Irritable Pouch Syndrome Research Articles

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

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

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

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

Management of pouch dysfunction in a tertiary centre.

Restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis is the operation of choice for ulcerative colitis (UC) and some cases of familial adenomatous polyposis (FAP). Although it offers improvement in quality of life and high patient satisfaction, pouch surgery is also associated with significant morbidity. The aim of this study was to describe the management of patients referred to a tertiary centre with pouch dysfunction. All patients referred with pouch dysfunction from other institutions between October 2006 and November 2014 were included in this retrospective study. Information regarding initial diagnosis before RPC, type of procedure, symptoms leading to referral, relation of the appearance of symptoms to the ileostomy closure, investigations, final diagnosis, treatment and follow-up was reviewed. One hundred and twenty-one patients were included, having had RPC mostly for UC (94%), and with diverting ileostomy (83%). The most frequent reasons for referral were high frequency of defaecation in 83 (69%) patients, abdominal pain and incontinence in 45 (37%) each and perianal pain in 44 (36%). The principal investigations performed were pouchoscopy in 97 (80%) patients, examination under anaesthesia (EUA) in 62 (51%), pelvic magnetic resonance imaging (MRI) in 56 (46%) and contrast radiology of the pouch (pouchogram) in 45 (35%). The commonest diagnoses were pouchitis (primary and secondary) in 24 (21%) patients and anastomotic leakage in 26 (22%). After full investigation a cause for the symptoms could not be found in 24 (20%) patients, resulting in the diagnosis of exclusion of 'irritable pouch syndrome' or functional disorder. The treatments given were long-term antibiotic therapy in 29 (25%) patients, ileostomy in 19 (16%), use of a Medena catheter to promote anal evacuation in 17 (15%) and dilatation of a stenosis under anaesthetic in 12 (10%). Six (5%) patients underwent major revision surgery of the pouch with a defunctioning ileostomy and the pouch was excised in another six (5%). Patients with ileoanal pouch dysfunction often have multiple symptoms. This study shows that a wide range of investigations and treatment modalities need to be available to manage such patients, with a specialized approach in a multidisciplinary setting.

Psychological Factors in Irritable Pouch Syndrome and Other Pouch Disorders.

Restorative proctocolectomy with ileal pouch-anal anastomosis is the surgical treatment of choice for patients with medically refractory ulcerative colitis. Postsurgery, functional and inflammatory complications of the ileal pouch often occur. Our previous study demonstrated that irritable pouch syndrome (IPS) is associated with the use of antidepressants or anxiolytics, suggesting an influence of psychological factors on patients' symptoms. The aim of this study was to identify the specific psychological factors and coping strategies in patients with functional (IPS) and inflammatory (pouchitis, cuffitis, Crohn's disease of the pouch) pouch disorders. Consecutive patients with functional pouch disorders (IPS), inflammatory pouch conditions, and asymptomatic ileal pouch-anal anastomosis patients were surveyed using validated measures of quality of life (the Cleveland Global Quality of Life [CGQL] and Irritable Bowel Syndrome-Quality of Life [IBS-QOL]), daily functional impairment (WSAS), coping mechanisms (brief COPE) and anxiety/depression (DASS-21). Of 243 patients surveyed, 157 (64.6%) completed the surveys, of whom 137 (56.4%) met inclusion criteria and were included in the analysis. Sixty-one percent of respondents had pouch inflammation (pouchitis, N = 35; cuffitis, N = 14; and Crohn's disease of the pouch, N = 35), 20% had IPS (N = 27) and 19% (N = 26) had asymptomatic normal pouches. The age of participants ranged from 20 to 79 years with the mean ages of patients with normal pouches, IPS and inflammatory pouch conditions being 51.7 ± 12.5, 47.1 ± 15.0, 47.2 ± 15.1 years, respectively. Patients with IPS were more likely to be taking antidepressants, anxiolytics, or narcotics than the other groups (P < 0.04). Patients with IPS or inflammatory pouches had significantly poorer quality of life (CGQL, P < 0.001; IBS-QOL, P < 0.003) than those with asymptomatic pouches, with differences particularly in the areas of food avoidance, activity interference, and sexual difficulties. Those with IPS (median = 11; interquartile range [IQR]: 3-19) or inflammatory pouch conditions (median = 7; IQR: 3-18) had a greater impairment in the domains of daily functioning related to the pouch condition than those with normal pouches (median = 1.5; IQR: 0-6; P = 0.003). The mean depression symptom scores were significantly higher in the IPS group than in the normal pouch group (11.7 ± 9.7 versus 4.4 ± 6.2; P = 0.012). IPS patients were more likely to have depressive symptoms and had a greater amount of impairment in daily functioning related to their pouch condition. Additionally, patients with functional pouch disorders are more likely to be concurrently treated with antidepressants, anxiolytic or narcotic agents than those with inflammatory pouches or normal pouches.

Serum Anti-GP2 Antibody Isoforms 1 and 4 Are associated With Crohnʼs Disease of the Pouch in Patients With Ileal-Pouch Anal Anastomosis (IPAA)

Introduction: IPAA is the standard therapy for ulcerative colitis (UC) patients requiring colectomy. Inflammatory and non-inflammatory complications of the ileal pouch are common. Serologic antimicrobial antibodies, such as pANCA, cBir1 or anti-glycan antibodies have been linked to pouchitis in IPAA subjects, but limited accuracy restricts their clinical use. Zymogen granule glycoprotein 2 (GP2) is the major autoantigen of CD-specific pancreatic autoantibodies. We tested two novel serologic anti-GP2 isoforms for association with pouch disorders in a cross-sectional analysis in IPAA patients. Methods: 157 serum samples of 143 consecutive and eligible pouch patients (mean age 43.6 +/- 13.4 years, 45.5% female) were obtained from the pouch clinic of a tertiary academic center. Serial samples were available for 13 subjects. Pouch disorders were diagnosed based on clinical, endoscopic, histologic and radiographic criteria. Presence of Anti-GP2 IgG and IgA Isoforms 1 & 4 was tested in serum samples using enzyme-linked immunosorbent assay (ELISA). Clinical data was recorded prospectively (pre-operative diagnosis, indication for colectomy, pouch type, pouch complications). Analysis was performed using Kruskal-Wallis, Pearson's chi square, Wilcoxon signed rank or Fisher's exact tests. Results: Median interval from construction of IPAA to sample procurement was 7.1 years (25th percentile 2.1; 75th percentile 13.2). 89.5% of participants had a J-pouch. Upon sample procurement, patient phenotypes included: normal pouch n=66, irritable pouch syndrome n=5, acute pouchitis n=17, refractory pouchitis n=24, CD of the pouch n=16, cuffitis n=30, other n=22. Presence of Anti-GP2 IgG Isoform 1 (p < 0.001) & 4 (p < 0.001) and Anti-GP2 IgA Isoform 1 (p=0.022) & 4 (p < 0.001) was associated with CD of the pouch. Presence of Anti-GP2 IgG Isoform 4 was linked to cuffitis (p=0.006). No marker was associated with pre-operative CD. Median interval time between serum procurement in IPAA subjects with serial samples was 3 months. There was no significant change in serum levels of Anti-GP2 antibodies over time. Conclusion: This study demonstrates a link between the two isoforms of Anti-GP2 antibodies with CD of the pouch in IPAA patients. Anti-GP2 was not associated with a pre-operative diagnosis of CD and anti-GP2 levels were stable over time. Serologic anti-GP2 antibodies could aid in diagnosis of CD of the pouch after IPAA.

Clinical Course of Cuffitis in Ulcerative Colitis Patients with Restorative Proctocolectomy and Ileal Pouch–Anal Anastomoses

Cuffitis, considered a form of reminiscent ulcerative colitis (UC), is one of the common complications of ileal pouch-anal anastomosis (IPAA) and its disease course has not been systematically characterized. The aim was to examine the disease course of cuffitis in a large historical cohort. All patients with cuffitis diagnosed based on a combined evaluation of symptom and pouch endoscopy at the initial visit to our Pouchitis Clinic were included. Pouch patients with diagnoses other than cuffitis served as controls. Patients with familial adenomatous polyposis were excluded. A total of 120 patients with cuffitis were included. The control group consisted of 811 patients (normal pouch, n = 85; irritable pouch syndrome, n = 155; acute pouchitis, n = 170; chronic pouchitis, n = 128; Crohn's disease [CD] of the pouch, n = 185; and surgical complications, n = 88). After a median follow-up of 6 years (interquartile range: 3-10 years) after pouch construction, there were 40 (33.3%) having 5-aminosalicylate (5-ASA)/steroid-responsive cuffitis; 22 (18.3%) having 5-ASA/steroid-dependent cuffitis, and 58 (48.4%) developing 5-ASA/steroid-refractory cuffitis. Further investigation of the 58 patients with refractory cuffitis showed that 19 (32.8%) had CD of the pouch and 14 (24.1%) had surgical complications including fistulae and anastomotic sinuses. There were 16 (13.3%) cuffitis patients who developed pouch failure during the follow-up period. Cuffitis may represent a spectrum of diseases. In patients with refractory cuffitis, a diagnosis of CD or surgery-associated anal transitional zone complications should be considered.

Correlation between serum serotonin and endoscopy inflammation scores in patients with ileal pouches

BackgroundInflammatory and functional complications are common in patients with inflammatory bowel disease (IBD) after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA). The pathogenesis of these complications remains poorly understood, and there is discrepancy between the clinical symptoms and objective endoscopic inflammation scores in these patients. While serum serotonin level has been reported to be associated with symptoms of irritable bowel syndrome, its association with ileal pouch disorders has not been studied. AimTo investigate the association between serum serotonin level and symptoms and endoscopic inflammation in patients with IPAA. MethodsA total of 185 consecutive eligible IPAA patients who presented to a specialized Pouchitis Clinic from Jan 2009 to May 2009 were prospectively recruited. Patients were divided into 4 groups: normal pouch, irritable pouch syndrome (IPS), inflammatory pouch disorders (Crohn's disease, acute and chronic pouchitis, and cuffitis), and surgical complications. Serum serotonin level was measured and analyzed for correlation with clinical and endoscopic inflammation scores. ResultsDemographic and clinical variables were evaluated, including age, gender, smoking history, duration of UC, duration of the pouch, and disease category of the pouch. The median fasting serum serotonin level was comparable among the 4 groups: 94.0ng/ml (interquartile range [IQR], 70.0, 128.1), 89.2ng/ml (IQR 54.2, 155.9), 90.3ng/ml (IQR 49.7, 164.1), 77.9ng/ml (IQR 54.7, 129.0), for normal pouch, irritable pouch, inflammatory pouch disorders, and surgical complication groups, respectively (p=0.91). A significant association between serum serotonin level and the Pouchitis Disease Activity Index (PDAI) endoscopy subscore of the pouch (odds ratio [OR]=1.9, 95% confidence interval [CI]: 1.2, 2.9, p<0.05) and total PDAI endoscopy score (OR=1.8; 95% CI: 1.2, 2.8, p<0.05) in the inflammatory complication group were noted. ConclusionsSerum serotonin level appears to correlate with the PDAI endoscopy subscores and total PDAI score in patients with inflammatory complications suggesting that the hormone may be involved in mechanisms of mucosal inflammation. These findings may promote future treatment strategies for patients with pouch inflammation.

Ileal Pouch-Anal Anastomosis: A Gastroenterology Perspective

Total proctocolectomy with an ileal pouch-anal anastomosis (IPAA) is the treatment of choice in medically refractory ulcerative colitis. Patients with an IPAA are at risk of developing pouch disorders, ranging from pouchitis, Crohn disease of the pouch, cuffitis, pouch neoplasia, and irritable pouch syndrome. Pouchitis is an aberrant mucosal immune response to altered luminal microflora and constitutes the leading cause of pouch dysfunction. A combination of clinical, serologic, and genetic factors may predict the likelihood of developing pouchitis. Endoscopy remains the gold standard in diagnosing pouch disorders. Inflammatory markers in blood as well as stool are useful in monitoring disease activity and can be followed for accurate prognostication. Most patients with pouchitis respond to a course of antibiotics; however, a few develop chronic relapsing pouchitis that may require long-term antibiotics or probiotics. All patients with chronic antibiotic refractory pouchitis should undergo evaluation for underlying enteric infections as well as Crohn disease. Treatment of Crohn disease of the pouch may require immunomodulators or biological agents. IPAA decreases but does not eliminate the risk of subsequent neoplasia in the residual rectal mucosa or the pouch itself. A systematic approach to diagnosing and classifying pouch disorders is imperative in managing patients' post-IPAA.

Suppurative granulomatous inflammation in the ileo-anal pouch

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.

Mo1706 Psychological Factors in Irritable Pouch Syndrome and Other Pouch Disorders

Mo1706 Psychological Factors in Irritable Pouch Syndrome and Other Pouch Disorders

Acute and chronic pouchitis—pathogenesis, diagnosis and treatment

Restorative proctocolectomy with ileal pouch-anal anastomosis has become the procedure of choice for the majority of patients with ulcerative colitis who require surgical treatment. Pouchitis, the most common long-term complication of the procedure, involves a spectrum of disease processes with heterogeneous risk factors, clinical features, disease courses and prognoses. In addition, clinical symptoms of pouchitis are not specific and often overlap with those of other inflammatory and functional pouch disorders, such as Crohn's disease of the pouch and irritable pouch syndrome. Pouchoscopy and biopsy, along with laboratory and radiographic evaluations, are often required for accurate diagnosis in patients with symptoms indicative of pouchitis. Dysbiosis has been implicated as a triggering factor for pouchitis, and concurrent infection with pathogens, such as Clostridium difficile, might contribute to disease relapse and exacerbation. Antibiotic therapy is the main treatment modality. However, the management of antibiotic-dependent and antibiotic-refractory pouchitis remains challenging. Secondary causes of pouchitis, such as ischaemia, NSAID use, the presence of concurrent primary sclerosing cholangitis and other systemic immune-mediated disorders, should be evaluated and properly managed.

Diagnosis and treatment of pouchitis and pouch dysfunction

Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) has become the surgical treatment of choice for patients with medically refractory ulcerative colitis (UC) or UC with dysplasia and for the majority of patients with familial adenomatous polyposis. However, UC patients with IPAA are susceptible to a number of inflammatory and non-inflammatory sequelae, such as pouchitis, Crohn disease(CD) of the pouch, cuffitis, and irritable pouch syndrome, in addition to common surgery-associated complications, which adversely affect the surgical outcome and compromise patient's health-related quality of life. Pouchitis is the most frequent long-term complication of IPAA in patients with UC, with a cumulative prevalence of up to 50%. Pouchitis may be classified based on the etiopathogenesis into "idiopathic" and "secondary" types and the management is often different. Pouchoscopy is the most important tool for the diagnosis and differential diagnosis in patients with pouch dysfunction. Antibiotic therapy is the main stay of treatment for active pouchitis. Some patients may develop dependency on antibiotics, requiring long-term maintenance therapy. While management of antibiotic-dependent or antibiotic-refractory pouchitis has been challenging, secondary etiology for pouchitis should be evaluated and modified, if possible.

Utility of fecal and serum anti-Saccharomyces cerevisiae antibodies in the diagnosis of Crohn’s disease-like condition of the pouch

Fecal antibodies against bacterial products may directly reflect the interaction between luminal bacteria and mucosal immunity, and assays for these antibodies may be clinically useful in the diagnosis and differential diagnosis of Crohn's disease-like (CDL) condition of the pouch. This study aims to evaluate stool and serum anti-Saccharomyces cerevisiae antibodies (ASCA) in normal and diseased pouches, to assess the correlation between ASCA levels and endoscopic disease activity, and to ascertain the diagnostic utility of ASCA for CDL of the pouch. One hundred eighty-nine patients with ileal pouches were prospectively enrolled and corresponding serum and pouch aspirate samples were collected. Fecal and serum ASCA levels were measured with enzyme-linked immunosorbent assay in a blinded fashion. Statistical analysis was then conducted using the signed rank test, Spearman correlation coefficients, and analysis of variance. Forty-three patients (22.8 %) had irritable pouch syndrome or normal pouches, 74 (39.2 %) had pouchitis/cuffitis, 52 (27.5 %) had CDL, 9 (4.8 %) had familial adenomatous polyposis, and 11 (5.8 %) had surgical complications of the pouch. Receiver operating characteristic curves to distinguish CDL from other categories of pouch dysfunction had an area under the curve (AUC) of 0.608 for fecal ASCA and an AUC of 0.517 for serum ASCA. Neither fecal nor serum ASCA correlated with endoscopic disease activity scores. There was a significant difference in the mean values of fecal ASCA between inflammatory and fistulizing CDL (0.27 vs. 0.03 ELISA units/ml, P < 0.05). Fecal ASCA appears to be better than serum ASCA in differentiating CDL from other pouch disorders, although this distinction may be of limited clinical utility.

Role of surgery in severe ulcerative colitis in the era of medical rescue therapy

Despite the growing use of medical salvage therapy, colectomy has remained a cornerstone in managing acute severe ulcerative colitis (ASC) both in children and in adults. Colectomy should be regarded as a life saving procedure in ASC, and must be seriously considered in any steroid-refractory patient. However, colectomy is not a cure for the disease but rather the substitution of a large problem with smaller problems, including fecal incontinence, pouchitis, irritable pouch syndrome, cuffitis, anastomotic ulcer and stenosis, missed or de-novo Crohn's disease and, in young females, reduced fecundity. This notion has led to the widespread practice of offering medical salvage therapy before colectomy in most patients without surgical abdomen or toxic megacolon. Medical salvage therapies which have proved effective in the clinical trial setting include cyclosporine, tacrolimus and infliximab, which seem equally effective in the short term. Validated predictive rules can identify a subset of patients who will eventually fail corticosteroid therapy after only 3-5 d of steroid therapy with an accuracy of 85%-95%. This accuracy is sufficiently high for initiating medical therapy, but usually not colectomy, early in the admission without delaying colectomy if required. This approach has reduced the colectomy rate in ASC from 30%-70% in the past to 10%-20% nowadays, and the mortality rate from over 70% in the 1930s to about 1%. In general, restorative proctocolectomy (ileoanal pouch or ileal pouch-anal anastomosis), especially the J-pouch, is preferred over straight pull-through (ileo-anal) or ileo-rectal anastomosis, which may still be considered in young females concerned about infertility. Colectomy in the acute severe colitis setting, is usually performed in three steps due to the severity of the inflammation, concurrent steroid treatment and the generally reduced clinical condition. The first surgical step involves colectomy and constructing an ileal stoma, the second - constructing the pouch and the third - closing the stoma. This review focuses on the role of surgical treatment in ulcerative colitis in the era of medical rescue therapy.

Evaluation of Upper and Lower Gastrointestinal Histology in Patients with Ileal Pouches

BackgroundInflammatory complications of ileal pouch–anal anastomosis (IPAA), including pouchitis and Crohn’s disease (CD) of the pouch, are common in patients with restorative proctocolectomy for ulcerative colitis. It is not clear whether these inflammatory conditions can affect upper GI tract. The aim of the study was to evaluate correlation between duodenal and pouch histology in patients with healthy and diseased pouches. MethodsAll IPAA patients who had esophagogastroduodenoscopy with biopsy after colectomy (N = 96) were included. H&E slides of gastric, duodenal, neo-terminal ileum, and pouch body biopsies were blindly re-reviewed by an expert GI pathologist for acute and chronic inflammation. Demographic and clinical variables and pouch outcome were analyzed. ResultsThere was a significant correlation between acute inflammation in the duodenum as measured by neutrophil infiltration score and the presence of chronic pouchitis (kappa coefficient = 0.21, P < 0.05). Intraepithelial lymphocytosis of the duodenum, though uncommon, only occurred in patients with irritable pouch syndrome, chronic pouchitis, or CD of the pouch. Crypt distortion of duodenal epithelium was only seen in patients with inflammatory or structural diseases of the pouch, including acute (18.2%) and chronic (5%) pouchitis, CD of the pouch (14.3%), and surgical complications of the pouch (14.4%). ConclusionHistologic evaluation of duodenal biopsy may provide additional information in patients with ileal pouches, as patients with normal histology of the pouch may have an abnormal duodenal histology.

Transmural inflammation is not pathognomonic for Crohn’s disease of the pouch

Transmural inflammation shown by imaging and histology has been considered a hallmark of Crohn's disease (CD). However, the diagnostic and prognostic value of this feature in CD of the pouch has not been evaluated. This study aimed to evaluate the clinical utility of transmural inflammation in patients with ileal pouch-anal anastomosis (IPAA) using in vivo optical coherence tomography (OCT) and histopathology. All the patients were recruited from the subspecialty Pouchitis Clinic. The study consisted of two parts: (1) a prospective study with in vivo through-the-scope OCT for the evaluation of transmural disease in patients with normal or diseased pouches and (2) a retrospective pathology re-review for transmural inflammation in excised pouch specimens of CD and chronic pouchitis. This prospective OCT study enrolled 53 patients: 11 (20.8%) with normal pouches or irritable pouch syndrome, 10 (18.9%) with acute pouchitis, 11 (20.8%) with chronic antibiotic-refractory pouchitis (CARP), and 21 (39.6%) with CD of the pouch. Transmural inflammation, characterized by the loss of layered structure on OCT, was detected in 16 patients (30.2%): 4 with chronic pouchitis and 12 with CD of the pouch. None of the patients with normal pouches, irritable pouch syndrome, or acute pouchitis had transmural disease shown on OCT. Of the 26 patients with pouch failure who had pouch excision, the surgical specimens showed transmural disease in 30% of the CARP patients (3/10) and 12.5% (2/16) of those with CD of the pouch. Transmural disease in the setting of IPAA is not pathognomonic of CD. Transmural inflammation shown by imaging or histopathology was seen in both CD and CARP. Transmural inflammation of the pouch appeared to be associated with poor pouch outcome.

Irritable pouch syndrome is characterized by visceral hypersensitivity

Irritable pouch syndrome (IPS) is a functional disorder in patients with ileal pouch-anal anastomosis (IPAA), which presents with symptoms in the absence of structural abnormalities of the pouch. Thus, it resembles other functional disorders, such as irritable bowel syndrome characterized by visceral hypersensitivity in the presence of normal rectal biomechanics. The aim was to assess pouch biomechanics and perception of balloon distension in different groups of subjects with IPAA and to correlate the findings with clinical features. Pouch tone, compliance, and sensation to balloon distension were measured in 18 patients with IPS, 11 patients with active pouch inflammation (pouchitis or Crohn's disease of the pouch), and 12 asymptomatic subjects with normal pouches. All patients were recruited from a subspecialty Pouchitis Clinic. Scores of sensation of gas, urge to defecate, and pain measured by visual analog scales at various distension pressures were significantly higher in IPS than pouchitis and normal pouch patients. Pouch tone was comparable among the groups and compliance was reduced in the pouchitis group. The visual analog scale showed a trend of correlation with the Pouchitis Disease Activity Index symptom scores in IPS. IPS, like other gut functional disorders, is characterized by visceral hypersensitivity, with normal pouch biomechanics.

Risks and benefits of ileal pouch–anal anastomosis for ulcerative colitis

Restorative proctocolectomy with ileal pouch–anal anastomosis (IPAA) is the surgical treatment of choice for patients with medically refractory ulcerative colitis (UC) or UC with dysplasia, and for the majority of patients with familial adenomatous polyposis. Colectomy substantially reduces the risk for UC-associated colonic neoplasia and for the long-term need of immunosuppressive medications. The pouch procedure is a safe operation, with a low postoperative mortality rate at 0–1%, which significantly improves patients’ quality of life. However, patients with IPAA are susceptible to a number of surgical/mechanical, inflammatory and functional complications, such as anastomotic leaks, pelvic sepsis, pouchitis, Crohn’s disease of the pouch, cuffitis and irritable pouch syndrome. IPAA may also impact the patient’s sex life and fertility. There is also a small risk for the development of neoplasia of the anal transitional zone. These complications adversely affect the outcome and compromise the improvement i...

Diagnosis and Management of Pouchitis and Ileoanal Pouch Dysfunction

Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) has become the surgical treatment of choice for patients with medically refractory ulcerative colitis (UC) or UC with dysplasia and for the majority of patients with familial adenomatous polyposis. However, UC patients with IPAA are susceptible to inflammatory and noninflammatory sequelae, such as pouchitis, Crohn's disease of the pouch, cuffitis, and irritable pouch syndrome, in addition to common surgery-associated complications, which adversely affect the surgical outcome and compromise health-related quality of life. Pouchitis is the most frequent long-term complication of IPAA in patients with UC, with a cumulative prevalence of up to 50%. Pouchitis may be classified based on the etiology into idiopathic and secondary types, and the management is often different. Pouchoscopy is the most important tool for the diagnosis and differential diagnosis in patients with pouch dysfunction. Antibiotic therapy is the mainstay of treatment for active pouchitis. Some patients may develop dependency on antibiotics, requiring long-term maintenance therapy. Although management of antibiotic-dependent or antibiotic-refractory pouchitis has been challenging, secondary etiology for pouchitis should be evaluated and modified, if possible.

Pyloric gland metaplasia and pouchitis in patients with ileal pouch‐anal anastomoses

Diagnosis and management of chronic antibiotic-refractory pouchitis and Crohn's disease of the pouch can be challenging. Pyloric gland metaplasia is a histological feature indicative of chronic mucosal inflammation. Its value in diagnosis and prognosis of pouch disorders has not been investigated. To assess the prevalence, diagnostic and prognostic value, and risk factors of pyloric gland metaplasia in pouch patients. Patients were identified from our prospectively maintained Pouchitis Database. Pouch biopsy specimens were re-reviewed for pyloric gland metaplasia and other histological features. Two cohorts of patients were studied: a historical cohort (n = 111) and the second, a validation cohort (n = 100). Univariate and multivariate analyses were performed to assess risk factors for pyloric gland metaplasia. The prevalence of pyloric gland metaplasia in the historical cohort and validation cohort was 45 (40.1%) and 24 (24.0%), respectively. The sensitivity and specificity of pyloric gland metaplasia for the diagnosis of chronic antibiotic-refractory pouchitis or Crohn's disease were 70.7% and 92.5%, respectively, for the first cohort and 39.0% and 86.4%, respectively, for the 2nd validation cohort. In multivariate analysis of the first cohort, patients with refractory pouchitis or Crohn's disease were 28 times (95% CI, 7.3-107.1) more likely to have pyloric gland metaplasia than those with a normal pouch or irritable pouch syndrome. The factor of refractory pouchitis or Crohn's disease remained in the model for the 2nd validation cohort with odds ratio of 4.58 (95% CI, 1.6-13.4). Pyloric gland metaplasia is associated with diagnosis of chronic antibiotic-refractory pouchitis or Crohn's disease of the pouch and appears to be a specific marker for both disease entities.