Development Of Pouchitis Research Articles

Assessing the Value of Histology and Anatomic Segment Evaluation Among Patients Undergoing Pouchoscopy.

The value of histologic assessment after ileal pouch-anal anastomosis (IPAA) has not been definitively determined. We evaluated the correlation between histology and endoscopic findings, as well as the proportion of patients with inflammation in areas beyond the pouch body on their initial pouchoscopy after IPAA. In a retrospective cohort study, we evaluated patients who underwent IPAA for UC between 2012 and 2020 and subsequently underwent a pouchoscopy with routine biopsies of the pouch body, pre-pouch ileum, and rectal cuff. We compared endoscopic and histologic assessments in each location using χ2 testing and Spearman correlation, as well as the development of pouchitis and Crohn's-like disease of the pouch (CLDP) in longitudinal follow-up. Among 126 patients, the median time to pouchoscopy after IPAA was 384 days, with 82 patients (65%) having inflammation of the pouch body. Significantly more patients with pouch body inflammation had histologic inflammation compared with patients without pouch body inflammation (96% vs 22%, P < .001, r = 0.769). Additionally, 16 patients (13%) were found to have endoscopic inflammation of the pre-pouch ileum with corresponding histologic inflammation in 88%; of these, 31% later developed CLDP. In contrast, 13% of patients with no endoscopic inflammation displayed histologic inflammation, with none later developing CLDP. Forty-six percent of patients had rectal cuff inflammation (correlation with histologic inflammation r = 0.580). In our evaluation, the added benefit of histology in the presence of visible endoscopic inflammation for disease activity assessment scores is unclear. The prognostic value of histologic inflammation without endoscopic inflammation warrants a longitudinal study.

Acute Pouchitis is Common in Pregnant and Postpartum Women.

The impact of pregnancy on the development of pouchitis in women who have undergone total proctocolectomy with ileal pouch anal anastomosis for ulcerative colitis is poorly understood. This was a retrospective study of women with ulcerative colitis who underwent total proctocolectomy with ileal pouch anal anastomosis and subsequently became pregnant at Mount Sinai Hospital. The primary outcome was acute pouchitis during pregnancy or the postpartum period defined as symptoms of increased stool frequency and urgency treated with antibiotics. A total of 44 women with 63 pregnancies and complete data were identified. Acute pouchitis occurred in 14 pregnancies (22.2%) in 12 women and in the postpartum period of 10 pregnancies (15.9%) in 9 women. Acute pouchitis occurred more frequently in women with a history of acute pouchitis immediately before, during, or after pregnancy. Acute pouchitis was common during pregnancy and the postpartum period, likely due to microbial shifts. Although not statistically significant, these results provide insight into the impact of pregnancy on the risk of pouchitis and establish the framework for preconception counseling that focuses on prevention and management of pouchitis during pregnancy.

Dietary Interventions and Supplementation in Patients With an Ileal Pouch-Anal Anastomosis: A Systematic Review.

Lay Summary The restorative proctocolectomy with ileal pouch–anal anastomosis is the preferred surgery for patients with medically refractory ulcerative colitis. Although the ileal pouch–anal anastomosis provides gastrointestinal continuity and is an excellent alternative to a permanent end ileostomy, it is not without its complications including acute pouchitis, which occurs in up to 80% of patients. Diet may have a significant impact on pouch function and the development of pouchitis by virtue of its impact on motility and the microbiome. Multiple studies have evaluated the ability of different diets and supplements to improve pouch function and manage pouchitis, yet results are conflicting; thus, evidence-based dietary recommendations are lacking. Patients with an ileoanal pouch routinely ask about dietary interventions to maintain pouch health, and it is crucial that concrete evidence-based recommendations are identified to provide guidance. The goal of this systematic review is to summarize the available data on dietary patterns in patients with an ileoanal pouch, dietary interventions in this cohort, and the impact of supplements on pouch function and pouchitis.

Pyoderma Gangrenosum Is Associated With Increased Risk of Inflammatory Pouch-Related Complications: A Retrospective Cohort Study.

Pyoderma gangrenosum (PG) is a rare, neutrophilic dermatosis that is a well-established extraintestinal manifestation (EIM) of inflammatory bowel disease. The clinical implications of developing PG in patients with ulcerative colitis (UC) who undergo total proctocolectomy colectomy and ileal pouch anal anastomosis (TPC-IPAA) surgery remain unknown. Study participants were selected from patients enrolled in the Carlino Family Inflammatory Bowel and Colorectal Disease Biobank between 1998 and 2021 with a pre-colectomy diagnosis of UC and who underwent TPC-IPAA surgery. A retrospective study comparing patients with PG and those without PG was performed. The outcomes measured included the development of pouchitis, pouchitis classification, presence of pouch fistula, anal fistula, anal stenosis, and pouch failure. In this study, 357 IPAA patients were included, 10 of whom suffered PG. Patients with PG and without PG had similar demographics and clinical characteristics. Both groups had similar rates of pouchitis (80% in PG patients and 64% in patients without PG, P = .504). However, IPAA patients with PG had a higher risk of developing pouch fistula (50% vs 10%, P = .002), anal fistula (40% vs 12%, P = .031), and Crohn's-like disease of the pouch (70% vs 15%, P = .003) compared to patients without PG. Patients who developed PG prior to their first episode of pouchitis were more likely to eventually experience pouch failure (odds ratio: 20.7, 95% confidence interval: 3.9, 110.7, q = 0.003 after false discovery rate adjustment). Among UC patients who undergo TPC-IPAA surgery, the development of PG portends poor pouch outcomes and is predictive of pouch failure.

Review of long-term complications and functional outcomes of ileoanal pouch procedures in patients with inflammatory bowel disease.

In medically refractory Ulcerative Colitis (UC), proctocolectomy with ileoanal pouch procedure (IAPP) is the preferred continence-preserving surgical option. Functional outcomes post-surgery and long-term complication rates in the biologic era remain ambiguous. This review primarily aims to provide an update on these outcomes. Secondarily, risk factors associated with chronic pouchitis and pouch failure are explored. Two online databases (MEDLINE and EMBASE) were searched on 4 October 2022 for English studies from 2011-present relating to long-term outcomes of IAPP in inflammatory bowel disease (IBD) patients. Adult patients with 12 month follow-up were included. Studies focused on 30-day post-operative outcomes, non-IBD patients or studies including less than 30 patients were excluded. Following screening and full-text review of 1094 studies, 49 were included. Median sample size was n = 282 (IQR: 116-519). Median incidences for chronic pouchitis and pouch failure were 17.1% (IQR: 12-23.6%) and 6.9% (IQR: 4.8-10.8%), respectively. Upon multivariate analysis, chronic pouchitis development was most significantly associated with pre-operative steroid use, pancolitis and extra-intestinal IBD manifestations, whilst pouch failure was most significantly associated with pre-operative diagnosis of Crohn's disease (compared to UC), peri-operative pelvic sepsis and anastomotic leak. Overall patient satisfaction was very high with four included studies reporting greater than 90% satisfaction rates. Long-term complications for IAPP were common. However, despite this, patient satisfaction post-IAPP was high. Up-to-date knowledge of complication rates and their risk factors improves pre-operative counselling, management planning and patient outcomes.

Associations between Pouchitis and Fecal Calprotectin after Restorative Proctocolectomy in Patients with Ulcerative Colitis

Introduction: Recently, fecal calprotectin has been identified and used as an assessment tool for the confirmation of disease activity in ulcerative colitis. Although a meta-analysis suggested the usefulness of fecal calprotectin for the assessment of pouchitis, the number of participants was still insufficient. Therefore, we prospectively measured fecal calprotectin levels during pouchoscopy and analyzed their associations with pouchitis. Methods: Patients who underwent pouchoscopy after total proctocolectomy and ileal pouch-anal anastomosis for ulcerative colitis were included. Fecal samples were collected for the measurement of calprotectin during pouchoscopy. Patients either with or without suspicious pouchitis were included. Pouchitis was defined as a modified pouchitis disease activity index (m-PDAI) score of ≥5. The associations between the development of pouchitis and the m-PDAI score and fecal calprotectin and serum markers, including C-related protein, albumin, and white blood cells, were assessed. Results: A total of 170 patients were included. Seventy-two patients were diagnosed with pouchitis with an m-PDAI score of 7.3 ± 1.5. The values of fecal calprotectin were 1,500 ± 1,544 μg/g in patients with pouchitis and 259 ± 402 μg/g in patients without pouchitis (p < 0.01). The correlation coefficient between calprotectin and the m-PDAI score was significant (r² = 0.279, p < 0.001). The cutoff value of fecal calprotectin in receiver operating characteristic analysis was 246 μg/g (area under curve 0.85, sensitivity 83.9%, specificity 71.0%). Fecal samples were able to be collected from 6 patients. The levels of fecal calprotectin significantly decreased from 2,101.3 ± 880.3 μg/g to 284.2 ± 96.9 μg/g in response to the treatment. Conclusions: Elevated fecal calprotectin appeared to be significantly correlated with pouchitis. We should consider the alteration of this marker during treatments in further studies.

Microbiota DNA Translocation Into Mesentery Lymph Nodes Is Associated With Early Development of Pouchitis After IPAA for Ulcerative Colitis.

The role of bacterial translocation in Crohn's disease has been extensively studied. However, data regarding bacterial translocation into the mesentery in patients with ulcerative colitis were scarce. This study aimed to explore the relationship between bacterial translocation and postoperative outcome by comparing the microbiome profile of different anatomical sites in patients with ulcerative colitis who underwent proctocolectomy and IPAA. A prospective study. This study was conducted at the Jinling Hospital from August 2017 to May 2018. Samples of 27 patients with ulcerative colitis who had IPAA and 15 healthy controls who underwent routine colonoscopy were collected. The microbiome profile of different tissue sites and short- and long-term outcomes after IPAA in patients with ulcerative colitis. Bacterial DNA was detected in mesenteric lymph nodes of 51.9% of patients with ulcerative colitis (14/27) and in mesenteric adipose tissue of 66.7% of patients (18/27). The microbiome in mesenteric lymph nodes and mesenteric adipose tissue resembled the mucosal microbiome to a greater extent than the fecal microbiome. Positive bacterial DNA in mesenteric lymph nodes (8/14 vs 0/13; p = 0.002) was associated with pouchitis within 12 months after IPAA, whereas Bray-Curtis distance in mesenteric lymph nodes was significantly different between patients with pouchitis and without ( p = 0.009). This study was limited by its small sample size and lacked situ experiment to confirm the true bacterial translation. Bacterial translocation was highly prevalent in patients with ulcerative colitis. The translocated bacteria DNA in mesenteric adipose tissue and mesenteric lymph nodes was highly correlated and more likely to originate from mucosal than fecal microbiome. Also, the extent of bacterial translocation and translocation of certain bacteria might be associated with the early development of pouchitis after IPAA. This might represent an unprecedented technique to predict pouchitis using mesenteric lymph node bacterial profiles. See Video Abstract at http://links.lww.com/DCR/C119 . ANTECEDENTES:El papel de la translocación bacteriana en la enfermedad de Crohn se ha estudiado ampliamente en los últimos años. Sin embargo, los datos sobre la translocación bacteriana en el mesenterio en pacientes con colitis ulcerosa fueron escasos.OBJETIVO:El objetivo de este estudio fue explorar la relación entre la translocación bacteriana y el resultado postoperatorio comparando el perfil del microbioma de diferentes sitios anatómicos en pacientes con colitis ulcerosa que se sometieron a proctocolectomía y anastomosis ileoanal con bolsa.DISEÑO:Estudio prospectivo.AJUSTE:Este estudio se realizó en el Hospital Jinling desde agosto de 2017 hasta mayo de 2018.PACIENTES:Se recogieron muestras de 27 pacientes con colitis ulcerosa que tenían anastomosis de bolsa ileoanal y 15 controles sanos que se sometieron a una colonoscopia de rutina.PRINCIPALES MEDIDAS DE RESULTADO:El perfil del microbioma de diferentes sitios de tejido y los resultados a corto y largo plazo después de la anastomosis ileoanal con bolsa en pacientes con colitis ulcerosa.RESULTADOS:Se detectó ADN bacteriano en los ganglios linfáticos mesentéricos del 51,9 % (14/27) de los pacientes con colitis ulcerosa y en el tejido adiposo mesentérico del 66,7 % (18/27) de los pacientes, respectivamente. El microbioma en los ganglios linfáticos mesentéricos y el tejido adiposo mesentérico se parecía más al microbioma de la mucosa que al microbioma fecal. El ADN bacteriano translocado en los ganglios linfáticos mesentéricos y el tejido adiposo mesentérico estaban altamente correlacionados. El ADN bacteriano positivo en los ganglios linfáticos mesentéricos (8/14 frente a 0/13, p = 0,002) se asoció con reservoritis dentro de los 12 meses posteriores a la anastomosis ileoanal con reservorio, mientras que la distancia de Bray-Curtis en los ganglios linfáticos mesentéricos fue significativamente diferente entre reservoritis y no reservorios. -pacientes con reservorio (p = 0,009). Ruminococcus, Bacteroides y Clostridiales se encontraron exclusivamente en los ganglios linfáticos mesentéricos de pacientes con reservoritis.LIMITACIÓN:Este estudio estuvo limitado por el pequeño tamaño de la muestra y la falta de un experimento in situ para confirmar la verdadera traducción bacteriana.CONCLUSIÓN:La translocación bacteriana fue altamente prevalente en pacientes con colitis ulcerosa. El ADN bacteriano translocado en el tejido adiposo mesentérico y los ganglios linfáticos mesentéricos estaba altamente correlacionado y era más probable que se originara en el microbioma de la mucosa que en el fecal. Además, la extensión de la translocación bacteriana y la translocación de ciertas bacterias podría estar asociada con el desarrollo temprano de reservoritis después de la anastomosis del reservorio ileoanal. Esto podría representar una técnica sin precedentes para predecir la reservoritis utilizando perfiles bacterianos de los ganglios linfáticos mesentéricos. Consulte Video Resumen en. http://links.lww.com/DCR/C119(Traducción-Dr. Felipe Bellolio ).

Ileal Pouch-Anal Anastomosis in the Older Adult: a Review of Postoperative Outcomes and Pouchitis Treatment.

Ileal pouch-anal anastomosis (IPAA) has become the preferred surgical treatment for patients with medically refractive ulcerative colitis (UC). Previous studies have suggested that outcomes of this procedure may be worse in older patients; however, more recent reports have suggested that IPAA in select patients is safe, feasible, and results in good quality of life. In this review, we discuss the recent literature surrounding clinical considerations and treatment management of IPAA in older adults. IPAA complication rates and adverse events are similar in the older adult population, as compared to the younger adult patient population. Although fecal urgency and incontinence may be more common among older adults, chronological age alone is not a contraindication for IPAA surgery, as good quality of life can still be achieved. In this review, we will also discuss the development of pouchitis after IPAA, particularly among older adults, as the emergence of newer biologic drugs has shifted the treatment landscape. IPAA can be a safe and effective treatment modality for older adults with UC, with high self-reported patient satisfaction. Patient optimization and careful case selection are vital to achieving these outcomes, and specialized preoperative assessments and counseling can help facilitate the proper treatment.

S752 Early Pouchitis Is Associated With an Increased Likelihood of Chronic Antibiotic Dependent Pouchits and Crohn’s-Like Disease of the Pouch

Introduction: Approximately 80% of patients will develop pouchitis at some point after an IPAA for ulcerative colitis (UC), with 17% of patients developing chronic antibiotic dependent pouchitis (CADP) and and 10% developing Crohn’s-like disease of the pouch. Few reliable risk factors for these chronic inflammatory conditions of the pouch have been identified. We aimed to investigate the relationship between early pouchitis, defined as acute pouchitis within the first 180 days of the final stage of IPAA surgery, and the future development of CADP and Crohn’s-like disease of the pouch. Methods: We performed a retrospective cohort study, evaluating patients who underwent proctocolectomy with IPAA at our center between January 1, 2004 and December 31, 2016. Multivariable logistic regression was used to evaluate the relationship between early pouchitis and the development of CADP and Crohn’s-like disease of the pouch, adjusting for other relevant clinical and demographic factors. Results: Among 626 patients undergoing IPAA for UC, 137 (22%) developed early pouchitis, 75 (12%) developed CADP, and 59 (9%) developed Crohn’s-like disease of the pouch. Patients developing early pouchitis were significantly more likely to be of Hispanic ethnicity compared to patients who did not develop early pouchitis (5.6% vs. 1.4%, p=0.006, Table). Early pouchitis was associated with a significant increase in the odds of developing CADP (adjusted odds ratio [aOR] 3.65, 95% CI 2.19-6.10). A preoperative diagnosis of PSC was also associated with an increase in the odds of developing CADP (aOR 3.97, 95% CI 1.44-11.0). Early pouchitis was also associated with an increased likelihood of developing Crohn’s-like disease of the pouch (aOR 2.68, 95% CI 1.50-4.80) as was a family history of inflammatory bowel disease (aOR 2.10, 95% CI 1.11-3.96). The median duration of follow up for all patients in the study was 5.18 years (interquartile range 0.94 – 10.8 years). Conclusion: In a cohort of patients with UC who underwent IPAA, the development of pouchitis within the first 180 days of surgery was associated with an increased risk of developing CADP and Crohn’s-like disease of the pouch. These findings highlight early pouchitis as a unique risk factor for chronic pouch-related disorders and the need for future studies evaluating potential interventions including secondary prophylaxis strategies in this population. Table 1. - Univariate comparison of demographic and clinical characteristics of patients with and without pouchitis in the two years following an ileal pouch-anal anastomosis Patients without early pouchitis (n=489) Patients with early pouchitis (n=137) p-value Median IQR Median IQR Age at surgery, in years 40.3 28.8-52.4 43.1 33.7-54.5 0.094 Disease duration prior to surgery 5.9 2.2-14.2 6.3 2.0-13.6 0.854 n % n % Race 0.923 White 424 89.3 121 89.0 Non-White 51 10.7 15 11.0 Hispanic 6 1.4 7 5.6 0.006 Family history of Crohn's disease or ulcerative colitis 83 16.2 14 20.0 0.421 Indication for surgery 0.059 Medically-refractory colitis 376 76.9 118 86.1 Dysplasia or cancer 72 14.7 11 8.0 Other indications/multiple indications 41 8.4 8 5.8 Disease extent prior to surgery 0.405 Proctitis 23 5.0 3 2.3 Left-sided colitis 133 29.1 40 30.8 Extensive colitis 301 65.9 87 66.9 Stages involved in IPAA surgery 0.977 1 92 18.9 24 17.5 2 173 35.5 51 37.2 Modified 2 183 37.5 11 37.2 3 40 8.2 51 8.0 Abscess or pelvic sepsis after IPAA surgery 94 19.2 23 16.8 0.518 Evidence of an IPAA leak immediately after IPAA surgery 38 7.8 8 5.8 0.444 Primary Sclerosing Cholangitis 13 2.7 6 4.4 0.299 Medications used prior to colectomy Systemic aminosalicylate 380 77.7 115 83.9 0.113 Topical aminosalicylate 230 47.0 72 52.6 0.253 Thiopurine 299 61.2 91 66.4 0.256 Methotrexate 58 11.9 9 6.6 0.077 Anti-TNF 252 51.5 69 50.4 0.809 Vedolizumab 11 2.3 6 4.4 0.175 Cyclosporine 13 2.7 13 9.5 < 0.001 Prednisone use at the time of last stage of surgery 192 39.3 58 42.7 0.487

Increasing Incidence of Pouchitis Between 1996 and 2018: A Population-Based Danish Cohort Study

Current knowledge regarding the epidemiology of pouchitis is based on highly selected, mostly single-center, patient cohorts. Our objective was to prospectively determine the population-based incidence of pouchitis in patients with ulcerative colitis in the first 2 years after ileal pouch-anal anastomosis and analyze time trends of the incidence of pouchitis. Using national registries, we established a population-based cohort of all Danish patients undergoing proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis between 1996 and 2018. The primary outcome was the development of pouchitis within the first 2 years after surgery, evaluated by time period. We used Kaplan-Meier and Cox proportional hazard modeling to evaluate the time to development of pouchitis. Overall, 1664 patients underwent an ileal pouch-anal anastomosis. The cumulative incidence of pouchitis in the 2 years after ileal pouch-anal anastomosis increased throughout the study period, from 40% in the period from 1996 to 2000 (95% CI, 35%-46%) to 55% in the period from 2015 to 2018 (95% CI, 48%-63%). Patients undergoing surgery between 2015 and 2018 also showed an increased risk of pouchitis compared with the earliest study period (1996-2000) after adjusting for sex, age, and socioeconomic status (hazard ratio, 1.57; 95% CI, 1.20-2.05). This population-based study showed a 15% absolute and 38% relative increase in the incidence of pouchitis among patients undergoing surgery between 1996 and 2018, with the greatest cumulative incidence of pouchitis shown in the most recent era (2015-2018). The striking increase in the incidence of pouchitis highlights the need for further research into causes and prevention of pouchitis.

Relationship Between Stages of Ileal Pouch-Anal Anastomosis, Timing of Restoration of Fecal Continuity, and Pouchitis.

The most common complication following ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC) is pouchitis. We aimed to investigate whether a shorter period between pouch creation and restoration of fecal flow through an IPAA was associated with an increased risk of development of pouchitis within the first 2years after IPAA. We performed a retrospective cohort study evaluating patients undergoing colectomy with IPAA for UC between January 1, 2004 and December 31, 2016. We used Kaplan-Meier testing and Cox Proportional Hazards Modeling to evaluate the relationship between the time between restoration of fecal continuity and time to subsequent development of pouchitis, adjusting for other clinical and demographic factors. We identified 624 patients who underwent proctocolectomy with IPAA for UC, of whom 246 (39%) developed pouchitis within the first 2years after IPAA. There was no difference when comparing the median time to restoration of continuity among those patients who developed pouchitis and those who did not (49days vs. 49days, p = 0.85) or in multivariable analysis. Primary sclerosing cholangitis (Hazard Ratio [HR] 2.14, 95% CI 1.12-4.08), family history of inflammatory bowel disease (HR 1.49, 95% CI 1.08-2.06), and delayed pouch creation (HR 0.75, 95% CI 0.57-1.00) were significantly associated with time to development of pouchitis. Although a staged approach to IPAA may have benefits in the surgical management of UC, the timing interval between pouch creation and restoration of continuity did not impact the subsequent development of early pouchitis in this cohort.

Prediction of pouchitis after ileal pouch-anal anastomosis in patients with ulcerative colitis using artificial intelligence and deep learning.

Pouchitis is one of the major postoperative complications of ulcerative colitis (UC), and it is still difficult to predict the development of pouchitis after ileal pouch-anal anastomosis (IPAA) in UC patients. In this study, we examined whether a deep learning (DL) model could predict the development of pouchitis. UC patients who underwent two-stage restorative proctocolectomy with IPAA at Keio University Hospital were included in this retrospective analysis. The modified pouchitis disease activity index (mPDAI) was evaluated by the clinical and endoscopic findings. Pouchitis was defined as an mPDAI ≥ 5.860; endoscopic pouch images before ileostomy closure were collected. A convolutional neural network was used as the DL model, and the prediction rates of pouchitis after ileostomy closure were evaluated by fivefold cross-validation. A total of 43 patients were included (24 males and 19 females, mean age 39.2 ± 13.2years). Pouchitis occurred in 14 (33%) patients after ileostomy closure. In less than half of the patients, mPDAI scores matched before and after ileostomy closure. Most of patients whose mPDAI scores did not match before and after ileostomy closure had worse mPDAI scores after than before. The prediction rate of pouchitis calculated by the area under the curve using the DL model was 84%. Conversely, the prediction rate of pouchitis using mPDAI before ileostomy closure was 62%. The prediction rate of pouchitis using the DL model was more than 20% higher than that using mPDAI, suggesting the utility of the DL model as a prediction model for the development of pouchitis. It could also be used to determine early interventions for pouchitis.

DOP35 Increasing incidence of pouchitis among patients undergoing ileal pouch-anal anastomosis between 1996 and 2018: A population-based Danish cohort study

Abstract Background Current knowledge regarding the epidemiology of pouchitis is based on highly selected, mostly single-center, patient cohorts. Our objective was to prospectively determine the population-based incidence of pouchitis in patients with ulcerative colitis (UC) in the first 2 years after ileal pouch-anal anastomosis (IPAA) and analyze time trends of the incidence of pouchitis. Methods We used national registries to establish a population-based cohort of all Danish patients undergoing proctocolectomy with IPAA UC between 1996 and 2018. The primary outcome was the development of pouchitis within the first 2 years after IPAA, evaluated by time period of IPAA. The period of IPAA was categorized as follows: 1996–2000 (pre-biologic-1), 2001–2005 (pre-biologic-2), 2006–2010 (early-anti-TNF), 2011–2014 (expanding anti-TNF), 2015–2018 (current biologic). Pouchitis was defined using a previously developed case-finding definition for use in administrative claims data. Kaplan Meier and Cox Proportional Hazard modeling were utilized in the evaluation of time to development of pouchitis. Results We identified 1,664 patients that underwent an IPAA for UC. The cumulative incidence of pouchitis in the 2 years after IPAA increased throughout the study period, from 40% in 1996–2000, (95% CI:35%-46%) to 55% in 2015–2018, (95% CI:48%-63%, Table 1). Patients undergoing surgery between 2015–2018 also demonstrated an increased risk of pouchitis compared to the earliest study period (1996–2000) after adjusting for sex, age, and socioeconomic status (Hazard Ratio [HR] 1.57, 95% CI:1.20–2.05, Table 2, Figure 1). In a separate model adjusting for the same clinical and demographic factors, there was no significant relationship between the preoperative use of anti-tumor necrosis factor alpha therapy use and the risk of pouchitis when evaluated in the entire population (HR 1.14, 95% CI:0.93–1.40) and when evaluated by time period of surgery. Conclusion This first population-based study demonstrated a 15% absolute and 38% relative increase in the incidence of pouchitis among patients undergoing surgery between 1996 and 2018, with the greatest cumulative incidence of pouchitis demonstrated in the most recent era (2015–2018). The striking increase in the incidence of pouchitis highlights the need for further research into causes and prevention of pouchitis.

Pyloric gland metaplasia: Potential histologic predictor of severe pouch disease including Crohn’s disease of the pouch in ulcerative colitis

Crohn’s disease of the pouch (CDP) is seen in a subset of ulcerative colitis (UC) patients following ileal pouch-anal anastomosis (IPAA). Histologic or clinical predictors of CDP are unknown. UC patients with subsequent CDP diagnosis were identified. The rationales for the diagnosis, the interval from the initial signs of CDP to the diagnosis, family history and smoking history were reviewed. Archived pathology materials were reviewed for the presence of pyloric gland metaplasia (PGM) and compared with those from UC with similar severity of pouchitis with CDP (matched UC controls), random UC controls, and ileocolectomies from primary CD patients. CDP diagnosis was made in 26 (18.1%) of 144 patients; all of them met commonly used diagnostic criteria for CDP. The diagnosis was rendered on average 15 months after the initial CD-like signs. PGM was found in 58% of CDP, more common than random UC controls but no different from primary CD and matched UC controls. PGM preceded first signs of CD in a subset. Patients with a family history of CD were more likely to develop CDP than those without a family history of any type of inflammatory bowel disease. Smoking status did not affect the likelihood of developing CDP. Finding PGM in proctocolectomy, ileostomy and follow-up biopsies in UC patients post IPAA may warrant close follow up for the potential development of pouchitis. Some of these patients, especially those with family history of CD, may further progress and develop severe disease meeting the clinical diagnostic criteria for CDP.

THE CUMULATIVE INCIDENCE OF POUCHITIS AND POUCH-RELATED COMPLICATIONS IN PEDIATRIC PATIENTS WITH ULCERATIVE COLITIS

Abstract Background &amp; Aims Despite highly effective therapies, many children develop medically refractory ulcerative colitis (UC) and undergo proctocolectomy with ileal pouch anal anastomosis (IPAA). There is little real world evidence regarding IPAA outcomes in pediatric UC patients. We sought to determine the risk of pouchitis, recurrent pouchitis, and change in diagnosis to Crohn’s disease (CD) within two years of IPAA surgery among pediatric patients with UC using a large, geographically diverse insurance claims database. Methods Within the IQVIA Legacy PharMetrics Adjudicated Claims Database, we identified pediatric patients (age &amp;lt;18 years) with UC who underwent proctocolectomy with IPAA between January 1, 2007 and June 30, 2015. We utilized International Classification of Diseases (ICD-9-CM or ICD-10-CM) codes to identify patients with UC and Current Procedural Terminology III codes to identify IPAA. The primary outcome was the development of pouchitis in the first 2 years following surgery, as identified by a previously validated case-finding definition. Secondary outcomes included the incidence of recurrent pouchitis, and the cumulative incidence of a new diagnosis of Crohn’s disease (CD) in the first two years post-IPAA. A change in diagnosis to CD was identified by an ICD-9-CM or ICD-10-CM code for CD on at least three separate occasions. Bivariate analyses were used for all comparisons, utilizing chi-square and t-test as appropriate. Results A total of 68 patients with an IPAA with at least two years of continuous health plan enrollment following surgery were identified. Among all patients undergoing surgery, the median age was 15 years (interquartile range 11.5–16), with 29 (43%) female patients. In the first 2 years following IPAA, the cumulative incidence of pouchitis was 54%. Characteristics and prior medical treatments in patients without pouchitis and with ≥ one episode of pouchitis were similar (Table 1). The cumulative incidence of recurrent pouchitis during this period was 22%. The cumulative incidence of a new diagnosis of CD in the two years after IPAA for UC was 9%. Conclusions In a geographically diverse cohort from the United States, 54% of pediatric patients undergoing proctocolectomy with IPAA for UC developed pouchitis within the first two years after surgery. Furthermore, 9% had a change in diagnosis to CD. These data indicate that for many pediatric UC patients, surgery is non-curative and patients continue to have a substantial burden of illness. Future efforts should attempt to identify novel, actionable, predictors of pouchitis in this population.

Transmural Inflammation, Ileitis, and Granulomas at the Time of Proctocolectomy in Patients with Ulcerative Colitis Do Not Predict Future Development of Pouchitis

Background: The most common complication following ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC) is pouchitis. Our study aimed to investigate the relationship between histopathologic findings of ileitis, granuloma, or transmural inflammation on the colectomy specimen of patients with clinically and endoscopically diagnosed UC and the development of pouchitis within the first 2 years after IPAA. Methods: We performed a retrospective cohort study evaluating patients undergoing colectomy with IPAA for UC between January 1, 2004 and December 31, 2016. Bivariate analyses were conducted to evaluate the relationship between clinical factors and the development of pouchitis. We performed multivariate logistic regression to evaluate the relationship between histologic, clinical, and demographic factors at the time of colectomy and subsequent development of pouchitis. Results: Among 626 patients, pouchitis occurred in 246 (39%). Patients with primary sclerosing cholangitis were more likely to develop pouchitis (adjusted odds ratio [aOR] 2.81, 95% confidence interval [CI] 1.02–7.72), as were patients with a family history of inflammatory bowel disease (aOR 1.75, 95% CI 1.11–2.77). Histologic findings of ileitis, granuloma, or transmural inflammation were not associated with an increased odds of developing pouchitis (aOR 0.70, 95% CI 0.45–1.08). Discussion/Conclusion: Patients with ileitis, granulomas, or transmural inflammation at the time of colectomy were not at greater risk for development of pouchitis in the 2 years after IPAA. These pathological findings should not preclude IPAA for UC.

Pouchitis in inflammatory bowel disease: a review of diagnosis, prognosis, and treatment.

Patients with inflammatory bowel disease (IBD) occasionally need a restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) because of medically refractory colitis or dysplasia/cancer. However, pouchitis may develop in up to 70% of patients after this procedure and significantly impair quality of life, more so if the inflammation becomes a chronic condition. About 10% of patients with IBD who develop pouchitis require pouch excision, and several risk factors of the failure have been reported. A phenotype that has features similar to Crohn’s disease may develop in a subset of ulcerative colitis patients following proctocolectomy with IPAA and is the most frequent reason for pouch failure. In this review, we discuss the diagnosis and prognosis of pouchitis, risk factors for pouchitis development, and treatment options for pouchitis, including the newer biological agents.

Novel prognostic biomarkers of pouchitis after ileal pouch-anal anastomosis for ulcerative colitis: Neutrophil-to-lymphocyte ratio.

Pouchitis is a major complication after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC). Although there have been many investigations of the neutrophil-to-lymphocyte ratio (NLR) in various diseases, its role in predicting the development of pouchitis remains unclear. We aimed to evaluate the clinical utility of the NLR for predicting the development of pouchitis after IPAA in UC patients. UC patients who underwent IPAA at Osaka City University Hospital between May 2006 and March 2019 were included. The incidence of pouchitis was estimated using the Kaplan-Meier method. Potential preoperative, intraoperative, and postoperative predictors for pouchitis, including various demographic and clinical variables, were analyzed. The combined impact of the NLR and other known prognostic factors were investigated using Cox proportional hazard regression with inverse probability of treatment weighting (IPTW). Forty-nine patients with UC who underwent IPAA were included. The median follow-up period was 18.3 months (interquartile range: 10.7-47.2 months). Eighteen patients (36.7%) developed pouchitis. The incidence of pouchitis was 19.2%, 32.6%, and 45.9% at 1, 2, and 5 years, respectively. NLR was significantly associated with the development of pouchitis in the univariate Cox regression analysis (hazard ratio (HR), 1.14; 95% confidence interval (CI), 1.01-1.28; P = 0.03). The NLR cutoff value of 2.15 was predictive of the development of pouchitis according to receiver operating characteristic analysis (specificity: 67.7%, sensitivity: 72.2%). The incidence of pouchitis was significantly lower in the low NLR group than that in the high NLR group (P = 0.01, log-rank test). Cox regression analyses using IPTW also identified NLR as a prognostic factor for the development of pouchitis by statistically adjusting for background factors (HR, 3.60; 95% CI, 1.31-9.89; P = 0.01). NLR may be a novel and useful indicator for predicting the development of pouchitis after IPAA in UC and should be introduced in clinical practice.

S0726 A History of Smoking Is Not Associated With a Higher Risk of Pouchitis: A Systematic Review and Meta-Analysis

INTRODUCTION: Ileal pouch-anal anastomosis (IPAA) is a common surgical procedure in patients with an initial diagnosis of ulcerative colitis (UC), indeterminate colitis (IC), or familial adenomatous polyposis syndrome (FAP). Tobacco smoking has been associated with protection from onset of UC. Smoking has been reported to be both a protective factor and a risk factor for the development of pouchitis. In this systematic review and meta-analysis, we examine the influence of smoking on the risk of pouchitis. METHODS: We identified 16 studies evaluating smoking as a risk factor for developing pouchitis in patients with a history of IPAA in a systematic search performed from inception through May 2020. A meta-analysis was then performed using a random-effects model to generate risk ratios. RESULTS: A total of 2,389 IPAA patients were included in the systematic review and meta-analysis. In the included studies, the percentage of patients with a diagnosis of pouchitis ranged from 22% to 72%. The percentage of patients with a history of smoking ranged from 7% to 63%. In total, 919 patients had pouchitis (330 current or former smokers; 589 non-smokers), and 1,470 patients did not have pouchitis (485 current or former smokers; 985 non-smokers). A history of smoking compared with never smoking was not associated with an increased risk of developing pouchitis (RR = 0.96, 95% CI 0.78–1.17, I2 = 68.6%). There was also no significant risk of pouchitis when comparing current smokers versus non-smokers (RR = 1.09, 95% CI 0.93–1.28, I2 = 0%) and former smokers versus non-smokers (RR = 0.95, 95% CI 0.70–1.28, I2 = 79.8%). CONCLUSION: Smoking, past or present, is not associated with an increased risk for the development of pouchitis. This is important to consider when counseling patients on the risks of smoking and pouchitis.Figure 1.: History of smoking (current or former versus non-smokers) and risk of pouchitis.

S0797 Paneth Cell Phenotype at Ileal Resection Margin Obtained at the Time of Ileocolectomy for Ulcerative Colitis Predicts Time to Pouchitis Development

S0797 Paneth Cell Phenotype at Ileal Resection Margin Obtained at the Time of Ileocolectomy for Ulcerative Colitis Predicts Time to Pouchitis Development