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.

Perceived dietary intolerances, habitual intake and diet quality of patients with an ileoanal pouch: Associations with pouch phenotype (and behaviour).

BACKGROUND AND AIMS: Ileoanal pouch patients frequently attribute pouch-related symptoms and pouchitis with diet. We aimed to assess perceived food intolerance and habitual dietary intake and their relationship with pouch indication, symptoms and current or history of pouchitis. METHODS: In this cross-sectional study, patients with an ileoanal pouch completed a dietary intolerance and a food frequency questionnaire, that specifically quantifies habitual intake of FODMAPs. Perceived dietary intolerance rates, nutrient intake and diet quality, and their differences based on pouch indication, symptom, and current or history of pouchitis were assessed. Associations between intolerances and intake, and between dietary intake with pouchitis risk were analysed using univariable and multivariable regression analysis. RESULTS: Of the 58 (10 FAP and 48 UC) patients with complete data, 81% of UC and 80% of FAP patients reported dietary intolerances. Overall diet quality was good. Differences in dietary intake were limited to a few food groups. Patients with a history of pouchitis had a lower intake of fruits (p = 0.03) and nuts (p = 0.004). Patients with current pouchitis had a lower intake of nuts (p = 0.02). On multivariable logistic regression, intake of dietary fibre was associated negatively [OR 0.68(95%CI:0.51-0.92)] and of non-digestible oligosaccharides positively with pouchitis history [OR 5.5(95% CI:1.04-29.1)]. CONCLUSIONS: In patients with an ileoanal pouch, perceived dietary intolerances are common but had minimal impact on nutritional adequacy and diet quality. Negative associations of the intakes of fruits, nuts and dietary fibre and positive association with non-digestible oligosaccharides with a history of pouchitis require further study to inform dietary recommendations.

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.

Shedding New Light on High-Risk Phenotypes for Pouchitis.

Identifying those patients at the greatest risk for pouchitis at the time of ileal pouch-anal anastomosis for ulcerative colitis remains a challenge. We discuss the importance of this topic by reviewing recent data regarding the impact of acute severe ulcerative colitis on risk of pouchitis and the implications for future clinical decisions and studies of risk stratification.

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.

A Case of Severe Lumbar Necrotizing Soft Tissue Infection from an Ileal Pouch Fistula.

BACKGROUND: Necrotizing soft tissue infection (NSTI) is a rapidly progressive infection characterized by tissue necrosis, septic shock, and is associated with a high risk of death. Key aspects of successful treatment include early recognition and emergent surgical source control. Necrotizing soft tissue infection may occur from a range of etiologies but may also occur rarely from gastrointestinal routes. We report a case of severe lumbar NSTI arising from an ileal pouch fistula in a patient with inflammatory bowel disease. We report a case of a 62-year-old male with a history of ulcerative colitis and restorative proctocolectomy who presented with a severe NSTI of the lumbar region. METHODS: Our operative approach focused on debridement of infected necrotic tissue and abscess drainage to achieve source control. We elected to forego a transabdominal approach during the initial operation given that source control but not source elimination was deemed the initial priority. RESULTS: The patient subsequently underwent a diverting ileostomy and pouch salvage. After a prolonged hospital course, the patient recovered well. CONCLUSIONS: Fistulization from the gastrointestinal tract is a rare but potential source of NSTI. It is not necessary to address the fistula during the initial operation but should be done promptly after the patient stabilizes. Prompt surgical debridement of infected soft tissue as source control remains the cornerstone of the index operation.

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.

Endoluminal calprotectin measurement in assessment of pouchitis and a new index of disease activity: a pilot study

Pouchitis is the most common complication following proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis (UC). To provide a standardized definition of pouchitis clinical, endoscopic and histological markers were grouped and weighted in the pouch disease activity index (PDAI). However, the delay in the assessment of the final score due to the time requested for histological analysis remains the main obstacle to the index implementation in clinical practice so that the use of modified- PDAI (mPDAI) with exclusion of histologic subscore has been proposed. We tested the ability of calprotectin measurement in the pouch endoluminal content to mimic the histologic score as defined in the PDAI, the index that we adopted as gold standard for pouchitis diagnosis. Calprotectin was measured by ELISA in the pouch endoluminal content collected during endoscopy in 40 consecutive patients with J-pouch. In each patient PDAI and mPDAI were calculated and 15% of patients were erroneously classified by mPDAI. ROC analysis of calprotectin values vs. acute histological subscore ≥ 3 identified different calprotectin cut-off values with corresponding sensitivity and specificity allowing the definition and scoring of different range of calprotectin subscores. We incorporated the calprotectin score in the mPDAI obtaining a new score that shows the same specificity as PDAI for diagnosis of pouchitis and higher sensitivity when compared with mPDAI. The use of the proposed new score, once validated in a larger series of patients, might be useful in the early management of patients with symptoms of pouchitis (AU)

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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.

Risk factors and management of refractory or recurrent clostridium difficile infection in ileal pouch patients.

BACKGROUND: Clostridium difficile infection (CDI) is increasingly recognized in patients with ulcerative colitis with ileal pouch-anal anastomosis (IPAA). The aim of this study was to identify clinical risk factors for treatment-refractory or recurrent CDI in patients with IPAA. METHODS: We identified patients with IPAA for underlying ulcerative colitis and a positive polymerase chain reaction stool test for C. difficile at the Center for Ileal Pouch Disorders during the period from October 2010 to November 2013. Demographic clinical variables were compared between the refractory or recurrent CDI and nonrecurrent CDI groups. RESULTS: Patients with IPAA with refractory or recurrent symptoms (refractory/recurrent CDI, the study group, N = 19) were compared with patients with a single antibiotic-responsive episode of ileal pouch CDI (nonrecurrent CDI, the control group, N = 21). The frequency of pouchitis before the index CDI was similar in the study and control groups (63.2% versus 66.7%, P = 0.82). Postoperative mechanical abnormalities occurred in 16 patients (84.2%) in the study group versus 7 patients (33.3%) in the control group (P = 0.0008). There were no differences between the two groups regarding hospitalization, non-C. difficile antibiotic use, the use of gastric acid-reducing therapy, or immunosuppressives before or after the index CDI. Six of 15 patients (40.0%) in the study group versus 1 of 15 patients (7.1%) in the control group had a low serum level of IgG1 (P = 0.031). CONCLUSIONS: Refractory or recurrent disease is common in patients with ileal pouch with CDI. The presence of postsurgery mechanical intestinal complications or low serum immunoglobulin level may be risk factors for refractory or recurrent CDI in this patient population.

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.