Preoperative Use of Multiple Advanced Therapies Is Not Associated With Endoscopic Inflammatory Pouch Diseases.

BACKGROUND: Patients with an ileal pouch-anal anastomosis (IPAA) can experience pouch inflammation postoperatively. The use of antitumor necrosis factor (anti-TNF) biologics may be associated with pouch inflammation, but limited data exist on the impact of multiple advanced therapies on development of subsequent pouch inflammation. The aim of this study was to assess for an association between preoperative use of multiple advanced therapies and risk of endoscopically detected inflammatory pouch diseases (EIPDs). METHODS: We performed a retrospective analysis of ulcerative colitis (UC) and indeterminate colitis (IBDU) patients who underwent an IPAA at a quaternary care center from January 2015 to December 2019. Patients were grouped based on number and type of preoperative drug exposures. The primary outcome was EIPD within 5 years of IPAA. RESULTS: Two hundred ninety-eight patients were included in this analysis. Most of these patients had UC (95.0%) and demonstrated pancolonic disease distribution (86.1%). The majority of patients were male (57.4%) and underwent surgery for medically refractory disease (79.2%). The overall median age at surgery was 38.6 years. Preoperatively, 68 patients were biologic/small molecule-naïve, 125 received anti-TNF agents only, and 105 received non-anti-TNF agents only or multiple classes. Ninety-one patients developed EIPD. There was no significant association between type (P = .38) or number (P = .58) of exposures and EIPD, but older individuals had a lower risk of EIPD (P = .001; hazard ratio, 0.972; 95% confidence interval, 0.956-0.989). CONCLUSION: Development of EIPD was not associated with number or type of preoperative advanced therapies.

Predictors of pouch failure: A tertiary care inflammatory bowel disease centre experience.

AIM: Rates of pouch failure after total proctocolectomy with ileal pouch-anal anastomosis (IPAA) range from 5% to 18%. There is little consistency across studies regarding the factors associated with failure, and most include patients who underwent IPAA in the pre-biologic era. Our aim was to analyse a cohort of patients who underwent IPAA in the biologic era at a large-volume inflammatory bowel disease institution to better determine preoperative, perioperative and postoperative factors associated with pouch failure. METHODS: A retrospective cohort analysis was performed with data from an institutional review board approved prospective database with ulcerative colitis or unclassified inflammatory bowel disease patients who underwent total proctocolectomy with IPAA at Mount Sinai Hospital between 2008 and 2017. Preoperative, perioperative and postoperative data were collected and univariate and multivariate analyses were performed to identify factors associated with increased risk of pouch failure. RESULTS: Out of 664 patients included in the study, pouch failure occurred in 41 (6.2%) patients, a median of 23.3 months after final surgical stage. Of these, 17 (41.4%) underwent pouch excision and 24 (58.5%) had diverting ileostomies. The most common indications for pouch failure were Crohn's disease like pouch inflammation (CDLPI) (n = 17, 41.5%), chronic pouchitis (n = 6, 14.6%), chronic cuffitis (n = 5, 12.2%) and anastomotic stricture (n = 4, 9.8%). On multivariate analysis, pre-colectomy biologic use (hazard ratio [HR] 2.25, 95% CI 1.09-4.67), CDLPI (HR 3.18, 95% CI 1.49-6.76) and pouch revision (HR 2.59, 95% CI 1.26-5.32) were significantly associated with pouch failure. CONCLUSIONS: Pouch failure was significantly associated with CDLPI, preoperative biologic use and pouch revision; however, reassuringly it was not associated with postoperative complications.

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

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

Early Pouchitis Is Associated With Crohn's Disease-like Pouch Inflammation in Patients With Ulcerative Colitis.

BACKGROUND: Despite the initial diagnosis of ulcerative colitis (UC), approximately 10% to 20% of patients develop Crohn's disease-like pouch inflammation (CDLPI) after restorative proctocolectomy (RPC) with ileal pouch anal anastomosis (IPAA). The aim of this study was to evaluate whether early pouchitis, defined as pouchitis within the first year after IPAA, is a predictor of CDLPI. METHODS: This was a retrospective cohort analysis of patients with UC or IBD unclassified (IBDU) who underwent RPC with IPAA at Mount Sinai Hospital between January 2008 and December 2017. The primary outcome was development of CDLPI. Predictors of CDLPI were analyzed via univariable and multivariable Cox regression models. RESULTS: The analytic cohort comprised 412 patients who underwent at least 1 pouchoscopy procedure between 2009 and 2018. Crohn's disease-like pouch inflammation developed in 57 (13.8%) patients a median interval of 2.1 (interquartile range, 1.1-4.3) years after surgery. On univariable analysis, older age at colectomy (hazard ratio [HR], 0.97; 95% CI, 0.95-0.99) was associated with a reduced risk of CDLPI; although early pouchitis (HR, 2.43; 95% CI, 1.32-4.45) and a greater number of pouchitis episodes (HR, 1.38; 95% CI, 1.17-1.63) were associated with an increased risk. On multivariable analysis, early pouchitis (HR, 2.35; 95% CI, 1.27-4.34) was significantly associated with CDLPI. Time to CDLPI was significantly less in patients who developed early pouchitis compared with those who did not (P = .003). CONCLUSION: Early pouchitis is significantly associated with subsequent CDLPI development and may be the first indication of enhanced mucosal immune activation in the pouch.

In a retrospective cohort analysis of 412 patients with ulcerative colitis who underwent restorative proctocolectomy with ileal pouch anal anastomosis, early pouchitis that occurred within the first year after surgery was significantly associated with subsequent Crohn's disease­like pouch inflammation.

Appendiceal inflammation in colectomy is independently correlated with early pouchitis following ileal pouch anal anastomosis in ulcerative colitis and indeterminate colitis.

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.

Adherence to the Mediterranean diet is associated with decreased fecal calprotectin in patients with ulcerative colitis after pouch surgery.

BACKGROUND: Mediterranean diet (MED) is associated with health benefits, yet scarce data exist regarding the role of MED in inflammatory bowel diseases (IBD). Herein, we aimed to evaluate the association between MED and inflammatory markers in patients with IBD after pouch surgery. METHODS: Consecutive patients after pouch surgery due to ulcerative colitis (UC) were recruited at a comprehensive pouch clinic. Adherence to MED was calculated according to MED score, ranging from 0 (low adherence) to 9 (high adherence), based on food-frequency questionnaires. Pouch behavior was defined as normal pouch (NP) or pouchitis based on Pouchitis Disease Activity Index (PDAI) and disease activity was defined as active or inactive. C-reactive protein (CRP) and fecal calprotectin were assessed. RESULTS: Overall 153 patients were enrolled (male gender 47%; mean age 46 ± 14 years; mean pouch age 9.5 ± 7 years). MED scores were higher in patients with normal vs. elevated CRP and calprotectin levels (4.6 ± 1.8 vs. 4.4 ± 1.6, p = 0.28; 4.8 ± 1.8 vs. 4.07 ± 1.7, p < 0.05, respectively). In a multivariate regression, MED score was associated with decreased calprotectin levels (OR = 0.74 [0.56-0.99]). Adherence to MED was associated with dietary fiber and antioxidants intake. Finally, in a subgroup of patients with NP followed up for 8 years, higher adherence to MED trended to be inversely associated with the onset of pouchitis (log rank = 0.17). CONCLUSIONS: In patients with UC after pouch surgery, adherence to MED is associated with decreased calprotectin levels. Thus, MED may have a role in modifying intestinal inflammation in IBD.

Ustekinumab Is Effective for the Treatment of Crohn's Disease of the Pouch in a Multicenter Cohort.

BACKGROUND: Crohn's disease (CD) of the pouch and chronic pouchitis occur in approximately 10% of patients after ileal pouch-anal anastomosis (IPAA) for refractory ulcerative colitis (UC) or UC-related dysplasia. The efficacy of anti-tumor necrosis factor (anti-TNF) agents and vedolizumab have been reported for the treatment of CD of the pouch and chronic pouchitis, but little is known regarding the use of ustekinumab in these settings. Our primary aim was to evaluate the efficacy of ustekinumab for these conditions. METHODS: This is a retrospective, multicenter cohort study evaluating the efficacy of ustekinumab in patients with CD of the pouch and chronic pouchitis. Clinical response or remission was judged by the treating physician's assessment at 6 months. RESULTS: Fifty-six patients (47 with CD of the pouch and 9 with chronic pouchitis) were included the study. Of these, 73% had previously been treated with either anti-TNF therapy, vedolizumab, or both after IPAA. Among patients with CD of the pouch and chronic pouchitis, 83% demonstrated clinical response 6 months after induction with ustekinumab. Responders demonstrated significantly less pouch inflammation on endoscopy when compared with nonresponders (29% vs 100%; P = 0.023). Higher mean body mass index at induction (26.3 vs 23.7; P = 0.033) and male sex (83% vs 30%; P = 0.014) were significant predictors of nonresponse to ustekinumab in those with CD of the pouch. CONCLUSION: In this refractory patient population, ustekinumab appears to be a safe and effective treatment for chronic pouchitis and CD of the pouch in biologic-naïve patients and those with prior anti-TNF or vedolizumab therapy failure. 10.1093/ibd/izx005_video1 izy302.video1 5844889626001.

Reliability among central readers in the evaluation of endoscopic disease activity in pouchitis.

BACKGROUND AND AIMS: Pouchitis is a common adverse event after proctocolectomy with ileal pouch anal anastomosis for ulcerative colitis. Evaluation of pouchitis disease activity and response to treatment requires use of validated indices. We assessed the reliability of items evaluating endoscopic pouchitis disease activity. METHODS: Twelve panelists used a modified RAND appropriateness methodology to rate the appropriateness of items evaluating endoscopic pouchitis disease activity derived from a systematic review and also identified additional potential endoscopic items based on expert opinion. Four central readers then evaluated 50 pouchoscopy videos in triplicate, in random order. Intra- and inter-rater reliability for each item was assessed by calculating and comparing intraclass correlation coefficients (ICCs). A Delphi process identified common sources of disagreement among the readers. RESULTS: Ten existing endoscopic items were identified from the systematic review and an additional 7 exploratory items from the panelists. ICCs for inter-rater reliability were highest for the existing item of pouch ulceration (.72; 95% confidence interval [CI], .60-.82) and for the exploratory item of ulcerated surface in the pouch body (.67; 95% CI, .53-.75). Inter-rater reliability for all other existing and exploratory items was "moderate" (ICC < .60). The item "ulcerated surface in the pouch body" demonstrated the best correlation with a global evaluation of lesion severity (r = .80; 95% CI, .73-.85). CONCLUSION: Substantial reliability was observed only for the endoscopic items of ulceration and ulcerated surface in the pouch body. Future studies should assess responsiveness to treatment in the next stage toward development of an endoscopic pouchitis disease activity index.

The prevalence of chronic peri-pouch sepsis in patients treated for antibiotic-dependent or refractory primary idiopathic pouchitis.

AIM: Chronic peri-pouch sepsis (CPPS) may be mistaken for antibiotic-dependent or refractory primary idiopathic pouchitis (ADRP), but requires different treatment such as drainage. The study aimed to identify the prevalence of CPPS in patients thought to have ADRP. The secondary aims were to identify any specific features on pouchoscopy suggesting CPPS and to determine the results of treatment for CPPS. METHOD: The records of patients who had been treated for ADRP between March 2006 and June 2015 were reviewed retrospectively. Only those with endoscopic evidence of pouch inflammation who had also undergone MRI of the pelvis were included. The findings on pouchoscopy and the outcome of treatment were determined. RESULTS: Sixty-eight patients (43 men, 63%) were identified with apparent ADRP between March 2006 and June 2015. MRI of the pelvis showed CPPS in 26 (38%). In those with CPPS, the inflammation was more often located in the upper pouch alone (15%) compared with patients without CPPS (0%) (P = 0.0184). Examination under anaesthesia was performed in 13 of those with CPPS. In five a collection was identified and drained; symptoms improved in only one (4%). Eighteen patients (69%) remained on antibiotics and seven (27%) had a defunctioning stoma or underwent pouch excision. CONCLUSION: In patients thought to have ADRP, 38% had CPPS on MRI. There was no clinically relevant specific feature on pouchoscopy suggestive of CPPS. The possibility of CPPS should be considered early in patients with apparent ADRP and pelvic MRI performed. This might lead to earlier detection of CPPS and appropriate treatment.

Tight junctions in inflammatory bowel diseases and inflammatory bowel disease associated colorectal cancer.

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.

IPAA-related sepsis significantly increases morbidity of ileoanal pouch excision.

BACKGROUND: Perineal wound complications after ileoanal pouch excision remain a significant cause of morbidity. OBJECTIVE: The purpose of this work was to describe the incidence, outcomes, and predictors of perineal wound complications after pouch excision. DESIGN: This was a retrospective medical chart review. SETTINGS: The study was conducted in a single clinical institution. PATIENTS: Patients who underwent pouch excision at our institution from July 1992 through July 2012 were identified. Patient and perioperative variables were reviewed. Multivariate and univariate analyses were undertaken. MAIN OUTCOME MEASURES: Perineal wound (including perineal wound infection and persistent perineal sinus [nonhealing by 6 months]) and perineal hernia were measured. RESULTS: A total of 47 patients (mean age, 46 years; 42.6% men) with familial adenomatous polyposis (10.6%), mucosal ulcerative colitis (61.7%), or Crohn's disease (27.7%) underwent pouch excision, including 36.2% for IPAA-related sepsis (presacral abscess; perineal-, sacral-, or pouch-vaginal fistula; and anastomotic defect), 44.7% for pouch dysfunction, 10.6% for refractory pouchitis, and 8.5% for neoplasia. Fourteen (29.8%) developed perineal wound complications, including 100% perineal wound infection, 28.6% persistent perineal sinus, and 7.1% perineal hernia. Perineal wound infection was associated with delayed healing (>6 weeks; 71.4% vs 24.2%; p = 0.002) and IPAA-related sepsis (28.6% vs 0%; p = 0.001). Patients with and without perineal wound complications were similar in age, diagnoses, fecal diversion, immunosuppression, comorbid conditions, nutrition, and surgical variables. Most patients underwent intersphincteric dissection (87.2%) with primary perineal closure (97.0%). Perineal wound complications were significantly associated with IPAA-related sepsis as an indication for pouch excision (57.1% vs 27.2%; p = 0.05), intraoperative pouch perforation (35.7% vs 9.1%, p =0.03), and smoking (21.4% vs 3.0%; p = 0.04). IPAA-related sepsis and a current smoking status (OR, 19.3 [95% CI, 1.8 -488.1]) are significant independent predictors on multivariate logistic regression (OR, 6.4 [95% CI, 1.4-30.2]) of perineal wound complications. All of the patients with persistent perineal sinus achieved successful healing at a median of 734 days (range, 363-2182 days), requiring a median of 1.5 procedures. LIMITATIONS: This was a single-center retrospective review with a small sample size. CONCLUSIONS: Preoperative IPAA-related sepsis and current smoking are significant risk factors for perineal wound complications after pouch excision.

Adenocarcinoma of the ileal pouch mucosa: case report and literature review.

PURPOSE: Cancers developing near the site of the ileoanal pouch anastomosis (IPAA) have been reported, but uncommonly in the ileal pouch mucosa itself. We present a recently encountered case of ileal pouch cancer and review the literature to examine the prevalence, risk factors, and natural history of ileal pouch adenocarcinoma as well as pouch surveillance. METHODS: A chart review of the case from our institution was conducted, and a PubMed search was undertaken for articles describing adenocarcinoma arising from the ileal pouch mucosa. RESULTS: Twenty articles containing 26 cases were reviewed in addition to our described case. More than half were reported in the last decade. Only three cases were definitively stage 1. All seven patients who underwent regular surveillance were diagnosed with stage 1 or 2 disease. Seventeen patients had neoplasia in their original proctocolectomy specimen and six did not. The mean time from pouch creation to adenocarcinoma was 8.9 years. CONCLUSIONS: The risk of developing ileal pouch mucosa adenocarcinoma appears low. However, increasing reports of these cancers are concerning as most patients present with advanced disease after many years. Patients with a previous history of dysplasia/cancer may be at increased risk. We believe surveillance after IPAA should include the anal transition zone and the ileal pouch mucosa. The establishment of expert consensus guidelines on pouch surveillance should be considered in the near future.

Managing intractable proctitis and the problematic pouch.

Proctitis accounts for a significant proportion of cases of ulcerative colitis (UC), and some patients subsequently develop more extensive disease. However, most patients continue to have limited inflammation, although the changes in the distal colon and rectum can occasionally be severe, and symptoms of increased frequency, rectal bleeding and urgency can be as disabling as they are for patients with more extensive colitis. Furthermore, although symptoms are typically well controlled with standard medications, medically refractory proctitis poses particular problems. Patients generally are not systemically unwell, and there is no added fear of cancer. Therefore, the prospect of colectomy for such limited disease is resisted by patients, physicians and surgeons alike. Unusual therapies, often delivered locally by enema or suppository, have been tested in small case series without definitive outcomes. The pathogenesis of such limited, yet intractable inflammation remains unclear, and the differential diagnosis should be carefully reviewed to ensure that local disease, whether it is infectious, vascular, or a result of injury or degeneration, is not overlooked. Ileo-anal pouch formation is the surgery of choice for about 20% of patients with UC who undergo colectomy. In the majority of cases, this surgery results in an acceptable quality of life and freedom from a stoma. However, in a sizeable minority of cases, pouch dysfunction can cause intractable problems. The causes of pouch dysfunction are varied and must all be considered carefully, particularly in refractory cases. Pouchitis is a common issue and is usually transient and easily treated. However, refractory and chronic pouchitis can be challenging. Ischaemia, injury, infection and Crohn's disease can all cause refractory pouch dysfunction. In a minority of cases, there appears to be no apparent organic pathology, and the presumptive diagnosis is that of a functional pouch disorder. Although it is much rarer, neoplastic changes in the pouch must also be considered, and the risk managed appropriately. The management of both intractable proctitis and the problematic pouch is made more challenging by the wide differential diagnosis that must be considered and by the paucity of high-quality clinical trials to support any one therapy. Key strategies to overcoming these limitations include methodical and systematic investigation and review, and a willingness to tailor therapy to the individual patient. Clinical trials of new treatments should be supported, and data from the experience with small cohorts of patients should be meticulously collected, critically analysed and widely disseminated.

Chronic pouchitis is associated with pouch polyp formation in patients with underlying ulcerative colitis.

BACKGROUND: Polypoid lesions can develop in ileal pouches. The risk factors associated with the development of pouch polyps have not been studied. AIM: To characterize clinical features, risk factors, and disease course of pouch polyp in a cohort of patients with underlying inflammatory bowel disease (IBD) from a subspecialty clinic. METHOD: A total of 1094 patients with restorative proctocolectomy and IPAA for IBD presenting to our Pouchitis Clinic from 2002 to 2010 were included. Demographic, clinical, and endoscopic variables were analyzed. RESULTS: The median durations from UC diagnosis to colectomy and from pouch creation to the last follow-up for the whole cohort were 6 (interquartile range [IQR]: 3-13) and 9years (IQR: 5-14), respectively. A total of 2472 surveillance and/or diagnostic pouchoscopies were performed for the cohort with a median follow-up of 5 (IQR: 2-6) years in the Pouchitis Clinic. The median number of pouchoscopies per patient was 2 (IQR: 1-3). Of the 1094 patients, 96 (8.8%) were found to have pouch polyps. The median size of the polyps was 1.2 (IQR: 1.0-2.0) cm. On histology, 93 patients (96.9%) had inflammatory-type polyps and 3 (3.1%) had polyps with low-grade dysplasia or indefinite for dysplasia. Multivariate logistic regression analysis demonstrated that chronic pouch inflammatory change was a risk factor for the development of pouch polyp with an odds ratio of 2.26 (95% confidence interval: 1.35-3.79; P=0.002). CONCLUSION: The majority of pouch polyps in patients with underlying UC were benign. Patients with concomitant chronic pouch inflammatory changes had an increased risk for developing pouch polyps.

Preoperative pelvic radiation increases the risk for ileal pouch failure in patients with colitis-associated colorectal cancer.

BACKGROUND AND AIMS: To evaluate the impact of preoperative radiation on pouch outcomes in patients with colitis-associated cancer (CAC). METHODS: CAC patients who underwent restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) from 1984 to 2009 were identified from our registry. The impact of preoperative pelvic radiation for CAC or other pelvic cancer on pouch related outcomes was evaluated. RESULTS: Sixty-three pouch patients with confirmed CAC were included (37 male, 58.7%). The mean age at pouch construction was 46.9±10.6 years. Seven patients were excluded due to the presence of persistent diverting ileostomy (n=2) or no follow-up (n=5). The remaining 56 patients were analyzed, including 9 who received pelvic radiation prior to IPAA creation for CRC or other cancers. Preoperative pelvic radiation was significantly associated with chronic pouchitis (P=0.024). There was, however, no correlation between pelvic radiation and pouch/anal transitional zone neoplasia, pouch stricture, pelvic abscess and pouch fistula/sinus. Pouch failure occurred in 13 patients after a median follow-up of 66.4 (range: 2.7-322.2) months. Although a simple statistical analysis based on the number of patients with pouch failure did not achieve significance (4/9 vs. 9/47, P=0.19), Kaplan-Meier analysis showed a strong association between preoperative pelvic radiation and the risk for pouch failure (P<0.001). A subgroup analysis of rectal cancer patients revealed that 3/7 patients (42.9%) with radiation and 3/17 (17.6%) without had pouch failure (P=0.31). Again, the association between pelvic radiation and pouch failure was confirmed using Kaplan-Meier analysis (P=0.02). CONCLUSIONS: Pelvic radiation administered prior to IPAA creation appears to be associated with poor pouch outcomes. Oncological benefits and pouch functional outcomes should be carefully balanced before pelvic radiation is considered prior to restorative proctocolectomy.

Seroreactivity to E. coli outer membrane protein C antibodies in active inflammatory bowel disease; diagnostic value and correlation with phylogroup B2 E. coli infection.

BACKGROUND: Several serologic tests, including anti-outer membrane porin C antibody (Omp C), are used for screening and as marker of disease course in inflammatory bowel diseases (IBD). Our aim was to investigate possible differences in Omp C level in patients with active and inactive IBD compared to controls. METHODS: All blood samples were tested for Omp C. Disease activity was evaluated by Harvey Bradshaw Index, Simple Clinical Activity Index and Modified Pouchitis Disease Activity Index. RESULTS: Blood samples were collected from 113 patients and 60 controls. Patients with active IBD did not have a higher level of Omp C than patients in remission. Surprisingly, in patients with active Crohn's disease a significantly lower level of Omp C was found compared with patients with inactive Crohn's disease (p < 0.05). All other groups among patients with IBD did have a significantly higher level of Omp C, compared with controls, including patients with acute gastroenteritis (p < 0.05). Although IBD patients with phylogroup B2 E. coli cultured from their fecal samples, were more likely to have a positive Omp C test (p < 0.05), this could not explain the low Omp C level in the subgroup of patients with active Crohn's disease. CONCLUSIONS: Omp C titer was not raised in patients with active IBD compared with patients in remission. In addition, there was no difference in Omp C level in patients with active Crohn's disease compared with controls. These observations do not support the use of Omp C serology testing, either in disease activity assessment, or in screening for active Crohn's disease.

Tissue infiltration of IgG4+ plasma cells in symptomatic patients with ileal pouch-anal anastomosis.

BACKGROUND: Inflammatory bowel disease (IBD) is reported to be associated with autoimmune pancreatitis. The aim of the study was to investigate serum IgG4 and tissue infiltration of IgG4+ plasma cells in symptomatic patients with ileal pouches. METHODS: Ninety-seven consecutive persistent symptomatic patients with ileal pouches from our subspecialty Pouchitis Clinic from January to December 2010 were included in the study. Serum IgG4 was measured at the time of presentation. All patients underwent pouchoscopy with pouch biopsies immunostained for IgG4+ plasma cells. Patients with ≥10 per high-power field of IgG4+ plasma cells were considered positive for the stain. RESULTS: Twenty-eight (28.9%) patients had positive IgG4 immunostaining of pouch and/or afferent limb biopsy, while the remaining 69 patients (71.1%) were IgG4 negative. Demographic and symptoms were similar between the two groups. The median serum IgG4 in the IgG4 positive group was 21.3 (interquartile range 0-41.3) mg/dL vs. 0 (interquartile range 0-18) in the IgG4 negative group. (p=0.04). On multivariate analysis, the Pouchitis Disease Activity Index (PDAI) endoscopy score in the pouch (odds ratio [OR] 1.66, 95% confidence interval [CI]: 1.21-2.29, p=0.002) and number of concomitant autoimmune disorders (OR 3.04, 95% CI: 1.22-7.53, p=0.017) were independent risk factors for the presence of IgG4+ plasma cell infiltration. CONCLUSIONS: Increased IgG4+ plasma cells were found in 1/4 of IPAA patients with persistent symptoms. The presence of tissue infiltration of IgG4+ plasma cells appeared to be associated with chronic pouch inflammation and concurrent autoimmune disorders.

Elevated serum IgG4 is associated with chronic antibiotic-refractory pouchitis.

BACKGROUND AND AIM: We recently reported mucosal infiltration of IgG4-expressing plasma cells in a patient with chronic antibiotic-refractory pouchitis (CARP). The role of serum IgG4 in the pathogenesis and clinical course of ileal pouch disorders has not been investigated. We hypothesized that IgG4-mediated autoimmunity may be a contributing factor in for CARP. The aims of the study were to investigate the prevalence of elevated serum IgG4 in symptomatic patients with ileal pouches and to characterize clinical features of pouch disorders in these patients. METHODS: A total of 124 consecutive symptomatic patients with ileal pouches from our subspecialty Pouchitis Clinic were enrolled in the study from January to October 2010. Serum IgG4 was measured at the time of presentation. Demographic, clinical, and laboratory characteristics were compared between the study (with serum IgG4 ≥112 mg/dl) and control (with serum IgG4 <112 mg/dl) groups. RESULTS: There were ten patients (8.0%) with high serum IgG4 in the study group, while the remaining 114 (92%) patients were in the control group. The prevalence of elevated serum IgG4 in this series was 8%. None of the patients had a confirmed diagnosis of autoimmune pancreatitis. The median serum IgG4 in the study group was 144.5 vs. 14 mg/dl in the control group. The mean age of patients in the study and control groups was 35.5 ± 14.5 and 42.0 ± 13.2 years, respectively (p = 0.137). Two patients in the study group (20.0%) had concurrent autoimmune disorders as compared to 19 patients (16.7%) in the control group (p = 0.788). Three (30.0%) patients in the study group had coexisting primary sclerosing cholangitis (PSC) in contrast to 15 (13.2%) in the control group (p = 0.147). Among the study group patients, five (50.0%) had CARP and one (10%) had Crohn's disease (CD) of the pouch, while in the control group, 23 (20.2%) had CARP and 24 (21.1%) patients had CD of the pouch (p = 0.273). CARP was more commonly seen in patients with high serum IgG4 than patients with a normal IgG4 (50.0% vs. 20.2%, p = 0.03). CONCLUSIONS: Approximately 8% of pouch patients presenting with symptoms of pouch dysfunction to our clinic had elevated serum IgG4. Patients with elevated serum IgG4 were more likely to have CARP.

Prevalence and clinical implications of positive serum anti-microsomal antibodies in symptomatic patients with ileal pouches.

BACKGROUND AND AIM: Autoimmune disorders (AID) have been shown to be associated with chronic antibiotic-refractory pouchitis (CARP). The role of anti-microsomal antibodies in ileal pouch disorders has not been investigated. The aims of the study were to investigate the prevalence of positive anti-microsomal antibody in symptomatic patients with ileal pouches and to investigate its clinical implications. METHODS: A total of 118 consecutive symptomatic patients with ileal pouches were included between January and October 2010. Anti-microsomal antibodies were measured at the time of presentation. Demographic, clinical, and laboratory characteristics were compared between patients with positive and negative anti-microsomal antibody. RESULTS: There were 14 patients (11.9%) with positive serum anti-microsomal antibody. The mean age of patients in the antibody positive and negative groups were 41.8 ± 14.4 and 42.0 ± 14.0 years, respectively (p = 0.189). All 14 patients in the antibody positive group (100%) had some form of AID, as compared to 20 patients (19.2%) in the antibody negative group (p < 0.001). Four (28.6%) patients in the antibody positive group had at least one AID in addition to Hashimoto's thyroiditis in contrast to four (3.8%) in the antibody negative group (p = 0.003). In addition, five (35.7%) patients had associated primary sclerosing cholangitis (PSC) in the antibody positive group compared to nine (8.7%) in the antibody negative group (p = 0.012). Eleven patients (78.6%) in the antibody positive group required steroids for treatment of pouch related symptoms in contrast to 26/104 (25%) patients in the antibody negative group (p = 0.002). CONCLUSIONS: Anti-microsomal antibodies were common in pouch patients presenting with symptoms. Patients with positive anti-microsomal antibodies were much more likely to have concurrent AID and PSC. These patients were more likely to require therapy with steroids.