Evaluation of Genetic Variants Associated with the Risk of Thiopurine-Related Pancreatitis: A Case Control Study from ENEIDA Registry.

INTRODUCTION: Risk factors for developing pancreatitis due to thiopurines in patients with inflammatory bowel disease (IBD) are not clearly identified. Our aim was to evaluate the predictive pharmacogenetic risk of pancreatitis in IBD patients treated with thiopurines. METHODS: We conducted an observational pharmacogenetic study of acute pancreatitis events in a cohort study of IBD patients treated with thiopurines from the prospectively maintained ENEIDA registry biobank of GETECCU. Samples were obtained and the CASR, CEL, CFTR, CDLN2, CTRC, SPINK1, CPA1, and PRSS1 genes, selected based on their known association with pancreatitis, were fully sequenced. RESULTS: Ninety-five cases and 105 controls were enrolled; a total of 57% were women. Median age at pancreatitis diagnosis was 39 years. We identified 81 benign variants (50 in cases and 67 in controls) and a total of 35 distinct rare pathogenic and unknown significance variants (10 in CEL, 21 in CFTR, 1 in CDLN2, and 3 in CPA1). None of the cases or controls carried pancreatitis-predisposing variants within the CASR, CPA1, PRSS1, and SPINK1 genes, nor a pathogenic CFTR mutation. Four different variants of unknown significance were detected in the CDLN and CPA1 genes; one of them was in the CDLN gene in a single patient with pancreatitis and 3 in the CPA1 gene in 5 controls. After the analysis of the variants detected, no significant differences were observed between cases and controls. CONCLUSION: In patients with IBD, genes known to cause pancreatitis seem not to be involved in thiopurine-related pancreatitis onset.

Diagnosis of Helicobacter pylori Infection by the Arrangement of Collecting Venules Using White Light Endoscopy: Evaluation of Interobserver Agreement.

BACKGROUND: Regular arrangement of collecting venules (RAC) in gastric mucosa accurately identifies patients without Helicobacter pylori (H pylori) infection. The aim of our study was to evaluate the reproducibility of RAC using white light endoscopy without magnification, in a European country, and to assess the impact of proton pump inhibitors (PPIs). METHODS: A multicenter prospective study with image capture of the distal lesser gastric curvature and gastric biopsies was performed. The presence of starfish-like minute points regularly distributed throughout lesser curvature was considered as RAC positive (RAC+). A set of 20 images was used for the training phase and inter and intra-observer agreements were calculated. RESULTS: 174 patients were included and 85 (48.9%) were taking PPIs. Kappa values for interobserver and intra-observer agreements were substantial (0.786) and excellent (0.906), respectively. H. pylori infection was diagnosed in 29 patients (16.7%): 10/85 with PPIs and 19/89 without PPIs (11.8% vs. 21.3%; p = 0.09). All RAC + patients were free of H. pylori infection, with a sensitivity and negative predictive value of 100%, regardless of PPI intake. CONCLUSION: The endoscopic diagnosis of H. pylori by RAC is an easy-to-learn and highly reproducible technique, even with PPI intake. Our results warrant RAC as a real-time diagnostic method for H. pylori-negative infection in Western practice.

Gastroenterologists' attitudes on the detection and management of gastric premalignant conditions: results of a nationwide survey in Spain.

INTRODUCTION: Gastric premalignant conditions (GPC) surveillance has been proposed to improve the prognosis of gastric cancer (GC), but the early GC detection rate remaining low, and missing GC during an esophago-gastro-duodenoscopy is still a problem. We aimed to explore the gastroenterologists' attitudes on the detection and management of GPC. METHODS: A cross-sectional study was designed based on a survey among gastroenterologists from Asociación Española de Gastroenterología. RESULTS: The participation rate was 12% (146/1243). Eighty-one percent worked at secondary or tertiary-care hospitals with the capability to perform mucosectomy (80%), but with a lesser availability of endoscopic submucosal dissection (35%). Most respondents had high-definition endoscopes (88%), and virtual chromoendoscopy (86%), but during performing an upper endoscopy, 34% never or rarely use chromoendoscopy, and 73% apply a biopsy protocol often/very often when atrophy or intestinal metaplasia (IM) is suspected. Half of the respondents self-reported their ability to recognize atrophy or IM ≤7 (on a scale from 0 to 10), whereas ≤6 for dysplasia or early GC. Helicobacter pylori infection is eradicated and verified by ≥90%. Endoscopic surveillance of atrophy/IM is performed by 62%. An immediate endoscopy for dysplasia is not always performed. For low-grade dysplasia, 97.6% consider endoscopic management, but for high-grade dysplasia, 23% regard gastric surgery. CONCLUSION: There is a wide variability in the detection and management of GPC among Spanish gastroenterologists, and compliance with guidelines and biopsy protocols could be improved. Performance of high-quality gastroscopies including use of virtual chromoendoscopy, that might allow an improvement in the GPC detection, needs also to be generalized.

Gastric cancer missed at esophagogastroduodenoscopy in a well-defined Spanish population.

BACKGROUND: Although esophagogastroduodenoscopy (EGD) is the standard procedure for the diagnosis of gastric cancer (GC), some GCs are missed. There are no published data on the missed rate of GC in Spain. AIMS: To determine the frequency and characteristics of missed GCs and assess the quality of the EGD in a specific population with GC. METHODS: Records of all patients diagnosed with gastric adenocarcinoma between 2012 and 2016 in a defined geographic area were reviewed. Missed GC was defined as a case with a prior negative EGD for cancer. Quality indicators from the prior EGDs were measured. RESULTS: From 212 cases of GC, 25 cases were excluded. Seventeen out of 187 patients had a prior EGD (9.1%). Twelve of those 17 missed GC had a prior EGD with some abnormal findings. In 6 of them, biopsies were taken. Survival was no different between patients with missed and non-missed GC. Quality indicators that failed to meet standards were recording time, image documentation, and a protocol of biopsies. CONCLUSIONS: Missed GC in an EGD in a defined population in Spain is not uncommon (9.1%). The endoscopist is an important factor in missed GC due to lack of adequate detection and sampling error. Compliance with performance of quality indicators could reduce missed GC.