Ileal Pouch-anal Anastomosis Research Articles

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.

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.

MULTIMODAL PREHABILITATION MAY IMPROVE SURGICAL OUTCOMES FOR PATIENTS WITH INFLAMMATORY BOWEL DISEASE

Abstract BACKGROUND Surgery is associated with loss of lean body mass and physical deconditioning, which can delay healing and lead to complications. Multimodal prehabilitation (PH) with nutrition optimization and physical therapy improves outcomes after cancer surgery. However, the effects of prehabilitation for inflammatory bowel disease (IBD) surgery are not established. We aimed to assess surgical outcomes among IBD patients exposed to prehabilitation relative to no prehabilitation. METHODS We conducted a case-controlled study of the impact of prehabilitation in patients with IBD who underwent major abdominal surgery for Crohn’s disease (CD) or ulcerative colitis (UC) between May 1st, 2022 and June 6th, 2023 at a tertiary care center. Cases were defined as those who participated in a multimodal PH program that included nutrition counseling (weight optimization, preoperative carbohydrate loading and perioperative immunonutrition), medication management, physical therapy, and psychosocial evaluation beginning 4 weeks prior to surgery; controls received standard of care (SOC) written preoperative surgical instructions without PH. We assessed postoperative complications (defined by the comprehensive complications index (CCI)), severe complications (CCI>20), reoperation rate, 30-day readmission, post operative length of stay (LOS) and post-operative opioid use (defined by daily morphine milligram equivalents (MME)). Statistical tests included linear and logistic regression, Mann-Whitney U test, Chi-Square test, and Fisher’s exact test, as appropriate. RESULTS A total of 68 patients were identified, including 20 PH (cases) and 48 SOC (controls). Among PH, 75% had CD with the remainder UC; surgeries included ileocecal resection (45%), colectomy with ileostomy (25%), ileal pouch-anal anastomosis (25%), and small bowel resection (5%). Among SOC, 31% had CD with the remainder UC, and surgeries included colectomy with ileostomy (60%), stage 2 IPAA (29%), and small bowel (6%) or ileal (4%) resections. Age, sex, race, and ethnicity was similar between groups. Overall and severe complication rates were similar between PH and SOC (mean CCI scores 13.42 PH vs 11.25 SOC (p = 0.58), and CCI > 20 in 40% PH patients vs 29% SOC (p = 0.56)). Median post-operative LOS was shorter among PH vs SOC (3.0 vs 3.5d, p=0.02), and median post-operative opioid use was lower among PH vs SOC (19.5 vs 20.8 MME, p = 0.04). Readmission within 30 days occurred in 30% of PH and 17% of SOC (p = 0.22). Reoperation within 30 days occurred in 5% of PH and 17% of SOC (p = 0.37). CONCLUSION: Multimodal prehabilitation may improve select surgical outcomes in IBD, including length of stay and opioid use after surgery. Larger, prospective, controlled studies may help to further clarify the impact of PH on surgical outcomes for IBD, including complications, readmissions, and functional status. Table 1. Patient Characteristics and Outcomes by Prehabilitation Exposure Status

MEDICAL, ENDOSCOPIC, AND SURGICAL THERAPIES FOR THE TREATMENT OF RECTAL CUFFITIS IN ULCERATIVE COLITIS PATIENTS WITH AN ILEAL POUCH-ANAL ANASTOMOSIS: A SYSTEMATIC REVIEW

Abstract BACKGROUND Patients who undergo ileal pouch-anal anastomosis (IPAA) without mucosectomy are left with a rectal cuff, which can develop inflammation known as cuffitis. Treatment of cuffitis typically includes mesalamine suppositories or corticosteroids, but individuals with refractory cuffitis may require advanced therapies, endoscopic intervention, or surgical intervention. The aim of this review is to summarize the existing literature regarding treatments options for cuffitis. METHODS A broad search strategy was created by a medical librarian to capture rectal cuffitis in IPAA patients. The following databases were searched: Ovid Medline® ALL, Ovid Embase, Cochrane Central Register of Controlled Trials (Wiley), and 3 indexes in Web of Science from Clarivate: Science Citation Index-Expanded, Conference Proceedings Citation Index, and BIOSIS Citation Index. A total of 1,652 citations were identified, and 836 studies remained after removal of 816 duplicates. Two reviewers screened all 836 abstracts and 241 full-text articles to determine if they were eligible for inclusion in this review. RESULTS A total of 21 studies (10 cohort studies, 9 case-series, 2 open-label clinical trials) met the inclusion criteria. Medical interventions were investigated in 15 studies (Table 1) with mesalamine being the most common (4 studies) followed by corticosteroids (3 studies), ustekinumab (3 studies), vedolizumab (2 studies), tofacitinib (1 study), and infliximab (1 study). Studies investigating mesalamine and corticosteroid use generally had larger sample sizes (ranging 4-120 patients) and showed symptomatic improvement in 51.7-100% of patients and decreases of 1.14-1.8 points in endoscopic disease activity indices. In contrast, studies investigating advanced therapies had small sample sizes (ranging 1-21 patients) and showed variable responses ranging from no clinical (tofacitinib) or endoscopic (ustekinumab, vedolizumab) improvements to clinical (ustekinumab) or endoscopic (vedolizumab) responses in 75% of patients. Endoscopic and surgical approaches were explored in 6 studies (Table 2) and included secondary mucosectomy (2 studies), endoscopic cuff resection, transanal minimally invasive surgery, endoscopic needle-knife therapy, and balloon dilation for cuffitis patients with concomitant outlet strictures (1 study each). These techniques generally resulted in resolution of symptoms but were limited by small sample sizes (ranging 3-16 patients). CONCLUSIONS Most studies evaluating therapies used to treat rectal cuffitis suggest beneficial effects of conventional mesalamine or corticosteroid-based therapies, whereas data regarding the efficacy of advanced therapies and interventional procedures are inconsistent given small sample sizes. Further research is needed to effectively characterize additional management options for this condition. Table 1. Medical therapies used for treatment of cuffitis. Abbreviations – BM: bowel movements, CRP: C-reactive protein, UST: ustekinumab, HBOT: hyperbaric oxygen therapy, mPDAI: modified Pouch Disease Activity Index, 5-ASA: 5-aminosalicylate, ESR: erythrocyte sedimentation rate, PDAI: Pouch Disease Activity Index, CGQOL: Cleveland Global Quality of Life score, IPS: Irritable Pouch Syndrome, CAI: Cuffitis Activity Index. Table 2. Endoscopic and surgical therapies used for treatment of cuffitis. Abbreviations – FISI: Fecal Incontinence Severity Index, CGQOL: Cleveland Global Quality of Life score, PDAI: Pouch Disease Activity Index, BM: bowel movements.

P725 Predictive factors for biologic therapy initiation after ileal pouch-anal anastomosis

Abstract Background Patients with ulcerative colitis (UC) undergoing proctocolectomy and Ileal Pouch-Anal Anastomosis (IPAA) frequently develop long-term complications, such as chronic pouchitis and Crohn’s-like disease of the pouch. These may eventually require biologic therapy. We aimed to identify peri-operative predictors for biologic therapy after IPAA. Methods All patients after IPAA followed at Rabin Medical Center pouch clinic and consenting to prospective observational follow up were included. Patients undergoing IPAA due to familial adenomatous polyposis (FAP) and those with ileostomy were excluded. Primary outcome was the initiation of biologic therapy after IPAA. We used Cox proportional hazard models to evaluate the following potential predictors: gender, race, smoking status, BMI category, UC duration until surgery, surgery indication, immediate post-operative complications (bowel obstruction, infection and leakage), and pre-operative treatment with 5-ASA, steroids, immunomodulators, and biologic therapy. Results Out of 174 patients in our cohort, 18 were excluded due to FAP and 8 due to ileostomy, leaving 148 for analysis. Prior to IPAA, 52 patients (35%) were treated with biologic therapy. Median follow-up from ileostomy closure to last documented visit was 15.14 years. During this period, 32 patients (21.6%) initiated biologic therapy, including 18 with adalimumab (12.2%), 10 with infliximab (6.7%), 2 with ustekinumab (1.3%), 1 with golimumab (0.6%), and 1 with vedolizumab (0.6%). Median time-to biologic therapy initiation was 10.1 years (IQR 10.0). Significant hazard ratios (HR) for biologic therapy initiation were pre-operative treatment with biologic therapy (HR 4.8, 95% CI; 2.3-10, p<0.001); Arab descent (HR 4.7, 95% CI; 1.6-14, p=0.005); pre-operative treatment with immunomodulators (HR 3.0, 95% CI; 1.3-7, p=0.011); UC duration of less than 10 years before ileostomy closure (HR 2.7, 95% CI; 1.2-6.3, p=0.02); past smoking status (HR 2.6, 95% CI; 1.22-5.7, p=0.013); and immediate post-operative complications (HR 2.0, 95% CI; 1.0-4.1, p=0.05). None of the patients undergoing IPAA due to dysplasia (n=27), required biologic therapy. Conclusion Pre-operative treatment with either biologic therapy or immunomodulators, Arab descent, short disease duration prior to IPAA, past smoking status, and post-operative complications were significant predictors of biologic therapy initiation post-IPAA. Patients with these risk factors may benefit from closer post-operative follow-up and earlier initiation of biologic therapy.

P1142 Antibiotic use in the twelve months prior to ileal pouch-anal anastomosis increases the risk for pouchitis: A population-based Danish cohort study

Abstract Background Pouchitis is the most common complication after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC), however clinical and environmental risk factors for pouchitis remain poorly understood. We explored the relationship between specific clinical factors and the incidence of pouchitis. Methods We established a population-based cohort of all adult persons in Denmark undergoing proctocolectomy with IPAA for UC between January 1, 1996 and May 31, 2020. We used Cox Proportional Hazard modeling and logistic regression to assess the impact of antibiotic and non-steroidal anti-inflammatory drug (NSAID) exposure and appendectomy on the primary outcome of diagnosis of acute pouchitis in the first 2 years after IPAA surgery. A 2-year time window was utilized given the clinical relevance of early pouchitis and to mirror prior studies in both administrative claims and the Danish health registers. Results Among 1,616 eligible patients, 738 (46%) developed pouchitis in the first 2 years after IPAA. Among all patients undergoing IPAA surgery for UC, 51% were prescribed antibiotics in the 12 months prior to the index date and 17% were prescribed NSAIDs in the 12 months prior to the index date. In Kaplan-Meier analyses, those persons who were prescribed antibiotics in the 12 months prior to the final stage of IPAA surgery were significantly more likely to develop pouchitis in the 2 years after the index date when compared to patients who were not prescribed antibiotics (p<0.001, Figure 1B). Additionally, male patients demonstrated a decreased risk for pouchitis in the first 2 years after the index date when compared to female patients (p=0.014, Figure 1A). Antibiotic exposure in the 12 months prior to IPAA was associated with an increased risk of pouchitis (adjusted Hazard Ratio [aHR] 1.40, 95% CI 1.21-1.62) after adjusting for year of surgery and sex (Table 1). In a secondary analysis, compared to persons without any antibiotic prescriptions in the 12 months prior to IPAA, the risk of pouchitis was increased in those with 1 or 2 courses of antibiotics in that period (aHR 1.29, 95% CI 1.10-1.51) and 3 or more courses (aHR 1.79, 95% CI 1.43-2.23, Figure 1C). NSAID exposure in the 12 months prior to IPAA and appendectomy were not associated with risk of acute pouchitis (p=0.201 and p=0.865 respectively). Conclusion In this population-based cohort study, we demonstrated that antibiotic exposure in the 12 months prior to IPAA is associated with an increased risk of acute pouchitis. Future prospective studies may isolate specific microbial changes in at-risk patients to drive earlier interventions.

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.

P214 Effects of rectal stump proctitis on short-term postoperative complications after proctectomy and ileal pouch-anal anastomosis for Ulcerative Colitis

Abstract Background Inflammation of the rectal stump (proctitis) after subtotal colectomy with ileostomy for ulcerative colitis (UC) is common. Proctitis may affect the postoperative outcomes of ileal pouch-anal anastomosis (IPAA). This study aims to explore associations between rectal stump proctitis and short-term postoperative complications (POCs) after proctectomy and IPAA for UC. Methods This retrospective single-centre study included patients who underwent proctectomy, IPAA and protective ileostomy for UC from 2000-2023. Data were retrieved from our prospectively-maintained database. Exclusion criteria were dysplasia or cancer (103 pts), missing pathology results (50 pts), undetermined colitis or Crohn’s Disease features at proctectomy (18 pts). All patients underwent three-staged IPAA and were divided into four groups according to the rectal stump proctitis status at pathology: remission, mild, moderate, and severe proctitis. A stepwise binary logistic regression analysis was performed for each short-term outcome. Models included variables with a different distribution according to the outcome (p-value ≤0.1). Results We included 785 patients who underwent proctectomy and IPAA. At pathology, remission was achieved by 162 (20.6%) patients, while proctitis of the rectal stump was mild in 211 (26.9%), moderate in 246 (31.3%), and severe in 166 (21.1%) patients, respectively. Table 1 details population characteristics and outcomes according to the proctitis status. Patients with moderate and severe proctitis received more preoperative biologics and ongoing systemic steroids at surgery. While they underwent previous abdominal surgery less frequently, the laparoscopy rate was lower with a longer postoperative length of stay. At multivariate (Table 2), Medical POCs were independently associated with ongoing antibiotics (OR 2.29 [1.01-5.20] p=0.047) and ASA score≥3 (OR 1.93 [1.11-3.35] p=0.019). Surgical POCs were independently associated with ongoing systemic steroids (OR 2.09 [1.19-3.68] p=0.011, while ongoing antibiotics (OR 0.2 [0.04-0.86] p=0.031) and laparoscopy (OR 0.53 [0.28-1.00] p=0.049) were protective. Intra-abdominal septic complications (IASCs) and abdominal/pelvic abscesses were independently associated with the proctitis status (OR 1.1 [1.06-2] p=0.018 and OR 1.56 [1.08-2.25] p=0.017, respectively). Conclusion Rectal stump proctitis was independently associated with postoperative abdominal and pelvic abscesses and IASCs after proctectomy and IPAA for UC. The association between proctitis and IPAA’s long-term outcomes and pouch failure need to be further explored.

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 < 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 < 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.

DOP41 Mucosal single-cell profiling of Crohn's-like disease of the pouch reveal unique pathogenesis and therapeutic targets

Abstract Background 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), a chronic inflammatory condition that affects both the pouch body and extra-pouch organs including the 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 after IPAA with and without CDP using single cell analyses. Methods Endoscopic samples from the pouch body 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 both pouch body and pre-pouch ileum of patients with normal pouch/ileum and CDP using scRNA-seq. CyTOF was performed on mucosal immune cells from independent cohorts of patients with normal pouch/ileum, CDP, and pouchitis. Mucosal samples from patients with familial adenomatous polyposis (FAP) after colectomy and pouch formation were also analyzed by CyTOF. ScRNA-seq and CyTOF findings were independently validated using immunohistochemistry. Results We revealed distinct cell clusters in normal pouch body versus normal pre-pouch ileum in UC patients. Colitogenic immune cells expanded in normal UC pouch body compared to normal FAP pouch body. Compared to normal pouch/ileum, CDP pouch/ileum exhibited expanded TCR clonotypes, elevated Th17 signaling, and diminished T cell exhaustion markers. Elevated plasma cells, inflammatory fibroblasts and monocytes were noted in CDP pouch/ileum (Figure 1). 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 body and pre-pouch ileum of CDP. Ligand-receptor analysis further revealed a stromal – myeloid – lymphocyte circuit in CDP. Integrated analysis showed that upregulated immune mediators in CDP tissues were similar to those in CD and pouchitis, but not UC. In addition, the pouch body and pre-pouch ileum of CDP exhibited prominent activation of the unfolded protein response (UPR) across all major immune and non-immune cell compartments (Figure 2), which was not present in UC, CD or pouchitis based on reanalysis of published databases. Conclusion CDP demonstrates altered immune and non-immune cell populations/states in the pouch body 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.

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.

P366 Risk factors and outcomes of chronic antibiotic-refractory pouchitis in Korean ulcerative colitis patients: a single center retrospective study

Abstract Background Chronic inflammation of the pouch after total proctocolectomy with ileal pouch-anal anastomosis (IPAA) remains a morbid complication in ulcerative colitis (UC). The goal of this study was to investigate risk factors and clinical outcomes of chronic antibiotic-refractory pouchitis (CARP) in Korean patients with UC. Methods This was a single center retrospective study on patients with UC who underwent total proctocolectomy with IPAA at Asan Medical Center in Korea between January 1987 and December 2022. CARP was defined as failure to respond to a 4-week course of a single antibiotic, needing more than 4 weeks of therapy with 5-aminosalicylates, steroids, immunomodulators or biologics/small molecules, while chronic antibiotic-dependent pouchitis (CADP) was defined as more than 3 episodes of pouchitis per year or persistent symptoms requiring long-term antibiotics to maintain disease remission. Primary outcomes were endoscopic remission defined as complete mucosal healing of chronic pouchitis and pouch failure defined as the requirement of diverting loop ileostomy or pouch excision. Univariable and multivariable logistic regression analysis were used to identify risk factors of CARP. Results A total of 251 patients were included and 232 were analyzed (Male, 57.3%; Current smoker, 13.4%; Median age at surgery, 44 years; Disease duration at surgery, 4 years; Previous exposure to biologics/small molecules, 23.7%; Extra-intestinal manifestations, 8.2%; Preoperative cytomegalovirus infection, 19.4%). The most common cause of surgery was steroid refractoriness (50.9%), followed by dysplasia/colorectal cancer (26.7%). The median time from surgery to chronic pouchitis was 48 months (interquartile range 23.5–100.0). Among 74 patients (31.9%) with chronic pouchitis, 31 patients (13.4%) were CARP and 43 patients (18.5%) were CADP. The most frequent endoscopic phenotype according to Chicago classification was focal inflammation of the pouch in all groups (chronic pouchitis, 47.3%; CARP, 35.5%; CADP, 55.8%). Patients with CARP were less likely to have concomitant probiotics compared with CADP (29.0% vs 72.1%; p<0.01). Endoscopic remission rate in chronic pouchitis, CARP, and CADP were 14.9% (11/74), 9.7% (3/31), and 18.6% (8/43), respectively (Table 1). Pouch failure rate in chronic pouchitis, CARP, and CADP were 13.5% (10/74), 16.1% (5/31), and 11.6% (5/43), respectively (Table 1). In a multivariable analysis, current smoking status was positively associated with CARP development (OR: 3.56; 95% confidence interval 1.33–9.52; p=0.01). Conclusion Current smoker with UC who underwent IPAA had a higher risk of CARP. Concomitant use of probiotics was less likely to be associated with developing CARP.

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.

P854 Tofacitinib demonstrates preliminary efficacy in induction of remission in chronic pouchitis

Abstract Background Pouchitis is common following total proctocolectomy for ulcerative colitis (UC) and ileal pouch-anal anastomosis (IPAA) and generally responds to antibiotics. However, up to 20% of patients develop either antibiotic-dependent or antibiotic-refractory pouchitis, collectively referred to as chronic pouchitis. Methods We report our preliminary induction results from a multi-center open label induction with randomized withdrawal trial to assess the efficacy of tofacitinib in chronic pouchitis. All eligible participants received 10mg tofacitinib twice daily for 8 weeks, with an additional 8 weeks of therapy given to patients with an inadequate initial clinical response. The primary endpoint was clinical response (a reduction of clinical PDAI≥2) at week 8. Secondary endpoints included endoscopic response (a reduction of endoscopic PDAI≥2), mPDAI remission (modified pouchitis disease activity index (mPDAI)≤ 4 and a reduction of mPDAI≥2), mPDAI response (a reduction of mPDAI≥2) and improvement in health-related quality of life (HRQoL) using the short inflammatory bowel disease questionnaire (SIBDQ). Serum cytokine levels was analyzed using LEGENDplex human inflammation panel 1. Univariate analysis was performed to identify clinical and biochemical predictors of response to tofacitinib. Results A total of 33 patients with chronic pouchitis (Table 1) were included in the preliminary analysis. The clinical and endoscopic response rates at week 8 were 55% and 58% respectively, with a median improvement of 1 (p<0.05) and 3 (p<0.05) respectively (Figure 1). The mPDAI remission rate was 49% at week 8 with an mPDAI response rate of 73%. Endoscopic responders exhibited significant improvements in endoscopic oedema, granularity, friability, and mucous exudate (p<0.05). There was significant improvement in HRQoL, with the median SIBDQ score increasing from 35 at baseline to 54 at week 8 (p<0.05). Eleven patients received a further 8 weeks of therapy with a clinical response rate of 36%, yielding an overall response rate including extended induction of 67%. Univariate analysis did not reveal significant differences in baseline characteristics, clinical, or biochemical markers between responders and non-responders. However, a history of corticosteroid use (p=0.08) and high baseline levels of faecal calprotectin (p=0.15) demonstrated a non-significant association with treatment response. Elevated baseline serum levels of IL-1b, IFN-a and IL-33 were associated with a treatment response at week 8 (p<0.05). Conclusion Tofacitinib demonstrated preliminary efficacy in inducing both clinical and endoscopic response in patients with chronic pouchitis who have undergone IPAA for UC.

P1240 Systematic review with meta-analysis: faecal microbiota transplantation as treatment of chronic pouchitis

Abstract Background Pouchitis is inflammation of the ileal pouch-anal anastomosis after proctocolectomy in the surgical treatment of ulcerative colitis. Cohort studies have found evidence that allogenic faecal microbiota transplantation (FMT) can induce short term beneficial effects in patients with chronic pouchitis. Until recently results from randomized controlled trials (RCTs) have been missing. In this systematic review and meta-analysis, we investigated whether FMT treatment was superior to placebo in inducing remission in patients with chronic pouchitis. Methods We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from inception to 15th of November 2023, for RCTs assessing the efficacy of allogenic FMT in the treatment of chronic pouchitis. Autologous FMT or placebo was accepted as control treatment. The primary outcome was the improvement of symptoms as defined by the authors following four weeks. Results The systematic literature search identified a total of three RCTs on the efficacy of FMT in chronic pouchitis comprising 62 patients with 32 patients treated with FMT. Both treatments (FMT and Placebo) and definition of treatment response varied between studies (Table 1). Meta-analysis revealed that FMT was not superior to placebo (risk ratio=0,68;95% CI=(0,47-0,99); p=0.35) in improvement of symptoms four weeks following treatment (Figure 1). Conclusion FMT was not superior to placebo in inducing short-term beneficial effects four weeks after initial treatment in patients with chronic pouchitis. Whether FMT may induce long-term beneficial effects remains to be established.

P521 Impact of pouch leaks on quality of life and symptoms in patients after ileal pouch-anal anastomosis surgery

Abstract Background Ileal pouch-anal anastomosis(IPAA)is the procedure of choice in patients requiring total proctocolectomy.The reported leak rates after IPAA surgery range from 1-12% with well described significant impact on postoperative morbidity and recovery.However, the long-term impact of salvaged pouch leaks on the broader quality of life outcome and pouch function remains poorly understood.The aim of this study was to compare between patients with and without postoperative leaks after IPAA surgery, hypothesizing that patients with salvaged pouch leaks would have worse long-term quality of life and pouch function compared to matched patients without leaks. Methods This retrospective cohort study included patients who underwent IPAA(n=4058) between 1995-2022.Leak was defined as abscess or fistula requiring intervention, who had definitive resolution of their pouch leaks, whether with conservative treatment or after salvage surgery or pouch excision with end ileostomy creation. The Leak group consisted of 194 patients with treated leaks.The No Leak group included 963 patients without leaks,matched 1:5 on sex, age(± 3 years),and surgery date.Questionnaire data were available for 85 of 194 patients with leaks and 614 of 963 without leaks. Quality of life(QoL) was assessed using SF-36, health status using EORTC QLQ-C30(QoH),and life enjoyment(QoE) using a standardized scale.Bowel movements,seepage,and pad usage were recorded.Outcomes were compared using Mann-Whitney U,t-tests, and chi-square tests. Results A total of 699 patients with IPAA were included, with 85(12%)in the leak group. The median age was 42 (IQR, 31-53) years, and 54% were male. Median time from surgery to the last QoL assessment was 6.58(IQR: 3.5-11.3) years in the Leak group and 6.05 (IQR: 2.5-11.2) days in the No Leak group. Patients with Leaks reported significantly lower QoL (median 7(IQR:5-9)vs8 (IQR:7-9);p<0.001), lower health status on the QoH scale (median 7(IQR: 5-8) vs 8 (IQR :7-9); p<0.001), and lower life enjoyment on the QoE scale (median 7(IQR: 5-8)vs7(IQR :6-9);p=0.003) compared to the No Leak group. A higher proportion of patients in the Leak group reported daytime (49%vs.20%,p<0.001) and nocturnal seepage (66%vs.38%, p=0.001), along with greater daytime(40%vs.22%,p=0.01) and nighttime pad usage (53%vs.30%,p=0.001). There were no significant differences in the number of bowel movements per 24h (p=0.54), daytime bowel movements(p=0.7), or nighttime bowel movements (p=0.695) between the groups. Conclusion In matched cohorts,salvaged pouch leaks were associated with reduced quality of life,health status,and life enjoyment compared with matched patients without leaks.Patients with leaks also had increased rates of seepage and pad usage,indicating worse pouch function.

Evolution of laparoscopic ileal pouch-anal anastomosis: impact of enhanced recovery program, medication changes, and staged approaches on outcomes

Although laparoscopic Ileal pouch-anal anastomosis (IPAA) has become the gold standard in restorative proctocolectomy, surgical techniques have experienced minimal changes. In contrast, substantial shifts in perioperative care, marked by the enhanced recovery program (ERP), modifications in steroid use, and a shift to a 3-staged approach, have taken center stage. Data extracted from our prospective IPAA database focused on the first 100 laparoscopic IPAA cases (historic group) and the latest 100 cases (modern group), aiming to measure the effect of these evolutions on postoperative outcomes. The historic IPAA group had more 2-staged procedures (92% proctocolectomy), whereas the modern group had a higher number of 3-staged procedures (86% proctectomy) (P<.001). Compared with patients in the modern group, patients in the historic group were more likely to be on steroids (5% vs 67%, respectively; P<.001) or immunomodulators (0% vs 31%, respectively; P<.001) at surgery. Compared with the historic group, the modern group had a shorter operative time (335.5±78.4 vs 233.8±81.6, respectively; P<.001) and length of stay (LOS; 5.4±3.1 vs 4.2±1.6 days, respectively; P<.001). Compared with the modern group, the historic group exhibited a higher 30-day morbidity rate (20% vs 33%, respectively; P=.04) and an elevated 30-day readmission rate (9% vs 21%, respectively; P=.02). Preoperative steroids use increased complications (odds ratio [OR], 3.4; P=.01), whereas 3-staged IPAA reduced complications (OR, 0.3; P=.03). ERP was identified as a factor that predicted shorter stays. Although ERP effectively reduced the LOS in IPAA surgery, it failed to reduce complications. Conversely, adopting a 3-staged IPAA approach proved beneficial in reducing morbidity, whereas preoperative steroid use increased complications.