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Chromatin architecture governs cell lineages by regulating the specific gene expression; however, its role in the diversity of cancer development remains unknown. Among pancreatic cancers, pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasms (IPMN) with an associated invasive carcinoma (IPMNinv) arise from 2 distinct precursors, and their fundamental differences remain obscure. Here, we aimed to assess the difference of chromatin architecture regulating the transcriptional signatures or biological features in pancreatic cancers.We established 28 human organoids from distinct subtypes of pancreatic tumors, including IPMN, IPMNinv, and PDAC. We performed exome sequencing (seq), RNA-seq, assay for transposase-accessible chromatin-seq, chromatin immunoprecipitation-seq, high-throughput chromosome conformation capture, and phenotypic analyses with short hairpin RNA or clustered regularly interspaced short palindromic repeats interference.Established organoids successfully reproduced the histology of primary tumors. IPMN and IPMNinv organoids harbored GNAS, RNF43, or KLF4 mutations and showed the distinct expression profiles compared with PDAC. Chromatin accessibility profiles revealed the gain of stomach-specific open regions in IPMN and the pattern of diverse gastrointestinal tissues in IPMNinv. In contrast, PDAC presented an impressive loss of accessible regions compared with normal pancreatic ducts. Transcription factor footprint analysis and functional assays identified that MNX1 and HNF1B were biologically indispensable for IPMN lineages. The upregulation of MNX1 was specifically marked in the human IPMN lineage tissues. The MNX1-HNF1B axis governed a set of genes, including MYC, SOX9, and OLFM4, which are known to be essential for gastrointestinal stem cells. High-throughput chromosome conformation capture analysis suggested the HNF1B target genes to be 3-dimensionally connected in the genome of IPMNinv.Our organoid analyses identified the MNX1-HNF1B axis to be biologically significant in IPMN lineages.

Background & Aims We performed a large, multicenter, randomized controlled trial to determine the efficacy and safety of early colonoscopy on outcomes of patients with acute lower gastrointestinal bleeding (ALGIB). Methods We performed an open-label study at 15 hospitals in Japan of 170 patients with ALGIB randomly assigned (1:1) to groups that underwent early colonoscopy (within 24 hours of initial visit to the hospital) or elective colonoscopy (24–96 hours after hospital admission). The primary outcome was identification of stigmata of recent hemorrhage (SRH). Secondary outcomes were rebleeding within 30 days, endoscopic treatment success, need for transfusion, length of stay, thrombotic events within 30 days, death within 30 days, and adverse events. Results SRH were identified in 17 of 79 patients (21.5%) in the early colonoscopy group vs 17 of 80 patients (21.3%) in the elective colonoscopy group (difference, 0.3; 95% confidence interval, –12.5 to 13.0; P = .967). Rebleeding within 30 days of hospital admission occurred in 15.3% of patients in the early colonoscopy group and 6.7% of patients in the elective colonoscopy group (difference, 8.6; 95% confidence interval, –1.4 to 18.7); there were no significant differences between groups in successful endoscopic treatment rate, transfusion rate, length of stay, thrombotic events, or death within 30 days. The adverse event of hemorrhagic shock occurred during bowel preparation in no patient in the early group vs 2 patients (2.5%) in the elective colonoscopy group. Conclusions In a randomized controlled study, we found that colonoscopy within 24 hours after hospital admission did not increase SRH or reduce rebleeding compared with colonoscopy at 24–96 hours in patients with ALGIB. ClinicalTrials.gov, Numbers: UMIN000021129 and NCT03098173

Question: An asymptomatic, 31-year-old man was referred to our hospital because of a gastric tumor. He underwent esophagogastroduodenoscopy as part of a health checkup, which revealed a gastric submucosal tumor (SMT) approximately 30 mm in size in the upper third of the greater wall of the stomach (Figure A). Physical examination was within normal limits. On endoscopic ultrasonography (EUS), the mass, a 20 23-mm lesion, involved the fourth layer of the gastric wall, and a hypoechoic homogeneous pattern was seen (Figure B, see Supplementary Video 1). Abdominal computed tomography revealed an ellipsoidal uniformly enhancing mass with intra-gastric growth (Figure C). From these examinations, an endoscopic diagnosis of gastric mesenchymal tumor with intramural growth as made. EUS-guided fine needle aspiration biopsy (FNA) with a 22-gauge needle attached to suction (EchoTip Ultra; Cook Medical, Cook, apan) was performed to obtain a tissue diagnosis (Figure D). What is the differential diagnosis? Look on page 1121 for the answer and see the GASTROENTEROLOGY web site (www.gastrojournal.org) for more information n submitting your favorite image to Clinical Challenges and Images in GI. Acknowledgments: The authors are grateful to Dr Kazumichi Kawakubo (Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan) for technical assistance.

BACKGROUND: Recently, there has been a growing body of evidence suggesting a relationship between H. pylori gastritis and hypoferritinemia or IDA . AIM: To systematically review the role of H. pylori infection in hypoferritinemia and IDA, and to perform a meta-analysis of case-control studies. METHODS: Selection of studies: Case-control studies comparing a) the prevalence of H. pylori infection in patients with and without IDA/hypoferritinemia, and b) the prevalence of IDA/hypoferritinemia in patients with and without H. pylori infection. Search strategy: electronic and manual bibliographical searches. Data synthesis: Meta-analysis combining the Odds Ratios (OR). RESULTS: a) Eight studies compared the prevalence of H. pylori infection in patients with (637 patients) and without (2,305 patients) IDA, showing a higher prevalence of H. pylori infection in anaemic patients (34% vs. 22%; OR=1.6; 95%CI= 1.26-2.03). Only one study compared the prevalence of infection in patients with and without hypoferritinemia (29% vs. 19%; p

Backgrounds: Eradication of Helicobacter pylori (HP) has been reported to result in regression of gastric low-grade MALT lymphoma (LG-MALT) in 60 to 92% of cases. However, It is controversial on which timing and by which wayan additional treatment should be started in cases of persistent lymphoma. Aims: In order to know the optimal timing of additional treatments after eradication, we investigated the time course of the histological and endoscopic changes in LG-MALT. Patients & Methods: From December 1993 to October 1999, 45 patients (mean age: 55 y.o., M!F: 22/23) with LG-MALT and positive HP were treated with two weeks triple therapy (Iansoprazole: 30 mg/day, clarithromycin: 400 mg/day and arnoxicillin: 1500 mg/day). Endoscopic examinations were performed I and 3 months after eradication and then every 3 months (median follow-up duration: 18 months, range I to 66 montbs). Histological evaluation of biopsy was graded according to Wotherspoon AC et al (Lancet 1993;342: 575-77) and persistent lymphoma was defined as grade 4 and 5 and disappearance as grade 0 to 2. Results: HP was eradicated successfully in all patients. Lymphoma has disappeared histologically in 32 patients (71%) (the median duration between eradication and disappearance of lymphoma is 6 months, range I to 45 months). Histological persistence on endoscopic regression has been observed in 6 patients, in none of whom new lesions have appeared without additional treatments (median follow-up duration: 6 months, range 3 to 45 months). An Additional surgery was performed in 3 patients with persistent lymphoma on endoscopic progression 12, 12 and 34 months after eradication, respectively. The latter patient resulted in the appearance of paraaortic lymph node involvement and an additional chemotherapy had to be performed. The other 4 patients have been followed with histological grade 3 on endoscopic regression. Conclusions: We did not find the optimal timing of an additional treatment for persistent lymphoma. Histological evaluation alone is not enough to decide whether an additional treatment should be performed. To watch until endoscopic progression, on the other hand, may make the optimal timing lost like the matastatic case we experienced. To know the optimal timing, a new predictive maker possible to evaluate on the molecular level is needed.