Endoscopic Ultrasound-Guided Biliary Drainage for Unresectable Hilar Malignant Biliary Obstruction

Endoscopic transpapillary biliary drainage is the current standard of care for unresectable hilar malignant biliary obstruction (MBO) and bilateral metal stent placement is shown to have longer patency. However, technical and clinical failure is possible and percutaneous transhepatic biliary drainage (PTBD) is sometimes necessary. Endoscopic ultrasound-guided biliary drainage (EUS-BD) is increasingly being reported as an alternative rescue procedure to PTBD. EUS-BD has a potential advantage of not traversing the biliary stricture and internal drainage can be completed in a single session. Some approaches to bilateral biliary drainage for hilar MBO under EUS-guidance include a bridging method, hepaticoduodenostomy, and a combination of EUS-BD and transpapillary biliary drainage. The aim of this review is to summarize data on EUS-BD for hilar MBO and to clarify its advantages over the conventional approaches such as endoscopic transpapillary biliary drainage and PTBD

Life sciences

Aims: To examine the circadian expression changes in bladder clock genes in Dahl salt-sensitive rats following high salt intake. Main methods: Eighteen rats were divided into three groups: the high-salt diet group (HS group), the normal-salt diet group (NS group), and the salt-load interruption group (from a 4 % salt diet to a normal diet; salt-load interruption group [SI group]). Each rat was placed in an individual metabolic cage for 24 h twice weekly. Water intake, urine production, voiding frequency, and voided volume per micturition were recorded. Furthermore, 108 control rats were prepared. Bladders were harvested every 4 h at six time points. Furthermore, the mRNA expression of clock genes and mechanosensors was analyzed. Key findings: In the HS group, the bladder clock genes showed lower mRNA levels than in the NS group. The amplitude of circadian expression changes in bladder clock genes in the HS group was lower than that in the NS group. However, after changing from a 4 % salt diet to a normal diet, the waveforms of the clock gene expression in the SI group were closer to those of the NS group. The 24-h water intake and urinary volume of the SI group decreased to levels comparable to those of the NS group. Significance: Reduced salt intake partially restored the circadian rhythms of bladder clock genes.博士（医学）・甲第857号・令和4年12月22日Copyright © 2022 Elsevier Inc. All rights reserved

Multicenter retrospective and comparative study of 5-minute versus 15-second endoscopic papillary balloon dilation for removal of bile duct stones

Background and study aims Endoscopic papillary balloon dilation (EPBD) is a method of bile duct stone removal that has a better long-term outcome but a high risk of post-ERCP pancreatitis (PEP). Recent studies have suggested that 5-minute EPBD can reduce the incidence of PEP. This study aimed to examine the safety and effectiveness of longer duration EPBD compared with shorter duration EPBD (5 minutes vs. 15 seconds after disappearance of the waist of a dilation catheter). Patients and methods Patients without a history of endoscopic sphincterotomy or EPBD who underwent EPBD to remove bile duct stones were selected retrospectively from five centers. The incidence of PEP, other early adverse events, and outcomes of EPBD were compared between the groups. A multivariable analysis of risk factors for PEP was performed. Results: A total of 607 patients (157 and 450 in the 5-minute and 15-second EPBD groups, respectively) were included. There were no statistically significant differences between the groups in terms of the incidence of PEP (8.3 % and 8.9 % in the 5-minute and 15-second EPBD groups, respectively; P = 0.871) and the incidence of overall early adverse events ( P = 0.999). Although 5-minute EPBD elongated the procedure time (45 vs. 37 minutes, P < 0.001), it increased the rate of complete stone removal during a single session ( P < 0.001) and decreased the use of lithotripsy ( P < 0.001). Conclusions: Compared with 15-second EPBD, 5-minute EPBD did not reduce the incidence of PEP

TOKYO criteria: Standardized reporting system for endoscopic biliary stent placement

Placement of a plastic or metal stent via endoscopic retrograde cholangiopancreatography (ERCP) currently serves as the first-line procedure for obstructive jaundice and acute cholangitis. Dysfunction of the biliary stent causes recurrence of symptoms and often requires reinterventions and hospitalizations. Therefore, duration of stent patency is commonly used as the primary endpoint in clinical studies of biliary stents. However, owing to considerable heterogeneity between studies in reporting of biliary stent patency, it has been difficult to compare and integrate results of independent studies. There has been between-study heterogeneity in definitions of stent patency, statistics reported for survival curves of stent patency, and methods to treat censored cases. In addition to stent occlusion, stent migration is a major cause of recurrent biliary obstruction after covered metal stent placement, which further complicates the reporting of stent patency. Reporting of functional success and adverse events has been also inconsistent between the studies. From the perspective of evidence-based medicine, the variations in the definitions of outcome variables potentially hinder robust meta-analyses. To overcome the issues due to the lack of outcome reporting guidelines on the topic, the TOKYO criteria 2014 for reporting outcomes associated with endoscopic transpapillary placement of biliary stents have been proposed. Due to their comprehensiveness, the TOKYO criteria can be readily utilized to evaluate various types of biliary stent placement using ERCP, irrespective of types of stents and location of biliary stricture. In this article, we review the TOKYO criteria as a standardized reporting system for endoscopically-placed biliary stents. We also discuss potential controversial issues in the application of the TOKYO criteria. Given that endoscopic ultrasound-guided biliary drainage is increasingly utilized for cases with failed ERCP or altered gastrointestinal anatomy, we further propose a potential application of the TOKYO criteria to reporting of outcomes of this procedure

Usefulness of stent placement above the papilla, so-called, ‘inside stent’

Stent occlusion and cholangitis are common complications after endoscopic biliary stenting caused by duodenobiliary refluxes and food impaction. To prolong the stent patency, the concept of stenting above the papilla, so-called inside stent, has been developed. Various studies of the inside stent in the treatment of both benign and malignant biliary obstruction have been published, with a promising result. However, most studies were retrospective, with wide variation of stent type and the etiology of biliary obstruction. This review aims to summarize the principle, evidence, and the usefulness of inside biliary stent

PC3-secreted microprotein is expressed in glioblastoma stem-like cells and human glioma tissues

Glioblastoma multiforme (GBM) is the most prevalent malignant primary brain tumor with a high recurrence rate. Despite multimodal therapy including surgical resection, chemotherapy, and radiotherapy, the median survival time after the initial diagnosis of GBM is approximately 14 months. Since cancer stem cells (CSCs) are considered the leading cause of cancer recurrence, glioblastoma stem cell-targeted therapy is a promising strategy for the treatment of GBM. However, because CSC heterogeneity has been implicated in the difficulties of CSC-target therapy, more in-depth knowledge of CSC biology is still required to develop novel therapies. In this study, we established single cell-derived tumorspheres from human glioblastoma U87MG cells. One of these tumorspheres, P4E8 clone, showed CSC-like phenotypes, such as self-renewal capacity, expression of CSC markers, resistance to anti-cancer agents, and in vivo tumorigenicity. Therefore, we used P4E8 cells as a cell-based model of glioblastoma stem cells (GSCs). Gene expression analysis using microarray indicated that the most highly expressed genes in P4E8 cells compared to the parental U87MG were PC3-secreted microprotein (MSMP). Furthermore, MSMP was expressed in patient-derived GSCs and human glioma tissues at the protein level, implying that MSMP might contribute to glioma development and progression