomic location can be prone to the development of structural, inflammatory, or neoplastic disorders. For example, ulcers and strictures are common at the stoma closure site, inlet, and anastomosis. Leaks are commonly detected at the tip of the "J" and anastomosis. Characterization of the anastomotic distribution of inflammation is critical for the differential diagnosis of subtypes of pouchitis and other inflammatory disorders of the pouch. Neoplastic lesions, albeit rare, mainly occur at the cuff, anal transition zone, or anastomosis. This is a qualitative, not quantitative, review of mainly case series. Most structural, inflammatory, and neoplastic disorders can be reliably diagnosed with a careful pouchoscopy. The endoscopist and other clinicians taking care of pouch patients should be familiar with the anatomy of the ileal pouch and be able to recognize common abnormalities. See video from symposium.

Normal Ileal Mucus Is Inadequate for Epithelial Protection in Ileal Pouch Mucosa.

Clinical, nonspecific pouchitis is common after restorative proctocolectomy for ulcerative colitis, but its cause is unknown. A possible lack of protection for the ileal mucosa in its role as a reservoir for colonic-type bacteria may be the missing piece in defining the causes of pouchitis. The study aimed to review the causes of pouchitis and introduce the hypothesis that inadequate mucus protection in the pouch, combined with a predisposition to abnormal inflammation, is the most common cause of nonspecific pouchitis. Review of PubMed and MEDLINE for articles discussing pouchitis and intestinal mucus. Studies published from 1960 to 2023. The main search terms were "pouchitis," and "intestinal mucus," whereas Boolean operators were used with multiple other terms to refine the search. Duplicates and case reports were excluded. Current theories about the cause of pouchitis, descriptions of the role of mucus in the physiology of intestinal protection, and evidence of the effects of lack of mucus on mucosal inflammation. The crossreference of "intestinal mucus" with "pouchitis" produced 9 references, none of which discussed the role of mucus in the development of pouchitis. Crossing "intestinal mucus" with "pouch" resulted in 32 articles, combining "pouchitis" with "barrier function" yielded 37 articles, and "pouchitis" with "permeability" yielded only 8 articles. No article discussed the mucus coat as a barrier to bacterial invasion of the epithelium or mentioned inadequate mucus as a factor in pouchitis. However, an ileal pouch produces a colonic environment in the small bowel, and the ileum lacks the mucus protection needed for this sort of environment. This predisposes pouch mucosa to bacterial invasion and chronic microscopic inflammation that may promote clinical pouchitis in patients prone to an autoimmune response. No prior studies address inadequate mucus protection and the origin of proctitis. There is no objective way of measuring the autoimmune tendency in patients with ulcerative colitis. Studies of intestinal mucus in the ileal pouch and its association with pouchitis are warranted.

MUCOSAL SINGLE-CELL PROFILING OF CROHN’S-LIKE DISEASE OF THE POUCH REVEALS COMMON PATHOGENICS AND THERAPEUTIC TARGETS

Abstract BACKGROUND & AIMS After restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC), a subset of patients develop Crohn’s-like disease of the pouch (CDP), an inflammatory condition that affects both the ileoanal pouch and extra-pouch organs including pre-pouch ileum. The cellular and molecular identities of CDP are unknown, and its diagnosis and treatment remain challenging. To define the pathophysiology of CDP, we examined mucosal cells from patients with and without CDP using single cell analyses. METHODS Endoscopic samples from the pouch and pre-pouch ileum of 50 patients with an IPAA were collected for single-cell RNA sequencing (scRNA-seq) or mass cytometry (or CyTOF). We analyzed immune and non-immune cells from pouch and ileal tissues of patients with normal pouch/ileum and CDP (n = 5 or 6) using scRNA-seq. CyTOF was performed on mucosal immune cells from independent cohorts of patients with normal pouch/ileum, CDP, and pouchitis (n = 9 or 10). Mucosal samples from patients with familial adenomatous polyposis (FAP) after pouch formation were also analyzed by CyTOF. Some scRNA-seq and CyTOF findings were independently validated using immunohistochemistry (n = 6 or 8). RESULTS We revealed distinct immune and non-immune cell clusters in normal pouch and pre-pouch ileum. Colitogenic immune cells expanded in normal UC pouch compared to normal FAP pouch. Compared to normal pouch/pre-pouch ileum, CDP tissues exhibited expanded TCR clonotypes, elevated Th17 signaling, and diminished T cell exhaustion markers. Elevated frequencies of plasma cells, inflammatory fibroblasts and monocytes were noted in CDP pouch and ileum (Fig 1; only pouch data were shown). CDP also harbored elevated Th17-inducing cytokines such as IL23, IL1B, and IL6 produced by myeloid cells. ScRNA-seq and CyTOF identified increased CD14+TREM1+ pathogenic monocytes in both pouch and pre-pouch ileum of CDP. Ligand-receptor interactions further uncovered an essential role of proinflammatory myeloid cells in the pathogenesis of CDP. In addition, pouch and pre-pouch ileum of CDP showed prominent activation of the unfolded protein response (UPR) across all major cell compartments (Fig 2), which was not present in UC, CD or pouchitis based on integrated analysis of published databases. CONCLUSIONS CDP demonstrates altered immune and non-immune cell populations/states in the pouch and pre-pouch ileum. CDP represents a distinct entity of inflammatory bowel disease with extensive UPR activation, a unique feature that may serve as novel diagnostic markers and therapeutic targets using ER stress-alleviating agents including chemical chaperones. Fig 1 CDP reshapes immune and non-immune landscapes in pouch and pre-pouch ileum. (A) UMAP visualization of all cells from the pouch and ileum of CLDP and normal controls. (B) Diversity of epithelial cells, stromal cells, myeloid cells, T cells, innate lymphoid cells (ILCs), B cells and plasma cells in CLDP vs. normal controls in the pouch estimated by scRNA-seq (n = 5 or 6). *p<0.01. Fig 2 Extensive UPR activation in CDP tissues. (A) UPR gene expression in major cell compartments in CDP and normal controls, highlighted genes including CALR, XBP1, and SERP1 were upregulated in all 5 cell compartments. (B) ER stress/UPR pathways are enriched in CDP. (C) IHC of UPR proteins XBP1 and HSPA5/BiP.

EPITHELIAL MITOCHONDRIAL DYSFUNCTION IN CHRONIC POUCHITIS

Abstract BACKGROUND Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgical procedure of choice for patients with refractory ulcerative colitis (UC). However, patients with IPAA are at risk of pouch-related disorders like “pouchitis” with an incidence rate range from 20-50%. The underlying etiopathogenesis of pouchitis has been unclear, which makes management and treatment of active pouchitis difficult. Mitochondrial (Mito) dysfunction is commonly associated with pathogenesis of inflammatory bowel diseases (IBD). We posit the reduced Mito function contributes to chronic pouchitis in IPAA patients. In this study we performed comparative analysis of Mito complex levels in pouchitis patients compared to normal controls. METHODS Biopsies collected from ileal pouches +/- inflammation (n=6), and normal (n=3) and inflamed ileum (CD Ileitis; n=3 mean SES=5.2) were preserved in Allprotect® or formalin. Total RNA was extracted, cDNA synthesized and analyzed by RT-qPCR for genes specific for Mito biogenesis and complexes, cytokines and cellular antioxidant machinery. Formalin-fixed tissues were processed for IHC staining of Mito complex-I (NDUFB6) and complex-IV (MTCO1). RESULTS Transcriptomic analysis of active pouchitis tissue showed significant (**p<0.01) reduction of Mito biogenesis genes (PGC1α: 69.5±13.9%, TFAM: 48.7±14.5%, NRF1:48.9±17.7%) compared to normal pouch. Similar mRNA analysis in CD-ileitis showed 90.6±15.2% reduction in PGC1α gene (**p<0.01) and more than 62% reduction in TFAM and NRF1 genes compared normal ileum. We also observed 21.6±9.8% reduction in Mito complex I (Ndufa1, Ndufa4, Ndufb2, Ndufb6), 33.6±8.7% reduction in complex-IV (Cox5a Cox6a1, Cox5e) and 38.8±11.8% reduction in complex-V (ATP5a, ATP5b, ATP5e) in chronic pouchitis compared to normal controls. In contrast, CD-ileitis showed 59.5±10.2% reduction in Mito complexes at mRNA level compared to normal ileum. Altogether, CD-ileitis showed 26.3% and 23.8% reduction in Mito complexes and biogenesis genes, respectively, compared to pouchitis. At protein level, tissues from chronic pouchitis showed significantly reduced expression of NDUFB6 and MTCO1 compared to normal controls. However, the decreased expression of NDUFB6 and MTCO1 was more pronounced in active CD-ileitis patients. Concertedly, suppression of Mito biogenesis and complex genes correlated with upregulation of pro-inflammatory cytokines (IL1β and IL-6) and concomitant reduction of anti-oxidant genes (Sod1, Sod2, Gpx, Prdx-2,3,4,6). CONCLUSION These data indicate decreased levels of Mito complexes in pouchitis, although reductions are less prominent in active CD. We postulate that Mito dysfunction plays a role in the pathogenesis of chronic pouchitis after IPAA surgery in IBD patients. Furthermore, we posit mitochondria-targeted therapy may deliver therapeutic benefits in refractory pouchitis.

P358 Impact of end-ileostomy versus ileal pouch-anal anastomosis on graft-survival following liver transplantation for primary sclerosing cholangitis

Abstract Background IBD-PSC patients may require both liver transplantation and ileoanal pouch (IPAA) construction. Recently, concerns have been raised regarding an increased rates of hepatic artery thrombosis, biliary strictures, and graft loss in individuals who underwent IPAA after liver transplantation compared to those who underwent end-ileostomy (EI). We hypothesized that graft survival was not negatively affected by IPAA compared with EI. Methods A prospectively maintained database from a large tertiary center was searched for patients meeting the inclusion criteria for liver transplantation, primary sclerosing cholangitis, ulcerative colitis, and total colectomy with IPAA or EI. Univariate analysis and Kaplan-Meier survival curves were calculated. Results Between January 1990 and December 2023, 55 patients met inclusion criteria. Of these, 46 (83.6%) underwent IPAA, and 9 (16.4%) underwent EI. The average age at colectomy (41.7 vs. 45.7 years; p=0.44), sex distribution (female: 26.1% vs. 22.2%, p=1), and MELD score before transplantation (20.3 vs. 14; p=0.06) were comparable between patients with IPAA and EI patients. The rates of re-transplantation (21.7% vs. 22.2%; p=1), hepatic artery thrombosis (8.7% vs. 0; p=1), episodes of acute rejection (32.6% vs. 44.4%; p=0.7), chronic rejection (4.3% vs. 11.1%; p=0.42), recurrence of primary sclerosing cholangitis (23.9% vs. 22.2%; p=1), and biliary complications (21.7% vs. 33.3%; p=0.43) were similar between the IPAA and EI groups, respectively. None of the EI patients developed parastomal varices. Survival analyses for time to re-transplantation (p=0.97), overall survival (p=0.3), and time to graft loss or mortality (p=0.73) were similar. Conclusion In contrast to a previous study, we observed similar rates of liver transplant graft loss, biliary complications, and recurrent PSC after IPAA compared to those after end-ileostomy. IPAA may be associated with an increased rate of hepatic artery thrombosis.

P609 Artificial intelligence in the image recognition of pouchoscopies in patients who have undergone restorative proctocolectomy with ileal pouch anal-anastomosis (IPAA)

Abstract Background Restorative proctocolectomy with ileal pouch anastomosis (IPAA) has become the gold standard in the surgical treatment of ulcerative colitis, with pouchitis being the most common late complication of IPAA. Pouchoscopy is the diagnostic tool of choice to examine the pouch in cases of pouchitis. Artificial intelligence (AI)-based image recognition programmes can assist the examiner in making a diagnosis, support in the education of physicians in training and potentially improve patient outcomes. The use of artificial intelligence has not yet been demonstrated in patients with IBD. The aim of this study is the development of an image recognition algorithm based on Convolutional Neural Networks (CNN) that reliably detects the endoscopic findings of pouchitis analogue to the PDAI score in endoscopic images. Methods The dataset consisted of 10 pouchoscopy videos, which were split into individual frames and assessed using a specially developed labelling tool. In the training process, the labelled images were divided into training, validation and test datasets (ratio 60:20:20). Pre-trained networks and hyperparameters were selected by cross-validation. The defined networks were then fine-tuned through tenfold cross-validation and evaluated for accuracy, specificity, precision F1 score and AUC. Results Our dataset consisted of 7130 images, with 1961 images in the „Inflammation“ group, 2326 images in the „Not assessable“ group and 2843 images in the „Healthy“ group. The final model has been cross-validated 10 times and has been shown to be able to correctly assess the endoscopic features of pouchitis to a certain extent. However, its performance is not yet sufficient for clinical use. Conclusion The work has shown that it is possible to develop an image recognition programme using artificial intelligence that is capable of detecting endoscopic features of pouchitis to a certain extent. Our model is not yet able to make a reliable classification, so it is not yet ready for practical use. However, it should be noted that this project was a feasibility study with a small number of cases and a limited patient population. Further research and more data are needed to sufficiently train the model. Once this is done, the model could be further developed to make reliable classifications and be used in clinical practice.

P270 Male Genitourinary Dysfunction after Primary and Reoperative Ileoanal Pouch Surgery

Abstract Background Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the preferred surgical treatment for patients with IBD or FAP. As these diseases often manifest during adolescence or early adulthood, treatment effects on genitourinary function (GU) and sexual function are of paramount importance. However, the reoperative IPAA (R-IPAA) effects on male GU function and sexual function compared to primary IPAA (P-IPAA) are not known. Therefore, we conducted an observational survey to compare the long-term GU functionality of P-IPAA and R-IPAA long-term GU functionality male patients. We hypothesized that R-IPAA is associated with higher GU-dysfunction compared to R-IPAA. Methods All adult male patients who underwent IPAA at a single tertiary hospital between 1983 and 2022 were identified and demographics and clinical data were obtained from our prospectively maintained pouch registry. Patients were surveyed using validated questionnaires (Table 1). The primary outcome was composite survey scores. Patients were stratified into P-IPAA or R-IPAA groups; R-IPAA was defined as IPAA excision, reconstruction, or revision. Patients status-post prostatectomy were excluded. Results A total of 1,836 male patients were surveyed, and 457 (24.9%) submitted a response. After exclusion criteria, 339 responses were analyzed:296 (87.3%) P-IPAA and 38 (11.2%) R-IPAA, which included 22 redo IPAA, 9 excisions, and 7 revisions. In both groups, most patients had ulcerative colitis (89 vs. 90%). P-IPAA compared to R-IPAA had a similar age at surgery (40.8 vs. 42, p=0.59), similar age at survey (56.2 vs. 56.4, p=0.94), and a similar interval between surgery and survey (15.4 vs. 14.4, p=0.51). The P-IPAA group had less severe sexual dysfunction than the R-IPAA group (IBD-MSDS, 2.0 vs. 7.0, p=0.002). No significant difference was observed between P-IPAA and R-IPAA in erectile dysfunction (SHIM score 21 vs. 18.5, p=0.24), urinary tract symptoms (CLLS, 5.5 vs. 8.0, p=0.06), use of therapeutic aids for sexual activity (6 vs. 7, p=0.29), or orgasm ability (4 vs. 4, p=0.3). Patients with P-IPAA had a higher CGQoL (0.83 vs. 0.7, p=0.02). There were no differences between patients who had difficulty conceiving a child (4 vs. 7, p=0.5) and those who experienced infertility (3 vs. 1, p=0.43). In patients with fertility problems, no quality-of-life differences were observed between the groups (FertiQoL, 85.9 vs. 88.5, p=0.62). Conclusion Primary-IPAA was associated with increased sexual function and overall higher global quality of life compared to R-IPAA. No difference in erectile function, LUTS, and the need for therapeutic aids for sexual function, orgasm ability, or fertility were observed.

P252 Male Genitourinary Dysfunction after Minimally Invasive and Open Ileoanal Pouch

Abstract Background Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the preferred surgical treatment for IBD or FAP. As these diseases often manifest during adolescence or early adulthood, treatment effects on genitourinary function (GU), sexual function, and fertility are of paramount importance. However, the difference in male GU function and sexual function after minimally invasive IPAA (MIS-IPAA) compared to open-IPAA are unclear. We conducted an observational survey to compare long-term GU functionality in male patients’ post MIS-IPAA or open-IPAA. Methods All adult male patients who underwent IPAA at a single tertiary hospital between 1983 and 2023 were identified, and demographics and clinical data were obtained from our prospectively maintained pouch registry. Patients were surveyed using validated questionnaires (Table 1). The primary outcome was the composite survey scores. Patients were stratified into MIS-IPAA (laparoscopic, robotic, single-incision surgery) or open-IPAA groups based on the mode of pelvic/rectal dissection. Reoperative IPAA procedures (revisions, redo, and excisions), incomplete surveys, patients with permanent ileostomy, and status post prostatectomy were excluded. Results A total of 1,836 patients were surveyed, and 457 (24.9%) submitted a response. After exclusion criteria, 296 responses were analyzed: 236 (79.7%) open-IPAA and 60 (20.3%) MIS-IPAA. In both groups, most patients had ulcerative colitis (88 vs. 89%). Compared to open-IPAA, MIS-IPAA had a similar age at surgery (40.6 vs. 40.9, p=0.88), younger age at survey (48.2 vs 58.2, p<0.001), and shorter interval between surgery and survey (7.7 vs. 17.4, p<0.001). Male MIS-IPAA patients were able to achieve orgasm more successfully than those with open-IPAA (5 vs. 4, p=0.001). No significant difference was observed between MIS- and open-IPAA in erectile function (SHIM score 22.5 vs 21, p=0.22), IBD-specific male sexual dysfunction (IBD-MSDS, 3 vs. 2, p=0.19), lower urinary tract symptoms (LUTS) (CLLS, 4 vs. 6, p=0.16), or use of therapeutic aids for sexual activity (6 vs. 6, p=0.7). There was no difference in global quality of life (CGQoL, 0.83 vs 0.80, p=0.6). There were no differences between the patients who had difficulty conceiving a child (4 vs. 7, p=0.46) and those who experienced infertility (1 vs. 2, p=0.54). Patients experiencing infertility showed no difference in quality of life between the MIS- and open-IPAA groups (FertiQoL, 84.9 vs 85.9, p=0.64). Conclusion Minimally invasive IPAA had a higher preservation of orgasm ability than did open IPAA. There was no difference in erectile function, LUTS, need for therapeutic aids for sexual function, or fertility between MIS and open approach to pelvic dissection in IPAA.

P500 Systematic review of sexual function measurement instruments in the context of pelvic and perineal surgery for Inflammatory Bowel Disease

Abstract Background Sexual dysfunction after Inflammatory Bowel Disease (IBD), pelvic and perineal surgery is common but poorly discussed, investigated and treated in the peri-operative period. There remains no standardised measurement tool to assess sexual function in routine use for patients undergoing benign pelvic colorectal surgery. The necessity for open dialogue regarding sexual dysfunction was evidenced in a patient-led study conducted by Dames et al. Our primary objective was to undertake a systematic review of sexual function measurement instruments, to identify the need for a novel sexual function patient-reported outcome measure (sex-PROM) that may be used in the context of pelvic and perineal surgery for IBD e.g. fistula surgery, defunctioning ostomy formation, ileo-anal pouch formation and proctectomy. Methods We performed a systematic review according to Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) criteria (Prospero registration: CRD42023403396). Embase, Medline and PubMed Databases were searched for previously validated patient-reported outcome measures that could be used in the assessment of sexual function. These instruments were evaluated for their psychometric properties, in addition to their overall quality, utility and suitability in the context of IBD and other benign surgery. A global rating was attained according to COSMIN criteria. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) checklist was applied to evaluate the quality of evidence. In addition, patient involvement in instrument development was assessed. Results Some 2331 articles were screened, 305 full-text studies were assessed for eligibility and 56 measurement instruments were identified and evaluated. All studies showed limited psychometric validation. The Female Sexual Function Index and the International Index of Erectile Function were among the highest-scoring instruments, however conveyed significant limitations, including an anatomical focus, limited exploration of quality of life and relationship satisfaction, and a lack of significant patient involvement in their development. All identified measurement instruments carried limited specific clinical utility for patients after IBD surgery. Conclusion Sexual dysfunction after pelvic surgery for inflammatory bowel pathology is multi-factorial. It can result from anatomical nerve damage but can also occur secondary to the psychological impact of altered body image, sexual self-esteem, and relationships and intimacy. We recommend the development of a novel patient-centred sexual function measurement instrument that may be used after benign pelvic/perineal colorectal surgery to be used in the clinical and research settings.

P1173 Higher total antioxidant capacity of diet is associated with reduced surgery risk in individuals with Inflammatory Bowel Disease in a prospective cohort study

Abstract Background Oxidative stress exacerbates inflammatory Bowel Disease (IBD), and dietary antioxidants are proposed as a promising manner to counteract this imbalance. However, the role of individual antioxidants in the complex milieu of the human body may exhibit synergistic or interactive effects. The research has yet to comprehensively examine the impact of dietary total antioxidant capacity (TAC) on IBD prognosis. To fill this knowledge gap, this study aimed to investigate the assocaitions between dietary TAC and risk of related surgery among individuals with IBD in a prospectively recruited cohort. Methods We included 2439 individuals with IBD at baseline from UK Biobank. All participants have completed a web-based validated 24-h dietary recall up to five rounds in 2009-2012, reporting their consumption of more than 200 foods and beverages. We calculated the TAC of the diet using the oxygen radical absorbance capacity method and were grouped by quintiles. The outcomes of interest were IBD-related surgery (bowel resection, perianal-related surgery, Strictureplasty, and ileoanal pouch formation), ascertained via linkage to national inpatient data. Cox proportional hazard models were applied to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). Results During a mean follow-up of 10.4 years, we identified 261 incident surgical cases related to IBD. The mean age of the participants was 56.9 years, and 51% were females. When comparing extreme quintiles of dietary TAC, individuals with higher dietary TAC were associated with a lower risk of related surgery (HR 0.57, 95% CI 0.38-0.86, P=0.007). The inverse associations between dietary TAC and related surgery were consistent among individuals with ulcerative colitis (HR comparing extreme quintiles 0.59, 95% CI 0.36-0.96, P=0.036). For individuals with Crohn’s disease, the associations were not significant when comparing extreme quintiles of dietary TAC (HR 0.51, 95% CI 0.25-1.03, P=0.060), while we observed a significant 9% risk reduction (HR 0.81, 95% CI 0.65-1.00, P=0.048) of related surgery by per 1-SD increment in dietary TAC among individuals with Crohn’s disease.(Table 1) Conclusion In this large large-scale population-based cohort study, we observed that higher dietary TAC was associated with reduced risk of related surgery in individuals with IBD. Our findings provide insights that could inform dietary recommendations and potentially improve IBD management strategies.

P584 Complication rates after two-stage vs three-stage restorative proctocolectomy with ileoanal pouch construction in the era of biologics

Abstract Background Patients with proctocolectomy and ileoanal pouch construction typically undergo a two-stage or three-stage surgical procedure, depending on the general condition and recent immunosuppressive therapy. Our single center database prospectively records all surgeries performed since 2021 and retrospectively of patients before this year. Complications are registered by Clavien-Dindo classification. Methods All patients with two-stage or three-stage proctocolectomy and ileoanal pouch construction were identified from the database. The prevalence and severity of complications was analyzed according to Clavien-Dindo, with scores of 3 and above classified as severe complication. Patients were grouped by having either one or more severe complications or none at any surgical procedure. Results 102 patients were identified from the database, of those 44 (43%) had a two-stage procedure and 58 (57%) a three-stage procedure. In the three-stage group, 25 (43%) patients were on active systemic corticosteroid therapy at the time of the first surgery compared to 0 patients in the two-stage group (p<0.001). Biological therapy within the last 3 months before the first surgery was received by 35 (60%) of the patients in the three-stage group versus 16 (36%, p=0.016 ) in the two-stage group. The three-stage procedure resulted in 11 out or 58 patients (19%) having at least one major complication compared to 3 out of 44 patients (7%) of the group with two-stage approach (p=0.077). Conclusion There is a trend towards a higher major complication rate in patients operated by a three- versus a two-stage approach in restorative proctocolectomy. This may be due to a selection bias as patients undergoing a three-stage procedure had significantly more often steroids at the time of first surgery and significantly more often biological therapy three months before the first surgery. Further data collection and then multivariate analysis including further risk factors, need to be done in order to better define the preferable individual surgical strategy.

P621 Safety and effectiveness of vedolizumab and ustekinumab in inflammatory bowel disease patients after liver transplantation for primary sclerosing cholangitis: results from an ECCO-confer case series

Abstract Background Primary sclerosing cholangitis (PSC) is a chronic progressive cholestatic liver disease often necessitating liver transplantation (LTX). Approximately 70% of PSC patients have a concomitant diagnosis of inflammatory bowel disease (IBD) and could need treatment with biological therapy on top of the immunosuppression to prevent transplant rejection. Vedolizumab (VDZ) and ustekinumab (UST), both agents with a favorable safety profile, are often used in this population despite lack of data concerning safety and effectiveness in the post-LTX setting. Methods A retrospective multicenter case series was performed as a part of the European Crohn's and Colitis Organisation [ECCO] Collaborative Network of Exceptionally Rare case reports [CONFER] project. Primary endpoints were clinical and endoscopic remission at week 52, occurrence of infectious complications, occurrence of malignancy, hospitalizations, and death after liver transplantation. Results In this retrospective study, 58 patients (male n= 34 (59%), median age 42 (interquartile range (IQR) 32-52) were included across 16 participating centers of which 24 (38%) were treated with UST and 40 (63%) with VDZ. Twelve patients (20%) were diagnosed with Crohn’s disease (CD), 44 (76%) with ulcerative colitis (UC), 2 (3%)- with unclassified IBD (IBD-U) and in 12 (20%) patients had an ileal pouch anal anastomosis (IPAA). Median disease duration was 16 years (IQR 13-26) and 33 (56%) had received biological therapy prior to LTX (33% anti-TNF, 11% VDZ, 5% UST). Median disease duration for PSC was 15.5 years (IQR 11-25) and median time since LTX was 6 years (IQR 4-10). Clinical remission, assessed according to physician global assessment, at week 52 was achieved in 44% of VDZ compared to 38% of UST treated patients (p=0.17), while endoscopic remission was seen in 17% of patients in the VDZ group versus 33% in the UST treated patients (p=0.87). Clinical effectiveness was similar across CD (respectively 33% and 20%), UC (33% and 37%) and IPAA patients (36% vs 60%). Infectious complications occurred in 21 patients (29%; 27% VDZ vs 33% UST) post LTX on biological therapy (p=0.66), malignancy occurred in 10 patients (14.1%, 12.8% VDZ vs 16.7% UST, p=0.66), hospitalizations in 32 (45%; 51% VDZ vs 34% UST, p=0.15), and death in 2 patients (3.4%; 2.1% VDZ vs 4.2% UST, p=0.66) (see table). Conclusion In IBD-PSC patients who underwent LTX both UST and VDZ show similar effectiveness with clinical remission rates of respectively 44% and 38% after 1 year. Safety profiles are similar although infectious complications and occurrence of malignancy remains an important concern in this patient group.

P988 Preliminary report on short-term post-operative outcomes of robotic versus laparoscopic approach for restorative procto-colectomy with ileal-pouch-anal anastomosis in ulcerative colitis: a comparative study

Abstract Background Restorative proctocolectomy with ileal pouch–anal anastomosis (IPAA) performed in two or three stages has become the standard surgical treatment in patients with ulcerative colitis (UC) in which the medical management fails. It is a technically complex operation associated with significant morbidity that can be performed with a laparoscopic or robotic approach. Robotic colorectal surgery is gaining popularity because it overcomes many of the mechanical and optical disadvantages of laparoscopy, although limited data are available regarding its safety, efficacy, and costs. This study compares the postoperative short-terms surgical outcomes of the two surgical approaches. Methods Robotic and laparoscopic restorative proctocolectomy procedures with IPAA consecutively performed between June 2015 and May 2023 were retrospectively collected. Inclusion criteria was UC not responders to medical therapy. Exclusion criteria was conversion to open surgery. Primary analyzed outcome were complications rate in the first month (30 days) according to Clavien Dindo Score and length of hospital stay (days). Statistical analysis was performed with a dedicated software (SPSS). Results A total of 54 patients with UC refractory to medical therapy were included, with 31 laparoscopic procedure and 23 robotic procedures. Demographic data were comparable between two groups in terms of age (48.7 vs 45.7 years; p= 0.62), BMI (22,0 vs 23,7 Kg/m2; p= 1.311) and ASA score (p=0,72).Short-term complications defined as Clavien Dindo scores 2-3, (compared with score 1) were 13% in the robotic group and 31% in the laparoscopic group (RR= 0.27, 95% conf. interv. 0.11-1.06). In particular, no high-grade Clavien-Dindo complications occurred in the robotic group while 3 events (grade 3) occurred in the laparoscopic group. No surgical reintervention was needed in both groups. Length of hospital stay was a mean of 7.3 days in lap-group and 6.3 days in rob-group with no statistical significativity (p=0,09). Conclusion This preliminary study concludes that robot-assisted surgery allows a reduction of short-term complications compared to laparoscopic approach. Moreover, robotic surgery allows a reduction of length of hospital stay although not statistically significant. Limits of the study were the retrospective design and the low numerosity of the sample, although comparable with the experiences already published.

P682 A Retrospective Comparison of Different Treatment Modalities in Patients with Chronic Pouchitis

Abstract Background Chronic pouchitis affects ~30% of patients post total colectomy with ileal pouch anal anastomosis (IPAA) surgery. Treatment with anti-TNF, anti-integrin α4β7, anti-IL-12/23, or Crohn's disease exclusion diet (CDED), have shown promise in different studies. We aimed to compare the efficacy of these treatments in a real-world context and to detect factors that can aid in treatment choices. Methods A retrospective cohort study encompassing demographic, clinic, endoscopic, histologic and lab values of adult ulcerative colitis (UC) patients post-IPAA surgery with chronic pouchitis, treated with biologics or CDED at the Tel Aviv Medical Center. Data were collected at baseline, 12, 26, and 52 weeks of treatment. Primary outcomes were assessed using the modified Pouchitis Disease Activity Index (mPDAI). mPDAI response was defined as a reduction from baseline of ≥2 points, while mPDAI remission was defined as mPDAI response in addition to mPDAI score ≤4. Results Therapeutic interventions among 51 patients included CDED (n=10), vedolizumab (n=21), ustekinumab (n=7) and adalimumab (n=13) [Table 1]. At 12 and 26 weeks, overall mPDAI response rates were 52% and 48%, respectively, with no significant difference between groups. At 52 weeks, mPDAI response rates were significantly higher for ustekinumab and vedolizumab (60% and 55%, respectively) compared with adalimumab and CDED (27.3% and 0%, respectively), p=0.043. Fecal calprotectin reduction at week-26 was greatest for ustekinumab (93%), followed by vedolizumab (73%), adalimumab (55%), and CDED (-13%), p=0.003. Treatment persistence over 150 weeks was significantly higher for ustekinumab (100%) compared with adalimumab (46%), vedolizumab (33%), and CDED (20%), p<0.001 [Figure 1]. The predominant cause for treatment discontinuation was secondary loss of response (50%), followed by primary non-response and surgical complications (14.7% each), poor compliance (11.8%), side-effects (5.9%), and development of antibodies (2.9%). Patients without prior biologic or immunomodulator treatment for pouchitis had significantly higher mPDAI response rates at 12 weeks (90%, p=0.016 and 73.3%, p=0.03, respectively). Patients with surgical pouch complications showed a trend towards lower mPDAI-defined response rates at 12 weeks (25% vs. 64.7%; p = 0.064). Conclusion Ustekinumab and vedolizumab demonstrate higher likelihood of maintaining long-term clinical and endoscopic response, along with greater reduction in fecal calprotectin compared with adalimumab and CDED. Biologic and immunomodulator therapy-naïve patients achieved higher induction response rates.

A novel conjugative transposon carrying an autonomously amplified plasmid.

Tetracyclines serve as broad-spectrum antibiotics to treat bacterial infections. The discovery of new tetracycline resistance genes has led to new questions about the underlying mechanisms of resistance, gene transfer, and their relevance to human health. We tracked changes in the abundance of a 55-kbp conjugative transposon (CTn214) carrying tetQ, a tetracycline resistance gene, within a Bacteroides fragilis metagenome-assembled genome derived from shotgun sequencing of microbial DNA extracted from the ileal pouch of a patient with ulcerative colitis. The mapping of metagenomic reads to CTn214 revealed the multi-copy nature of a 17,044-nt region containing tetQ in samples collected during inflammation and uninflamed visits. B. fragilis cultivars isolated from the same patient during periods of inflammation harbored CTn214 integrated into the chromosome or both a circular, multi-copy, extrachromosomal region of the CTn214 containing tetQ and the corresponding integrated form. The tetracycline-dependent mechanism for the transmission of CTn214 is nearly identical to a common conjugative transposon found in the genome of B. fragilis (CTnDOT), but the autonomously amplified nature of a circular 17,044-nt region of CTn214 that codes for tetQ and the integration of the same sequence in the linear chromosome within the same cell is a novel observation. Genome and transcriptome sequencing of B. fragilis cultivars grown under different concentrations of tetracycline and ciprofloxacin indicates that tetQ in strains containing the circular form remains actively expressed regardless of treatment, while the expression of tetQ in strains containing the linear form increases only in the presence of tetracycline.IMPORTANCEThe exchange of antibiotic production and resistance genes between microorganisms can lead to the emergence of new pathogens. In this study, short-read mapping of metagenomic samples taken over time from the illeal pouch of a patient with ulcerative colitis to a Bacteroides fragilis metagenome-assembled genome revealed two distinct genomic arrangements of a novel conjugative transposon, CTn214, that encodes tetracycline resistance. The autonomous amplification of a plasmid-like circular form from CTn214 that includes tetQ potentially provides consistent ribosome protection against tetracycline. This mode of antibiotic resistance offers a novel mechanism for understanding the emergence of pathobionts like B. fragilis and their persistence for extended periods of time in patients with inflammatory bowel disease.

The Fundamentals of Inflammatory Bowel Disease Management in Pregnancy: A Practical Review for the Gastroenterologist.

This narrative review explores the management of Inflammatory Bowel Disease (IBD) during pregnancy, emphasizing its unique challenges to maternal and fetal health, particularly within the Canadian Gastroenterology setting. Seven key principles are highlighted: 1) Preconception counselling, aiming for steroid-free remission confirmed by objective markers, should be routine for female IBD patients. 2) Medication safety, with an eye to future pregnancies, should be addressed upon initiation. Methotrexate and small molecules are contraindicated during pregnancy, while most 5-ASA therapies, biologics, and thiopurines can be continued throughout pregnancy and breastfeeding. Steroids, though not without risks, can be utilized if necessary. 3) Routine monitoring during remission should include serum biomarkers and fecal calprotectin each trimester. 4) Routine endoscopy and imaging are not required, but if indicated, lower GI endoscopy, ultrasound, and unenhanced MRI can be used. Computed tomography and gadolinium enhanced MRI should be avoided. 5) Caesarean section is advised for patients with previous ileal pouch surgeries or active perianal disease, but other patients should follow obstetric indications for delivery. 6) Postpartum period may see more active disease, requiring continued monitoring. Breastfeeding is encouraged, and routine childhood vaccinations are advised, but live vaccinations in the first 6 months warrant detailed review. 7) Complex IBD patients may benefit from a multidisciplinary approach with robust communication between gastroenterologists and obstetricians.

Treatment of Complex Desmoid Tumors in Familial Adenomatous Polyposis Syndrome by Intestinal Transplantation.

Desmoid tumors are fibroblastic lesions which often have an unpredictable and variable clinical course. In the context of familial adenomatous polyposis (FAP), these frequently occur intra-abdominally, especially in the small-bowel mesentery resulting in sepsis, fistulation, and invasion of the abdominal wall and retroperitoneum. In selected cases where other modalities have failed, the most radical option is to perform a total enterectomy and intestinal transplantation (ITx). In this study, we present our center's experience of ITx for desmoid in patients with FAP. We performed a retrospective review of our prospectively collected database between 2007 and 2022. All patients undergoing ITx for FAP-related desmoid were included. Between October 2007 and September 2023, 144 ITx were performed on 130 patients at our center. Of these, 15 patients (9%) were for desmoid associated with FAP (7 modified multivisceral transplants, 6 isolated ITx, and 2 liver-containing grafts). The median follow-up was 57 mo (8-119); 5-y patient survival was 82%, all with functioning grafts without local desmoid recurrence. These patients presented us with several complex surgical issues, such as loss of abdominal domain, retroperitoneal/abdominal wall involvement, ileoanal pouch-related issues, and the need for foregut resection because of adenomatous disease. ITx is a viable treatment in selected patients with FAP and extensive desmoid disease. The decision to refer for ITx can be challenging, particularly the timing and sequence of treatment (simultaneous versus sequential exenteration). Delays can result in additional disease burden, such as secondary liver disease or invasion of adjacent structures.

Incidence and Risk Factors for Low Anterior Resection Syndrome following Trans-Anal Total Mesorectal Excision.

Trans-anal total mesorectal excision (Ta-TME) is a novel approach for the resection of rectal cancer. Low anterior resection syndrome (LARS) is a frequent functional disorder that might follow restorative proctectomy. Data regarding bowel function after Ta-TME are scarce. The aim of this study was to evaluate the incidence and risk factors for the development of LARS following Ta-TME. A prospectively maintained database of all patients who underwent Ta-TME for rectal cancer at our institution was reviewed. All patients who were operated on from January 2018 to December 2021 were evaluated. The LARS score questionnaire was used via telephone interviews. Incidence, severity and risk factors for LARS were evaluated. Eighty-five patients underwent Ta-TME for rectal cancer between January 2018 and December 2021. Thirty-five patients were excluded due to ostomy status, death, local disease recurrence, ileal pouch or lack of compliance. Fifty patients were included in the analysis. LARS was diagnosed in 76% of patients. Anastomosis distance from dentate line was identified as a risk factor for LARS via multivariate analysis (p = 0.042). Neo-adjuvant therapy, hand sewn anastomosis and anastomotic leak did not increase the risk of LARS. LARS is a frequent condition following ta-TME, as it is used for other approaches to low anterior resection. Anastomosis distance from dentate line is an independent risk factor for LARS. In this study neo-adjuvant therapy, hand sewn anastomosis and anastomotic leak did not increase the risk of LARS. Further studies with longer follow-up times are required to better understand the functional outcomes following Ta-TME.

Endoscopic therapy of stoma closure site strictures in ileal pouches is safe and effective.

Strictures are a common complication after ileal pouch surgery with the most common locations being at the anastomosis, pouch inlet, and stoma closure site. No previous literature has described endoscopic therapy of stoma site stricture. This study aimed to assess the safety and efficacy of endoscopic therapy in the treatment of stoma closure site strictures. Patients diagnosed with stoma closure site strictures following ileal pouch surgery who underwent endoscopic treatment at the Center for Colorectal Diseases, Inflammatory Bowel Disease (IBD), and Ileal Pouch between 2018 and 2022 were analysed. Primary outcomes (technical success and surgery-free survival) were compared between endoscopic balloon dilation (EBD) and stricturotomy and/or strictureplasty. A total of 30 consecutive eligible patients were analysed. Most patients were female (66.7%) and most patients were diagnosed with IBD (93.3%). Twenty patients (66.7%) had end-to-end anastomosis. A total of 52 procedures were performed, with EBD in 16 (30.8%) and stricturotomy and/or strictureplasty in 36 (69.2%). The mean stricture length was 1.7 ± 1.0 cm. Immediate technical success was achieved in 47 of 52 interventions (90.4%). During a mean follow-up of 12.7 ± 9.9 months, none of the patients underwent surgical intervention for the stricture. Fourteen (46.7%) required endoscopic re-intervention for their strictures with an interval between index and re-interventional pouchoscopy of 8.8 ± 6.3 months. Post-procedural complications were reported in 2 (6.7%) with bleeding and none with perforation. Upon follow-up, 20 (66.7%) patients reported improvement in their symptoms. EBD and endoscopic stricturotomy and/or strictureplasty are safe and effective in treating stoma closure site strictures in patients with ileal pouches, providing symptomatic relief in most patients as well as avoiding surgery.