Pouchitis is a common late complication in patients with ulcerative colitis (UC) who undergo ileal pouch-anal anastomosis (IPAA). The heterogeneous nature of the clinical and endoscopic presentations could affect the evaluation of therapeutic interventions for pouchitis. Thus, identifying the risk factors and clinical outcomes of pouch inflammation at different sites and severity is becoming increasingly important for colorectal surgeons.

Data on patients who underwent IPAA January from 2008 to June 2022 in our three pouch centers affiliated with the China UC Pouch Center Union were retrospectively collected. Pouchitis was categorized as a different phenotype according to the Chicago Classification. J pouches were classified into short (14 ± 2 cm) and long pouches (22 ± 2 cm) according to the distribution of ileal pouch length in our institute.

Altogether, 143 patients with a median follow-up time of 5.0 years (interquartile range: 2.0-8.0) were enrolled. Among them, 41 patients (28.7%) developed pouchitis and 32 patients (78%) had diffuse inflammation of the pouch. Patients with diffuse pouchitis had a higher pouchitis disease activity index and more seriously impaired improvement of long-term quality of life than those with pouch phenotypes. A short J pouch, recurrent UC, and preoperative high white blood cell count were independent risk factors for diffuse pouchitis. Furthermore, a short J pouch could effectively predict the occurrence of diffuse pouchitis with an area under the receiver-operating characteristic curve of 0.614, a sensitivity of 62.5%, and a specificity of 60.4% (p = 0.049) and significantly decreased the overall diffuse pouchitis-free survival compared to a long J pouch (p = 0.0002).

Diffuse pouchitis is a common phenotype of pouchitis that seriously impairs long-term prognosis. For colorectal surgeons, decision-making regarding pouch construction with an appropriate length should be considered to prevent the development of diffuse pouchitis.

Primary sclerosing cholangitis (PSC) is a progressive liver disease with poor prognosis and no effective therapies to prevent progression. An aetiopathological link between PSC and gastrointestinal microbial dysbiosis has been suggested.

To evaluate all potential medical therapies which may exert their effect in PSC by modulation of the gut-liver axis.

We conducted a comprehensive scoping review of PubMed and Cochrane Library, including all articles evaluating an intervention aimed at manipulating the gastrointestinal microbiome in PSC.

A wide range of therapies proposed altering the gastrointestinal microbiome for the treatment of PSC. In particular, these considered antibiotics including vancomycin, metronidazole, rifaximin, minocycline and azithromycin. However, few therapies have been investigated in randomised, placebo-controlled trials. Vancomycin has been the most widely studied antibiotic, with improvement in alkaline phosphatase reported in two randomised controlled trials, but with no data on disease progression. Unlike antibiotics, strategies such as faecal microbiota transplantation and dietary therapy can improve microbial diversity. However, since these have only been tested in small numbers of patients, robust efficacy data are currently lacking.

The gut-liver axis is increasingly considered a potential target for the treatment of PSC. However, no therapies have been demonstrated to improve transplant-free survival. Innovative and well-designed clinical trials of microbiome-targeted therapies with long-term follow-up are required for this orphan disease.

Ileal pouch-anal anastomosis (IPAA) is commonly used to restore gastrointestinal continuity after surgical treatment of mucosal ulcerative colitis (MUC) and familial adenomatous polyposis (FAP). The aim of the present systematic review was to compare the outcomes of patients with MUC and patients with FAP who underwent IPAA.

A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant systematic review was performed. PubMed, Scopus, and Web of Science were searched through December 2021. Cohort and randomized studies were eligible for inclusion if they directly compared patients with MUC and FAP who underwent IPAA. The main outcome measures were pouch failure, complications, and need for pouch excision or revision. ROBINS-I tool was used to assess the risk of bias across the studies. A random-effect meta-analysis was conducted.

Twenty-three studies (9200 patients) were included in this meta-analysis. Seven thousand nine hundred fifty (86.4%) had MUC and 1250 (13.6%) had FAP. The median age of patients was 33.1 years. The male to female ratio was 1.4:1. MUC had higher odds of pouchitis (OR 3.9, 95% CI 2.8-5.4, p < 0.001), stricture (OR 1.82, 95% CI 1.25-2.65, p = 0.002), fistula (OR 1.74, 95% CI 1.18-2.54, p = 0.004), and total complications (OR 1.89, 95% CI 1.3-2.77, p < 0.001) as compared to FAP. Both groups had similar odds of pelvic sepsis, leakage, pouch failure, excision, revision, and fecal incontinence.

Although patients with MUC undergoing IPAA may be at a higher risk of developing complications, particularly pouchitis, stricture, and fistula; the ultimate and functional outcome of the pouch is similar to patients with FAP. Pouch failure, excision and revision were similar in the two groups.

Pouchitis is the most frequent complication after IPAA in patients with ulcerative colitis. Antibiotics represent the mainstay of treatment, suggesting a crucial role of dysbiosis in the pathogenesis of this condition. Anti-tumor necrosis factor agents have been shown to adversely impact the gut microbiome and local host immunity.

The aim of this study is to assess the effect of prior exposure to biologics on the development of pouchitis in patients who have ulcerative colitis.

This is a retrospective case-control study.

This study was conducted at a tertiary-care IBD center.

Consecutive patients with ulcerative colitis who underwent restorative proctocolectomy between 2000 and 2010 were included.

The primary outcome measured was the incidence of pouchitis.

Four hundred seventeen patients with ulcerative colitis who underwent IPAA were included. The incidence of pouchitis was 40.4%. There were no differences in patient demographics, disease-specific factors, surgical approach, and short-term postoperative complications between patients who developed pouchitis compared to those that did not. Patients exposed to anti-tumor necrosis factor agents or preoperative steroids were significantly more likely to develop pouchitis (anti-tumor necrosis factor: 47.9% vs 36.5%, p = 0.027; steroids: 41.7% vs 23.3%, p = 0.048). However, on multivariable analysis, only anti-tumor necrosis factor therapy was an independent predictor for pouchitis (p = 0.05). Pouchitis was not associated with adverse long-term outcomes.

The retrospective design was a limitation of this study.

In a large cohort of patients undergoing IPAA for ulcerative colitis with at least a 5-year follow-up, anti-tumor necrosis factor exposure was the only independent risk factor for the development of pouchitis. These agents may "precondition" the pouch to develop pouchitis through alterations in the microbiome and/or local host immunity of the terminal ileum. See Video Abstract at http://links.lww.com/DCR/B19. LA EXPOSICIÓN A MEDICAMENTOS ANTI-TNF AUMENTA LA INCIDENCIA DE POUCHITIS DESPUÉS DE LA PROCTOCOLECTOMÍA RESTAURADORA EN PACIENTES CON COLITIS ULCEROSA:: La pouchitis es la complicación más frecuente después de la anastomosis anal de bolsa ileal en pacientes con colitis ulcerosa. Los antibióticos representan el pilar del tratamiento, lo que sugiere un papel crucial de la disbiosis en la patogénesis de esta afección. Se ha demostrado que los agentes anti-TNF tienen un impacto adverso en la microbiota intestinal y en la inmunidad local del huésped.El objetivo de este estudio es evaluar el efecto de la exposición previa a terapía biológica sobre el desarrollo de la pouchitis en pacientes con colitis ulcerosa.Estudio retrospectivo de casos y controles.Centro de tercer nivel de atención en enfermedades inflamatorias intestinales.Pacientes consecutivos con colitis ulcerosa que se sometieron a proctocolectomía restaurativa entre 2000-2010.Incidencia de pouchitis.Cuatrocientos diecisiete pacientes con colitis ulcerativa se sometieron a anastomosis anal de bolsa ileal. La incidencia de pouchitis fue del 40.4%. No hubo diferencias en la demografía del paciente, los factores específicos de la enfermedad, el abordaje quirúrgico y las complicaciones postoperatorias a corto plazo entre los pacientes que desarrollaron pouchitis en comparación con los que no lo hicieron. Los pacientes expuestos a agentes anti-TNF o esteroides preoperatorios fueron significativamente más propensos a desarrollar pouchitis (anti-TNF: 47.9% vs 36.5%, p = 0.027; esteroides: 41.7% vs 23.3%, p = 0.048). Sin embargo, en el análisis multivariable, solo la terapia anti-TNF fue un predictor independiente para la pouchitis (p = 0.05). La pouchitis no se asoció con resultados adversos a largo plazo.Diseño retrospectivo.En una gran cohorte de pacientes sometidos a anastomosis anal de bolsa ileal para la colitis ulcerosa con al menos 5 años de seguimiento, la exposición a terapía anti-TNF fue el único factor de riesgo independiente para el desarrollo de pouchitis. Estos agentes pueden "precondicionar" la bolsa para desarrollar una pouchitis a través de alteraciones en el microbioma y / o inmunidad local del huésped del íleon terminal. Vea el Resumen del video en http://links.lww.com/DCR/B19.

Ulcerative colitis (UC) is a chronic idiopathic inflammatory bowel disorder of the colon that causes continuous mucosal inflammation extending from the rectum to the more proximal colon, with variable extents. UC is characterized by a relapsing and remitting course. UC was first described by Samuel Wilks in 1859 and it is more common than Crohn's disease worldwide. The overall incidence and prevalence of UC is reported to be 1.2-20.3 and 7.6-245 cases per 100,000 persons/year respectively. UC has a bimodal age distribution with an incidence peak in the 2nd or 3rd decades and followed by second peak between 50 and 80 years of age. The key risk factors for UC include genetics, environmental factors, autoimmunity and gut microbiota. The classic presentation of UC include bloody diarrhea with or without mucus, rectal urgency, tenesmus, and variable degrees of abdominal pain that is often relieved by defecation. UC is diagnosed based on the combination of clinical presentation, endoscopic findings, histology, and the absence of alternative diagnoses. In addition to confirming the diagnosis of UC, it is also important to define the extent and severity of inflammation, which aids in the selection of appropriate treatment and for predicting the patient's prognosis. Ileocolonoscopy with biopsy is the only way to make a definitive diagnosis of UC. A pathognomonic finding of UC is the presence of continuous colonic inflammation characterized by erythema, loss of normal vascular pattern, granularity, erosions, friability, bleeding, and ulcerations, with distinct demarcation between inflamed and non-inflamed bowel. Histopathology is the definitive tool in diagnosing UC, assessing the disease severity and identifying intraepithelial neoplasia (dysplasia) or cancer. The classical histological changes in UC include decreased crypt density, crypt architectural distortion, irregular mucosal surface and heavy diffuse transmucosal inflammation, in the absence of genuine granulomas. Abdominal computed tomographic (CT) scanning is the preferred initial radiographic imaging study in UC patients with acute abdominal symptoms. The hallmark CT finding of UC is mural thickening with a mean wall thickness of 8 mm, as opposed to a 2-3 mm mean wall thickness of the normal colon. The Mayo scoring system is a commonly used index to assess disease severity and monitor patients during therapy. The goals of treatment in UC are three fold-improve quality of life, achieve steroid free remission and minimize the risk of cancer. The choice of treatment depends on disease extent, severity and the course of the disease. For proctitis, topical 5-aminosalicylic acid (5-ASA) drugs are used as the first line agents. UC patients with more extensive or severe disease should be treated with a combination of oral and topical 5-ASA drugs +/- corticosteroids to induce remission. Patients with severe UC need to be hospitalized for treatment. The options in these patients include intravenous steroids and if refractory, calcineurin inhibitors (cyclosporine, tacrolimus) or tumor necrosis factor-α antibodies (infliximab) are utilized. Once remission is induced, patients are then continued on appropriate medications to maintain remission. Indications for emergency surgery include refractory toxic megacolon, colonic perforation, or severe colorectal bleeding.

Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) has become the preferred surgical treatment for refractory or complicated ulcerative colitis (UC) and familial adenomatous polyposis (FAP). Pouchitis is the most common complication of this procedure and can occur in about 50% of patients. Treatment of pouchitis depends on the phenotype of disease. Pouchitis can be classified as acute, chronic/refractory, or secondary pouchitis, which includes pouchitis occurring due to Crohn's disease (CD). CD of the pouch is becoming an increasingly recognized problem, and management is challenging. This article reviews the literature and offers treatment recommendations regarding management of pouchitis and CD of the pouch.

Inflammatory complications including chronic refractory pouchitis and Crohn's disease (CD)-like complications of the pouch are common complications after ileal pouch-anal anastomosis (IPAA) following colectomy for ulcerative colitis (UC). We performed a systematic review and meta-analysis to evaluate the efficacy of anti-TNF therapy in distinguishing patients with chronic refractory pouchitis from those with CD-like complications of the pouch.

We performed a systematic literature search to identify articles and abstracts reporting anti-TNF agents efficacy in treating inflammatory complications of the pouch after IPAA for UC. Short-term and long-term remissions were evaluated at 8 weeks 95%CI[5-10] and 12 months 95%CI[12-18.5], respectively.

We identified 21 articles and 3 abstracts including 313 patients treated either with infliximab (n = 194) or adalimumab (n = 119) for inflammatory complications of the pouch. The rates of short-term and long-term clinical remission were 0.50 (95%CI [0.37-0.63]; I2 = 0.57) and 0.52 (95%CI[0.39-0.65]; I2 = 0.59), respectively. The rate of remission after anti-TNF induction therapy seemed to be higher in CD-like complications of the pouch 0.64 (95%CI[0.5-0.77]; I2 = 0.18), compared to refractory pouchitis 0.10 (95%CI [0.00-0.35]; I2 = 0.00) (P = 0.06), whereas no such difference appeared after long-term maintenance therapy 0.57 (95%CI[0.43-0.71]; I2 = 0.32) and 0.37 (95%CI [0.14-0.62]; I2 = 0.47), respectively (P = 0.57). Sensitivity analyses suggested no difference in outcomes. No significant publication bias has been detected.

Anti-TNF agents have a clear trend to have higher and faster efficacy in CD-like complications of the pouch compared to refractory pouchitis, highlighting the need to differentiate these two entities both in daily practice and clinical trials.

Ileal pouch-anal anastomosis (IPAA) is recommended for patients with ulcerative colitis (UC) in terms of surgical treatment. Measuring surgical complications of IPAA and long-term quality of life (QOL) are important to achieve an acceptable risk/benefit ratio for patients with UC.

Patients with UC who underwent total proctocolectomy (TPC) with IPAA from February 2008 to July 2016 at our institute were included. Early surgical complications were defined as mechanical/infectious events within one month after IPAA. Assessment of QOL was performed using the Cleveland Global Quality of Life instrument (CGQL), with 50% improvement as a cut-off value. Demographic and clinical variables were compared with univariable analysis and step-wise logistic regression models were also performed.

A total of 58 eligible patients had a median follow-up time of 78.5 months [interquartile range (IQR), 34.4-92.8] from February2008 to March 2017, including 25 cases (43.1%) developed early surgical complications. Age at pouch surgery and excessive blood loss were risk factors associated with early surgical complications (p < 0.05). In multivariate analysis, older age at surgery [odds ratio (OR), 1.05; 95% confidence interval (CI), 1.01-1.1] and significant blood loss (≧400 ml) (OR, 4.31; 95% CI, 1.21-16.87) were contributing factors for developing early surgical complications. The CGQL score was significantly increased after IPAA (0.728 ± 0.151 vs. 0.429 ± 0.173, p < 0.001). Early surgical complications (OR, 5.55; 95%CI, 1.44-21.37), older age at surgery (OR, 1.06; 95% CI, 1.01-1.12) and use of immunomodulatory (OR, 17.50; 95% CI, 1.52-201.39) were associated with poor long-term QOL.

The study demonstrated that early surgical complications might contribute to develop a poor CGQL score, suggesting intentional control of risk factors associated with early surgical complications should be taken into consideration for patients with UC for pouch surgery.

Pouchitis is a major problem after ileal pouch-anal anastomosis in patients with ulcerative colitis. Chronic pouchitis is particularly troublesome. This study aimed to identify risk factors for the development of chronic pouchitis in a Japanese population.

We retrospectively reviewed 100 patients who underwent pouchoscopy for a functioning ileal pouch. The diagnosis of pouchitis was made according to the modified pouchitis disease activity index. The incidence of pouchitis was estimated using the Kaplan-Meier curve, and Cox regression analysis was used to identify risk factors for the development of chronic pouchitis.

Twenty-two patients developed pouchitis; 12 of them had chronic pouchitis. The incidences of chronic pouchitis were 3.3%, 7.6%, and 16.6% at 2, 5, and 10 years, respectively, after the pouch operation. The incidence of pouchitis was significantly higher in patients with preoperative extraintestinal manifestations (EIMs) than in those without (log-rank test, P = 0.002 and P = 0.005 for overall and chronic pouchitis, respectively). Cox regression analysis revealed that the presence of extraintestinal manifestations was an independent risk factor for the development of overall (hazard ratio: 4.48, 95% confidence interval, 1.77-11.30, P = 0.002) and chronic (hazard ratio: 5.81, 95% confidence interval, 1.67-20.23, P = 0.006) pouchitis.

The presence of preoperative extraintestinal manifestations was found to be an independent risk factor for the development of overall and chronic pouchitis.

Data about the effectiveness of biologics, including anti-tumor necrosis factor (TNF) therapy and anti-integrin strategies, in antibiotic refractory pouchitis or Crohn's disease-associated pouch complications are sparse. We performed a systematic review of the literature in Medline and Web of Science. All English language publications and meeting abstracts describing patients with pouchitis treated with anti-TNF or anti-integrin therapies were included. We identified a total of 17 papers and 2 abstracts, most of these retrospective case series, including a total of 192 patients treated either with infliximab (n=140) or adalimumab (n=52). No reports were found for anti-integrin therapies or other anti-TNF agents such as certolizumab pegol or golimumab. Because of the heterogeneity of the studies, small numbers of patients, differing cotreatments, and subjective outcome definitions, the exact efficacy of these biological therapies cannot be assessed in a combined fashion. Overall infliximab appears to have good clinical effectiveness in selected patients achieving up to 80% short-term and around 50% long-term response, whereas the few data available for adalimumab are not sufficient to draw valid conclusions. Larger prospectively collected multicenter data with clearly defined inclusion criteria and outcomes are necessary to better define the clinical value of anti-TNF therapy in patients with antibiotic refractory pouchitis or Crohn's-like complications of the pouch.

Potential non-invasive markers of pouchitis would have a great deal of significance within clinical practice.

This study is aimed at assessing the diagnostic accuracy of fecal calprotectin and matrix metalloprotease-9 as potential markers in patients both with and without pouchitis.

Stool and blood samples were collected from 33 ileal pouch-anal anastomosis patients before a follow-up pouchoscopy. Biopsy samples were taken for histological purposes. The presence of cuffitis and stenosis was evaluated with an endoscopy. Calprotectin and matrix metalloprotease-9 were quantified with an enzyme-linked immunosorbent assay.

Pouchitis was detected in 30.3% of the patients. The levels of fecal calprotectin and matrix metalloprotease-9 increased significantly in patients with pouchitis. The sensitivity and specificity of matrix metalloprotease-9 was higher than that of fecal calprotectin. Only matrix metalloprotease-9 correlated significantly with the severity of pouchitis.

Fecal matrix metalloprotease-9 has a high specificity in the diagnosis of pouchitis.

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.

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.

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.

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.

In this work, we propose that for further studies of the physiopathology and treatment for inflammatory bowel diseases, an integral view of the conditions, including the triad of microbiota-heat shock proteins (HSPs)-probiotics, ought to be considered. Microbiota is the complex microbial flora that resides in the gut, affecting not only gut functions but also the health status of the whole body. Alteration in the microbiota's composition has been implicated in a variety of pathological conditions (e.g., ulcerative colitis, UC), involving both gut and extra-intestinal tissues and organs. Some of these pathologies are also associated with an altered expression of HSPs (chaperones) and this is the reason why they may be considered chaperonopathies. Probiotics, which are live microorganisms able to restore the correct, healthy equilibrium of microbiota composition, can ameliorate symptoms in patients suffering from UC and modulate expression levels of HSPs. However, currently probiotic therapy follows ex-adiuvantibus criteria, i.e., treatments with beneficial effects but whose mechanism of action is unknown, which should be changed so the probiotics needed in each case are predetermined on the basis of the patient's microbiota. Consequently, efforts are necessary to develop diagnostic tools for elucidating levels and distribution of HSPs and the microbiota composition (microbiota fingerprint) of each subject and, thus, guide specific probiotic therapy, tailored to meet the needs of the patient. Microbiota fingerprinting ought to include molecular biology techniques for sequencing highly conserved DNA, e.g., genes encoding 16S RNA, for species identification and, in addition, quantification of each relevant microbe.

Proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the established surgical therapy for familial adenomatous polyposis (FAP) and refractory ulcerative colitis (UC). Despite general patient satisfaction with preserved fecal continence, this procedure is associated with a significant long-term morbidity approaching 70% after 10 years, and with a non-negligible rate of pouch failure leading to removal and permanent ileostomy. Following a concise description of the surgical technique, the normal imaging appearance of the ileal "pouch" reservoir at pelvic CT and MRI is explained. Since awareness of their imaging appearances is needed for a correct diagnosis, we discuss and illustrate common and unusual pouch-related complications, including pouchitis and irritable pouch disease; anastomotic leakages and pelvic abscess collections; fistulas involving the ano-perianal region, urinary bladder, vagina, perineal skin, and subcutaneous planes; anal stenosis and small-bowel obstruction. In our experience, pelvic contrast-enhanced MRI has proven invaluable for the diagnostic assessment of patients with suspected pouch-related complications, allowing differentiation of uncomplicated pouchitis from pelvic sepsis, the latter requiring aggressive therapy and possible even in patients with normal endoscopic findings.

Ileal pouch-anal anastomosis is the definitive therapy for ulcerative colitis that is refractory to medical treatment or that has developed neoplasia. Patients with this procedure are routinely followed using directed endoscopic biopsies to monitor for dysplasia in the rectal cuff, residual/recurrent ulcerative colitis, and nonspecific acute inflammation of the ileal pouch (pouchitis), which have different clinical management and outcomes. Thus, accurate localization of mucosal biopsies is crucial to a definitive histological diagnosis, but is complicated by overlapping clinical presentations of pouchitis and ulcerative colitis, post-surgical and inflammatory changes to the mucosa, and altered endoscopic anatomy, resulting in difficulty determining whether a mucosal biopsy is ileal or rectal in origin for both the endoscopist and the pathologist. We explored the utility of CD10 immunohistochemistry to aid diagnosis in this clinical setting by highlighting the enteric mucosa, based on previous studies showing its utility in brush border staining and in the diagnosis of microvillous inclusion disease. We found uniformly positive CD10 immunostaining in normal enteric mucosa, but variable loss of expression in the setting of active enteritis. Specifically, CD10 staining was lost in up to 10% of the mucosa in 1/12 ileostomies and 4/13 enteric anastomoses, in 10-80% of the mucosa in 9/10 cases of Crohn's ileitis, in 10-60% of the mucosa in 7/16 ileal pouches, and in 20-90% of the mucosa in 6/8 cases of backwash ileitis, usually in the presence of active inflammation. There was no CD10 expression by normal or diseased colonic mucosa. Therefore, while CD10 immunostaining identifies normal enteric mucosa with 100% specificity, negative staining does not definitively exclude small intestinal mucosa in the setting of active enteritis, a common condition in ileal pouch mucosa.

The accuracy of ileo-anal pouch biopsy reporting was assessed.

The pathology reports of 100 consecutive pouch biopsies were reviewed to assess the accuracy and consistency with which the St Mark's histological scoring criteria were applied. The quality of pouch biopsy sampling and provision of clinical and endoscopic information on pathology request forms was also assessed.

In 27% of cases no relevant endoscopic or clinical information was provided with the pathology request form. Separately labelled biopsies from the prepouch ileum, pouch and columnar cuff were submitted in only 4% of cases. In 32% of pathology reports, no acute or chronic St Mark's score was included. In 2% of cases the St Mark's scoring criteria were applied inappropriately. Twenty per cent of cases histologically diagnosed as pouchitis did not include a numerical score. In 30% of cases diagnosed histologically as pouchitis, an acute inflammatory score of < 4 (i.e. insufficient for this diagnosis) was included in the report.

Pouchitis is a combined clinical, endoscopic and histological diagnosis. The correct interpretation and application of the St Mark's histological scoring criteria for pouch biopsies is an important part of this diagnostic process.

Pouchitis occurs in up to 50% of patients with ulcerative colitis (UC) undergoing ileal pouch anal anastomosis (IPAA). Pouchitis rarely occurs in patients with familial adenomatous polyposis (FAP) who undergo IPAA. Our aim was to compare mucosal and luminal flora in patients with UC-associated pouchitis (UCP), healthy UC pouches (HUC), and healthy FAP pouches (FAP).

Nineteen patients were enrolled in this cross-sectional study (nine UCP, three HUC, seven FAP). Patients with active pouchitis were identified using the Pouchitis Disease Activity Index (PDAI). Ileal pouch mucosal biopsies and fecal samples were analyzed with a 16S rDNA-based terminal restriction fragment length polymorphism (TRFLP) approach. Pooled fecal DNA from four UCP and four FAP pouches were sequenced for further speciation.

TRFLP data revealed statistically significant differences in the mucosal and fecal microbiota between each group of patients. UCP samples exhibited significantly more TRFLP peaks matching Clostridium and Eubacterium genera compared to HUC and FAP pouches and fewer peaks matching Lactobacillus and Streptococcus genera compared to FAP. DNA Sanger sequencing of a subset of luminal samples revealed UCP having more identifiable sequences of Firmicutes (51.2% versus 21.2%) and Verrucomicrobia (20.2% versus 3.2%), and fewer Bacteroidetes (17.9% versus 60.5%) and Proteobacteria (9.8% versus 14.7%) compared to FAP.

The pouch microbial environment appears to be distinctly different in the settings of UC pouchitis, healthy UC, and FAP. These findings suggest that a dysbiosis may exist in pouchitis which may be central to understanding the disease.

To highlight the recent studies which have enhanced our appreciation of the composition of the microbiota in the human small intestine and its relevance to the health of the host.

In the past number of years, the composition of the microorganisms present in our small intestines has been the subject of greater scrutiny than ever before. These investigations have been possible as a consequence of the development and utilization of new molecular tools which have revolutionized the field of microbial ecology and have focused predominantly on the small intestinal microbiota associated with pediatric celiac disease, inflammatory bowel disease, irritable bowel syndrome and pouchitis. The impact of invasive procedures, such as small bowel transplant, ileostomy and ileal pouch anal anastomosis, on the ileal microbiota has also been investigated.

The ever greater appreciation of the link between the small intestinal microbiota and the health status of the host has the potential to lead to the development of new strategies to alter this microbiota in a targeted way to prevent or treat specific disorders.

In patients with symptoms of pouchitis retractable to antibiotic therapy, serology is often ordered to exclude concurrent celiac disease. The clinical utility of celiac serology in patients with ileal pouches is unknown. The aim of this study was to investigate the clinical implications of false-positive celiac serology in patients with ileal pouches.

All patients with pouches who had underlying ulcerative colitis and available celiac serology were included from the subspecialty Pouchitis Clinic at the Cleveland Clinic between 2002 and 2007. Chronic antibiotic-refractory pouchitis was diagnosed based on persistent symptomatic pouchitis after a 4-week single- or dual-antibiotic therapy.

A total of 126 patients were studied, and a false-positive celiac serology was observed in 19 patients. Chronic antibiotic-refractory pouchitis was diagnosed in 47% (9/19) of patients with false-positive celiac serology compared with 14% (15/107) of patients with a negative celiac serology (P = .003). In multivariate analysis, the association between false-positive celiac serology and chronic antibiotic-refractory pouchitis remained significant (odds ratio, 5.4; 95% confidence interval, 1.7-16.7; P = .004) after adjusting for sex (P = .03), pouch duration (P = .83), the presence of autoimmune disorders (P = .46), and extraintestinal manifestations (P = .63).

False-positive celiac serology appeared to be common in patients with ileal pouch-anal anastomosis and it may be associated with chronic antibiotic-refractory pouchitis.

Although a majority of patients with pouchitis respond favorably to antibiotic therapy, many relapse frequently, and nonabsorbable and non-antibiotic-based agents are desirable for reducing bacterial resistance and the systemic adverse effects associated with long-term antibiotic exposure. AST-120 (a spherical carbon adsorbent) comprises highly adsorptive, porous carbon microspheres with the ability to adsorb small-molecular-weight toxins, inflammatory mediators,and harmful bile acids. The aim of this pilot trial was to evaluate the efficacy and tolerability of AST-120 in the treatment of active pouchitis.

Eligible patients were recruited from two subspecialty pouchitis clinics. Inclusion criteria were(i) ileal pouch-anal anastomosis performed for ulcerative colitis; (ii) active pouchitis with Pouchitis Disease Activity Index (PDAI) scores > or =7; and (iii) discontinuation of antibiotic therapy for at least 2 weeks. Exclusion criteria included Crohn's disease of the pouch, isolated cuffitis, pouch strictures, abscess, and sinuses. All eligible patients received AST-120 in 2-g sachets (oral) open label, thrice a day for 4 weeks. The primary efficacy end point was remission as defined by a PDAI score of < 7 points; the main secondary end point was clinical response, defined by a reduction of the PDAI score of > or =3 points.

Nineteen of 20 patients completed the trial. Eleven patients (55.0 % ) had a clinical response to the therapy and 10 patients (50.0 % ) entered remission. Median reduction in the PDAI symptom, endoscopy, and histology subscores, and PDAI total scores after 4 weeks were -2( P = 0.002), -2 ( P = 0.003), 0 ( P = 0.32), and -4 ( P = 0.001) points, respectively. The agent was well tolerated; one patient experienced transient mild elevation of alkaline phosphatase of uncertain significance and one patient experienced an upper respiratory infection after taking one dose of AST-120 and was excluded from the fi nal analysis for the calculation of pre- and post-trial PDAI scores.

AST-120 seems to be effective and well tolerated in treating patients with active pouchitis.A randomized, placebo-controlled trial is warranted for assessing the long-term efficacy and safety of AST-120 in the disease.

Ileal pouch-anal anastomosis is the procedure of choice in the surgical management of refractory ulcerative colitis. Pouchitis affects up to 60% of patients following ileal pouch-anal anastomosis for ulcerative colitis. It overlaps significantly with ulcerative colitis such that improvements in our understanding of one will impact considerably on the other. The symptoms are distressing and impinge significantly on patients' quality of life. Despite 30 years of scientific and clinical investigation, the pathogenesis of pouchitis is unknown; however, recent advances in molecular and cell biology make a synergistic hypothesis possible. This hypothesis links interaction between epithelial metaplasia, changes in luminal bacteria (in particular sulfate-reducing bacteria), and altered mucosal immunity. Specifically, colonic metaplasia supports colonization by sulfate-reducing bacteria that produce hydrogen sulfide. This causes mucosal depletion and subsequent inflammation. Although in most cases antibiotics lead to bacterial clearance and symptom resolution, immunogenetic subpopulations can develop a chronic refractory variant of pouchitis. The aims of this paper are to discuss proposed pathogenic mechanisms and to describe a novel mechanism that combines many hypotheses and explains several aspects of pouchitis. The implications for the management of both pouchitis and ulcerative colitis are discussed.

While the overall incidence of pouchitis is low, extensive research continues at clinical and experimental levels in attempts to unravel its etiology. The ileal pouch and pouchitis together represent a unique in vivo opportunity to study mucosal adaptation and inflammation in depth. In the recent past, molecular data relating to pouchitis has significantly expanded. These data provide invaluable insight into intracellular and extracellular events that underpin mucosal adaptation and inflammation. Advances in classification, risk factor evaluation, and prevention have meant that a review of this data, as well as its relationship to our current understanding of pouchitis, is both timely and warranted. Therefore, the aim of this review is to summarize recent data in the context of the established literature.

We designed and evaluated a novel concept in enhancing postoperative care of patients following restorative proctocolectomy (RPC) for ulcerative colitis (UC) and determined the risk factors, incidence, and nature of RPC-associated complications in this population.

The study cohort consisted of consecutive UC patients post-RPC attending a comprehensive pouch clinic run by a gastroenterologist and a colorectal surgeon in a tertiary care medical center (from January 2003 to December 2005). Data were collected on their medical history, physical examination, laboratory tests, pouch endoscopy and biopsies, and anonymous in-house patient satisfaction questionnaires mailed to the first 90 patients. Assessment was also done on data regarding risk factors, incidence, and nature of RPC-associated complications.

A total of 120 UC patients with a functioning pouch visited the clinic: mean age 37 years, range 13-75; 57 males; mean disease duration 11 years; mean follow-up 65 months. Of the 55 patients who responded to the questionnaire, 48 (87%) felt that the comprehensive clinic significantly improved the quality of their care. The major complications were pouchitis (52%), extraintestinal manifestations, pouch-related fistula, and mechanical dysfunction. The risk factors for the development of pouchitis were time since surgery, >1-stage surgery, and reason for surgery (acute exacerbation/intractable disease more than dysplasia/cancer); the latter was the only independent risk factor.

The pouch clinic concept significantly enhanced patient satisfaction. The most common RPC-associated complication was pouchitis. Risk factors for developing pouchitis were duration since operation, >1-stage operation, and indication for surgery.

Pouchitis is the most common long-term complication of in patients with restorative proctocolectomy and ileal pouch-anal anastomosis. Patients often develop antibiotic-dependent form of pouchitis requiring long-term antibiotic therapy for remission maintenance. Rifaximin, an oral, non-systemic, broad-spectrum antibiotic with a favorable safety profile, may be a promising candidate agent for maintenance therapy. This historical cohort open-label study investigated the efficacy and tolerability of rifaximin in maintaining symptomatic and endoscopic remission in patients with antibiotic-dependent pouchitis.

Adult patients with antibiotic-dependent pouchitis received a 2-week course of various antibiotics for induction of remission. Patients in remission then began maintenance therapy with rifaximin 200 mg/day (to 1800 mg/day) for up to 24 months. Pouchitis Disease Activity Index symptom scores were assessed every 1-3 months to evaluate efficacy.

Fifty-one patients began maintenance therapy with rifaximin (median dose 200 mg/day); 33 (65%) maintained remission through 3 months (primary endpoint). Of these 33 patients, 26 (79%) successfully continued maintenance for 6 months after beginning maintenance, 19 (58%) successfully continued for 12 months, and two (6%) successfully continued for 24 months. Only one patient reported an adverse event (transient facial rash).

Patients' response to rifaximin as a maintenance therapy appears to be favorable in this open-labeled trial of antibiotic-dependent pouchitis. Randomized, placebo-controlled trials with a longer follow-up are warranted.

The primary end point of this study was to determine the risk factors that predict chronic pouchitis in those patients having ileal pouch-anal anastomosis.

A total of 237 patients with ulcerative colitis and undergoing ileal pouch-anal anastomosis by one surgeon at Oregon Health & Science University from 1993 to 2003 were evaluated. Data were gathered via retrospective chart reviews and by a questionnaire administered by telephone in 2004. Patients were excluded if there was less than one-year follow-up documented in the chart or they could not be contacted by telephone (n = 62), postoperative diagnosis of Crohn's disease (n = 3), failed ileoanal procedure (n = 1), and one-stage ileal pouch-anal anastomosis (n = 3), leaving 167 patients for evaluation. Patients were defined as having chronic pouchitis (> 3 episodes of pouchitis) or no pouchitis (< or = 3 episodes of pouchitis). Potential risk factors included number of operations used to perform ileal pouch-anal anastomosis, fulminant ulcerative colitis with two-stage operation, duration of diverting ileostomy after pouch formation, primary sclerosing cholangitis, other extraintestinal manifestations of ulcerative colitis, preoperative liver function tests, duration of ulcerative colitis, and the occurrence of postoperative complications. Initial univariate analysis was performed on all risk factors. Multivariate analysis was performed on all univariate risk factors with P values < 0.2.

The prevalence of chronic pouchitis in our population was 46 percent. The following variables were identified during univariate analysis and entered into a multivariate model: preoperative serum albumin (P = 0.07), PSC (P = 0.126), duration of diverting ileostomy (P = 0.111), fulminant ulcerative colitis with two-stage operation, (P = 0.051), the presence of postoperative complications (P = 0.031), and the type of postoperative complications (anastomotic complications, P = 0.013). Patients who did not undergo diverting ileostomy at the time of their ileal pouch-anal anastomosis trended toward a lower likelihood of developing chronic pouchitis (P = 0.06). Multivariate analysis showed that patients with postoperative complications (53 percent, P = 0.042), specifically anastomotic complications, were more likely to develop chronic pouchitis (P = 0.005). Eight percent of patients had primary sclerosing cholangitis and 11 percent of patients had at least one extraintestinal manifestation of ulcerative colitis. Patients with primary sclerosing cholangitis were not more likely to develop chronic pouchitis (P = 0.168). Patients with extraintestinal manifestations also were not more likely to develop chronic pouchitis (P = 0.273).

Chronic pouchitis is a frequent complication after ileal pouch-anal anastomosis. In this study patients with primary sclerosing cholangitis or other extraintestinal manifestations of ulcerative colitis were not more likely to develop chronic pouchitis. Patients with postoperative complications, specifically anastomotic complications after ileal pouch-anal anastomosis, were more likely to develop chronic pouchitis and may benefit from early strategies to prevent pouchitis.

Pouchitis after restorative proctocolectomy for ulcerative colitis is usually of ill-defined etiology and is encountered with sclerosing cholangitis, bacterial overgrowth, and ischemia. Recently, appendiceal involvement, ileitis, and fissures in the colectomy specimen have been associated with short- and long-term development of pouchitis. To corroborate these recent findings, the histology of 40 colectomies (70% males; mean age 46.3 years, age range 20-70 years; mean follow-up period 3.7 years, range 1-13 years) with yearly follow-up biopsies was correlated with pouchitis and clinical symptoms. Appendicitis, fissures, and ileitis were present in 47, 45 and 5% of the patients, respectively. Pouchitis in patients with appendicitis or with fissures was noted in 44 and 50% at first biopsy and in 70 and 58% during follow-up (p = NS). Of the patients without appendicitis or without fissures, 33 and 33% demonstrated pouchitis at the first biopsy and 30 and 55% during follow-up (p = NS). Clinico-histological correlation revealed normal/near-normal biopsies with the lowest clinical severity score in 77% and with the highest clinical score in 43% (p < 0.025). The histological findings of appendiceal involvement, fissuring ulcers, and ileitis in colectomies for ulcerative colitis do not correlate with the finding of pouchitis in early or late pouch biopsies. A high clinical suspicion score is frequently not correlated with significant inflammation of the pouch.

Approximately 10% to 30% of patients with ulcerative colitis and up to 70% of patients with Crohn's disease will undergo surgery at some point during their lifetime. Although patients with ulcerative colitis are considered "cured" by surgery, patients who have undergone an ileal pouch anal anastomosis may develop pouchitis, cuffitis, pouch irritability, or even Crohn's disease. Various therapies have shown success, including probiotics, in the prevention of pouchitis onset or relapse. Crohn's disease historically recurs following surgery; prophylaxis against disease recurrence has been attempted with a variety of agents, with variable success. Innovative therapies holding promise for the future treatment or prevention of these conditions are under exploration.