Greater Peripouch Fat Area on CT Image Is Associated with Chronic Pouchitis and Pouch Failure in Inflammatory Bowel Diseases Patients.

BACKGROUND: The causes of chronic antibiotic refractory pouchitis (CARP) and pouch failure in inflammatory bowel disease (IBD) patients remain unknown. Our previous small study showed peripouch fat area measured by MRI was associated with pouchitis. AIMS: To explore the relationship between peripouch fat area on CT imaging and pouch outcomes. METHODS: This is a historical cohort study. Demographic, clinical, and radiographic data of IBD patients with abdominal CT scans after pouch surgery between 2002 and 2017 were collected. Peripouch fat areas and mesenteric peripouch fat areas were measured on CT images at the middle pouch level. RESULTS: A total of 435 IBD patients were included. Patients with higher peripouch fat areas had a higher prevalence of CARP. Univariate analyses demonstrated that long duration of the pouch, high weight or body mass index, the presence of primary sclerosing cholangitis or other autoimmune disorders, and greater peripouch fat area or mesenteric peripouch fat area were risk factors for CARP. Multivariable analyses demonstrated that the presence of primary sclerosing cholangitis or autoimmuned disorders, and greater peripouch fat area (odds ratio [OR] 1.031; 95% confidence interval [CI] 1.016-1.047, P < 0.001) or mesenteric peripouch fat area were independent risk factors for CARP. Of the 435 patients, 139 (32.0%) had two or more CT scans. Multivariable Cox proportional hazard analyses showed that "peripouch fat area increase ≥ 15%" (OR 3.808, 95%CI 1.703-8.517, P = 0.001) was an independent predictor of pouch failure. CONCLUSIONS: A great peripouch fat area measured on CT image is associated with a higher prevalence of CARP, and the accumulation of peripouch fat is a risk factor for pouch failure. The assessment of peripouch fat may be used to monitor the disease course of the ileal pouch.

Lower peripouch fat area is related with increased frequency of pouch prolapse and floppy pouch complex in inflammatory bowel disease patients.

BACKGROUND: Pouch prolapse is a rare pouch complication which often leads to pouch failure in inflammatory bowel disease (IBD) patients. Its exact cause remains unknown. Floppy pouch complex (FPC) was defined as the presence of any one of the following pouch disorders: pouch prolapse, afferent limb syndrome (ALS), redundant loop, and pouch folding. We aimed to explore the role of peripouch fat area in the occurrence of pouch prolapse and FPC. METHODS: Pouch patients with available pouchoscopy and abdominal CT scans who were followed up between 2011 and 2017 in Cleveland Clinic were reviewed. Peripouch fat was measured on CT images. RESULTS: Of the 93 included patients, 31 were females; 87 had J pouches and 6 had S pouches. The median duration of pouch was 8.0 (interquartile range [IQR] 5.0-16.5) years. A total of 18 cases (19.4%, 18/93) were identified as FPC, including 12 pouch prolapse, 5 ALS, 1 redundant loop, and 3 pouch folding. Patients with pouch prolapse had lower peripouch fat area (13.6 (9.3-18.5) vs. 27.6 (11.0-46.2)cm2, P = 0.022) than those without. Patients with FPC had lower peripouch fat area (15.4 (11.4-20.6) vs. 27.6 (11.0-46.9)cm2, P = 0.040) than those without. Univariate and multivariate analyses demonstrated that lower peripouch fat area, lower weight, and family history of IBD were independent predictors of pouch prolapse and FPC. CONCLUSIONS: A lower peripouch fat area was observed in inflammatory bowel disease patients with pouch prolapse and FPC. Longitudinal studies are needed to further elucidate the role of peripouch fat in the pathogenesis of pouch prolapse and FPC.

Mucosal Biomarker of Innate Immune Activation Predicts Response to Vedolizumab in Crohn's Disease.

OBJECTIVE: Mucosal barrier dysfunction plays a crucial role in intestinal inflammation in Crohn's disease (CD). Intestinal epithelial cell (IEC) death resulting from innate immune activation, termed pyroptosis, was recently found to be a cause of this barrier defect. The aim of this study was to determine the predictive value of pretreatment ileal biopsy pyroptosis as a biomarker for clinical response to vedolizumab in CD. DESIGN: Crohn's disease patients ranging 18 to 80 years old from 5 IBD centers with pre-vedolizumab ileal biopsies during colonoscopy were enrolled. Biopsies were stained for activated caspases, and levels of ileal IEC pyroptosis levels were quantified. The primary outcome was clinical response 6 months after therapy, defined as a reduction of Harvey-Bradshaw Index (HBI) of ≥5 points from baseline. Secondary outcomes included clinical remission, defined as HBI <5, and endoscopic improvement, as measured by the Simple Endoscopic Score for Crohn's Disease (SES-CD). RESULTS: One hundred CD patients (45 male, 55 female), median age 47 (19, 78) years, were included; clinical response rate was 60%, and clinical remission was 36%. The response rate in patients with ileal pyroptosis <14 positive cells per 1000 IECs was significantly higher than those above the threshold: 89% (25 of 28) vs 49% (35 of 72), odds ratio (OR) 8.8 (95% CI, 2.3-48.6; P < 0.001). Corresponding remission rates were 54% (15 of 28) vs 29% (21 of 72; OR 2.8 [1.03-7.59; P = 0.036]). For endoscopic improvement, ileal pyroptosis of 22 positive cells per 1000 IECs was the optimal threshold that determines the magnitude SES-CD change. CONCLUSIONS: Ileal biopsy IEC pyroptosis was predictive of clinical response and endoscopic improvement to vedolizmab in CD patients.

Combined Endoscopic Fistulotomy and Clipping for the Treatment of Fistula From the Tip of the J-Pouch to Anastomosis.

Patients who undergo restorative protocolectomy with ileal pouch-anal anastomosis may develop mechanical complications such as presacral sinuses and fistulas. The current method of treatment may include medical therapy or redo surgery. Recently, endoscopic management for postoperative complications has shown effective results. We present a unique case of a pouch-to-pouch fistula, from the tip of the "J" to the anastomosis that was successfully treated with endoscopic needle-knife sinusotomy and over-the-scope clips.

Vedolizumab for chronic antibiotic-refractory pouchitis.

BACKGROUND: Chronic antibiotic-refractory pouchitis (CARP) is a complication of ileal pouch-anal anastomosis (IPAA), which poses a therapeutic challenge. Vedolizumab, a gut-selective monoclonal antibody to the α4ß7 of integrin, has been used in such patients, but data on its efficacy are limited. Our aim was to assess the efficacy and safety of vedolizumab as induction therapy in CARP patients. METHODS: In this single-center, historic cohort, patients with CARP who received vedolizumab between January 2015 to June 2017 were identified and analysed. Patients were included if they had active pouchitis with a total of modified pouch disease activity index (mPDAI) score ≥5 or if unavailable clinician diagnosis of active pouchitis. Pre-treatment and at 3-month post-therapy pouchoscopy and clinical visits were used to calculate mPDAI. RESULTS: A total of 19 patients were included in the study. The mean age was 26.7 ± 12.8 years, with 10 (53%) males. Nine (47%) patients had been treated with anti-tumor necrosis factor (TNF) agents before colectomy and 10 (53%) had anti-TNFs after colectomy and IPAA. Six (32%) patients had improvement in the mPDAI symptom subscores (P = 0.031) and 14 (74%) had improvement in both endoscopic and total mPDAI scores with a median change of -2 units (both P = 0.031). Adverse events were noted only in two (11%) patients and four (21%) required surgery for CARP. CONCLUSIONS: Our study suggests that vedolizumab has efficacy and can be safely used for CARP patients. Larger studies with a higher number of patients are required to confirm these findings.

Inflammation and Neoplasia of the Pouch in Inflammatory Bowel Disease.

PURPOSE OF REVIEW: Ileal pouch-anal anastomosis (IPAA) is the standard restorative procedure after proctocolectomy in patients with inflammatory bowel disease who require colectomy. The ileal pouch is susceptible to a variety of adverse outcomes including mechanical insult, ischemia, and infectious agents. There is also a risk for developing low-grade dysplasia (LGD), high-grade dysplasia (HGD), or even adenocarcinoma in the pouch. The purpose of this review is to highlight risk factors, clinical presentation, surveillance, and treatment of pouch neoplasia. RECENT FINDINGS: Patients with pre-colectomy colitis-associated neoplasia are at high risk for developing pouch neoplasia. Other purported risk factors include the presence of family history of colorectal cancer, the presence of concurrent primary sclerosing cholangitis, chronic pouchitis, cuffitis, or Crohn's disease of the pouch. Pouch adenocarcinoma tends to have a poor prognosis. It is recommended to have a combined clinical, endoscopic, and histologic approach in diagnosis and management. Surveillance and management algorithms of pouch neoplasia are proposed, based on the risk stratification.

Diagnosis and management of floppy pouch complex.

Restorative proctocolectomy with ileal pouch-anal anastomosis has become the surgical treatment of choice for patients with refractory ulcerative colitis, colitis-associated dysplasia or familial adenomatous polyposis. There are various pouch disorders and associated complications. Floppy pouch complex is defined as the presence of pouch prolapse, afferent limb syndrome, enterocele, redundant loop and folding pouch on pouchoscopy, gastrografin pouchogram or defecography. Common clinical presentation includes dyschezia, bloating, abdominal pain, straining or the sense of incomplete evacuation. Each disorder has its own unique endoscopic, radiographic and manometry findings. A range of therapeutic options are available for the management of the various causes of a pouch.

Vedolizumab in the treatment of Crohn's disease of the pouch.

BACKGROUND: Our recent study showed the efficacy and safety of vedolizumab in the treatment of chronic antibiotic-refractory pouchitis. However, there are no published studies on its efficacy and safety in Crohn's disease (CD) of the pouch. The aim of this study was to assess the efficacy and safety of vedolizumab in those patients. METHODS: This case series included all eligible patients with CD of the pouch from our prospectively maintained, IRB-approved Pouchitis Registry from 2015 to 2017. Disease activity in pouch patients can be monitored using the modified Pouchitis Disease Activity Index (mPDAI). mPDAI is the 18-point pouchitis disease activity index consisting of three principal component scores: symptom (range, 0-6 points), endoscopy, (range 0-6 points), and histology (range, 2-6 points). Pre- and post- treatment (minimum 6 months) pouchoscopy and clinical visits were used to calculate mPDAI. RESULTS: A total of 12 patients were included in this study, who had restorative proctocolectomy with ileal pouch anal anastomosis for medically refractory ulcerative colitis (UC). The mean age at the time of pre-colectomy diagnosis of UC was 25.0 ± 11.5 years. The mean current age was 41.0 ± 12.1 years, nine (75.0%) were female, three (25.0%) had smoked and eight (66.7%) had used anti-tumor necrosis factor agents prior to vedolizumab use. The mean duration of vedolizumab use was 1.0 ± 6.4 years. There was a significant reduction in mPDAI symptom subscores after vedolizumab therapy (3.50 ± 1.93 vs 5.08 ± 0.79, P = 0.015). The pre- and post-treatment mean endoscopy subscores were 1.25 ± 1.36 and 0.91 ± 1.50 in the afferent limb (P = 0.583); 2.58 ± 1.68 and 2.27 ± 2.05 (P = 0.701) in the pouch body; and 2.67 ± 1.93 and 2.09 ± 2.12 (P = 0.511) in the cuff, respectively. None of the patients experienced side effects throughout the vedolizumab therapy. CONCLUSION: The findings of our study suggests that vedolizumab appears to be effective and safe in reducing the symptoms in patients with CD of the pouch.

Distribution of Esophageal Motor Disorders in Diabetic Patients With Dysphagia.

BACKGROUND: Diabetes mellitus can cause various gastrointestinal symptoms. Assessment of esophageal dysmotility in diabetic patients has been scarcely studied. The aim of this study was to determine the esophageal motor characteristics of diabetic versus nondiabetic patients who present with dysphagia. METHODS: High-resolution esophageal manometries (HREMs) of 83 diabetic patients and 83 age and gender-matched nondiabetic patients with dysphagia from 2 medical centers were included in this study. Demographic information, medical comorbidities, and medication usage were recorded for each patient in a single registry. HREM of each patient was evaluated and the different functional parameters were recorded. KEY RESULTS: Overall, 46% of diabetic patients were found to have an esophageal motor disorder. Diabetic patients with dysphagia were more likely to have failed swallows on HREM (50.6% vs. 33.7%; P=0.03) as compared with nondiabetic patients. Among diabetic patients, those being treated with insulin were more likely to have failed (69.0% vs. 40.7%; P=0.01) and weak (65.5% vs. 33.3%; P=0.005) swallows as compared with diabetic patients not on insulin. Among diabetic patients, those with abnormal manometry were more likely to demonstrate diabetic retinopathy (27.0% vs. 8.7%; P=0.04). There was a trend toward increased incidence of esophagogastric junction outflow obstruction in diabetic patients (10.8% vs. 2.4%; P=0.057) as compared with nondiabetic patients. CONCLUSIONS: Nearly half of diabetic patients with dysphagia have some type of an esophageal motility disorder. Diabetic retinopathy and the use of insulin are predictive of esophageal motor abnormalities among diabetic patients.