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Background & Aims Adenoma detection rate (ADR) is an important quality assurance measure for colonoscopy. Some studies suggest that narrow-band imaging (NBI) may be more effective at detecting adenomas than white-light endoscopy (WLE) when bowel preparation is optimal. We conducted a meta-analysis of data from individual patients in randomized controlled trials that compared the efficacy of NBI to WLE in detection of adenomas. Methods We searched MEDLINE, EMBASE, and Cochrane Library databases through April 2017 for randomized controlled trials that assessed detection of colon polyps by high-definition WLE vs NBI and from which data on individual patients were available. The primary outcome measure was ADR adjusted for bowel preparation quality. Multilevel regression models were used with patients nested within trials, and trial included as a random effect. Results We collected data from 11 trials, comprising 4491 patients and 6636 polyps detected. Adenomas were detected in 952 of 2251 (42.3%) participants examined by WLE vs 1011 of 2239 (45.2%) participants examined by NBI (unadjusted odds ratio [OR] for detection of adenoma by WLE vs NBI, 1.14; 95% CI, 1.01–1.29; P = .04). NBI outperformed WLE only when bowel preparation was best: adequate preparation OR, 1.07 (95% CI, 0.92–1.24; P = .38) vs best preparation OR, 1.30 (95% CI, 1.04–1.62; P = .02). Second-generation bright NBI had a better ADR than WLE (second-generation NBI OR, 1.28; 95% CI, 1.05–1.56; P = .02), whereas first-generation NBI did not. NBI detected more non-adenomatous polyps than WLE (OR, 1.24; 95% CI, 1.06–1.44; P = .008) and flat polyps than WLE (OR, 1.24; 95% CI, 1.02–1.51; P = .03). Conclusions In a meta-analysis of data from individual patients in randomized controlled trials, we found NBI to have a higher ADR than WLE, and that this effect is greater when bowel preparation is optimal.

Background & Aims A system is needed to determine the risk of patients with Barrett's esophagus for progression to high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC). We developed and validated a model to determine of progression to HGD or EAC in patients with BE, based on demographic data and endoscopic and histologic findings at the time of index endoscopy. Methods We performed a longitudinal study of patients with BE at 5 centers in United States and 1 center in Netherlands enrolled in the Barrett's Esophagus Study database from 1985 through 2014. Patients were excluded from the analysis if they had less than 1 year of follow up, were diagnosed with HGD or EAC within the past year, were missing baseline histologic data, or had no intestinal metaplasia. Seventy percent of the patients were used to derive the model and 30% were used for the validation study. The primary outcome was development of HGD or EAC during the follow-up period (median 5.9 years). Survival analysis was performed using the Kaplan-Meier method. We assigned a specific number of points to each BE risk factor, and point totals (scores) were used to create categories of low, intermediate, and high risk. We used Cox regression to compute hazard ratios (HR) and 95% CIs to determine associations between risk of progression and scores. Results Of 4584 patients in the database, 2697 were included in our analysis (84.1% men; 87.6% Caucasian; mean age, 55.4±20.1 years; mean body mass index, 27.9±5.5; mean length of BE, 3.7 cm±3.2). During the follow-up period, 154 patients (5.7%) developed HGD or EAC, with an annual rate of progression of 0.95%. Male sex, smoking, length of BE, and baseline-confirmed low-grade dysplasia were significantly associated with progression. Scores assigned identified patients with BE that progressed to HGD or EAC with a c-statistic of 0.76 (95% CI, 0.72–0.80) ( P P =.99), determined from the validation cohort. Conclusions We developed a scoring system (called progression of BE (PIB) score) based on male sex, smoking, length of BE, and baseline low-grade dysplasia) that identified patients with BE at low, intermediate, and high risk groups for HGD or EAC. This scoring system might be used in management of patients.

The development of and adherence to quality indicators in gastroenterology, as in all of medicine, is increasing in importance to ensure that patients receive consistent high-quality care. In addition, government-based and private insurers will be expecting documentation of the parameters by which we measure quality, which will likely affect reimbursements. Barrett’s esophagus remains a particularly important disease entity for which we should maintain up-to-date guidelines, given its commonality, potentially lethal outcomes, and controversies regarding screening and surveillance. To achieve this goal, a relatively large group of international experts was assembled and, using the modified Delphi method, evaluated the validity of multiple candidate quality indicators for the diagnosis and management of Barrett’s esophagus. Several candidate quality indicators achieved >80% agreement. These statements are intended to serve as a consensus on candidate quality indicators for those who treat patients with Barrett’s esophagus.

BACKGROUND & AIMS: Topically applied methylene blue dye chromoendoscopy is effective in improving detection of colorectal neoplasia. When combined with a pH- and time-dependent multimatrix structure, a per-oral methylene blue formulation (MB-MMX) can be delivered directly to the colorectal mucosa. METHODS: We performed a phase 3 study of 1205 patients scheduled for colorectal cancer screening or surveillance colonoscopies (50-75 years old) at 20 sites in Europe and the United States, from December 2013 through October 2016. Patients were randomly assigned to groups given 200 mg MB-MMX, placebo, or 100 mg MB-MMX (ratio of 2:2:1). The 100-mg MB-MMX group was included for masking purposes. MB-MMX and placebo tablets were administered with a 4-L polyethylene glycol-based bowel preparation. The patients then underwent colonoscopy by an experienced endoscopist with centralized double-reading. The primary endpoint was the proportion of patients with 1 adenoma or carcinoma (adenoma detection rate [ADR]). We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for differences in detection between the 200-mg MB-MMX and placebo groups. False-positive (resection rate for non-neoplastic polyps) and adverse events were assessed as secondary endpoints. RESULTS: The ADR was higher for the MB-MMX group (273 of 485 patients, 56.29%) than the placebo group (229 of 479 patients, 47.81%) (OR 1.46; 95% CI 1.09-1.96). The proportion of patients with nonpolypoid lesions was higher in the MB-MMX group (213 of 485 patients, 43.92%) than the placebo group (168 of 479 patients, 35.07%) (OR 1.66; 95% CI 1.21-2.26). The proportion of patients with adenomas ≤5 mm was higher in the MB-MMX group (180 of 485 patients, 37.11%) than the placebo group (148 of 479 patients, 30.90%) (OR 1.36; 95% CI 1.01-1.83), but there was no difference between groups in detection of polypoid or larger lesions. The false-positive rate did not differ significantly between groups (83 [23.31%] of 356 patients with non-neoplastic lesions in the MB-MMX vs 97 [29.75%] of 326 patients with non-neoplastic lesions in the placebo group). Overall, 0.7% of patients had severe adverse events but there was no significant difference between groups. CONCLUSIONS: In a phase 3 trial of patients undergoing screening or surveillance colonoscopies, we found MB-MMX led to an absolute 8.5% increase in ADR, compared with placebo, without increasing the removal of non-neoplastic lesions. Clinicaltrials.gov no: NCT01694966. ispartof: GASTROENTEROLOGY vol:156 issue:8 pages:2198-+ ispartof: location:United States status: published

Background & Aims There is suboptimal inter-observer agreement, even among expert gastrointestinal pathologists, in the diagnosis of low-grade dysplasia (LGD) in patients with Barrett's esophagus (BE). We analyzed histopathologic criteria required for a diagnosis of LGD using the new subcategories of LGD with inflammatory and dysplastic features. We categorized each diagnosis based on the level of confidence and assessed inter-observer agreement among gastrointestinal pathologists from 5 tertiary centers in the United States and Europe. Methods In the first phase of the study, 3 pathologists held a consensus conference at which they discussed the diagnostic criteria for LGD. In the second phase, 79 slides from patients with BE (23 samples of non-dysplastic BE, 22 samples of LGD, and 34 samples of high-grade dysplasia) were identified, randomly assigned to 7 pathologists (4 from the United States and 3 from Europe), and interpreted in a blinded fashion. κ Values were calculated for inter-observer agreement. We performed multinomial logistic regression analysis to assess the weighting of histologic features with the diagnosis. Results The overall κ value for diagnosis was 0.43 (95% confidence interval [CI], 0.42−0.48). When categorized based on degree of dysplasia, the κ value was 0.22 (95% CI, 0.11−0.29) for non-dysplastic BE, 0.11 (95% CI, 0.004−0.15) for LGD, and 0.43 (95% CI, 0.36−0.46) for high-grade dysplasia. When all pathologists made a diagnosis with high confidence, the inter-observer agreement was substantial among the US pathologists (κ, 0.63; 95% CI, 0.61−0.66) and European pathologists (κ, 0.80; 95% CI, 0.74−0.97). The κ values for all diagnoses made by European pathologists were higher than those made by US pathologists. Conclusions In an analysis of criteria used in histopathologic diagnosis of LGD, we did not observe improvement in level of agreement among experienced pathologists, even after accounting for inflammation. The level of inter-observer agreement increased with level of pathologist confidence. There was also a difference in reading of histopathology samples of BE tissues between US and European pathologists.

Background & Aims Recent population-based studies have shown a low risk of esophageal adenocarcinoma (EAC) in patients with nondysplastic Barrett's esophagus (NDBE). We evaluated whether persistence of NDBE over multiple consecutive surveillance endoscopic examinations could be used in risk stratification of patients with Barrett's esophagus (BE). Methods We performed a multicenter outcomes study of a large cohort of patients with BE. Based on the number of consecutive surveillance endoscopies showing NDBE, we identified 5 groups of patients. Patients in group 1 were found to have NDBE at their first esophagogastroduodenoscopy (EGD). Patients in group 2 were found to have NDBE on their first 2 consecutive EGDs. Similarly, patients in groups 3, 4, and 5 were found to have NDBE on 3, 4, and 5 consecutive surveillance EGDs. A logistic regression model was built to determine whether persistence of NDBE independently protected against development of cancer. Results Of a total of 3515 patients with BE, 1401 patients met the inclusion criteria (93.3% white; 87.5% men; median age, 60 ±17 years). The median follow-up period was 5 ± 3.9 years (7846 patient-years). The annual risk of EAC in groups 1 to 5 was 0.32%, 0.27%, 0.16%, 0.2%, and 0.11%, respectively ( P for trend = .03). After adjusting for age, sex, and length of BE, persistence of NDBE, based on multiple surveillance endoscopies, was associated with a gradually lower likelihood of progression to EAC. Conclusions Persistence of NDBE over several endoscopic examinations identifies patients who are at low risk for development of EAC. These findings support lengthening surveillance intervals or discontinuing surveillance of patients with persistent NDBE.

Background/Purpose: Visceral hypersensitivity for acid, extension and temperature stimuli in stomach and duodenum are involved in functional dyspepsia (FD). While the involvement of TRPV1 and TRPA1 have been reported in a number of animal experiments, data remains conflicting. On the other hand, ATP-gated ion channels, especially P2X3 receptor have recently been worthy of attention for its role in visceral hypersensitivity. We have reported that TRPV4 is expressed in esophageal, gastric and intestinal epithelia (J Physiol 2011, DDW2013, Am J Physiol 2013) and that ATP exocytosis is induced by TRPV4 activation in esophageal keratinocytes. We hypothesized that various physiological stimuli induced ATP release from gastric and duodenal (intestinal) epithelia through each different receptor and that excessive ATP release was involved in the pathophysiology of visceral hypersensitivity. METHODS: TRPV4 expression was examined in normal rat gastric epithelial cell line (RGE), human gastric cancer cell line (AGS) and rat intestinal cell line (IEC-6) by RT-PCR, immunostaining or Western blotting. ATP releases responding to various physiological stimuli (chemicals, low osmotic pressure, acid, extension, temperature) from each cell line were examined using luciferin-luciferase reaction. Acidic (pH 4.0), warm (40 °C) and standard (25 °C, pH7.4) solutions were used as acidic, warm stimuli or a control, respectively. Stretch stimuli was applied to cells cultured on a silicon chamber using a stretching apparatus (STREX Inc, Osaka, Japan). RESULTS: TRPV4 was expressed in RGE, IEC-6 but not in AGS. Specific TRPV4 agonist (GSK1016790A) or endogenous TRPV4 activator (5,6-EET) significantly enhanced ATP release from RGE cells but not AGS. Low osmotic, acidic, stretch or temperature stimuli significantly enhanced ATP release in RGE or IEC-6 cells. Stretchinduced ATP release from RGE cells was inhibited by pretreatment with a specific TRPV4 inhibitor, HC067047. Cell viability after each stimulus was confirmed by Trypan blue staining. Conclusion: Gastric and duodenal (intestinal) epithelial cells release ATP responding various physiological stimuli partially via TRPV4 activation . Excessive ATP release from epithelial cells might be involved in the pathophysiology of visceral hypersensitivity.

Increased Detection of Barrett's Esophagus (BE)-Associated Neoplasia Using Wide-Area Trans-Epithelial Sampling in Conjunction With 4-Quadrant Biopsies: Interim Results From a Multi-Center, Prospective, Randomized Trial Prashanth Vennalaganti, Glenn Eisen, Gary W. Falk, Lauren B. Gerson, Seth A. Gross, John R. Goldblum, Neil Gupta, Gregory B. Haber, Anthony Infantolino, Prasad G. Iyer, David A. Johnson, Vivek Kaul, Shivangi Kothari, Charles J. Lightdale, Nicholas J. Shaheen, Michael S. Smith, Felice Schnoll-Sussman, Kenneth K. Wang, Yaxia Zhang, Prateek Sharma

Background: Abdominal pain is a common reason for ER visits. Acid suppression therapy (AST) using proton pump inhibitors and H2-blockers is commonly prescribed in ER for abdominal pain. As inappropriate use of AST can contribute to drug interactions, pneumonia, and increased health care expenditure, we wanted to look for factors which influence prescribing patterns of AST in ER. Objectives: To evaluate if age, gender differences, severity of abdominal pain and length of ER stay influence prescription of acid suppression therapy (AST) in patients presenting to ER with abdominal pain. Methods: We analyzed the limited access dataset of National Hospital Ambulatory Medical Care Survey (2006 to 2009) for ER visits. We included all patients above 15 years of age presenting to ER with upper abdominal pain. We calculated and compared AST prescription rates based on age, gender, severity of pain and length of ER visit. Statistical analysis was done using multivariate logistic regression. Results: There were a total of 1, 12,810 patient visits. Of these, 11,496 visits were for abdominal pain consisting of 70% women and 30% men. Men were 36% more likely to receive AST compared to women (OR 1.35 95% CI 1.18 to 1.57). Patients in age group 45-64 years were more likely to receive AST compared to younger age groups (OR 1.32 CI 1.11 to 1.56). Patients with ER visit longer than 9 hours were more likely to receive AST compared to shorter ER visits (OR 1.82 CI 1.43 to 2.30). Patients with severe abdominal pain were more likely to receive AST compared to patients with milder degree of pain (OR 1.37 CI 1.08 to 1.74). Conclusion: Age, gender differences, length of ER visit and severity of abdominal pain have significant impact on the prescription of AST for the treatment of abdominal pain in ER. The higher prevalence of gastritis/ ulcers in men and presence of additional sources of abdominal pain in women could explain the higher prescription rate in men. Middle aged patients have higher AST prescription rate which probably reflects the higher prevalence of upper GI pathology as patients get older. A tendency to prescribe AST when a definite diagnosis is not reached or when pain is refractory could explain the higher prescription rates in patients with longer ER visits and severe abdominal pain. Further studies are needed to investigate and frame guidelines for appropriate use of AST.