Pre-pouch Ileitis Research Articles

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.

Crohn's Disease of the Ileoanal Pouch: A High Rate of Potential Overdiagnoses.

Approximately 1 in 10 patients with an ileal pouch-anal anastomosis is diagnosed with Crohn's disease of the pouch (CDP). However, this diagnosis may be established inappropriately, as alternative underlying causes necessitating an alternative treatment approach, such as long-term surgical sequelae, may mimic CDP. In this study, we aimed to identify patients diagnosed with and treated for CDP with a (concurrent) alternative diagnosis. Ulcerative colitis and inflammatory bowel disease unclassified patients who underwent ileal pouch-anal anastomosis surgery in a tertiary center between 1990 and 2017 were retrospectively reviewed. Patients with a postoperative diagnosis of CDP for which medical treatment was initiated were identified. Presence of pouchitis, prepouch ileitis, stricture, and fistulas was assessed and histopathological reports were evaluated. Thereafter, cross-sectional images of the pouch in CDP patients were re-evaluated to identify potential long-term surgical sequelae (ie, chronic presacral sinus or perianastomotic fistulas). After a median postoperative follow-up of 6.2 (interquartile range, 2.3-13.5) years, 47 (10%) of 481 patients were diagnosed with CDP. CDP patients had pouchitis (n = 38 [81%]), prepouch ileitis (n = 34 [74%]), strictures (n = 17 [36%]), fistulas (n = 15 [32%]), or a combination. Multiple granulomas were found in 1 pouch resection specimen. Re-evaluation of 40 (85%) patients who underwent magnetic resonance imaging revealed presence of long-term surgical sequelae in 17 (43%) patients. Six (15%) patients demonstrated isolated nonanastomotic fistulas. Re-evaluation of cross-sectional imaging of the pouch revealed that potential alternative causes were found in nearly half of CDP patients. Cross-sectional imaging is therefore recommended early in the diagnostic pathway to exclude an alternative diagnosis.

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

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

P287 Clinical characteristics and outcomes of ileal pouch–anal anastomosis (IPAA) inflammation in a Latin American (LA) IBD reference Center (I.

Abstract Background Restorative proctocolectomy with ileal pouch–anal anastomosis (IPAA) can be associated with a wide spectrum of complications, ranging from a frequently mild acute pouchitis (AP) to Chronic pouch inflammation (CPI, either antibiotic dependent or refractory, CADP and CARP respectively) and Crohn's disease like pouch inflammation (CDLPI). The pathogenesis, still largely unknown, probably is multifactorial, and environment may play a role. We aimed to describe clinical characteristics and outcomes of IPAA inflammation in a Latin American (LA) IBD reference Center. Our main focus is CDLPI, because, despite of UC is reported more frequent in LA, epidemiology is changing, and notably, colon location (within CD) reach the half of the CD casuistic in our hospital, as well as other Argentina locations (Cordoba) and Uruguay, a neighbor Country. Probably, this epidemiological feature could impact in our patient′s evolution. Methods Our hospital has a Coloproctology Team pioneer of IPAA surgery in Argentine and as Clinical IBD Service, we performed a revision in our electronic data base (included from 1990 to current date, and detected 437 pts. with IPAA. Criteria were; modified PDAI (for disease activity), for CPI and CDLPI we adopted that of Shen B, Clin. Gastrienterol hepatol 200, 6:145-58. Results Results We compare 46 CDLPI with 24 CPI pts. (CADP and CARP) and 24 AP. A total of 55 M, 39 F, were evaluated for demographic data and disease complications. Mean age ±SD at complication: CDLPI 33.8±13.8, CPI 34.2±11.2, AP 40.1±13.7, (NS for gender and Age). Median time (IQR) up to each one of 3 complications: 1.6 (4.19), 2.09 (7.17) and 1.34 (2.67), respectively (NS, Median test). Follow–up time was similar: 20.11 (10.9), 13.7 (12.2), 13.9 (15.6), respectively. CDLPI presented inflammatory pattern in: 37 (80.4%), stricturing in 6 (13.04%), fistulizing in 16 (34.8%) Perianal complication: 43.5%. Pre-pouch ileitis in CDLP: 26 (56 5%) vs. CPI 1(4.2%), in AP 0% (p.00000), prepouch strictures (13.04% vs. 0%), significant different, as well as prepouch fistulas (17.4%), with suboclusion in 29% Pouch vaginal fistulas and pouch-cutaneous in 1/5 of patients. Cuffitis in 19%. The original IBD was more severe and extensive p <0.02 in the mentioned subgroup. As regard treatment, IMM treatment in CDLP: was required in 70% vs. 26% in CPI and biologics en 2/3 0.00016, 11% ≥2 biologics. Pouch failure (diversion and resection) was observed in 30% and 13% respectively. Conclusion We are a LA center with high CD prevalence. The complications of surgery must be taken into account. IPAA revolutionized UC surgery, but close monitoring, and new research are required with the future hope of acting proactively.

S2763 Post-Transplant Lymphoproliferative Disorder Presenting as an Isolated Pre-Pouch Ileal Ulcer in a Liver Transplant Patient With Crohn’s Disease

Introduction: Post-transplant lymphoproliferative disorder (PTLD) can occur in solid organ and hematopoietic cell transplant recipients in the setting of chronic immunosuppression. It often results from Epstein-Barr virus (EBV) affected B-cell propagation. We present a case of PTLD in a liver transplant (LT) patient with Crohn’s disease (CD) on biologic therapy. Case Description/Methods: A 67-year-old male with primary sclerosing cholangitis (PSC) cirrhosis status post living donor LT in 2001 on tacrolimus, multiple skin cancers, recurrent PSC after transplant and pan-ulcerative colitis on sulfasalazine underwent total proctocolectomy with ileo-anal anastomosis in 2013 to 2014 for colonic dysplasia. In 2019, he was diagnosed with moderate-to-severe CD of the J-pouch and pre-pouch ileum, up to 50cm from the entry site. Vedolizumab (VDZ), an α4β7 integrin monoclonal antibody, was initiated with steroid-free clinical response on every four week dosing. Repeat pouchoscopy on VDZ showed pre-pouch ileitis up to 30cm and a large, isolated ulcer in the pre-pouch ileum, 10cm proximal to the ileitis (Figure). Biopsies revealed B-cell lymphoma, consistent with PTLD. Negative EBV-encoded RNA (EBER) in-situ hybridization suggested that this diagnosis was unrelated to EBV exposure. Positron emission tomography (PET) scan did not identify distant disease activity, and bone marrow biopsy was unremarkable. VDZ was stopped due to loss of response, budesonide resumed and R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) was subsequently initiated. Follow-up pouchoscopy showed lymphoma regression but persistent CD activity. Discussion: PTLD typically presents as extra-nodal masses involving the central nervous system, lungs, gastrointestinal tract, liver, skin or allograft within one year of transplant. Immunosuppression reduction is the cornerstone of management; however, more aggressive cases, as in our patient, require systemic therapy. This case highlights a unique presentation of PTLD as an isolated ileal ulcer in a CD patient 19 years post-LT. Interestingly, the ulcer did not appear endoscopically distinct from CD-related ulceration. Furthermore, while malignancy is a potential risk of certain treatments for inflammatory bowel disease (IBD), our patient had never received thiopurines or anti-tumor necrosis factor (TNF) agents, and VDZ has not been associated with an increased risk of B-cell lymphoma. He is currently stable on low dose tacrolimus and budesonide.Figure 1.: Isolated pre-pouch ileal ulcer.

Biologic Therapies for the Treatment of Post-ileal Pouch Anal Anastomosis Surgery Chronic Inflammatory Disorders: Systematic Review and Meta-analysis.

Chronic inflammatory disorders after ileal pouch-anal anastomosis (IPAA) surgery are common. These include chronic pouchitis (CP), Crohn's disease (CD) of the pouch, prepouch ileitis (PI) and rectal cuff inflammation (cuffitis). The aim of this study was to evaluate the efficacy of biologic therapies in treating these disorders. Systematic review of all published studies from inception to August 1, 2021 was performed to investigate the efficacy of biologic therapies for post-IPAA chronic inflammatory disorders. The primary outcome was the efficacy of biologic therapies in achieving complete clinical response in patients with IPAA. A total of 26 studies were identified including 741 patients. Using a random-effect model, the efficacy of infliximab in achieving complete clinical response in patients with CP was 51% (95% CI, 36 to 66), whereas the efficacy of adalimumab was 47% (95% CI, 31 to 64). The efficacies of ustekinumab and vedolizumab were 41% (95% CI, 06 to 88) and 63% (95% CI, 35 to 84), respectively. In patients with CD/PI, the efficacy of infliximab in achieving complete clinical response was 52% (95% CI, 33 to 71), whereas the efficacy of adalimumab was 51% (95% CI, 40 to 61). The efficacies of ustekinumab and vedolizumab were 42% (95% CI, 06 to 90) and 67% (95% CI, 38 to 87), respectively. Only one study involved patients with cuffitis. Ustekinumab, infliximab, vedolizumab and adalimumab are effective in achieving complete clinical response in post-IPAA surgery chronic inflammatory disorders. More studies are needed to determine the efficacy of biologics in cuffitis.

Histopathology of Pouch and Para-Pouch Inflammatory and Neoplastic Disorders.

Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is used to treat patients with ulcerative colitis or familial adenomatous polyposis who need colectomy. While this procedure substantially improves patient's quality of life and reduces cancer risk, it is associated with a variety of sequelae' including surgical complications, inflammatory disorders, and neoplasia. Pouchitis, cuffitis, and Crohn's disease of the pouch are the most common inflammatory disorders of the pouch and para-pouch. This study aimed to elaborate on the histopathology of common inflammatory and neoplastic disorders of the pouch and para-pouch. A Medline search for English language studies published between 1981 and 2021 using the PubMed search engine. The terms "ileal pouch-anal anastomosis," "pouchitis," "pouchitis activity score," "secondary pouchitis," "Crohn's disease of the pouch," "Crohn's-like conditions of the pouch," "pre-pouch ileitis," "cuffitis," "pouch adenocarcinoma," and "pouch neoplasia" were used. The published human studies that reported histopathology of common inflammatory and neoplastic disorders of the ileal pouch were selected and reviewed. Histologic examination plays an essential role in confirming inflammation in pouchitis, identifying etiology and clues for secondary pouchitis, and diagnosing neoplasia. A standardized, simple, and reproducible histologic grading system for pouchitis is needed. Pouch and para-pouch glandular dysplasia diagnosis is challenging and should always be reviewed by at least one gastrointestinal pathologist.

OUTCOMES OF TOTAL PROCTOCOLECTOMY (TPC) WITH ILEAL POUCH ANAL ANASTOMOSIS (IPAA)

Abstract BACKGROUND Total proctocolectomy (TPC) followed by ileal pouch anal anastomosis (IPAA) is the surgery of choice for eligible ulcerative colitis patients who are refractory to medical therapy or develop complications such as adenocarcinoma or dysplasia. Although associated with excellent quality of life, IPAA can lead to complications including chronic antibiotic-refractory pouchitis, anatomical complications, and development of Crohn’s disease. These outcomes remain a clinical challenge. The aim of this study was to evaluate the rate of complications and their treatment following TPC with IPAA to assess for predictors of adverse postoperative outcomes. METHODS This was a single center, retrospective study from January 1,2010 to December 31, 2020. We included patients who underwent TPC with IPAA and reported at least one episode of pouchitis, some of whom also had additional complications. Chronic pouchitis was defined as recurrent episodes of biopsy-proven inflammation or as reported in the patient record based on clinical presentation and responsiveness to treatment. Crohn’s disease of the pouch was defined as pre-pouch ileitis or development of a fistula more than 6 months post-operatively. Data is presented as number of cases and proportions. RESULTS A total of 44 subjects who underwent IPAA (52% female, mean age 46.4 ± 11.3 years) were included. The rate of acute pouchitis was 9%, the rate of chronic pouchitis was 75%. In the chronic pouchitis group, 45% were antibiotic-dependent and 7% were antibiotic-refractory. We found that 70% of subjects required the initiation of medical therapy to treat symptoms of pouchitis, with the majority requiring chronic antibiotics (73%) (Table). A total of 10 subjects (23%) required biologics and 10 subjects (23%) required chronic steroid therapy. Anatomic complications were noted in 23 subjects (52%), the most common being abscess/fistula formation (30%), followed by stricture formation (27%). Anatomic complications appeared more likely to occur when more time had elapsed since the original surgery. 10 subjects (23%) needed repeat surgery and 9 subjects (20%) developed Crohn’s disease of the pouch. CONCLUSIONS In our cohort, we found that nearly two thirds of subjects required medical therapy to treat pouchitis following IPAA including 25% requiring treatment biologic/immunosuppressant therapy. In addition, one quarter required repeat surgery for treatment of complications. Limitations of this study include a tertiary patient population and small sample size. We found a lack of standardized characterization of pouchitis with respect to symptoms and lab abnormalities. In future work, we plan to use this data to develop a prospective, multi-center study to establish a standardized database of patients who underwent IPAA. This will help better understand factors that influence outcomes and guide management.

MASS CYTOMETRY ANALYSIS OF CROHN’S DISEASE-LIKE PHENOTYPE OF THE ILEOANAL POUCH FOLLOWING ILEAL POUCH-ANAL ANASTOMOSIS FOR ULCERATIVE COLITIS

Abstract BACKGROUNDS For patients with medically refractory ulcerative colitis (UC), total proctocolectomy and ileal pouch-anal anastomosis (IPAA) has been the definitive surgery of choice. Approximately 10% of patients who were initially diagnosed with UC and underwent an IPAA, subsequently develop a condition referred to as Crohn’s disease-like phenotype of ileoanal pouch (CDP). CDP is typified by ulcers in the pre-pouch ileum, stricture involving the pouch or pre-pouch ileum, and/or fistulas. The etiology of CDP remains unknown and remains difficult to diagnose and treat. To define the mucosal immunology of CDP, we analyzed ileal samples from patients with CDP and patients with a normal pouch and pre-pouch ileum using mass cytometry (CyTOF). METHODS Ileal mucosal biopsies from patients with a history of CDP with long-segmental pre-pouch ileitis (n=10) and those with a normal pouch and pre-pouch ileum after IPAA for UC (n=9) were collected during routine pouchoscopy, frozen in medium, and processed, barcoded and analyzed in one CyTOF experiment. Data were analyzed by using viSNE for dimensionality reduction and CITRUS for clustering in Cytobank. RESULTS Compared with patients with a normal pouch/ileum, we observed the following in ileal samples from CDP based on viSNE analysis (Figure 1): 1) A decreased abundance of CD8+CD103+ tissue-resident T cells (TRM). This result is similar to data from colonic mucosal samples in patients with UC (our internal data not shown here and others), but unlike data from prior studies derived from inflamed ileal mucosal specimens in patients with CD (native bowel anatomy without IPAA) which had increased CD8+ TRM. 2) An increase in CD4+CD103-CD161+ Th17 cells previously linked to an activated Th17 phenotype in Crohn’s disease specimens. 3) Increased CD4+CD103-CD45RA+ T cells associated with reduced IL-10/IL-4 and increased TNF-a in IBD. 4) A higher abundance of CD4+CD103-TIGIT+ T cells that were previously shown to predict severity of pediatric IBD. 5) A decrease in CD8+CD103+CD127+ TRM in CDP, although its role in IBD is unclear. The findings from viSNE were confirmed by CITRUS (Figure 2). Further analyses of pouch samples as well as ileal samples from UC and CD with native GI anatomy (for comparison) using CyTOF and scRNAseq are currently underway. CONCLUSIONS We used mass cytometry to identify immune cells specific to ileal mucosa from patients with CDP. Interestingly, immune cells from the inflamed pre-pouch ileum share some features of those from either UC or CD with native bowel anatomy. We also identified an altered immune cell population which appears to be specific to CDP. These data reveal a unique immune landscape of CDP which may serve as a foundation for identifying therapeutic approaches that target specific cell populations for medical management of CDP.

P254 Crohn’s disease of the pouch: an overdiagnosed condition?

Abstract Background Approximately 10% of ulcerative colitis (UC) patients undergoing ileal pouch-anal anastomosis (IPAA) are believed to develop ‘de novo Crohn’s disease’ (CD) of the pouch (1). Clear diagnostic criteria are lacking, but the diagnosis is mostly based on the development of fistula, strictures, treatment refractory disease, pre-pouch ileitis, or typical endoscopic findings fitting with CD, such as ulcers and patchy inflammation (1, 2). However, the findings on which this diagnosis is established may be caused by (unrecognized) surgical complications such as silent anastomotic leakage. It is important to distinguish these complications from what is truly a ‘de novo CD’ as treatment strategies differ in both groups. We aimed to investigate incidence rates and reasons for diagnosing CD of the pouch. Methods In total, 483 consecutive UC patients who underwent a proctocolectomy and IPAA in a tertiary IBD referral centre from January 1990 until December 2017 were retrospectively reviewed. Patients with a diagnosis ‘CD of the pouch’ were identified based on medical records, and could be based on either clinical, endoscopic, imaging and/or histological findings. Results Median follow-up time was 20 years (IQR 10 – 24). In 46 out of 483 patients (10%), de novo CD of the pouch was diagnosed, which was mostly based on endoscopic findings (29/46, 63%). Presence of pre-pouch ileitis was the most common reason to diagnose CD of the pouch, which was present in 18/29 patients (62%), followed by ulcerations in 6/29 (21%). On MRE, 19/46 (41%) patients had a fistula or sinus, 4/46 patients (9%) had a stricture (all proximal of the pouch). Interestingly, 12/46 patients (26%) never underwent cross sectional imaging after IPAA construction. Only ten patients (22%) showed histologic findings with a preference for CD in biopsies, revised colectomy specimen, and/or pouch excision specimen. Only two patients had granulomas, others showed signs of transmural inflammation, ulcerations or fibrosis. Other histologic findings were non-specific. Conclusion In our centre, 10% of patients were ‘diagnosed’ with de novo CD of the pouch. However, as confirmatory histological signs of CD were present in only 22%, chronic surgical complications as underlying cause might be of greater importance. It is advised to perform cross sectional imaging in every patient after a year after pouch construction to rule out silent leaks that might cause symptoms at a later stage mimicking Crohn’s disease, avoiding a diagnostic dilemma.

Appropriateness of Medical and Surgical Treatments for Chronic Pouchitis Using RAND/UCLA Appropriateness Methodology.

The treatment of chronic pouchitis remains a challenge due to the paucity of high-quality studies. We aimed to provide guidance for clinicians on the appropriateness of medical and surgical treatments in chronic pouchitis. Appropriateness of medical and surgical treatments in patients with chronic pouchitis was considered in 16 scenarios incorporating presence/absence of four variables: pouchitis symptoms, response to antibiotics, significant prepouch ileitis, and Crohn's disease (CD)-like complications (i.e., stricture or fistula). Appropriateness of permanent ileostomy in patients refractory to medical treatments was considered in eight additional scenarios. Using the RAND/UCLA appropriateness method, international IBD expert panelists rated appropriateness of treatments in each scenario on a 1-9 scale. Chronic antibiotic therapy was rated appropriate only in asymptomatic antibiotic-dependent patients with no CD-like complications and inappropriate in all other scenarios. Ileal-release budesonide was rated appropriate in 6/16 scenarios including patients with significant prepouch ileitis but no CD-like complications. Probiotics were considered either inappropriate (14/16) or uncertain (2/16). Biologic therapy was considered appropriate in most scenarios (14/16) and uncertain in situations where significant prepouch ileitis or CD-like complications were absent (2/16). In patients who are refractory to all medications, permanent ileostomy was considered appropriate in all scenarios (7/8) except in asymptomatic patients with no CD-like complications. In the presence of significant prepouch ileitis or CD-like complications, chronic antibiotics and probiotics are inappropriate. Biologics are appropriate in all patients except in asymptomatic patients with no evidence of complications. Permanent ileostomy is appropriate in most medically refractory patients.

Clinical Features and Therapeutic Outcomes of Post-colectomy Enteritis with Ulcerative Colitis.

Objectives: Few reports are available on post-colectomy enteritis (PCE) with ulcerative colitis (UC), which can be severe and sometimes fatal. The clinical characteristics are unclear, and treatment and diagnosis protocols have not been established. We aimed to investigate the incidence, clinical characteristics, diagnostic criteria, and therapeutic outcomes of PCE in this study. Methods: Patients with UC who underwent colectomy between April 2010 and December 2019 were included in this study. We retrospectively analyzed patients who developed PCE and excluded patients with other forms of enteritis. Results: We performed 829 colectomies because of a preoperative diagnosis of UC. Eleven and four patients were diagnosed with Crohn's disease and indeterminate colitis after surgery, respectively; 22 patients developed enteritis in the perioperative period. We excluded six patients with backwash ileitis, five with prepouch ileitis, three with infectious enteritis, and one with ischemic enteritis. In total, 7/814 (0.8%) patients developed PCE. All patients with PCE had pancolitis. PCE was observed a median of 33 (12-248) days after surgery. Endoscopy showed friable and granular mucosa. The extent of disease included various types such as pan-enteritis with diffuse type, pan-enteritis and mild inflammation in the middle ileum, and only ileitis. Gastroduodenitis-associated UC developed in 6/7 cases. All patients improved with tumor necrosis factor alpha (TNFα) antagonists even if TNFα antagonists had not been effective for colitis. Conclusions: PCE was rare. The mucosal endoscopic findings were similar to those of UC, and the extent of disease varied. TNFα antagonist administration for PCE was effective.

Successful Treatment of Prepouch Ileitis with Oral Mesalamine in Barnett Continent Ileal Reservoir

Barnett Continent Ileal Reservoir is rarely performed in patients with ulcerative colitis who require colectomy. Prepouch ileitis occasionally occurs in patients with ileal pouches. The role of oral mesalamine in the treatment of prepouch ileitis has not been established. We describe a case in which prepouch ileitis in Barnett Continent Ileal Reservoir was successfully treated with oral mesalamine. This is the first case in the literature showing that mesalamine is safe and effective in the treatment of prepouch ileitis in a patient with a continent ileostomy.

Accuracy of Gastrointestinal Ultrasound and Calprotectin in the Assessment of Inflammation and its Location in Patients with an Ileoanal Pouch.

In symptomatic patients with ileoanal pouches, pouchoscopy is needed for accurate diagnosis but is invasive. We aimed to assess the utility of non-invasive gastrointestinal ultrasound and faecal calprotectin in ileoanal pouch patients. Patients with an ileoanal pouch were consecutively enrolled in this cross-sectional study from clinics in Victoria, Australia. The pouchitis disease activity index was used as a reference standard. Video-recorded pouchoscopies were reviewed by three gastroenterologists. Pouch, pre-pouch, and cuff biopsies were reviewed by a single pathologist. Ultrasound was performed by a single gastroenterologist transabdominally and transperineally. Faecal calprotectin was measured from morning stool samples. All examiners were blinded to patients' clinical history. A total of 44 participants had a pouchoscopy, of whom 43 had a faecal calprotectin test and 42 had an ultrasound; 17 had pouchitis, 15 had pre-pouch ileitis, and 16 had cuffitis. Pouch wall thickness of <3 mm was 88% sensitive in excluding pouchitis, and pouch wall thickness of ≥4 mm was 87% specific in diagnosing pouchitis. Transabdominal ultrasound had good utility [area under the curve: 0.78] in diagnosing moderate-severe pre-pouch ileitis. Transperineal ultrasound had good utility for the diagnosis of pouchitis [area under the curve: 0.79]. Faecal calprotectin differentiated inflammatory from non-inflammatory pouch disorders, such as irritable pouch syndrome, with an area under the curve of 0.90. Faecal calprotectin <100 µg/g ruled out inflammatory pouch disorders with a sensitivity of 94%. Faecal calprotectin and ultrasound are accurate and complementary tests to diagnose and localise inflammation of the ileoanal pouch. Prospective studies are needed to validate proposed sonographic indices and calprotectin levels.

P104 Inflammatory complications of the pouch, and therapetic requirements after colectomy in patients with ulcerative colitis. Results from the RESERVO Study of GETECCU

Abstract Background Pouchitis and other inflammatory pouch diseases (IPD) are frequent in pouch-carrying patients operated for a previous diagnosis of ulcerative colitis. We evaluated characteristics and differences in therapeutic requirements between pouchitis, Crohn′s-like disease of the pouch (CDP) and cuffitis. Methods This is a retrospective and multicentric Spanish cohort of GETECCU (RESERVO Study), including pouch-carrying patients (operated 1995 to 2016) with previous ulcerative colitis, ileostomy closure and subsequent diagnosis of IPD (pouchitis, CDP or cuffitis), following ECCO diagnostic criteria1. Follow up extended to June 2020. Pouchitis was categorized attending current classifications. Use of medical and surgical therapies was collected and differences between pouchitis and CDP were analyzed using descriptive and comparative statistics. Results A total of 338 patients were included. Demographic and clinical characteristics are presented in Table 1. The most frequent IPD was pouchitis (n=258, 76%), followed by CDP (n=55, 16%) and cuffitis (n=25, 7.4%). Pouchitis was diagnosed at a median time of 27 (range 1–342) months. Prevalence according to pouchitis classification is presented in Figure 1. CDP was diagnosed at a median time of 77 (range 5–324) months, around 75% with a previous pouchitis diagnosis. Location of CDP (not mutually excludent) was pouch CDP (91%), 87% pre-pouch ileitis, and 41% perianal disease. Regarding behavior: 26 (47%) were inflammatory, 12 (22%) stricturing and 17 (31%) penetrating (8 rectovaginal fistulas). Cuffitis was diagnosed at a median time of 18 (range 1–219) months. Medical and surgical therapies used are shown in Figure 2. Immunosuppressants (58.2 vs 22.4%, p 0.001), biologics (74.5 vs 34.8%, p 0.0001), and surgery (41.8 vs 21.3%, p 0.003) were more used in CDP than in pouchitis. Conclusion Pouchitis and CDP are heterogeneous inflammatory pouch complications with a wide and high therapeutic requirement. CDP presents a later diagnosis and has higher therapeutic needs than pouchitis. 1. Fernando Magro, Paolo Gionchetti, Rami Eliakim et al, for the European Crohn’s and Colitis Organisation [ECCO], Third European Evidence-based Consensus on Diagnosis and Management of Ulcerative Colitis. Part 1: Definitions, Diagnosis, Extra-intestinal Manifestations, Pregnancy, Cancer Surveillance, Surgery, and Ileo-anal Pouch Disorders, J Crohns Colitis 2017; 11(6): 649–670.

Primary Sclerosing Cholangitis–Associated Pouchitis: A Distinct Clinical Phenotype

Patients with primary sclerosing cholangitis (PSC) commonly undergo ileal pouch-anal anastomosis (IPAA) for medically-refractory ulcerative colitis (UC) or colorectal dysplasia. Pouchitis develops more frequently in patients with PSC, potentially leading to increased morbidity. We aimed to assess clinical characteristics and treatment outcomes for pouchitis in patients with PSC compared to a matched, non-PSC cohort. All patients with PSC who underwent IPAA and were diagnosed with pouchitis (PSC-pouchitis) were identified. A matched cohort composed of non-PSC patients who underwent IPAA for UC and subsequently developed pouchitis (UC-pouchitis) was developed. Relevant demographic, clinical, endoscopic, histologic, and treatment data were collected and compared between groups. Of those with PSC-pouchitis (n=182), 53.9% and 46.1% underwent IPAA for medically-refractory disease and dysplasia, respectively, compared to 88.7% and 11.3% in the UC-pouchitis group (P < .001). Patients with PSC-pouchitis were more likely to develop chronic pouchitis (68.1% vs 34.1%; P < .001), have moderate-to-severe pouch inflammation (54.9% vs 32.4%; P < .001), and prepouch ileitis (34.1% vs 11.5%; P < .001) compared to UC-pouchitis. Of those with PSC-pouchitis, 50.6% and 17.6% developed chronic antibiotic-dependent or antibiotic-refractory pouchitis, respectively, compared to 25.8% and 7.7% with UC-pouchitis. There was no difference in treatment response between the two groups with use of thiopurines, anti-tumor necrosis factor agents, and newer biologics. PSC-associated pouchitis presents with a unique clinical phenotype, characterized by increased risk of chronic pouchitis, moderate-to-severe pouch inflammation, prepouch ileitis, and less response to conventional antimicrobial therapy.

Pre-pouch Ileitis is Associated with Development of Crohn's Disease-like Complications and Pouch Failure.

It is unclear whether pre-pouch ileitis heralds an aggressive inflammatory pouch disease in patients with ileal pouch-anal anastomosis [IPAA]. We compared outcomes of patients with pouchitis and concomitant pre-pouch ileitis with those with pouchitis alone. Patients undergoing IPAA surgery for inflammatory bowel disease, who subsequently developed pouchitis with concomitant pre-pouch ileitis [pre-pouch ileitis group], were matched by year of IPAA surgery and preoperative diagnosis [ulcerative colitis or inflammatory bowel disease-unclassified] with patients who developed pouchitis alone [pouchitis group]. Primary outcomes were development of Crohn's disease [CD]-like complications [non-anastomotic strictures or perianal disease >6 months after ileostomy closure] and pouch failure. Secondary outcomes were need for surgical/endoscopic interventions and immunosuppressive therapy. Log-rank testing was used to compare outcome-free survival, and Cox regression was performed to identify predictors of outcomes. There were 66 patients in each group. CD-like complications and pouch failure developed in 36.4% and 7.6% patients in the pre-pouch ileitis group and 10.6% and 1.5% in pouchitis group, respectively. CD-like complications-free survival [log-rank p = 0.0002] and pouch failure-free survival [log-rank p = 0.046] were significantly lower in the pre-pouch ileitis group. The pre-pouch ileitis group had a higher risk of requiring surgical/endoscopic interventions [log-rank p = 0.0005] and immunosuppressive therapy [log-rank p <0.0001]. Pre-pouch ileitis was independently associated with an increased risk of CD-like complications (hazard ratio [HR] 3.8; p = 0.0007), need for surgical/endoscopic interventions [HR 4.1; p = 0.002], and immunosuppressive therapy [HR 5.0; p = 0.0002]. Pre-pouch ileitis is associated with a higher risk of complicated disease and pouch failure than pouchitis. It should be considered a feature of CD.

S0695 Appropriateness of Medical and Surgical Treatments in Patients With Chronic Inflammation of the Ileal Pouch: A RAND Panel Approach

INTRODUCTION: The optimal treatment of chronic inflammatory pouch disorders remains a challenge due to the paucity of high-quality studies. We aimed to provide guidance for clinicians on the appropriateness of medical and surgical treatments in patients with these disorders. METHODS: The appropriateness of medical and surgical treatments in patients with pouchitis was considered in 16 clinical scenarios incorporating pouchitis symptoms, antibiotic response, prepouch ileitis (PI) (extending >10 cm proximal to pouch inlet) and Crohn's disease (CD)-like complications. Appropriateness of permanent ileostomy was considered in 8 additional scenarios. Using the RAND/UCLA modified Delphi method, 13 international inflammatory bowel diseases experts rated appropriateness of treatments on a 1–9 scale (1–3 inappropriate, 4–6 uncertain, 7–9 appropriate) via a web-based survey, then met to discuss and re-rate scenarios. Disagreement was assessed using a validated index; scenarios with disagreement were rated as uncertain. RESULTS: Chronic antibiotic therapy was rated appropriate only in asymptomatic antibiotic-dependent patients with no CD-like complications and was otherwise inappropriate (Table 1). Ileal-release budesonide was rated appropriate in 6/16 (38%) scenarios including patients with extensive PI but no CD-like complications. Its use was considered inappropriate (5/8) or uncertain (3/8) in the presence of CD-like complications. Probiotics were considered inappropriate in 14/16 (88%) and uncertain in 2/16 (12%) scenarios. Biologic therapy was considered appropriate in 14/16 (88%) scenarios and uncertain in the absence of extensive PI or CD-like complications (12%). Permanent ileostomy was considered appropriate in 3/16 (19%) scenarios including symptomatic patients with extensive PPI and CD-like complications (Table 2). In patients refractory to all medical treatments, permanent ileostomy was considered appropriate in all scenarios except in asymptomatic patients with no CD-like complications. CONCLUSION: In the presence of extensive PI or CD-like complications, chronic antibiotics and probiotics are inappropriate. Ileal-release budesonide is appropriate in patients who have chronic pouchitis with extensive PI but no CD-like complications. Biologic use is appropriate in patients with chronic pouchitis except in asymptomatic patients with no evidence of complications. Permanent ileostomy is appropriate in most patients who have failed all medical treatments.Table 1.: Appropriateness of medical and surgical treatments in patients with chronic pouch inflammationTable 2.: Appropriateness of a permanent ileostomy in patients with chronic pouch inflammation who have failed antibiotics, ileal release budesonide, probiotics and biologics

P120 PRE-POUCH ILEITIS IS A RISK FACTOR FOR DEVELOPMENT OF CROHN’S DISEASE-LIKE COMPLICATIONS, NEED FOR BIOLOGIC THERAPY AND POUCH FAILURE

Abstract Introduction Pre-pouch ileitis or afferent limb inflammation is generally considered to be suggestive of de novo Crohn’s disease in patients with ileal pouch. However, the data on whether these patients progress to develop CD-like complications is limited. We aim to study the evolution of pre-pouch ileitis in this study. Methods All patients who underwent an IPAA surgery by an expert surgeon between 1990 and 2018 for diagnosis of ulcerative colitis (UC) or inflammatory bowel disease-unclassified (IBD-U) at our institution and later went to develop pre-pouch ileitis were included. Patient charts were reviewed were reviewed subsequent to the diagnosis of pre-pouch ileitis to assess development of CD-like complications (non-anastomotic strictures and fistulae developing &amp;gt;6 months after ileostomy closure) or requirement of J-pouch surgery or ileostomy. Pre-pouch ileitis was defined by presence of erosions or ulcers in the afferent limb. Results 58 patients with J-pouch developed pre-pouch ileitis at a median of 21 months (range 1–216 months) from ileostomy closure. Baseline characteristics are shown in table 1. Median follow up duration after the diagnosis of pre-pouch ileitis was 48 months (range 2–204 months). 54/58 (93%) patients had concomitant pouchitis with pre-pouch ileitis. 36/58 (62%) patients were initiated on biologic therapy during their follow up course and 3/58 (5%) were treated with an immunomodulator. 20/58 (35%) patients developed Crohn’s disease-like complications (10 developed non-anastomotic strictures and 10 developed perianal complications) at a median follow up of 17 months (range 2–85 months) from the diagnosis of pre-pouch ileitis. 5/58 (8.6%) needed endoscopic stricture dilation and 6/58 (10%) needed perianal surgery for fistula or abscess. Pouch failure occurred in 5/58 (9%) of patients (3 with pouch resection, 1 with pouch revision and 1 with permanent ileostomy), while 3/58 (5%) patients required temporary ileostomy. Conclusions Patients who develop pre-pouch ileitis are at high risk of developing CD-like complications (non-anastomotic strictures and perianal complications). The risk of pouch failure and requirement for endoscopic procedures or surgery in this cohort also appears to higher than traditionally reported in patients with pouchitis. Hence, pre-pouch ileitis should be considered suggestive of Crohn’s disease and treated aggressively.

The Incidence and Definition of Crohn's Disease of the Pouch: A Systematic Review and Meta-analysis.

A subset of patients who undergo total proctocolectomy with ileal pouch-anal anastomosis (IPAA) creation for ulcerative colitis (UC) will later develop Crohn's disease (CD) of the pouch, which has been associated with significant morbidity. We aimed to analyze the incidence of CD of the pouch and to review the existing diagnostic criteria utilized. A systematic search performed through March 1, 2018, identified 12 studies that reported the incidence of CD of the pouch after IPAA for UC or indeterminate colitis (IC). We compiled all diagnostic criteria utilized in these studies and then performed a meta-analysis using random effects modeling to estimate the overall incidence of CD of the pouch in this population. Among 4843 patients with an IPAA for UC or IC, 10.3% of patients were ultimately diagnosed with CD of the pouch (95% confidence interval [CI], 6.1%-15.4%). The most commonly reported diagnostic criteria were (1) presence of fistula/fistulae, (2) stricture involving the pouch or prepouch ileum, and (3) presence of prepouch ileitis. In a secondary analysis, excluding those studies that included patients with a preoperative diagnosis of IC, the incidence of CD of the pouch was 12.4% (95% CI, 9.0%-16.1%). The estimated incidence of 10.3% will assist gastroenterologists and surgeons in preoperative counseling regarding the potential to develop CD of the pouch. There is an unmet need for common diagnostic criteria for a more standardized approach to the diagnosis of CD of the pouch.