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Background & Aims: The pathophysiology of Crohn's-like disease of the pouch (CDP) in patients with a history of ulcerative colitis (UC) is unknown. We examined mucosal cells from patients with and without CDP using single-cell analyses., Methods: Endoscopic samples were collected from pouch body and prepouch ileum (pouch/ileum) of 50 patients with an ileal pouch-anal anastomosis. Single-cell RNA sequencing was performed on pouch/ileal tissues of patients with normal pouch/ileum and CDP. Mass cytometry was performed on mucosal immune cells from patients with UC with normal pouch/ileum, CDP, pouchitis, and those with familial adenomatous polyposis after pouch formation. Findings were independently validated using immunohistochemistry., Results: The cell populations/states in the pouch body differed from those in the prepouch ileum, likely secondary to increased microbial burden. Compared with the familial adenomatous polyposis pouch, the UC pouch was enriched in colitogenic immune cells even without inflammation. CDP was characterized by increases in T helper 17 cells, inflammatory fibroblasts, inflammatory monocytes, TREM1 + monocytes, clonal expansion of effector T cells, and overexpression of T helper 17 cells-inducing cytokine genes such as IL23, IL1B, and IL6 by mononuclear phagocytes. Ligand-receptor analysis further revealed a stromal-mononuclear phagocytes-lymphocyte circuit in CDP. Integrated analysis showed that up-regulated immune mediators in CDP were similar to those in CD and pouchitis, but not UC. Additionally, CDP pouch/ileum exhibited heightened endoplasmic reticulum stress across all major cell compartments., Conclusions: CDP likely represents a distinct entity of inflammatory bowel disease with heightened endoplasmic reticulum stress in both immune and nonimmune cells, which may become a novel diagnostic biomarker and therapeutic target for CDP., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: 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., Methods: 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)., Results: 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., Conclusion: 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., (© 2023 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Purpose: The anatomical location of inflammation in and around the ileal pouch affects the pouch survival rate, and diffuse inflammation has poor pouch survival rates. We aimed to clarify the symptoms and histological findings of diffuse inflammation of the pouch., Methods: We evaluated the symptoms, treatment, and histological findings according to the endoscopic phenotypes of diffuse inflammation, focal inflammation, and normal as the pouch body phenotype and afferent limb involvement, inlet involvement, cuffitis, and fistula as the peripheral findings., Results: Of the 318 pouchoscopies, 47 had diffuse inflammation, 201 had focal inflammation, and 70 were normal. Symptomatic patients had diffuse inflammation more frequently (46.8%) than focal inflammation (13.4%) and normal (14.2%), with no difference between focal inflammation and normal. Antibiotics and steroids were higher rate administered in cases of diffuse inflammation, but not in cases of focal inflammation or in normal cases. Histological inflammation, inflammatory bowel disease (IBD)-specific finding, and colonic metaplasia showed severity in the order of diffuse inflammation > focal inflammation > normal. The number of peripheral inflammatory findings overlapped in the following order: diffuse inflammation > focal inflammation > normal. The number of symptomatic patients increased as the number of peripheral inflammatory findings increased., Conclusion: Pouches with diffuse inflammation are more symptomatic, have a higher use of therapeutic agents, and have more severe histological inflammation, IBD-specific finding, and colonic metaplasia accompanying peripheral inflammatory findings than the other groups. The higher the overlap of inflammatory findings in the surrounding tissues, the more symptomatic the patients will appear., (© 2024. The Author(s).)

Background: IPAA is often required for patients with ulcerative colitis or familial adenomatous polyposis after colectomy. This procedure reduces but does not completely eliminate the risk of neoplasia., Objective: This study focuses on the histopathology of neoplasia in the ileal pouch, rectal cuff, and anal transition zone., Data Sources: We performed a MEDLINE search for English-language studies published between 1981 and 2022 using the PubMed search engine. The terms "ileal pouch-anal anastomosis," "pouchitis," "pouch dysplasia," "pouch lymphoma," "pouch squamous cell carcinoma," "pouch adenocarcinoma," "pouch neoplasia," "dysplasia of rectal cuff," and "colitis-associated dysplasia" were used., Study Selection: Human studies of neoplasia occurring in the pouch and para-pouch were selected, and the full text was reviewed. Comparisons were made within and across studies, with key concepts selected for inclusion in this article., Conclusions: Neoplasia in the pouch is a rare complication in patients with IPAA. Annual endoscopic surveillance is recommended for familial adenomatous polyposis patients and ulcerative colitis patients with a history of prior dysplasia or carcinoma. In familial adenomatous polyposis, dysplastic polyps of the pouch are visible and readily amenable to endoscopic removal; however, glandular dysplasia in the setting of ulcerative colitis may be invisible on endoscopy. Therefore, random biopsies and adequate tissue sampling of the pouch and rectal cuff are recommended in this setting. The histological diagnosis of IBD-associated dysplasia can be challenging and should be confirmed by at least 1 expert GI pathologist. See video from the symposium., (Copyright © The ASCRS 2024.)

Introduction: The impact of histologic inflammation on subsequent risk of acute pouchitis in patients with ulcerative colitis (UC) has not been robustly examined., Methods: We examined the association between histologic inflammation in endoscopically normal-appearing ileal pouches in patients with UC with subsequent risk of antibiotic-responsive acute pouchitis., Results: Among 163 study patients, 53% had histologic inflammation in an endoscopically normal-appearing ileal pouch. Histologic inflammation in the pouch was associated with an increased risk of pouchitis (24.1% vs 6.8%, adjusted odds ratio 4.41, 95% confidence interval 1.48-13.20)., Discussion: Histologic inflammation in an endoscopically normal pouch was associated with an increased risk of acute pouchitis., (Copyright © 2022 by The American College of Gastroenterology.)

Background: Inflammatory bowel diseases (IBDs) are characterized by chronic inflammation and tissue damages in limited segments of the digestive tract. Pathogenesis in the tissue and mucosal inflammation probably differs according to disease location. Our aim was to further analyze transcriptomic profiles in different locations of IBD, differentiating ulcerative colitis (UC), colonic Crohn's disease (CD), ileal CD, and pouchitis, with respect to normal colonic and ileal mucosa. We thus performed a meta-analysis focusing on specific transcriptomic signatures of ileal and colonic diseases., Methods: We identified 5 cohorts with available transcriptomic data in ileal or colonic samples from active IBD and non-IBD control samples. The meta-analysis was performed on 1047 samples. In each cohort separately, we compared gene expression in CD ileitis and normal ileum; in CD colitis, UC, and normal colon; and finally in pouchitis and normal ileum., Results: We identified specific markers of ileal (FOLH1, CA2) and colonic (REG3A) inflammation and showed that, with disease, some cells from the ileum start to express colonic markers. We confirmed by immunohistochemistry that these markers were specifically present in ileal or colonic diseases. We highlighted that, overall, colonic CD resembles UC and is distinct from ileal CD, which is in turn closer to pouchitis., Conclusions: We demonstrated that ileal and colonic diseases exhibit specific signatures, independent of their initial clinical classification. This supports molecular, rather than clinical, disease stratification, and may be used to design drugs specifically targeting ileal or colonic diseases., (© 2021 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Several indices exist to measure pouchitis disease activity; however, none are fully validated. As an initial step toward creating a validated instrument, we identified pouchitis disease activity indices, examined their operating properties, and assessed their value as outcome measures in clinical trials., Methods: Electronic databases were searched to identify randomized controlled trials including indices that evaluated clinical, endoscopic, or histologic pouchitis disease activity. A second search identified studies that assessed the operating properties of pouchitis indices., Results: Eighteen randomized controlled trials utilizing 4 composite pouchitis disease activity indices were identified. The Pouchitis Disease Activity Index (PDAI) was most commonly used (12 of 18; 66.7%) to define both trial eligibility (8 of 12; 66.7%), and outcome measures (12 of 12; 100%). In a separate search, 21 studies evaluated the operating properties of 3 pouchitis indices; 90.5% (19 of 21) evaluated validity, of which 42.1% (8 of 19) evaluated the construct validity of the PDAI. Criterion validity (73.7%; 14 of 19) was evaluated through correlation of the PDAI with fecal calprotectin (FCP; r = 0.188 to 0.71), fecal lactoferrin (r = 0.570 to 0.582), and C-reactive protein (CRP; r = 0.584). Two studies assessed correlation of the modified PDAI (mPDAI) with FCP (r = 0.476 and r = 0.565, respectively). Fair to moderate inter-rater reliability of the PDAI (k = 0.440) and mPDAI (k = 0.389) was reported in a single study. Responsiveness of the PDAI pre-antibiotic and postantibiotic treatment was partially evaluated in a single study of 12 patients., Conclusions: Development and validation of a specific pouchitis disease activity index is needed given that existing instruments are not valid, reliable, or responsive., (© 2021 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aims: Currently used endoscopic items for the assessment of pouchitis and cuffitis have deficiencies in reliability and validation. We assessed the reliability and accuracy of new endoscopic items for pouchitis and of the Ulcerative Colitis Endoscopic Index of Severity [UCEIS] for cuffitis., Methods: Three new endoscopic items were assessed and included in the Monash pouchitis endoscopic subscore: bleeding [absent/contact/spontaneous]; erosions [absent/<10/≥10]; and ulceration [absent/<10%/≥10%]. Three raters evaluated 44 pouchoscopy videos in duplicates, in random order. Intra- and inter-rater reliability of all endoscopic items and UCEIS were assessed. Clinical and histological pouchitis disease activity index [PDAI] subscores were also assessed and faecal calprotectin was measured., Results: All three Monash endoscopic items had substantial intra-rater reliability with intraclass correlation coefficients [ICCs] >0.61 [95% CI >0.61], compared with only ulcers from the currently used PDAI endoscopic subscore, but inter-rater reliability was only substantial for ulceration and no better than those of the currently used endoscopic items. The Monash endoscopic subscore had a strong positive correlation with the reference standard global endoscopic lesion severity r = 0.80 [95% CI 0.80-0.80] and the reference standard PDAI endoscopic subscore r = 0.70 [95% CI 0.67-0.73], which was higher than the correlation observed for the currently used PDAI endoscopic subscore. The UCEIS had substantial intra-rater reliability, but only fair inter-rater reliability and poor diagnostic performance for cuffitis., Conclusions: The Monash endoscopic items, and endoscopic subscore they generate, have enhanced overall performance compared with the currently used PDAI items and subscore. Further validation and responsiveness to change in disease state are indicated., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Ileoanal pouch anastomosis is the surgical treatment of choice for patients with intractable ulcerative colitis. Perianal disease is a feature that is often present in Crohn's disease and infrequently in ulcerative colitis., Objective: The aim of this study is to identify the incidence and factors associated with the development of postoperative perianal fistula in patients undergoing ileoanal pouch anastomosis for ulcerative colitis., Design: A prospectively collected database at the time of surgery with subsequent follow-up was utilized., Setting: The study was conducted at a high-volume single institution., Patients: We studied a series of 475 consecutive patients with preoperative diagnosis of ulcerative colitis who underwent ileoanal pouch anastomosis., Main Outcome Measures: The incidence of postoperative perianal fistula and the factors correlating with its development were primary outcome measures of the study., Results: The overall number of patients developing perianal fistulas was 44 of 475 (9%). Eleven patients with perianal fistula (25%) required return to ileostomy, of which 7 had pouch excision. Patients who developed a postoperative perianal fistula had a younger age at the onset of disease, had a lower age at index surgery, and were more likely to be subsequently classified as indeterminate colitis or Crohn's disease. Patients developing perianal fistulas were also more likely to develop partial dehiscence or stricture of the ileoanal anastomosis., Limitations: This study spans nearly 40 years during which the surgical procedure evolved., Conclusions: Young age at the onset of disease, lower age at surgery, and postoperative diagnosis of Crohn's disease and indeterminate colitis were the factors correlating with perianal fistulas. Delayed healing of the ileoanal anastomosis with partial separation and/or stricture also correlated with the onset of perianal fistulas. The severity of rectal inflammation at the time of surgery or the presence of stapled versus handsewn anastomosis did not correlate with the development of perianal fistulas. See Video Abstract at http://links.lww.com/DCR/B705., Fstula Perianal Posterior a Reservorio Ileoanal En Pacientes Con Colitis Ulcerativa Una Revisin De Pacientes Operados En Un Centro Principal De Eii: ANTECEDENTES:El reservorio ileoanal es el tratamiento quirúrgico de elección para los pacientes con colitis ulcerativa intratable. La enfermedad perianal es una característica que a menudo está presente en la enfermedad de Crohn y con poca frecuencia en la colitis ulcerativa.OBJETIVO:El objetivo del estudio es identificar la incidencia y los factores asociados con el desarrollo de fístula perianal posoperatoria en pacientes sometidos a reservorio ileoanal por colitis ulcerativa.DISEÑO:Base de datos recopilada prospectivamente en el momento de la cirugía con seguimiento subsecuente.ENTORNO CLÍNICO:El estudio se llevó a cabo en una única institución de gran volumen.PACIENTES:Estudiamos una serie de 475 pacientes consecutivos con diagnóstico preoperatorio de colitis ulcerativa a los que se les realizó reservorio ileoanal.PRINCIPALES MEDIDAS DE VALORACIÓN:La incidencia de fístula perianal posoperatoria y los factores que se correlacionan con su desarrollo fueron las principales medidas de resultado del estudio.RESULTADOS:El número total de pacientes que desarrollaron fístulas perianales fue 44 de 475 (9%). Once pacientes con fístula perianal (25%) requirieron volver a la ileostomía, de los cuales 7 tuvieron resección del reservorio. Los pacientes que desarrollaron fístula perianal posoperatoria tenían edad más temprana al inicio de la enfermedad, menor edad en el momento de la cirugía inicial y tenían más probabilidades de ser clasificados posteriormente como colitis indeterminada o enfermedad de Crohn. Los pacientes que desarrollaron fístulas perianales también fueron más propensos a desarrollar dehiscencia parcial o estenosis de la anastomosis ileoanal.LIMITACIONES:Este estudio abarca casi 40 años durante los cuales ha evolucionado el procedimiento quirúrgico.CONCLUSIONES:Edad temprana al inicio de la enfermedad, menor edad al momento de la cirugía, diagnóstico postoperatorio de enfermedad de Crohn y colitis indeterminada fueron los factores que se correlacionaron con las fístulas perianales. El retraso en la cicatrización de la anastomosis ileoanal con separación parcial y/o estenosis también se correlacionó con la aparición de fístulas perianales. La gravedad de la inflamación rectal en el momento de la cirugía o la presencia de anastomosis con grapas versus anastomosis manual no se correlacionó con el desarrollo de fístulas perianales. Consulte Video Resumen en http://links.lww.com/DCR/B705., (Copyright © The ASCRS 2021.)

Background: Appendiceal inflammation in colectomy is one of the histologic predictors of pouchitis in ulcerative colitis (UC) following ileal pouch anal anastomosis (IPAA). Fecal calprotectin level has been shown to increase 2 months prior to the onset of pouchitis. We evaluated whether inflammation and calprotectin expression in appendiceal specimens correlate with early-onset pouchitis in UC and indeterminate colitis (IC)., Materials and Methods: IPAA (2000-2018) cases with appendix blocks available in colectomy specimens were identified (n = 93, 90 UC, 3 IC). Histologic features thought to predict pouchitis were evaluated. The degree of appendiceal inflammation was scored. Calprotectin immunostain was performed on the appendix blocks and the extent of mucosal staining was quantified. Electronic medical records were reviewed for demographics, smoking history, clinical pouchitis, time of onset of pouchitis, and clinical and endoscopic components of the Pouchitis Disease Activity Index (PDAI) score. Follow-up pouch biopsies were reviewed and scored to generate histologic PDAI score, when available., Results: Among the patients with clinical pouchitis (n = 73), moderate to severe appendiceal inflammation independently correlated with earlier pouchitis compared to no/mild inflammation (median time to pouchitis 12.0 vs. 23.8, log rank p = 0.016). Calprotectin staining correlated with inflammatory scores of the appendix (Spearman's rho, r = 0.630, p < 0.001) but not with early pouchitis (p > 0.05)., Conclusions: The presence of moderate to severe appendiceal inflammation at the time of colectomy was associated with a shorter time to pouchitis following IPAA. Calprotectin immunostain may be used to demonstrate the presence of inflammation in the appendix but its role in predicting early pouchitis remains limited., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Background & Aims: Restorative proctocolectomy with ileal pouch-anal anastomosis is a surgical procedure in patients with ulcerative colitis refractory to medical therapies. Pouchitis, the most common complication, is inflammation of the pouch of unknown etiology. To define how the intestinal immune system is distinctly organized during pouchitis, we analyzed tissues from patients with and without pouchitis and from patients with ulcerative colitis using single-cell RNA sequencing (scRNA-seq)., Methods: We examined pouch lamina propria CD45+ hematopoietic cells from intestinal tissues of ulcerative colitis patients with (n = 15) and without an ileal pouch-anal anastomosis (n = 11). Further in silico meta-analysis was performed to generate transcriptional interaction networks and identify biomarkers for patients with inflamed pouches., Results: In addition to tissue-specific signatures, we identified a population of IL1B/LYZ+ myeloid cells and FOXP3/BATF+ T cells that distinguish inflamed tissues, which we further validated in other scRNA-seq datasets from patients with inflammatory bowel disease (IBD). Cell-type-specific transcriptional markers obtained from scRNA-seq was used to infer representation from bulk RNA sequencing datasets, which further implicated myeloid cells expressing IL1B and S100A8/A9 calprotectin as interacting with stromal cells, and Bacteroidales and Clostridiales bacterial taxa. We found that nonresponsiveness to anti-integrin biologic therapies in patients with ulcerative colitis was associated with the signature of IL1B+/LYZ+ myeloid cells in a subset of patients., Conclusions: Features of intestinal inflammation during pouchitis and ulcerative colitis are similar, which may have clinical implications for the management of pouchitis. scRNA-seq enables meta-analysis of multiple studies, which may facilitate the identification of biomarkers to personalize therapy for patients with IBD. The processed single cell count tables are provided in Gene Expression Omnibus; GSE162335. Raw sequence data are not public and are protected by controlled-access for patient privacy., (Copyright © 2021. Published by Elsevier Inc.)

Introduction: Total proctocolectomy with ileal pouch anal anastomosis (IPAA) is performed in patients with adenomatous polyposis syndromes (APSs). Data regarding pouch outcomes in APS are scarce. The purposes of this study were to determine the prevalence of pouch-related symptoms in patients with APS and to identify the contributing factors., Methods: This is a prospective cohort study. Demographic, surgical, and clinical data were collected. Endoscopy was performed, and biopsies from the terminal ileum, pouch, and cuff were obtained in all patients and reviewed by a dedicated pathologist., Results: Fifty-one patients with APS after IPAA were followed. Twenty patients (39.2%) had pouch-related symptoms. Single-stage IPAA had better outcomes than 2-stage IPAA: fewer daily bowel movements (42.9% vs 13.8% with ≤5 daily bowel movement, P = 0.02), more solid consistency (52.4% vs 6.9%, P < 0.001), and less abdominal pain (19% vs 48.3%, P = 0.034). Younger age at IPAA (<20) was also associated with better outcomes: fewer daily bowel movement (58.3% vs 17.9% with ≤5 daily bowel movement, P = 0.011), less watery consistency (8.3% vs 53.8%, P = 0.005), and abdominal pain (8.3% vs 43.6%, P = 0.037). Eighteen patients (35.3%) had endoscopic signs of inflammation, and 22 patients (43.1%) had histologic signs of pouchitis. However, no correlation was found between symptoms and endoscopic or histologic findings. The median pouchitis disease activity index was low (2, interquartile range 1-4) and did not correlate with clinical symptoms., Discussion: Pouch-related symptoms are common in patients with APS after IPAA. One-stage IPAA and younger age at surgery are associated with better clinical outcomes. However, symptoms do not correlate well with endoscopic or histologic findings or with pouchitis disease activity index and might be attributed to a functional pouch disorder.

Background: Pouchitis is the most common long-term complication after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC) or familial adenomatous polyposis (FAP), which can eventually progress to pouch failure, necessitating permanent stoma construction. Hypoxia-inducible transcription factor prolyl hydroxylase-containing enzymes (PHD1, PHD2, and PHD3) are molecular oxygen sensors that control adaptive gene expression through hypoxia-inducible factor (HIF). Emerging evidence supports PHDs as being therapeutic targets in intestinal inflammation. However, pharmacological inhibition of PHDs has not been validated as a treatment strategy in pouchitis., Methods: PHD1-3 mRNA and protein expression were analyzed in mucosal pouch and prepouch ileal patient biopsies. After establishment of a preclinical IPAA model in rats, the impact of the pan-PHD small-molecule inhibitor dimethyloxalylglycine (DMOG) on dextran sulfate sodium (DSS)-induced pouchitis was studied. Clinical and molecular parameters were investigated., Results: PHD1, but not PHD2 or PHD3, was overexpressed in pouchitis in biopsies of patients with IPAA for UC but not FAP. In addition, PHD1 expression correlated with disease activity. DMOG treatment profoundly mitigated DSS-induced pouchitis in a rodent IPAA model. Mechanistically, DMOG restored intestinal epithelial barrier function by induction of tight junction proteins zona occludens-1 and claudin-1 and alleviation of intestinal epithelial cell apoptosis, thus attenuating pouch inflammation., Conclusions: Together, these results establish a strong therapeutic rationale for targeting PHD1 with small-molecule inhibitors in pouchitis after IPAA for UC., (© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aims: There are no universally accepted guidelines regarding surveillance of ulcerative colitis [UC] patients after restorative proctocolectomy and ileal pouch-anal anastomosis [IPAA]. There also exists a lack of validated quality assurance standards for performing pouchoscopy. To better understand IPAA surveillance practices in the face of this clinical equipoise, we carried out a retrospective cohort study at five inflammatory bowel disease [IBD] referral centres., Methods: Records of patients who underwent IPAA for UC or IBD unclassified [IBDU] were reviewed, and patients with <1-year follow-up after restoration of intestinal continuity were excluded. Criteria for determining the risk of pouch dysplasia formation were collected as well as the use of pouchoscopy, biopsies, and completeness of reports., Results: We included 272 patients. Median duration of pouch follow-up was 10.5 [3.3-23.6] years; 95/272 [35%] had never undergone pouchoscopy for any indication; 191/272 [70%] had never undergone pouchoscopy with surveillance as the specific indication; and 3/26 [12%] high-risk patients had never undergone pouchoscopy. Two cases of adenocarcinoma were identified, occurring in the rectal cuff of low-risk patients. Patients under the care of surgeons appeared more likely to undergo surveillance, but rates of incomplete reporting were higher among surgeons [78%] than gastroenterologists [54%, p = 0.002]., Conclusions: We observed wide variation in surveillance of UC/IBDU-IPAA patients. In addition, the rate of neoplasia formation among 'low-risk' patients was higher than may have been expected. We therefore concur with previous recommendations that pouchoscopy be performed at 1 year postoperatively, to refine risk-stratification based on clinical factors alone. Reports should document findings in all regions of the pouch and biopsies should be taken., (Copyright © 2018 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: A large-scale increase in microRNA (miRNA) expression was observed in patients with ulcerative colitis who underwent pouch surgery and developed inflammation of the pouch (pouchitis). In this study, we assessed miRNA expression in these patients and investigated how regulation of its expression changes in the setting of pouchitis., Methods: Autologous samples that included mucosal biopsies, peripheral blood cells, and plasma were collected from the patients. Candidate primary and mature miRNA expressions were analyzed by quantitative polymerase chain reaction. A human intestinal epithelial cell line was used to test DICER activity, and the expression of key miRNA processing factors was analyzed by Western blot. miRNA-424 and its potential target serotonin reuptake transporter (SERT) expressions were examined by quantitative reverse transcription polymerase chain reaction and Western blot in human pouch tissues and in a human intestinal epithelial cell line stimulated with inflammatory cytokines TNF-α, IL-1β, and INF-γ., Results: Candidate miRNA expression and protein expression of DICER-1, EXPORTIN-5, and AGO-2 were increased in association with pouch inflammation. Similarly, inflammatory cytokines increased protein expression of DICER-1, EXPORTIN-5, and AGO-2 and DICER activity in the epithelial cell line. The miRNA-424 expression increased whereas SERT expression decreased in the patients' mucosa. Similarly, incubation of the epithelial cell line with inflammatory cytokines resulted in increased miRNA-424 and decreased SERT mRNA and protein expression., Conclusions: The miRNA expression and processing are augmented in the inflamed intestinal mucosa of patients with pouchitis. These alterations are accompanied by increased expression of proteins involved in miRNA processing, suggesting that pouch inflammation contributes to miRNA processing and expression.

Background: The most common complication after ileal pouch anal anastomosis in up to 50% of patients is an acute pouchitis. The majority of patients respond to antibiotic treatment. However, 10%-15% develops chronic antibiotic-dependent or refractory pouchitis which is usually hard to treat., Aim: To evaluate the effectiveness of vedolizumab in patients with chronic pouchitis., Methods: Patients with chronic antibiotic-dependent or refractory pouchitis were treated with vedolizumab (300 mg at week 0, 2, 6 and 10) in 10 IBD centres and retrospectively registered. Data were recorded until week 14 of vedolizumab treatment. In total 20 patients (12 male, median age 43 years) were included for analysis. The effectiveness was measured using the Oresland Score (OS) at week 2, 6, 10 and 14 and the pouch disease activity index (PDAI) at week 0 and 14., Results: The mean OS declined from 6.8 (range 2-12) to 3.4 (range 0-11). Concordantly, the mean PDAI after 14 weeks of treatment dropped from 10 (range 5-18) to 3 (range 0-10). Only three patients reported moderate side effects. No serious side effects were recorded. In addition, symptomatic co-medication such as loperamide and tincture of opium could be terminated in 8 out of 12 patients as well as antibiotic treatment could be stopped in 17 out of 19 patients., Conclusion: Our data indicate that vedolizumab could be an option in the treatment of patients with chronic, antibiotic-dependent or refractory pouchitis., (© 2017 John Wiley & Sons Ltd.)

Background/aims: Pouchitis is one of the main complications after ileal pouch-anal anastomosis in patients with ulcerative colitis. The aim of this study was to determine whether the use of colonic histological criteria can predict the development of pouchitis., Methodology: We retrospectively reviewed 147 patients' clinical data and performed a histological evaluation of the resected total colon using Tanaka's criteria, which comprise the following 6 factors: ulceration (H1), crypt abscesses (H2), degree of mononuclear cell infiltration (MNCI) (H3), segmental distribution of MNCI (H4), eosinophil infiltration (H5), and extent of disease of resected colon (H6)., Results: The development of pouchitis and chronic pouchitis within 3 years after restoration of gastrointestinal continuity was recognized in 52 (35.4%) and 26 (17.7%) of the 147 patients, respectively. Using various combinations of each score, the H3 + H4 - H5 scores of patients with pouchitis or chronic pouchitis were significantly higher than those of patients without. A H3 + H4 - H5 score of >0.4 was a statistically significant risk factor for the development of both pouchitis and chronic pouchitis., Conclusions: The combination of the degree of MNCI, segmental distribution of MNCI, and eosinophil infiltration from histological criteria has utility in predicting the future development of pouchitis, especially chronic pouchitis., (© 2017 S. Karger AG, Basel.)

Background: Pouchitis occurs in approximately 50% of patients with ulcerative colitis after ileal pouch-anal anastomosis (IPAA) but the pathogenesis remains unclear. We used a rat model of dextran sulfate sodium (DSS)-induced ileal pouchitis to examine whether intestinal barrier disruption plays a role in the development and progression of the disease., Methods: Rats were randomly divided into DSS (underwent IPAA and administered 5% DSS orally), IPAA (underwent IPAA), and Sham groups (underwent switch abdominal surgery). In the DSS group, levofloxacin intervention and nonintervention subgroups were used to determine the influence of antibiotics on intestinal barrier dysfunction. Hematochezia and fecal scores were recorded. Ileum and pouch specimens were obtained for histological assessment. Immunohistochemistry was performed for myeloperoxidase and occludin protein expression. Levels of interleukin-1β (IL-1β), IL-6, IL-10, and tumor necrosis factor α mRNA were detected by real-time PCR. Plasma D-lactate concentrations were determined with colorimetry., Results: Only rats in the DSS group experienced hematochezia, and their fecal and histological scores significantly increased (P < 0.01). Compared with the IPAA and Sham groups, levels of myeloperoxidase, IL-1β, IL-6, tumor necrosis factor α, and plasma D-lactate significantly increased, whereas occludin and IL-10 reduced in the DSS group (P < 0.01). The levofloxacin subgroup showed increased occludin expression and more balanced inflammatory cytokine levels than the nonintervention subgroup. All differences showed linear correlations., Conclusions: The intestinal barrier was disrupted in this rat model of pouchitis. Increased proinflammatory and decreased anti-inflammatory factors aggravated the intestinal barrier damage. Antibiotics may ameliorate this process.

Following restorative proctocolectomy with an ileal pouch-anal anastomosis, the small bowel mucosa undergoes several specific histologic adaptions, which may be unrelated to the underlying disease or symptoms of pouchitis. An increase in intraepithelial lymphocytes (IELs) has not been described as part of this spectrum. Mucosal biopsies of the ileal pouch and afferent limb of 230 patients (mean age: 45.7y [18.3-74.7], gender [female/male]: 117/113) with a functioning ileal pouch-anal anastomosis (mean time since ileostomy closure: 10.8months) and associated clinically annotated outcome data were assessed for IELs/100 enterocytes. Forty-two patients (18.3%) showed an increase in IELs (≥20 IELs/100 enterocytes [range 20-39]), in pouch and/or afferent limb biopsies. Intraepithelial lymphocytosis was more commonly observed in afferent limb compared to pouch biopsies (18.8% vs 8.3%; P = .42) and in familial adenomatous polyposis compared to ulcerative colitis patients (16% vs 8%; P = 0.36), but neither difference reached statistical significance. No cases with increased IELs displayed severe villous blunting. Increased IELs were not significantly associated with age, sex, ethnicity, smoking history, time since ileostomy, use of antibiotics, biologic agents, anti-diarrheal agents or probiotics, C-reactive protein levels or differential white cell count. None of the 42 patients with increased IELs had positive celiac serology (anti-human tissue transglutaminase IgA [ELISA] with corresponding total serum IgA). Intraepithelial lymphocytosis in pouch biopsies may represent a subclinical response to an altered bacterial microenvironment. Pathologists should be aware that intraepithelial lymphocytosis is part of the spectrum of changes in pouch biopsies, and only rarely is due to celiac disease., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Inflammatory bowel diseases are characterised by inflammation that compromises the integrity of the epithelial barrier. The intestinal epithelium is not only a static barrier but has evolved complex mechanisms to control and regulate bacterial interactions with the mucosal surface. Apical tight junction proteins are critical in the maintenance of epithelial barrier function and control of paracellular permeability. The characterisation of alterations in tight junction proteins as key players in epithelial barrier function in inflammatory bowel diseases is rapidly enhancing our understanding of critical mechanisms in disease pathogenesis as well as novel therapeutic opportunities. Here we give an overview of recent literature focusing on the role of tight junction proteins, in particular claudins, in inflammatory bowel diseases and inflammatory bowel disease associated colorectal cancer.

The pathological diagnosis of inflammatory bowel disease (IBD) is often difficult because biopsy material may not contain pathognomonic features, making distinction between Crohn's disease, ulcerative colitis and other forms of colitides a truly challenging exercise. The problem is further complicated as several diseases frequently mimic the histological changes seen in IBD. Successful diagnosis is reliant on careful clinicopathological correlation and recognising potential pitfalls. This is best achieved in a multidisciplinary team setting when the full clinical history, endoscopic findings, radiology and relevant serology and microbiology are available. In this review, we present an up-to-date evaluation of the histopathological mimics of IBD.

Purpose: Restorative proctocolectomy is a current gold standard procedure for patients who require a colectomy for ulcerative colitis. The incidence of ileal pouch neoplasia is low. The aims of this study were to assess the prevalence of neoplasia in ileal pouch and investigate the risk factors for ileal pouch neoplasia., Methods: A total of 276 patients who underwent restorative proctocolectomy for ulcerative colitis between 1984 and 2009 were analyzed. Results of histological examinations of both original specimen and biopsies from the J-pouch taken during routine pouch endoscopy were evaluated. Patients' records were analyzed for ulcerative colitis duration, the time from pouch creation to pouch neoplasia, presence of pouchitis, as well as the concurrent primary sclerosing cholangitis., Results: Analyzing the original specimen of large bowel, fifty-six lesions of low-grade dysplasia, twenty-five high-grade dysplasia, and five adenocarcinoma were revealed. All patients with dysplasia (n = 8) or adenocarcinoma (n = 1) of the J-pouch were positive for dysplasia in the original specimen. Duration of ulcerative colitis before surgery and duration time following restorative proctocolectomy were found as risk factors for J-pouch neoplasia with a significant difference (p = 0.01 and p = 0.0003, respectively). Patients with pouch neoplasia developed significantly more severe pouchitis (p = 0.00001)., Conclusions: Neoplasia of the J-pouch is rare. Patients with neoplasia in the original specimen are more susceptible to develop neoplasia in the J-pouch. Precise follow-up in patients with neoplasia lesions in the original specimen should be recommended. Moreover, in patients with risk factors, the exact surveillance pouch endoscopy should be recommended.

Objectives: To evaluate molecular profiles in the small bowel (SB) mucosa proximal to the pouch in ulcerative colitis (UC) patients after pouch surgery., Design: Patients were prospectively recruited and stratified according to disease behaviour: normal pouch (NP), chronic pouchitis (CP), and Crohn's-like disease of the pouch (CLDP). Biopsies obtained from the pouch and the normal-appearing proximal SB (40 cm proximal to the anal verge) were compared to ileal biopsies from normal controls (NC). A histopathological score based on the degree of polymorphonuclear and mononuclear infiltrates was used to assess inflammation in the pouch and the proximal SB. Gene expression analysis was performed using microarrays, and validated by real-time PCR. Gene ontology and clustering were evaluated by bioinformatics., Results: Thirty-six subjects were recruited (age 18-71 years, 16 males). Histopathology scores demonstrated minimal differences in the normal-appearing proximal SB of all groups. Nonetheless, significant (fold change ≥2, corrected p [FDR] ≤ 0.05) molecular alterations in the proximal SB were detected in all groups (NP n=9; CP n=80; and CLDP n=230) compared with NC. The magnitude of DUOX2 alteration in the proximal SB was highest. An increase of 6.0, 9.8 and 21.7 folds in DUOX2 expression in NP, CP, CLDP, respectively was observed. This was followed by alterations in MMP1, SLC6A14 and PGC. Gene alterations in the proximal SB overlapped with alterations within the pouch (76% and 97% overlap in CP and CLDP, respectively). Gene ontology analysis in the proximal SB and pouch were comparable., Conclusions: Significant gene expression alterations exist in an apparently unaffected proximal SB. Alterations in the pouch and the proximal SB were comparable, suggesting that inflammation may not be limited to the pouch, but that it extends to the proximal SB., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Tight junction proteins (TJPs) and dendritic cells (DC) are critical in the pathogenesis of inflammatory bowel diseases. The ileal pouch formed by restorative proctocolectomy provides a unique human model for studying the pathogenesis of inflammatory bowel diseases. Data implicate the microbiota in the pathogenesis of pouchitis, while the role of innate immune factors remains unclear. We performed longitudinal and cross-sectional studies of patients after restorative proctocolectomy and assessed TJP and DC characteristics in the ileal pouch., Methods: Mucosal biopsies were taken from the ileal pouch of patients with ulcerative colitis (UC) and familial adenomatous polyposis (n = 8). Of patients with UC, one group (n = 5) was followed longitudinally over the first year after ileostomy closure, another group had pouchitis (n = 15), and another group no inflammation (n = 18). Dendritic cell phenotype and epithelial cell TJP expression were assessed using flow cytometric analysis., Results: Increased epithelial expression of the "pore-forming" TJP claudin 2, and DC expression of gut-homing markers CCR 9 and integrin β7, occurred early after ileostomy closure. In patients with UC with pouchitis, epithelial expression of ZO-1 and claudin 1 were reduced, DC were activated with increased CD40, and Toll-like receptor 4 expression increased. In pouchitis, DC expressing CCR 9 were decreased, whereas DC expressing β7 increased., Conclusions: Abnormalities were found in TJP expression in the pouch of patients with UC, in particular, increased expression of the pore-forming claudin 2 as an early event in the development of pouch inflammation and an aberrant DC phenotype was characterized in the ileal pouch of patients with UC.

Pouchitis is a common complication seen in patients with ulcerative colitis who undergo total proctocolectomy with ileal pouch anal anastomosis. Bacteria seem to play an important role in the development of pouchitis, although this role is not well defined. Because technology has advanced, we are able to apply molecular techniques to describe the structure and function of the pouch microbial community. In recent years, several studies have been performed comparing the pouch microbiota in patients with ulcerative colitis with healthy pouches and pouchitis. Many of these studies have suggested that pouchitis is characterized by dysbiosis and/or decreased microbial diversity. There has not been a clear pattern identifying a pathogenic organism or a group of organisms responsible for pouchitis. This review summarizes recent studies exploring the pouch microbiota in health and disease, the relationship of bacterial metabolites and pouchitis, and the role of antibiotics and probiotics for the treatment and prevention of pouchitis.

Aim: Limited data are available on the relationship between the histological features of the resected specimens in patients with ulcerative colitis (UC) or indeterminate colitis (IC) and the outcome of restorative proctocolectomy. The aim of our study was to determine if the histological features of the resected specimen in patients with UC and IC can predict ileal-pouch-related outcome., Method: A review of all patients who had a restorative proctocolectomy created following completion proctectomy or proctocolectomy for UC and IC was performed., Results: Between 1992 and 2011, 142 patients (132 with UC and 10 with IC) were reviewed. After a median follow-up of 36 (3-149) months, 51 (35.9%) developed a pouch-related complication. Forty-two (29.7%) developed pouchitis while three (2.1%) developed a pouch-cutaneous fistula. Four (2.8%) had pouch failure, while stricture of the anastomosis was seen in three (2.1%) patients. The presence of extension of the inflammation into the muscularis propria of the resected specimen was associated with an increased risk of pouch-related complications (P = 0.01). The presence of submucosal oedema was also a significant risk factor (P = 0.03)., Conclusion: The extension of inflammation into the muscularis propria appears to predict pouch-related complications following restorative proctocolectomy for UC or IC., (Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.)

Colectomy with ileoanal pouch formation is usually contraindicated in patients with Crohn's disease (CD) due to the risk of recurrent disease and pouch failure. We report the case of a patient, initially thought to have ulcerative colitis (UC), who underwent such surgery but subsequently developed perianal CD. She presented with diarrhoea and weight loss. Inflammatory markers were raised. Pouchoscopy revealed deep ulcers within the pouch. The main differential diagnoses were idiopathic pouchitis and recurrent CD. However, immunohistochemical staining demonstrated positivity for cytomegalovirus (CMV). Stool frequency, C reactive protein and albumin normalised within 48 h of starting oral valgancyclovir. At 15 weeks, pouch appearances were improved, no histological evidence of CMV was found and baseline pouch function had returned. This case highlights that CD can present many years after surgery for apparent UC. Also, CMV pouchitis should be considered as a differential cause of pouchitis especially as it is treatable with antiviral therapy., (2014 BMJ Publishing Group Ltd.)

Background & Aims: Pouchitis is the most common complication after ileal pouch-anal anastomosis (IPAA). However, symptoms are not specific. The Pouchitis Disease Activity Index (PDAI) and the Pouchitis Activity Score (PAS) have been used to diagnose pouchitis. We evaluated the correlation between the clinical components of these scores and endoscopic and histologic findings., Methods: We performed a cross-sectional study, analyzing data from 278 patients from Mount Sinai Hospital (Toronto, Canada) who had an IPAA. Patients underwent pouchoscopy with a biopsy, and data were collected on patients' clinical status. The PDAI and PAS were calculated for each subject. The Spearman rank correlation (ρ) statistical test was used to evaluate correlations between the PDAI scores and PAS, and between total scores and subscores., Results: The total PDAI scores and PAS scores were correlated; the clinical components of each correlated with the total score (ρ = 0.59 and ρ = 0.71, respectively). However, we observed a low level of correlation between clinical and endoscopic or histologic subscores, with ρ of 0.20 and 0.10, respectively, by PDAI, and ρ of 0.19 and 0.04, respectively, by PAS., Conclusions: There is a low level of correlation between clinical and endoscopic and histologic subscores of patients with IPAA; clinical symptoms therefore might not reflect objective evidence of inflammation. These findings, along with evidence of correlation between total scores and clinical symptoms, indicate that these indices do not accurately identify patients with pouch inflammation. Further research is required to understand additional factors that contribute to clinical symptoms in the absence of objective signs of pouch inflammation., (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Videocapsule endoscopy (VCE) has revolutionized our ability to visualize the small bowel mucosa. This modality is a valuable tool for the diagnosis of obscure small bowel Crohn's disease (CD), and can also be used for monitoring of disease activity in patients with established small-bowel CD, detection of complications such as obscure bleeding and neoplasms, evaluation of response to anti-inflammatory treatment and postoperative recurrence following small bowel resection. VCE could also be an important tool in the management of patients with unclassified inflammatory bowel disease, potentially resulting in reclassification of these patients as having CD. Reports on postoperative monitoring and evaluation of patients with ileal pouch-anal anastomosis who have developed pouchitis have recenty been published. Monitoring of colonic inflammatory activity in patients with ulcerative colitis using the recently developed colonic capsule has also been reported. Capsule endoscopy is associated with an excellent safety profile. Although retention risk is increased in patients with small bowel CD, this risk can be significanty decreased by a routine utilization of a dissolvable patency capsule preceding the ingestion of the diagnostic capsule. This paper contains an overview of the current and future clinical applications of capsule endoscopy in inflammatory bowel disease.

Aim: The aim of the study was to assess the impact of the long-term use of the composite probiotics in patients after restorative proctocolectomy., Method: Forty-three patients (20 females and 23 males, aged 21 to 68 years) after restorative proctocolectomy were included in the study. After randomization patients were divided into placebo group and treatment group with oral intake of probiotic containing Lactobacillus acidophilus, Lactobacillus delbrueckii subsp. bulgaricus, and Bifidobacterium bifidus. Patients were investigated during initial visit and during final visit after 9 months. All patients were subjected to standard clinical and endoscopic examination with microscopic study of the specimens. Concentrations of calprotectin and pyruvate kinase isoenzyme M2-PK were determined in all cases., Results: The average severity of pouchitis and the number of patients with pouchitis significantly decrease after 9 months of the probiotic taking. The concentrations of calprotectin and pyruvate kinase isoenzyme M2-PK significantly decreased after the therapy., Conclusions: Nine months of the probiotic treatment (Lactobacillus acidophilus, Lactobacillus delbrueckii subsp. bulgaricus, and Bifidobacterium bifidus) reduced the number of patients with pouchitis, decreased the PDAI score, and also decreased the fecal pyruvate kinase and calprotectin. The long-term probiotics use is safe and well accepted and can be an effective method of the pouchitis prevention.

Aim: Reservoir ileitis (pouchitis) is the most common complication after pelvic pouch surgery for ulcerative colitis and the aetiology remains largely unknown. The anal transition zone (ATZ) contains the only remaining colonic epithelium after ileal pouch anal anastomosis (IPAA) and may provide important clues as to whether ulcerative colitis and pouchitis share a common pathogenesis. The aim of this study was to evaluate longitudinally the long-term histological changes in the ATZ and their relationship to the incidence of pouchitis., Method: Patients with a double-stapled IPAA for ulcerative colitis at an academic medical centre with at least 10 years of clinical and histological follow-up were identified from a prospective database. Annual ATZ and pouch biopsies were taken and interpreted by two expert gastrointestinal pathologists. ATZ histological variability score, the incidence of pouchitis, and function were correlated over time. ATZ biopsies were scored from one to three based on the extent of inflammation., Results: Sixteen of the 114 patients having IPAA fulfilled the criteria for admission to the study. There were 179 biopsies of the ATZ. All exhibited variability in ATZ histology over time and 81% had a 2-unit change in their inflammatory score. There was no correlation between pouchitis and histological severity score of the ATZ. Similarly, function over time did not vary with the intensity of ATZ inflammation., Conclusion: ATZ inflammation varies substantially over time in most patients. But these changes from year to year did not correlate with function or the occurrence of pouchitis., (Colorectal Disease © 2013 The Association of Coloproctology of Great Britain and Ireland.)

A 62 year-old patient with therapy-refractory pouchitis after proctocolectomy for ulcerative colitis was admitted with hematochezia and abdominal discomfort. A malignant melanoma (MM) was found after repeated biopsies of the pouch. Complete staging revealed no evidence for distant metastases and the patient underwent abdominoperineal pouch resection. Six weeks later, the patient was readmitted because of severe general deterioration and diffuse metastatic spread to the liver was found. The patient died of hepatorenal syndrome shortly thereafter.Patients with inflammatory bowel disease are at increased risk of developing cancer, including rarities such as MM. Our experience stresses the importance of repeated biopsies in therapy-refractory pouchitis.

Background: There is no consensus on the need for and the interval of surveillance pouchoscopy in asymptomatic ileal pouch patients with underlying ulcerative colitis (UC). The purpose of this study was to evaluate the likelihood of finding dysplasia or incidental ileal pouch disorders in asymptomatic patients undergoing surveillance pouchoscopy., Methods: This study included all eligible consecutive asymptomatic UC patients undergoing surveillance pouchoscopy to our subspecialty Pouchitis Clinic from 2002 to 2011. Univariable and multivariable analyses were performed., Results: A total of 138 patients met the inclusion criteria, with 72 (52.2 %) being male. The mean age at pouch construction was 45.4 ± 15.0 years, and the mean interval from ileostomy closure to the inception of first surveillance pouchoscopy was 89.4 ± 78.8 months. One patient was found to have indefinite for dysplasia on pouch body mucosal biopsy (0.7 %), and two patients had non-caseating granulomas, suggesting Crohn's disease (CD) of the pouch. Of the 138 patients, 69 (50 %) had abnormal endoscopic findings, 102 (73.9 %) had acute and/or chronic inflammation on histology, and 62 (44.9 %) had both abnormal endoscopy and histology. The abnormal endoscopic findings included isolated pouch ulcer (n = 29, 21 %), active pouchitis (n = 31, 22.5 %), inflammatory polyps (n = 10, 7.2 %), strictures at the anastomosis (n = 5, 3.6 %), inlet (n = 10, 7.2 %) or outlet (n = 2, 1.4 %). Thirteen patients (13/17, 76.5 %) with pouch strictures underwent endoscopic balloon dilatation therapy and nine had (9/10, 90 %) endoscopic polypectomy. Multivariable analysis showed that patients with a preoperative diagnosis of CD and concomitant extraintestinal manifestations had a higher risk for abnormal pouch endoscopic findings with odds ratios of 2.552 (95 % confidence interval [CI] 1.108-16.545, p = 0.035) and 4.281 (95 % CI 1.204-5.409, p = 0.014), respectively., Conclusions: Dysplasia was rare in asymptomatic patients with restorative proctocolectomy who underwent surveillance pouchoscopy in this cross-sectional study. However, "incidental" abnormal endoscopic and/or histologic findings were common, which often needed endoscopic therapeutic intervention.

Background: Pouchitis may develop in patients with ulcerative colitis undergoing pouch surgery. We aimed to evaluate the de novo inflammation developing in the ileal pouch, hypothesizing that it may be similar to ileitis in Crohn's disease (CD)., Methods: Patients with ulcerative colitis pouch were prospectively recruited, stratified according to disease behavior into normal pouch, chronic pouchitis, and Crohn's-like disease of the pouch groups, and compared with controls. Gene expression analysis was performed using microarrays, validated by real-time polymerase chain reaction. Gene ontology and clustering were evaluated using bioinformatic tools., Results: Sixty-six subjects were recruited. Although in ulcerative colitis ileum there were no significant gene expression alterations, patients with normal pouch had 168 significant alterations (fold change ≥ 2, corrected P ≤ 0.05). In chronic pouchitis and Crohn's-like disease of the pouch, 490 and 1152 alterations were detected, respectively. High degree of overlap in gene expression alterations between the pouch subgroups was demonstrated. The magnitude of change correlated with pouch disease behavior. Gene expression profiles were more reflective of disease behavior compared with inflammatory indices. CD ileitis had 358 alterations, with a 90% overlap with pouchitis. Gene ontology analyses revealed multiple biological processes associated with pouch inflammation, including response to chemical stimulus, small molecule metabolic and immune system processes, and specific infection-related pathways such as Staphylococcus aureus, leishmaniasis, and tuberculosis., Conclusions: Gene alterations in pouch inflammation and CD overlap, suggesting that inflammatory bowel diseases is a spectrum, rather than distinct diseases. Pouchitis may serve as a model of CD. The novel pathways associated with inflammatory bowel diseases may decipher pathophysiology and suggest targets for intervention.

Background: A total of 10-15% of patients with an ileoanal pouch develop severe pouchitis necessitating long-term use of antibiotics or pouch excision. Probiotics reduce the risk of recurrence of pouchitis, but mechanisms behind these effects are not fully understood., Aim: To examine mucosal barrier function in pouchitis, before and after probiotic supplementation and to assess composition of mucosal pouch microbiota., Methods: Sixteen patients with severe pouchitis underwent endoscopy with biopsies of the pouch on three occasions: during active pouchitis; clinical remission by 4 weeks of antibiotics; after 8 weeks of subsequent probiotic supplementation (Ecologic 825, Winclove, Amsterdam, the Netherlands). Thirteen individuals with a healthy ileoanal pouch were sampled once as controls. Ussing chambers were used to assess transmucosal passage of Escherichia coli K12, permeability to horseradish peroxidase (HRP) and ⁵¹Cr-EDTA. Composition and diversity of the microbiota was analysed using Human Intestinal Tract Chip., Results: Pouchitis Disease Activity Index (PDAI) was significantly improved after antibiotic and probiotic supplementation. Escherichia coli K12 passage during active pouchitis [3.7 (3.4-8.5); median (IQR)] was significantly higher than in controls [1.7 (1.0-2.4); P < 0.01], did not change after antibiotic treatment [5.0 (3.3-7.1); P = ns], but was significantly reduced after subsequent probiotic supplementation [2.2 (1.7-3.3); P < 0.05]. No significant effects of antibiotics or probiotics were observed on composition of mucosal pouch microbiota; however, E. coli passage correlated with bacterial diversity (r = -0.40; P = 0.018). Microbial groups belonging to Bacteroidetes and Clostridium clusters IX, XI and XIVa were associated with healthy pouches., Conclusions: Probiotics restored the mucosal barrier to E. coli and HRP in patients with pouchitis, a feasible factor in prevention of recurrence during maintenance treatment. Restored barrier function did not translate into significant changes in mucosal microbiota composition, but bacterial diversity correlated with barrier function., (© 2013 John Wiley & Sons Ltd.)

Background: Pouchitis is the most common complication after restorative proctocolectomy for ulcerative colitis, and it leads to pouch failure. The administration of oral antibiotics is the main treatment for pouchitis; however, in some cases, antibiotic-refractory pouchitis may develop, which requires further medical therapy., Objective: We investigated the applicability of topical tacrolimus for refractory pouchitis., Design: We performed a prospective pilot study. The study protocols were registered with the University Hospital Medical Information Network Clinical Trials Registry, 000006658., Setting: This study was conducted in the Surgical Department of Hyogo College of Medicine., Patients: Patients with antibiotic-refractory pouchitis were treated for 8 weeks with a tacrolimus enema., Main Outcome Measures: The efficacy was assessed by comparing Pouchitis Disease Activity Index scores. Safety was assessed by measuring whole blood tacrolimus trough levels., Results: Ten patients with refractory pouchitis were enrolled. No severe adverse events occurred. The mean scores decreased from 15.9 ± 0.8 to 7.8 ± 0.8 during 8 weeks of treatment (p < 0.01). Specifically, the clinical symptom, endoscopic finding, and histological finding subscores decreased to 0.8 ± 0.6, 3.9 ± 0.2, and 2.9 ± 0.4. Nine patients recovered from their clinical symptoms, and 3 patients recovered from pouchitis., Limitations: This small study was neither blinded nor randomized., Conclusions: This study demonstrates that the use of topical tacrolimus for the treatment of refractory pouchitis is safe and effective in the short term for clinical symptoms. Although complete endoscopic healing was not achieved, this treatment may have early rescue efficacy in the treatment of antibiotic-refractory pouchitis.

Background: Approximately 5-10 % of ulcerative colitis (UC) patients who undergo ileal pouch-anal anastomosis (IPAA) will develop postoperative complications such as refractory pouchitis or a change in diagnosis to Crohn's disease (CD). Serological markers and histologic aspects of the pouch such as pyloric gland metaplasia (PGM) have been associated with a risk for these complications., Methods: Twenty-eight IPAA patients with either CD of the pouch or chronic pouchitis (cases) and 36 IPAA controls who experienced a normal postoperative course were originally consented. Of these 64 subjects, 22 cases and 17 controls had histopathologic and serologic data available and were subsequently enrolled. Demographic and clinical data were entered into a database, blood analyzed for serological markers (Prometheus Labs, San Diego, CA) and biopsies of the pouch and the afferent limb reviewed by two GI pathologists., Results: Of the cases, 55 % (12/22) had evidence of PGM in their pouch and/or small bowel biopsies, as compared to 12 % (2/17) of the controls (p = 0.006). Of 13 subjects with CD, 77 % (10/13) were found to have PGM versus subjects with chronic pouchitis in which 22 % (2/9) were found to have PGM (p = 0.03). There was a trend of ASCA positivity (both IgG and IgA, p = 0.20) and of higher ASCA titer levels (p = 0.07) with postoperative complications., Conclusion: This study suggests that the presence of ileal pouch PGM is associated with postoperative complications and favors a diagnosis of CD over UC with chronic pouchitis.

Background: Up to 30% of cases of pouchitis are felt to have a secondary cause. Cytomegalovirus (CMV) may represent a possible etiopathological agent. Here, we report our experience with CMV involvement of the pouch, including risk factors, clinical features, and pouch outcomes in patients with inflammatory bowel disease after proctocolectomy with ileal pouch-anal anastomosis., Methods: The pathology database at Mayo Clinic in Rochester was searched between January 1995 and October 2012 for patients with a tissue diagnosis of CMV of the pouch following ileal pouch-anal anastomosis., Results: Seven patients with CMV inclusions of the pouch were identified. The median age was 35 (range, 10-53) years, and the majority were female (71%). Five patients (71%) were on immunosuppressive medications including 4 who had undergone orthotopic liver transplantation for primary sclerosing cholangitis. The clinical presentation was similar among all patients: the majority had diarrhea (86%), fever (71%), and abdominal pain (57%). All had mucosal inflammation, with 71% having focal ulcerations in the pouch and 60% having inflammatory changes in the prepouch ileum. All patients improved with ganciclovir. None required pouch excision or had recurrent CMV infection. Three patients had recurrent nonspecific pouchitis., Conclusions: A high index of suspicion is needed to diagnose CMV of the pouch. An increase in stool frequency and fever in patients on immune suppression or in those who have failed empiric antibiotics should prompt assessment for CMV infection. Antiviral therapy seems to be effective, and postinfection pouch outcomes seem favorable, particularly in those presenting with their first episode of pouchitis.

Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is commonly performed for medically refractory ulcerative colitis (UC), however with multiple possible complications, most notably pouchitis, cuffitis, Crohn's disease of the pouch and irritable pouch syndrome. We present a unique case of suppurative granulomatous inflammation in the ileal pouch mucosa, most likely infective in nature, that is unrelated to recognised causes of such pathology, especially yersiniosis., (Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Background: Pouchitis appears to be the most common complication after restorative proctocolectomy., Material/methods: In experimental models we investigated the correlation between the width of anastomosis and the frequency of pouchitis. Twenty-three Wistar rats underwent restorative proctocolectomy under pentobarbital anesthesia. Normal width anastomosis was performed in 11 animals (Group I). In the remaining 12 animals (Group II) the diameter of anastomosis was reduced by 50%. All animals were sacrificed and the pouch mucosa was histologically (Moskowitz score) and immunohistochemically (IL-1, IL-6, IL-10, IL-12 expression) examined., Results: Morphological assessment of pouchitis symptoms based on Moskowitz scale revealed considerably more severe inflammation (p=0.0079) in the animals from Group II than in the rats from Group I. The expressions of investigated cytokines, assessed qualitatively in histopathological examination, were higher in rats with narrow anastomosis in comparison with animals with normal anastomosis., Conclusions: The stricture of anastomosis increases the intensity of pouchitis and stimulates the production of interleukins. It seems that anastomotic stricture plays an important role in the development of pouchitis.

Objective: To describe the multidetector-row computed tomography enterographic (MD-CTE) features of the ileal-anal pouch after ileal pouch anal anastomosis (IPAA) surgery and correlate them with pouch endoscopy and histopathologic findings., Methods: All MD-CTE examinations performed on patients who underwent IPAA from July 1, 2005 to December 1, 2010 (n = 35; 16 [45.7%] men; mean age, 37.7 years; age range, 22-72 years) were retrospectively evaluated in consensus by 2 radiologists. All studies were evaluated for the presence of multiple imaging features. Two radiographic scores were then calculated: a total radiographic score and a radiographic active inflammation score. In patients who underwent MD-CTE, pouch endoscopy, and biopsy within 30 days (n = 13), both scores were correlated with findings on pouch endoscopy and histopathology., Results: Of the 35 patients, 33 (94%) had at least one MD-CTE finding of active or chronic pouch inflammation and 27 patients (77%) had at least one MD-CTE finding of active pouch inflammation. Of the 13 patients who underwent endoscopy and biopsy, the total radiographic score demonstrated a strong positive correlation with endoscopic score (r = 0.81; P = 0.001) and a moderate positive correlation with histopathologic score (r = 0.56; P = 0.047). The radiographic active inflammation score demonstrated a strong positive correlation with endoscopic score (r = 0.83; P = 0.0004), but only a weak nonsignificant positive correlation with histopathologic score (r = 0.492, P = 0.087)., Conclusions: In patients who had IPAA surgery, findings on MD-CTE correlate positively with findings on pouch endoscopy and histopathology and are sensitive measures for pouch inflammation with high positive predictive value. Thus, MD-CTE can be a useful noninvasive test in the early evaluation of symptomatic patients.

Objective: Many changes in mucosal morphology are observed following ileal pouch construction, including colonic metaplasia and dysplasia. Additionally, one rare but potential complication is the development of adenocarcinoma of the reservoir. The aim of this study was to evaluate the most frequently observed histopathological changes in ileal pouches and to correlate these changes with potential risk factors for complications., Methods: A total of 41 patients were enrolled in the study and divided into the following three groups: a non-pouchitis group (group 1) (n = 20; 8 males; mean age: 47.5 years) demonstrating optimal outcome; a pouchitis without antibiotics group (group 2) (n = 14; 4 males; mean age: 47 years), containing individuals with pouchitis who did not receive treatment with antibiotics; and a pouchitis plus antibiotics group (group 3) (n = 7; 3 males; mean age: 41 years), containing those patients with pouchitis who were administered antibiotics. Ileal pouch endoscopy was performed, and tissue biopsy samples were collected for histopathological analysis., Results: Colonic metaplasia was found in 15 (36.6%) of the 41 patients evaluated; of these, five (25%) were from group 1, eight (57.1%) were from group 2, and two (28.6%) were from group 3. However, no correlation was established between the presence of metaplasia and pouchitis (p = 0.17). and no differences in mucosal atrophy or the degree of chronic or acute inflammation were observed between groups 1, 2, and 3 (p>0.45). Moreover, no dysplasia or neoplastic changes were detected. However, the degree of mucosal atrophy correlated well with the time of postoperative follow-up (p = 0.05)., Conclusions: The degree of mucosal atrophy, the presence of colonic metaplasia, and the degree of acute or chronic inflammation do not appear to constitute risk factors for the development of pouchitis. Moreover, we observed that longer postoperative follow-up times were associated with greater degrees of mucosal atrophy.

Development of dysplastic lesions that may potentially lead to cancer is sometimes reported within the ileal pouches. Dysplasia is in turn associated with increased expression of proliferation indices. The goal of this study was to evaluate the mitotic activity and possible expression of p53 in the epithelium within the ileal pouches in patients with chronic ulcerative colitis. The study involved archive material consisting of ileal pouches surgically removed from 17 patients diagnosed with ulcerative colitis. Several specimens were collected from each pouch. The immunohistochemistry (Ki-67 and p53 protein) control group (14 cases) consisted of the resection line specimens of colons removed due to colorectal adenocarcinoma. Intensity of the expression of the markers under study within the inflammatory infiltrates was assessed using a 5-point scale proposed by Berstein et al. Ki-67 expression was observed in all studied patients with marked intensity (Bernstein scale score +3, +4). Protein p53 expression was observed only in eight patients, and was mostly of low intensity (Bernstein scale score +1, +2). Immunohistochemical results confirmed the histopathological results that revealed dysplastic lesions, which are often an indication for radical procedures in ulcerative colitis patients. Our results suggest the usefulness of these examinations, also in the ileal pouch material.

Background: Chronic pouchitis is an important long-term complication following ileal pouch-anal anastomosis for ulcerative colitis. Antibiotic administration reduces symptoms of pouchitis, indicating that bacteria have a role in pathogenesis. The aim of the research was to investigate the bacterial content of pouches using nucleic acid-based methods., Methods: Stool microbiota of 17 patients with normal pouches (NP), 17 patients with pouchitis (CP) utilizing samples collected from each patient when antibiotic-treated (CP-on, asymptomatic) and when untreated (CP-off, symptomatic), and 14 familial adenomatous polyposis (FAP) patients were analyzed by high-throughput sequencing, fluorescence in situ hybridization technologies, and quantitative polymerase chain reaction (qPCR)., Results: Fluorescence in situ hybridization analysis revealed an expanded phylogenetic gap in NP and CP-off patients relative to FAP. Antibiotic treatment reduced the gap in CP stool. The phylogenetic gap of CP-off patients was due to members of the bacterial families Caulobacteriaceae, Sphingomonadaceae, Comamonadaceae, Peptostreptococcaceae, and Clostridiaceae. There was a greater diversity of phylotypes of Clostridiaceae in CP-off subjects. The phylogenetic gap of NP stool was enriched by Ruminococcaceae and Bifidobacteriaceae. CP stool microbiota had reduced diversity relative to NP and FAP stool due largely to a reduction in Lachnospiraceae/Insertae Sedis XIV/clostridial cluster IV groups., Conclusions: Bacterial groups within the expanded phylogenetic gap of pouch patients may have roles in the pathogenesis of pouchitis. Further research concerning the physiology of cultured members of these groups will be necessary to explain their specific roles. Members of the Lachnospiraceae, Incertae Sedis XIV, and clostridial cluster IV could be useful biomarkers of pouch health., (Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.)

Background: Restorative proctocolectomy with IPAA is the surgical treatment of choice in patients with ulcerative colitis who require colectomy. Pouchitis is the most common long-term complication in patients with IPAA. While immune-mediated disorders frequently coexist with IBD, they appear to be associated with an increased risk for chronic antibiotic-refractory pouchitis., Objective: This study aimed to evaluate histologic features of autoimmune-associated chronic antibiotic-refractory pouchitis in comparison with controls and to assess their possible diagnostic utility., Design: Clinical definition for autoimmune-associated chronic pouchitis included 1) chronic antibiotic-refractory pouchitis with response only to corticosteroids, immunomodulators, or biologics; 2) positive serum autoantibodies, including antinuclear antibody, rheumatoid factor, and antimicrosomal antibody; and 3) concurrent immune-mediated disorders. Various histologic features of pouch biopsy specimens were evaluated., Setting: The investigation was conducted at a tertiary referral center., Patients: From our Pouchitis Registry, all eligible patients with autoimmune-associated pouchitis (n = 17) were included. The control groups included 16 patients with nonautoimmune-associated chronic antibiotic-refractory pouchitis, 39 with antibiotic-responsive pouchitis, and 19 patients with normal pouches. Various histologic features of pouch biopsy specimens were evaluated., Results: In comparison with the control groups, the autoimmune-associated pouchitis group showed a significant increase in deep crypt apoptosis (p < 0.001). It also showed more pyloric gland metaplasia in comparison with antibiotic-responsive pouchitis and normal pouches. With the use of apoptosis score which we developed as a diagnostic marker for autoimmune-associated chronic antibiotic-refractory pouchitis, we constructed a receiver operating curve and obtained an area-under-curve value of 0.89 (95% CI: 0.79, 0.99)., Conclusion: Increased deep crypt apoptosis is a distinctive histologic feature of autoimmune-associated chronic antibiotic-refractory pouchitis, and this feature may aid in the diagnosis and differential diagnosis in pouchitis.