Objective: Bleeding after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) is a frequent adverse event after ESD. We aimed to develop and externally validate a clinically useful prediction model (BEST-J score: Bleeding after ESD Trend from Japan) for bleeding after ESD for EGC. Design: This retrospective study enrolled patients who underwent ESD for EGC. Patients in the derivation cohort (n=8291) were recruited from 25 institutions, and patients in the external validation cohort (n=2029) were recruited from eight institutions in other areas. In the derivation cohort, weighted points were assigned to predictors of bleeding determined in the multivariate logistic regression analysis and a prediction model was established. External validation of the model was conducted to analyse discrimination and calibration. Results: A prediction model comprised 10 variables (warfarin, direct oral anticoagulant, chronic kidney disease with haemodialysis, P2Y12 receptor antagonist, aspirin, cilostazol, tumour size >30 mm, lower-third in tumour location, presence of multiple tumours and interruption of each kind of antithrombotic agents). The rates of bleeding after ESD at low-risk (0 to 1 points), intermediate-risk (2 points), high-risk (3 to 4 points) and very high-risk (≥5 points) were 2.8%, 6.1%, 11.4% and 29.7%, respectively. In the external validation cohort, the model showed moderately good discrimination, with a c -statistic of 0.70 (95% CI, 0.64 to 0.76), and good calibration (calibration-in-the-large, 0.05; calibration slope, 1.01). Conclusions: In this nationwide multicentre study, we derived and externally validated a prediction model for bleeding after ESD. This model may be a good clinical decision-making support tool for ESD in patients with EGC.

Background and study aims: Endoscopic submucosal dissection (ESD) is a novel technique used for the treatment of gastrointestinal neoplasia. One of its major limitations, however, is the complication of perforation. Patients and methods: We included in our study all the cases of perforation that occurred during ESD procedures for gastrointestinal epithelial neoplasia between February 2000 and February 2005. Clinical outcomes after perforation were investigated. Results: Perforation was experienced at 27 lesions in 27 patients (four in the esophagus, fourteen in the stomach, seven in the colon, and two in the rectum). Fibrosis under the lesions was confirmed histologically in seven patients (26 %). Immediate closure using endoclips was performed in all patients except for three asymptomatic patients in whom a stomach perforation was first noticed when free air was noticed on a radiograph the morning after the ESD procedure. Air accumulation was detected radiographically in 21 patients (78 %). The mean duration of antibiotic treatment was 6.7 days and the patients were fasted for a mean period of 5.3 days. The mean maximum body temperature was 37.3 °C, the mean white blood cell count was 9733/mm³, and the mean C-reactive protein level was 5.0 mg/dl. All the patients were discharged well from the ward after a mean time of 12.1 days after ESD, and no recurrence caused by tumor spread from the perforation occurred in any patient after a median follow-up period of 36 months (range 9 - 52 months). Conclusion: Successful nonsurgical management after ESD complicated by perforation is a highly feasible option if intensive conservative treatments are used following immediate endoscopic closure of the perforation.

Enhanced de novo lipogenesis mediated by sterol regulatory element–binding proteins (SREBPs) is thought to be involved in nonalcoholic steatohepatitis (NASH) pathogenesis. In this study, we assessed the impact of SREBP inhibition on NASH and liver cancer development in murine models. Unexpectedly, SREBP inhibition via deletion of the SREBP cleavage–activating protein (SCAP) in the liver exacerbated liver injury, fibrosis, and carcinogenesis despite markedly reduced hepatic steatosis. These phenotypes were ameliorated by restoring SREBP function. Transcriptome and lipidome analyses revealed that SCAP/SREBP pathway inhibition altered the fatty acid (FA) composition of phosphatidylcholines due to both impaired FA synthesis and disorganized FA incorporation into phosphatidylcholine via lysophosphatidylcholine acyltransferase 3 (LPCAT3) downregulation, which led to endoplasmic reticulum (ER) stress and hepatocyte injury. Supplementation with phosphatidylcholines significantly improved liver injury and ER stress induced by SCAP deletion. The activity of the SCAP/SREBP/LPCAT3 axis was found to be inversely associated with liver fibrosis severity in human NASH. SREBP inhibition also cooperated with impaired autophagy to trigger liver injury. Thus, excessively strong and broad lipogenesis inhibition was counterproductive for NASH therapy; this will have important clinical implications in NASH treatment.

Endoscopic submucosal dissection (ESD) for early gastric cancer is a well-established procedure with the advantage of resection in an en bloc fashion, regardless of the size, shape, coexisting ulcer, and location of the lesion. However, gastric ESD is a more difficult and meticulous technique, and also requires a longer procedure time, than conventional endoscopic mucosal resection. These factors naturally increase the risk of various complications. The two most common complications accompanying gastric ESD are bleeding and perforation. These complications are known to occur both intraoperatively and postoperatively. However, there are other rare but serious complications related to gastric ESD, including aspiration pneumonia, stenosis, venous thromboembolism, and air embolism. Endoscopists should have sufficient knowledge about such complications and be prepared to deal with them appropriately, as successful management of complications is necessary for the successful completion of the entire ESD procedure.