Background: The most common complication following ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC) is pouchitis. Our study aimed to investigate the relationship between histopathologic findings of ileitis, granuloma, or transmural inflammation on the colectomy specimen of patients with clinically and endoscopically diagnosed UC and the development of pouchitis within the first 2 years after IPAA. Methods: We performed a retrospective cohort study evaluating patients undergoing colectomy with IPAA for UC between January 1, 2004 and December 31, 2016. Bivariate analyses were conducted to evaluate the relationship between clinical factors and the development of pouchitis. We performed multivariate logistic regression to evaluate the relationship between histologic, clinical, and demographic factors at the time of colectomy and subsequent development of pouchitis. Results: Among 626 patients, pouchitis occurred in 246 (39%). Patients with primary sclerosing cholangitis were more likely to develop pouchitis (adjusted odds ratio [aOR] 2.81, 95% confidence interval [CI] 1.02–7.72), as were patients with a family history of inflammatory bowel disease (aOR 1.75, 95% CI 1.11–2.77). Histologic findings of ileitis, granuloma, or transmural inflammation were not associated with an increased odds of developing pouchitis (aOR 0.70, 95% CI 0.45–1.08). Discussion/Conclusion: Patients with ileitis, granulomas, or transmural inflammation at the time of colectomy were not at greater risk for development of pouchitis in the 2 years after IPAA. These pathological findings should not preclude IPAA for UC.

Acute pouchitis is the most common complication after a restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis, affecting 40% of patients within the first year after surgery.1 Although up to 80% of patients can develop pouchitis symptoms,2,3 substantial gaps remain in our understanding of the epidemiology and burden of pouchitis. Administrative claims have been used to advance the knowledge of other areas of inflammatory bowel disease4-6; however, a prerequisite to conducting such studies in pouchitis is a valid, reliable case-finding algorithm. Given concerns that the International Classification of Diseases (ICD) code for pouchitis may not be reliably used by clinicians (resulting in a low sensitivity), the objectives of the study were to (1) develop a series of case-finding definitions for acute pouchitis and (2) compare the performance of these case-finding definitions to that of a single ICD code for pouchitis.

Background: Risk factors for the development of chronic antibiotic dependent pouchitis (CADP) are not well understood. Methods: Using multivariable logistic regression, we compared clinical factors between 194 patients with acute antibiotic responsive pouchitis or CADP. Results: Individuals with CADP were significantly older (40.9 vs 30.8 years, P < 0.001) and demonstrated a longer disease duration before IPAA (10.3 vs 7.0 years, P &= 0.004). Age >= 55 years at the time of IPAA was significantly associated with CADP (adjusted odds ratio &= 4.35, 95% confidence interval &= 1.01-18.7). Conclusions: Although older age should not represent a barrier to IPAA, further studies evaluating etiologies of this association are warranted.

BACKGROUND & AIMS:Despite the availability of endoscopic therapy, many patients in the United States undergo surgical resection for nonmalignant colorectal polyps. We aimed to quantify and examine trends in the use of surgery for nonmalignant colorectal polyps in a nationally representative sample.METHODS:We analyzed data from the Healthcare Cost and Utilization Project National Inpatient Sample for 2000 through 2014. We included all adult patients who underwent elective colectomy or proctectomy and had a diagnosis of either nonmalignant colorectal polyp or colorectal cancer. We compared trends in surgery for nonmalignant colorectal polyps with surgery for colorectal cancer and calculated age, sex, race, region, and teaching status/bed-size-specific incidence rates of surgery for nonmalignant colorectal polyps.RESULTS:From 2000 through 2014, there were 1,230,458 surgeries for nonmalignant colorectal polyps and colorectal cancer in the United States. Among those surgeries, 25% were performed for nonmalignant colorectal polyps. The incidence of surgery for nonmalignant colorectal polyps has increased significantly, from 5.9 in 2000 to 9.4 in 2014 per 100,000 adults (incidence rate difference, 3.56; 95% confidence interval 3.40-3.72), while the incidence of surgery for colorectal cancer has significantly decreased, from 31.5 to 24.7 surgeries per 100,000 adults (incidence rate difference, -6.80; 95% confidence interval -7.11 to -6.49). The incidence of surgery for nonmalignant colorectal polyps has been increasing among individuals age 20 to 79, in men and women and including all races and ethnicities.CONCLUSIONS:In an analysis of a large, nationally representative sample, we found that surgery for nonmalignant colorectal polyps is common and has significantly increased over the past 14 years.

reporter line enables monitoring of endogenous Egfr protein, overcoming the lack of antibodies for immunohistochemical detection of mouse Egfr.Using this reporter line, we observed Egfr-Em expression is 5-fold higher in male livers than female livers.Higher expression of Egfr-Em in males was also observed in the stomach of MT-Tgfa mice, a mouse model of Ménétrier's disease for which EGFR neutralizing antibodies provide the first effective medical therapy.The purpose of this study was to investigate whether the expression of Egfr is regulated by sex hormones (e.g.testosterone) and whether males and females exhibit differential responsiveness to the Egfr neutralizing antibody, MM-151, in MT-Tgfa mice.Methods: We injected testosterone (50 mg/kg) subcutaneously for seven days in male and female mice and evaluated the expression of Egfr in the liver.Male mice were castrated and the expression of Egfr in the liver was evaluated on day 7. Low (10 mg/kg) and high (100 mg/kg) concentrations of MM-151 were injected intraperitoneally every other day to male and female MT-Tgfa mice and the response to the treatment was evaluated by histologic examination.Results: Expression of Egfr-Em of female liver increased comparable to male liver after testosterone treatment.In addition, expression of Egfr-Em in male livers decreased 7 days after castration.Stomachs of female MT-Tgfa mice showed response to low and high concentrations of MM-151, whereas stomachs of male MT-Tgfa mice responded only to high concentrations of MM-151.Conclusions: We show that the expression of Egfr is higher in males than females in the normal mouse liver as well as in the stomachs of MT-Tgfa mice.The expression of Egfr in the liver is regulated by testosterone.Furthermore, male and female mice show differential responsiveness to the Egfr neutralizing antibody (MM-151) in a mouse model of Ménétrier's disease.We speculate that gender differences in EGFR expression may contribute to the gender difference in the incidence of HCC and there may be differential responses to EGFR neutralizing antibody treatment between males and females.

Background:Ulcerative colitis (UC) patients requiring colectomy often have a staged ileal pouch anal anastomosis (IPAA). There are no prospective data comparing timing of pouch creation. We aimed to compare 30-day adverse event rates for pouch creation at the time of colectomy (PTC) with delayed pouch creation (DPC).Methods:Using prospectively collected data from 2011-2015 through the National Surgical Quality Improvement Program, we conducted a cohort study including subjects aged ≥18 years with a postoperative diagnosis of UC. We assessed 30-day postoperative rates of unplanned readmissions, reoperations, and major and minor adverse events (AEs), comparing the stage of the surgery where the pouch creation took place. Using a modified Poisson regression model, we estimated risk ratios (RRs) with 95% confidence intervals (CIs) adjusting for age, sex, race, body mass index, smoking status, diabetes, albumin, and comorbidities.Results:Of 2390 IPAA procedures, 1571 were PTC and 819 were DPC. In the PTC group, 51% were on chronic immunosuppression preoperatively, compared with 15% in the DPC group (P < 0.01). After controlling for confounders, patients who had DPC were significantly less likely to have unplanned reoperations (RR, 0.42; 95% CI, 0.24-0.75), major AEs (RR, 0.72; 95% CI, 0.52-0.99), and minor AEs (RR, 0.48; 95% CI, 0.32-0.73) than PTC.Conclusions:Patients undergoing delayed pouch creation were at lower risk for unplanned reoperations and major and minor adverse events compared with patients undergoing pouch creation at the time of colectomy. 10.1093/ibd/izy082_video1izy082.video15776112442001.

Figure 2. Seasonal variation of EoE compared

BACKGROUND AND AIMS:Despite evidence that most nonmalignant colorectal polyps can be managed endoscopically, a substantial proportion of patients with a nonmalignant colorectal polyp are still sent to surgery. Risks associated with this surgery are not well characterized. We describe 30-day postoperative morbidity and mortality and explore risk factors for adverse events in patients undergoing surgical resection for nonmalignant colorectal polyps.METHODS:We analyzed data collected prospectively as part of the National Surgical Quality Improvement Program. Our analysis included 12,732 patients who underwent elective surgery for a nonmalignant colorectal polyp from 2011 through 2014. We report adverse events within 30 days of the index surgery. Modified Poisson regression was used to estimate risk ratios and 95% confidence intervals.RESULTS:Thirty-day mortality was .7%. The risk of a major postoperative adverse event was 14%. Within 30 days of resection, 7.8% of patients were readmitted and 3.6% of patients had a second major surgery. The index surgery resulted in a colostomy in 1.8% and ileostomy in .4% of patients. Patients who had surgical resection of a nonmalignant polyp in the rectum or anal canal compared with the colon had a risk ratio of 1.58 (95% confidence interval, 1.09-2.28) for surgical site infection and 6.51 (95% confidence interval, 4.97-8.52) for ostomy.CONCLUSIONS:Surgery for a nonmalignant colorectal polyp is associated with significant morbidity and mortality. A better understanding of the risks and benefits associated with surgical management of nonmalignant colorectal polyps will better inform discussions regarding the relative merits of management strategies.

BACKGROUND: Ulcerative colitis patients have been historically treated with standard single, 2-, and 3-stage operative approaches. We perform a variant 2-stage procedure beginning with total abdominal colectomy and end ileostomy followed by completion proctectomy and ileal pouch-anal anastomosis (IPAA) without a diverting loop ileostomy. This study evaluates the effectiveness of this innovative alternative.STUDY DESIGN: Patients with ulcerative colitis, admitted to the University of North Carolina Hospital between 2003 and 2010 for IPAA, were eligible for inclusion. The 3-year cumulative incidence of pouch leaks among patients undergoing variant 2-stage were compared with those undergoing classic 2-stage, using inverse probability-of-treatment weighted Kaplan-Meier survival curves, and 95% CIs were estimated using nonparametric bootstrapping.RESULTS: There were 248 patients who underwent IPAA; 139 (56.1%) underwent classic 2-stage and 109 (43.9%) underwent variant 2-stage. After standardization, there was no significant difference in the 3-year cumulative incidence of pouch leaks between patients undergoing variant 2-stage, compared with the standard single-or 2-stage procedure (risk difference 0.01; 95% CI -0.08, 0.15). At the time of the first surgical procedure, patients undergoing a variant 2-stage were more likely to have lower BMIs (median 22.5 kg/m(2) vs 26.7 kg/m(2); p < 0.0001), an urgent/emergent procedure (56.9% vs 0.0%; p < 0.0001), biologic use within 2 weeks of surgery (32.1% vs 17.5%; p = 0.003), and high dose steroid use (60.4% vs 16.7%; p <= 0.0001).CONCLUSIONS: Variant 2-stage IPAA is a safe and effective operative approach with comparable outcomes in a more acute population based on BMI, steroid use, and urgency of operation. (C) 2017 by the American College of Surgeons. Published by Elsevier Inc. All rights reserved.

these benefits should be weighed against SEMS related morbidity and mortality, and the uncertainty about long-term oncologic risks of SEMS in curative patients.Table 1| Study outcomes of SEMS compared to primary resection for acute right-sided colonic obstructions.Patients are subdivided based on treatment intend; palliative and curative since treatment algorithms differ between these two groups.# Minor and major morbidity in the SEMS group include complictions after SEMS placement as well as the elective resection if conducted.

Crohnu0027s disease (CD) is a chronic inflammatory disease of the gastrointestinal tract, characterized by an inappropriate immune response to the enteric microbiota. Chromatin based assays have successfully identified cell type and disease-specific regions of DNA accessibility, and have been linked to differential transcription of target genes, but this approach has yet to be explored in CD. In this study we performed formaldehyde-assisted isolation of regulatory elements (FAIRE-seq) to identify nucleosome-depleted regions associated with regulatory elements, and RNA-seq to quantify expression, to characterize disease-relevant changes in chromatin and establish links to putative target genes.Mucosal Biopsies for 21 CD and 12 non-IBD individuals were taken from macroscopically uninflamed portions of the ascending colon at time of surgery. We performed FAIRE-seq and RNA-seq on each tissue sample. Reads were aligned to personalized genomes constructed with genotypes assayed on the Illumina Immunochip platform. A genome-wide scan for differential regions and genes was performed using 2 sided t-tests on normalized read counts in 300bp regions (FAIRE-seq) and RPKM (RNA-seq).RNA-seq data analysis across all samples identified 2 distinct classes of patients associated with epithelial cell lipid transport (class I, n = 10, CD; n = 1, non-IBD) and maintenance of cellular and luminal pH (class II, n = 11, CD, n = 11, non-IBD). To unravel potential gene regulatory mechanisms we analyzed chromatin profiles using FAIRE-seq and histone annotations using tissue specific ChIP-seq data sets. Class I patients showed increased accessibility at distal sites marked for enhancer activity in small intestine, and reduced accessibility at sites marked as enhancers in colon, suggesting 2 distinct regulatory programs driving the expression of differential genes. This pattern was reversed in class II samples. In an analysis restricting to class II, which was characterized by normal colon enhancer activity, we found regulatory regions specific to CD and non-IBD, respectively, as well as 51 and 507 genes upregulated in the respective cohorts. Top ontologies of genes upregulated in CD included host response to bacteria and immune response. Differential regulatory genes were enriched near TSSs of differentially expressed genes, implying putative causal effect. In an integrative analysis, we identified 72 regulatory regions that associate with both disease status and expression of nearby genes. A retrospective analysis of patients in class I and II revealed that the majority of patients (10/11) in class I required post-operative anti-TNF therapy for disease recurrence compared to only 1/11 CD patients in the class II group.We used chromatin status as a novel marker of disease in Crohnu0027s. We identified a subset of CD patients that are characterized at the chromatin level in the colon by enrichment of enhancer marks specific to small intestine, and loss of enhancer activity specific to colon. Among individuals with enhancer activity indicative of normal colon, we integrated data from well-described transcriptional markers with novel chromatin variables to identify molecular associations and interactions that affect disease predisposition. Despite small patient numbers we were able to use chromatin profiles to identify patients that required post-operative management with anti-TNF agents.

Intestinal dysbiosis resulting in an inappropriate activation of intestinal mucosal immune responses leads to Crohn's disease. While studies have been done regarding the nature of intestinal microbiota in Crohn's disease, what role the intestinal microbiota play a role in initiating, maintaining, and determining the phenotype of Crohn's disease (CD) remains largely understudied. We collected mucosal samples from macroscopically non-inflamed and inflamed sections of resected colon and small intestine (ileum) from 181 CD and 34 non-CD control patients. For 31 of the CD patients, we obtained samples from both the inflamed and non-inflamed regions of the colon and ileum. For each mucosal tissue sample, we performed 16S rRNA sequencing (MiSeq) of the V1 and V2 regions of the intestinal bacteria. Using QIIME and R, we determined operational taxonomic units (OTUs), mean bacterial species diversity (α-diversity), and diversity between individuals with similar disease phenotypes (β-diversity). Differential OTU abundance was identified using DESeq2 (P ≤ 0.01) and differential α-diversity by Kruskal-Wallis tests across disease status, disease behavior, and inflammation status. Bacterial species diversity (α-diversity) declined, but not significantly, when comparing all samples from CD patients to non-IBD controls. Inflammation status had no impact on α-diversity in either colon or ileum. CD patients with penetrating phenotype (including perianal fistulizing disease) had significant lower α-diversity in their colon and trended lower in the ileum compared to non-IBD controls. But, α-diversity in patients without penetrating disease was not significantly different than non-IBD controls. Several genera from the Firmicutes phylum showed increased abundance (Dialister, Dorea, Lactobacillus, Caloramator) and several other Firmicutes and one genus (Collinsella) in the Actinobacteria phylum showed decreased abundance in the non-inflamed colon of CD patients compared to non-IBD patients. When similarly considering the ileum, we only found increases in abundance in one genus (Bifidobacterium) in the Actinobacteria phylum and multiple genera (Streptococcus, Blautia, Oscillospira) from the Firmicutes phylum. CD patients with the penetrating disease showed increased abundance from the Bacteroides (Parabacteroides, Bacteroides genera) and Firmicutes (Streptococcus genus) phylum, and decreased abundance of bacteria from the Firmicutes (Streptococcus, Clostridium, VeillonellaI, Coprococcus, Blautia genera) and Proteobacteria (Haemophilus, Halomonas genera) phylum compared to patients with a non-penetrating and non-fistulizing disease. There was also increased abundance of bacteria from the Vagococcus genus (Firmicutes) in the inflamed ileum of CD patients compared to non-inflamed ileum. Finally, we measured the β-diversity within matched inflamed and uninflamed CD ileal samples using weighted Unifrac. Using this metric, we found that samples clustered better based on patient of origin than on inflammation status. Our study highlights yet to be defined microbial associations with Crohn's disease phenotype. We show that reduction in α-diversity appears to be primarily driven by patients with a penetrating disease phenotype, but not by inflammation. The majority of the shifts seen between penetrating and non-penetrating disease phenotypes seem to heavily involve bacteria from the Firmicutes phylum. Prospective postoperative follow of these patients is underway, which will determine whether this distinct microbiome signature associated with CD phenotype at the time of surgical resection can determine disease recurrence.

Hepatocelluar carcinoma (HOC) has rarely been associated with familial adenomatosis polyposis (FAP). Between 1950 and 2011, only a few cases of HOC associated with classic FAP (cFAP) have been reported in the literature.Here, we report the first case to our knowledge of HOC associated with attenuated FAP (aFAP). The patient possessed a single nucleotide mutation in noncoding region after exon 4, which is rarely observed in aFAP, and not previously reported in cFAP-associated HCC. Our patient underwent liver transplant for a 22-cm-large HOC (in China), however her HOC recurred 1.5 years after the transplant. Here we review the literature on FAP and HOC, with a particular focus on the role of the Wnt/APC/beta-catenin pathway toward a better understanding of HOC pathogenesis.In summary, patients with FAP can have extracolonic manifestations of their diseases, including HCC. If a patient with FAP develops clinically related symptoms such as right upper quadrant abdominal pain, jaundice or unintentional weight loss, a work-up for HOC may be warranted.