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Objective evidence of inflammation has been associated with the risk of relapse in patients with ulcerative colitis (UC) who are in clinical remission. We compared endoscopic and histologic grades for their ability to predict clinical relapse in this patient population.Patients with UC in clinical remission were prospectively enrolled into an observational cohort. Baseline endoscopic scores (Mayo) and histological (Geboes) grades and blood markers were collected. All subjects were followed for 12 months and relapse determined using clinical indices.A total of 179 subjects were enrolled into the study and followed for 12 months. Clinical relapse occurred in 23%; 5% were hospitalized, and 2% underwent colectomy. In univariate analysis, the baseline Mayo endoscopy score and the Geboes histology grade were significantly associated with the later development of clinical relapse (P0.001 for both), but only the histology grade remained significant in a multivariate model (P=0.006). The relative risk of clinical relapse was 3.5 (95% CI 1.9-6.4, P0.0001) in subjects whose baseline Geboes grade was ≥3.1. The area under the curve was 0.73 for the Geboes histology grade to identify subjects at risk of future clinical relapse. Of the patients in clinical, endoscopic, and histological remission at baseline (n=82), only 7% had a clinical relapse over the subsequent 12 months.Histology grade has the strongest association with the risk of clinical relapse in patients with UC who are in clinical remission. Consideration should be given to including this end point in evaluating therapy for UC.

BACKGROUND Rectal mesalamine is an effective induction and maintenance therapy for ulcerative colitis. Little is known about the adherence rates to rectal mesalamine or barriers to its use. The aim was to quantify the prevalence of nonadherence to rectal mesalamine and to identify patient-reported barriers to adherence. METHODS A cohort of patients with ulcerative colitis was prospectively enrolled in this observational study and followed for 12 months. Adherence was assessed by tracking pharmacy refills (medication possession ratio). Individual interviews were undertaken in a subset of subjects. Transcripts from the focus groups and interviews were analyzed to identify themes and links between these themes using qualitative data software (MaxQDA). RESULTS Seventy patients prescribed rectal mesalamine were prospectively enrolled in the study. At enrollment, 39 of 70 subjects (55%) self-reported "occasional nonadherence" to rectal mesalamine. Over the 12-month follow-up period, only 20 subjects (26%) completed 3 or more refills. Males, or subjects prescribed a once-a-day suppository, were significantly more likely to refill than females (odds ratio = 3.3, 95% confidence interval, 1.1-10.9) or those prescribed suppositories more than once a day (odds ratio = 1.3, 95% confidence interval, 1.1-1.7). By medication possession ratio criteria, 71% of all subjects were nonadherent with their prescribed regimen (medication possession ratio

Background and study aims: Endoscopic mucosal resection (EMR) of laterally spreading lesions (LSLs) involving the ileocecal valve (ICV) is technically demanding. Conventionally, these lesions are considered too challenging for endoscopic therapy and are primarily managed surgically. The aims of the study were to describe effectiveness, safety, and outcomes following EMR of LSLs at the ICV. Patients and methods: This was a single-center, prospective, observational, cohort study performed at an academic, tertiary referral center. Patients undergoing EMR for LSLs ≥ 20 mm involving the ICV were recruited over a 5-year period. Standard or cap-assisted colonoscopy with inject-and-resect EMR technique was performed with standardized post-EMR management. Procedural success, safety, and outcomes compared with non-ICV LSLs managed during the same period were analyzed. Results: A total of 53 patients with ICV LSLs were referred for EMR (median age 69 years; median lesion size 35.0 mm; 52.8 % females). Six patients went directly to surgery because of an endoscopic diagnosis of malignancy (n = 2) or technical failure of EMR (n = 4). EMR achieved complete adenoma clearance in 44 out of 47 attempted (93.6 %). Surgery was ultimately avoided in 43/53 (81.1 %). Complications included bleeding in 6.4 %. There were no perforations or strictures. Early adenoma recurrence was detected in 7/40 patients (17.5 %), and 1/22 (4.5 %) had late recurrence. All were successfully managed endoscopically. Factors associated with failure of ICV EMR were ileal infiltration and involvement of both ICV lips. Conclusions: In the majority of cases, LSL involving the ICV can be effectively treated by EMR on an outpatient basis. In specialized centers, complications are infrequent, and > 80 % of patients ultimately avoid surgery. Trial registered at ClinicalTrials.gov (NCT01368289).

OBJECTIVES Antibodies to infliximab (ATIs) have been associated with a risk of infusion reactions in some studies of patients with inflammatory bowel disease. However, many factors, such as immunomodulators and dosing schedule, may influence this association. The aim of this article was to provide a pooled estimate of the risk of infusion reactions according to patients' ATI status and analyze the relationship of immunomodulators to this risk. DESIGN Public databases were searched for eligible studies. Quality assessment was undertaken for all studies using Grading of Recommendations Assessment, Development and Evaluation criteria. Raw data from studies meeting inclusion criteria were pooled for meta-analysis of effect estimates. Sensitivity analysis was performed for all outcomes. Funnel plot was performed to assess for publication bias. RESULTS Eight studies met the inclusion criteria, with a pooled total of 1351 subjects. Seven of the 8 studies had a high risk of bias in at least 1 quality domain. The cumulative data indicated that there was a higher risk ratio (RR) of any acute infusion reaction (RR 2.4; 95% confidence interval [CI] 1.5-3.8, P < 0.001) and severe infusion reactions (RR 5.8, 95% CI 1.7-19, P = 0.004) in patients with ATIs when compared with patients without ATIs. The RR of delayed hypersensitivity reactions was not significantly different between ATI+ and ATI- patients (RR 2.8, 95% CI 0.2-33, P = 0.4). Patients prescribed immunomodulators during maintenance infliximab therapy had a reduction in their risk for ATI development (RR 0.6, 95% CI 0.4-0.9, P = 0.02) and infusion reactions (RR 0.6, 95% CI 0.4-0.8, P < 0.001). CONCLUSIONS The presence of ATIs is associated with a significantly higher risk of acute infusion reactions, but not delayed hypersensitivity reactions, in patients with inflammatory bowel disease. Concomitant immunomodulators reduce this risk.

Mucosal healing, based on histologic analysis, is an end point of maintenance therapy for patients with ulcerative colitis (UC). There are few data on how histologic signs of inflammation correlate with endoscopic and peripheral blood measures of inflammation in these patients. We investigated patterns of histologic features of inflammation in patients with UC in clinical remission, and correlated these with endoscopic and biochemical measures of inflammation.We performed a prospective observational study of 103 patients with UC in clinical remission undergoing surveillance colonoscopy while receiving maintenance therapy with mesalamine or thiopurines; 2674 biopsy specimens were collected from 708 colonic segments. Each colonic segment was evaluated based on the Mayo endoscopic subscore and the Geboes histology score (range, 0-5.4). Biomarkers were measured in peripheral blood samples.Histologic features of inflammation were found in 54% of patients receiving maintenance therapy; 37% had at least moderate inflammation based on histology scores. Of the 52 patients with endoscopic evidence only of left-sided colitis, 34% had histologic features of inflammation in their proximal colon. Histology scores correlated with endoscopic scores for per-segment inflammation (Spearman ρ = 0.65; P.001). Patients with histology scores greater than 3.1 had a significantly higher mean level of C-reactive protein than those with scores less than 3.1. There were no differences among treatment groups in percentages of patients with histologic scores greater than 3.1.Patients in clinical remission from UC still frequently have histologic features of inflammation, which correlate with endoscopic appearance. Patients with at least moderate levels of inflammation, based on histologic grading (score3.1), have higher serum levels of C-reactive protein, which could be used as a surrogate marker of histologic inflammation.

Flat and sessile colonic lesions are being identified more frequently because of increased awareness, improved endoscopic skills, and enhanced imaging. Endoscopic mucosal resection (EMR) is now a well-developed technique in the treatment of large sessile lesions and advanced mucosal neoplasia of the colon. Significant cost, morbidity, and mortality benefits may be obtained from this minimally invasive technique. Careful lesion assessment is mandatory, and the patient's general health and comorbidities should be factored into the therapeutic plan. Recent technical advances allow resection of larger and more complex lesions in excess of 50 mm and involving more than two-thirds of the circumference of the colonic wall as an outpatient. Meticulous resection technique is crucial to maximize procedural success. EMR is associated with a small, but significant, risk of bleeding and perforation. Endoscopists need to be aware of risk factors for these events and techniques of early detection. Early identification and endoscopic treatment ameliorates the frequency and severity of adverse events. This review will discuss the general principles of EMR, including lesion assessment, equipment selection, endoscopic technique, and early identification and treatment of complications.

Antibodies to infliximab (ATIs) have been associated with loss of clinical response and lower serum infliximab (IFX) levels in some studies of patients with inflammatory bowel disease (IBD). This has important implications for patient management and development of novel biologic therapies. The objective of this study was to perform a systematic review and meta-analysis of studies that reported clinical outcomes and IFX levels according to patients' ATI status.MEDLINE, Web of Science, CINAHL, Scopus, and EMBASE were searched for eligible studies. Quality assessment was undertaken using GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria. Raw data from studies meeting inclusion criteria was pooled for meta-analysis of effect estimates. Sensitivity analysis was performed for all outcomes. Funnel plot was performed to assess for publication bias.Thirteen studies met the inclusion criteria, and reported results in 1,378 patients with IBD. All included studies had a high risk of bias in at least one quality domain. The pooled risk ratio (RR) of loss of clinical response to IFX in patients with IBD who had ATIs was 3.2 (95% confidence interval (CI): 2.0-4.9, P0.0001), when compared with patients without ATIs. This effect estimate was predominantly based on data from patients (N=494) with Crohn's disease (RR: 3.2, 95% CI: 1.9-5.5, P0.0001). Data only from patients with ulcerative colitis (n=86) exhibited a non-significant RR of loss of response of 2.2 (95% CI: 0.5-9.0, P=0.3) in those with ATIs. Heterogeneity existed between studies, in both methods of ATI detection, and clinical outcomes reported. Three studies (n=243) reported trough serum IFX levels according to ATI status; the standardized mean difference in trough serum IFX levels between groups was -0.8 (95% CI -1.2, -0.4, P0.0001). A funnel plot suggested the presence of publication bias.The presence of ATIs is associated with a significantly higher risk of loss of clinical response to IFX and lower serum IFX levels in patients with IBD. Published studies on this topic lack uniform reporting of outcomes. High risk of bias was present in all the included studies.

Endosonography (EUS)-guided drainage of paragastric fluid collections using fully covered self-expanding metal stents (FCSEMS) is now a well-established procedure. Recently, new and specially designed lumen-apposing, fully-covered metal cystgastrostomy stents have been employed for this indication. In this case series, the use of these new stents for the drainage of malignant fluid collections in three symptomatic patients is described. Cases included a large pancreatic pseudocyst, secondary to underlying acute lymphoblastic leukemia, and two large collections of loculated ascites due to metastatic ovarian and cervical cancer, respectively. Technical success in inserting the new stents was achieved in all three patients, and resulted in symptomatic relief. There were no clinically significant complications directly attributed to the stents. These new lumen-apposing cystgastrostomy stents may provide a viable, minimally invasive, and effective alternative for drainage of malignant fluid collections, either for definitive treatment or for palliation of symptoms.

The serrated neoplasia pathway accounts for up to 30% of all sporadic colorectal cancers (CRCs). Sessile serrated adenomas/polyps (SSA/Ps) with cytological dysplasia (SSA/P-D) are a high-risk serrated CRC precursor with little existing data. We aimed to describe the clinical and endoscopic predictors of SSA/P-D and high grade dysplasia (HGD) or cancer.Prospective multicentre data of SSA/Ps ≥20 mm referred for treatment by endoscopic mucosal resection (September 2008-July 2013) were analysed. Imaging and lesion assessment was standardised. Histological findings were correlated with clinical and endoscopic findings.268 SSA/Ps were found in 207/1546 patients (13.4%). SSA/P-D comprised 32.4% of SSA/Ps ≥20 mm. Cancer occurred in 3.9%. On multivariable analysis, SSA/P-D was associated with increasing age (OR=1.69 per decade; 95% CI (1.19 to 2.40), p0.004) and increasing lesion size (OR=1.90 per 10 mm; 95% CI (1.30 to 2.78), p0.001), an 'adenomatous' pit pattern (Kudo III, IV or V) (OR=3.98; 95% CI (1.94 to 8.15), p0.001) and any 0-Is component within a SSA/P (OR=3.10; 95% CI (1.19 to 8.12) p0.021). Conventional type dysplasia was more likely to exhibit an adenomatous pit pattern than serrated dysplasia. HGD or cancer was present in 7.2% and on multivariable analysis, was associated with increasing age (OR=2.0 per decade; 95% CI 1.13 to 3.56) p0.017) and any Paris 0-Is component (OR=10.2; 95% CI 3.18 to 32.4, p0.001).Simple assessment tools allow endoscopists to predict SSA/P-D or HGD/cancer in SSA/Ps ≥20 mm. Correct prediction is limited by failure to recognise SSA/P-D which may mimic conventional adenoma. Understanding the concept of SSA/P-D and the pitfalls of SSA/P assessment may improve detection, recognition and resection and potentially reduce interval cancer.NCT01368289.

8. Miller T, Singhal S, Neese P, et al. Non-operative repair of a transected bile duct using an endoscopic-radiologic rendezvous procedure. J Dig Dis 2013;14:509-11. 9. Chang JH, Lee IS, Chun HJ, et al. Usefulness of the rendezvous technique for biliary stricture after adult right-lobe living-donor liver transplantation with duct-to-duct anastomosis. Gut Liver 2010;4: 68-75. 10. Aytekin C, Boyvat F, Yilmaz U, et al. Use of the rendezvous technique in the treatment of biliary anastomotic disruption in a liver transplant recipient. Liver Transpl 2006;12:1423-6. 11. Nasr JY, Hashash JG, Orons P, et al. Rendezvous procedure for the treatment of bile leaks and injury following segmental hepatectomy. Dig Liver Dis 2013;45:433-6.

The failure of the immune response to clear the Hepatitis C virus (HCV) results in chronic inflammation that leads to liver cirrhosis. In general, women have a better prognosis than men and this may be associated with increased levels of anti-inflammatory mediators that are positively regulated by female sex hormones. Our aim was to determine if a cohort of Irish women who acquired infection through administration of HCV genotype 1b-contaminated anti-D immunoglobulin from a single source, had altered levels of circulating cytokine levels compared to women who spontaneously resolved infection, men with HCV infection or age-matched healthy controls. Twenty post-menopausal women and 20 men with chronic HCV infection (genotype 1), 20 post-menopausal women who resolved infection and age and sex-matched controls were recruited for the study. Levels of circulating cytokines were assessed by ELISA. Circulating IL-6, Oncostatin-M, TNF-α, CXCL10, CCL18, VEGF and GM-CSF did not differ between groups. Both men and women with HCV had significantly elevated levels of circulating Osteoprotegerin (OPG). However, male but not female HCV patients had elevated levels of circulating Matrix Metalloprotease-9 (MMP-9). An increased OPG: MMP-9 ratio in the circulation of females compared to males with chronic HCV may help protect against HCV-associated liver disease and explain the slow progress of liver disease in this cohort.

Background & Aims Limited data are available on the contribution of chronic HCV infection to the development of bone disease in postmenopausal women. We studied whether women who acquired HCV infection through administration of HCV genotype 1b–contaminated anti-D immunoglobulin from a single source had decreased bone mineral density (BMD) or altered levels of bone turnover markers (BTMs), compared with women who spontaneously resolved infection or age-matched healthy controls. Methods From a cohort of postmenopausal Irish women, we compared BMD, determined by dual-energy x-ray absorptiometry, and a panel of BTMs in 20 women chronically infected with HCV (PCR + ), 21 women who had spontaneously resolved infection (PCR − ), and 23 age-matched healthy controls. Results Levels of BTMs and BMD were similar in PCR + and PCR − women and healthy age-matched controls. However, there was an increased frequency of fractures in PCR + (n = 6) compared with PCR − women (n = 0, P = .007). PCR + women with fractures were postmenopausal for a longer time (median, 15.5, range, 5–20 years vs 4.5, range, 1–20 years in PCR + women without fractures; P = .033), had lower BMD at the hip (0.79, range, 0.77–0.9 g/cm 2 vs 0.96, range, 0.81–1.10 g/cm 2 ; P = .007), and had a lower body mass index (23.7, range 21.2–28.5 kg/m 2 vs 25.6, range 22.1–36.6 kg/m 2 ; P = .035). There was no difference in liver disease severity or BTMs in PCR + women with or without fractures. Conclusions Chronic HCV infection did not lead to discernable metabolic bone disease in postmenopausal women, but it might be a risk factor for bone fractures, so preventive measures should be introduced. To view this article's video abstract, go to the AGA's YouTube Channel.

Background: The occurrence of hyperplastic polyps during colonoscopy is usually considered an incidental finding of little or no clinical significance. We pursued the hypothesis that diagnosis of hyperplastic polyps on index colonoscopy predicted the occurrence of adenomatous polyps on follow-up colonoscopy. Methods: Miraca Life Sciences is a centralized pathology laboratory that serves 1,500 gastroenterologists distributed throughout the United States with more than 400,000 pathology specimens processed annually. From its computerized database, we selected 13,929 subjects who were represented in the database by two consecutive colonoscopies. On the first colonoscopy, patients harbored only hyperplastic polyps (3,000 subjects) or no polyps at all (10,929 subjects). In a case-control study, we compared whether the occurrence of adenomatous polyps on second colonoscopy (in 2,549 subjects) was influenced by the initial diagnosis of hyperplastic polyps on first colonoscopy. Odds ratios (OR) and their 95% confidence intervals (CI) were calculated to describe the strengths of the associations between various types of colonic neoplasms. Multivariate logistic regression was used to adjust the odds ratios for age, sex, and other patient characteristics. Results: The prevalence of hyperplastic polyps on first colonoscopy was similar in males and females, 22% vs. 21%, respectively. Males harbored more adenomatous polyps on second colonoscopy, 20% vs. 17%, respectively, with OR = 1.27, 1.17-1.39. The prevalence of hyperplastic and adenomatous polyps both increased with older age. Compared with hyperplastic polyps the age distribution of adenomatous polyps was shifted towards older age groups, with mean ages (SD) of 59.9 (11.7) vs. 62.8 (11.3) years and t = 9.19, p ,0.001. Increasingly longer time intervals between the first and second colonoscopy were associated with a significant increase in the diagnosis of adenomatous polyps during the second colonoscopy. The finding of hyperplastic polyps during the first colonoscopy was significantly associated with the occurrence of colonic neoplasms on second colonoscopy, the odds ratios (CI) being 3.06 (2.79-3.36) for any type of adenoma, 2.14 (1.71-2.66) for advanced adenoma, and 6.85 (5.44-8.62) for sessile serrated adenoma. Conclusion: Male sex, old age, length of interval between the two colonoscopies, and presence of hyperplastic polyps during the initial colonoscopy were all positive and statistically significant predictors for the diagnosis of adenoma during a second subsequent colonoscopy. The presence of hyperplastic polyps may indicate a general underlying tendency of the colonic mucosa for neoplastic growth.

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon that typically manifests as diarrhea, abdominal pain, and bloody stool. Complications, such as colorectal cancer and extraintestinal manifestations, may also develop. The goals of management are to induce and maintain clinical remission and to screen for complications of this disease. Mesalamine is a 5-aminosalicylic acid compound that is the first-line therapy to induce and maintain clinical remission in patients with mild-to-moderate UC. For patients who are refractory to mesalamine or have more severe disease, steroids, azathioprine/mercaptopurine, cyclosporine, or infliximab may be used, induce and/or maintain remission. The various formulations of mesalamine available are primarily differentiated by the methods of delivery of the active compound of the drug to the colon. Mesalamine with Multi-Matrix System® (MMX) technology (Cosmo SpA, Milan, Italy) is an oral (1.2 g), once-daily tablet formulation of mesalamine used for the treatment of UC (Lialda® or Mezavant®, Shire Pharmaceuticals Inc, Wayne, PA). In clinical studies, MMX mesalamine (taken as a once-daily dose of 2.4 or 4.8 g) effectively induced and maintained clinical remission in patients with active mild-to-moderate UC. The overall safety profile of MMX mesalamine is similar to other oral mesalamine formulations. The use of such once-daily formulations has led to intense interest in whether simplified pill regimens can improve patient adherence to mesalamine therapy.

Background. Percutaneous endoscopic gastrostomy (PEG) placement using the “pull” technique is commonly utilized for providing nutritional support in head and neck cancer (HNC) patients, but it may be complicated by peristomal metastasis in up to 3% of patients. Overtube-assisted PEG placement might reduce this risk. However, this technique has not been systemically studied for this purpose to date.Methods. Retrospective analysis of consecutive patients with HNC who underwent overtube-assisted PEG placement at Westmead Hospital, Australia, between June 2011 and December 2013. Data were extracted from patients’ endoscopy reports and case notes. We present our technique for PEG insertion and discuss the feasibility and safety of this method.Results. In all 53 patients studied, the PEG tubes were successfully placed using 25 cm long flexible overtubes, in 89% prophylactically (before commencing curative chemoradiotherapy), and in 11% reactively (for treatment of tumor related dysphagia or weight loss). During a median follow-up period of 16 months, 3 (5.7%) patients developed peristomal infection and 3 others developed self-limiting peristomal pain. There were no cases of overtube-related adverse events or overt cutaneous metastases observed.Conclusions. Overtube-assisted PEG placement in patients with HNC is a feasible, simple, and safe technique and might be effective for preventing cutaneous metastasis.