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Objectives Most previous studies have analyzed bacteria in tumors using resected pancreatic cancer (PC) tissues, because it is difficult to obtain tissue samples from unresectable advanced PC. We aimed to determine whether minimal tissue obtained by endoscopic ultrasound-guided fine-needle aspiration is useful for microbiome analysis. Methods Thirty PC and matched duodenal and stomach tissues (N = 90) were prospectively collected from 30 patients who underwent endoscopic ultrasound-guided fine-needle aspiration. Bacterial DNA was extracted, and 16S rRNA sequencing was performed. The primary outcome was the success rate of bacterial detection in tumors. Bacterial diversity and structure were investigated. Results The bacterial detection rates were 80%, 100%, and 97% in PC, gastric, and duodenal samples, respectively. Pancreatic cancer tissues showed a lower alpha-diversity and a significantly different microbial structure than stomach and duodenal tissues. Proteobacteria were more abundant, whereas Firmicutes, Bacteroidetes, and Fusobacteria were less abundant in PC tissues than in stomach and duodenal tissues. Acinetobacter was more abundant in PC tissues than in stomach and duodenal tissues, and Delftia was more frequently detected in resectable PC. Conclusions Endoscopic ultrasound-guided fine-needle aspiration samples were valuable for PC microbiome analysis, revealing that the bacterial composition of PC is different from that of the stomach and duodenum.

Introduction: Preoperative endoscopic biliary drainage (PEBD) for malignant hilar biliary obstruction (MHBO) is widely accepted. Recent PEBD consists of endoscopic nasobiliary drainage (ENBD), conventional endoscopic biliary stenting (CEBS) with plastic stents across the papilla, and endoscopic biliary inside stenting (EBIS) with plastic stents above the papilla, while ENBD is the primary procedure in Asian countries. Thus, we aimed to compare the efficacy of ENBD with those of CEBS and EBIS as a means of PEBD for MHBO. Methods: We retrospectively identified patients with MHBO who underwent upfront surgery between January 2011 and December 2018 in a multicenter setting. The outcome measures were cumulative dysfunction of PEBD, risk factors for PEBD dysfunction, and adverse events. Results: We analyzed a total of 219 patients, comprising 163 males (74.4%); mean age, 69.7 (±7.6) years; Bismuth-Corlette (BC) classification I, II, IIIa, IIIb, and IV in 68, 49, 43, 30, and 29 patients, respectively; and diagnosis of hilar cholangiocarcinoma and gallbladder cancer in 188 and 31 patients, respectively. PEBD procedures were performed in 160 patients with ENBD, 31 patients with CEBS, and 28 patients with EBIS. PEBD dysfunction occurred in 58 patients (26.5%), and the cumulative dysfunction rates were not significantly different among PEBD methods (p = 0.60). Multivariate analysis showed that BC-IV was significantly associated with the occurrence of PEBD dysfunction (hazard ratio = 2.10, p = 0.02). The adverse event rates were not significantly different among PEBD groups (p = 0.70). Conclusion: ENBD as a means of PEBD for MHBO is comparable with CEBS and EBIS in rates of dysfunction and adverse events.

Background One of the major complications of gastric endoscopic submucosal dissection (ESD) is delayed bleeding. The treatment of exposed vessels after completed dissection should be effective to avoid delayed bleeding. However, it’s sometimes difficult to detect the detection of exposed blood vessels on ulcers induced by ESD. A recent study reported that red dichromatic imaging (RDI) was useful for detecting exposed vessels. In this study, we aimed to measure the visibility of exposed vessels and the quantitative color difference between the exposed vessels and surrounding tissue on ulcers, as observed using RDI after completed dissection. Methods Sixty-four vessels (14 patients) in gastric ESD-induced ulcers were evaluated using both white light imaging (WLI) and RDI. The Commission Internationale de l’Eclairage 1976 (L*a*b*) color space was used to measure the color difference. The color difference was evaluated by comparing the color values of regions of interest for the point of an exposed vessel and three points surrounding an exposed vessel. The visibility of exposed vessels was evaluated using a visibility scoring system. The primary endpoint was color differences (ΔE) between the exposed vessels and surrounding tissue in each modality. Results The average ΔE values (± SEM) for WLI and RDI were 24.85 (± 1.19) and 31.83(± 1.31), respectively. The ΔE value for RDI was significantly higher than that for WLI (p < 0.01). The visibility score was improved in 54.7% (35/64) of cases. Conclusions The color differences between the exposed vessels and surrounding tissue on gastric ESD-induced ulcers were higher with RDI than with WLI, and RDI improved the visibility of exposed vessels.

Hepatocellular carcinoma (HCC) hemorrhaging/rupture is a rare adverse effect of lenvatinib, and only limited pathological examinations have been reported. This report presents the case of a 69-year-old man who suffered from cardiac arrest and died 7 days after starting lenvatinib treatment for HCC, with an autopsy subsequently performed. Crack and coagulated blood were observed in the largest tumor. Pathologically, the hemorrhaging area was scattered in nearly all of the HCC lesions, regardless of tumor differentiation. This pathological feature is unusual in normal HCC. Thus, it is believed to have been the effect of lenvatinib.

Background Few studies have focused on the risk factors for dysfunction of endoscopic biliary drainage (EBD) in preoperative patients with malignant hilar biliary obstruction (MHBO). Methods We searched the database between February 2011 and December 2018 and identified patients with MHBO who underwent radical operation. The rate of dysfunction of the initial EBD, risk factors for dysfunction of the initial EBD and survival after surgery were retrospectively evaluated. Results We analyzed a total of 131 patients [95 males (72.5%); mean age, 69.5 (±7.3) years; Bismuth-Corlette classification (BC) I/II/IIIa/IIIb/IV, 50/26/22/17/16; hilar cholangiocarcinoma/gall bladder cancer, 115/16]. Dysfunction of the initial EBD occurred in 28 patients (21.4%). The cumulative incidences of dysfunction of the initial EBD in all patients were 18.4%, 38.2% and 47.0% at 30, 60 and 90 days, respectively (Kaplan-Meier method). The rate of dysfunction of the initial EBD increased in patients with BC-IV (P = .03). Multivariate analysis showed that BC-IV and pre-EBD cholangitis were significantly associated with the occurrence of dysfunction of the initial EBD. Survival rates were not significantly different according to the initial biliary drainage methods and presence/absence of the initial EBD dysfunction. Conclusions Dysfunction of the initial EBD frequently occurs in patients with the BC-IV and those with pre-EBD cholangitis.

Common bile duct stones (CBDSs) occasionally cause serious diseases, and endoscopic extraction is the standard procedure for CBDS. To prevent biliary complications, cholecystectomy is recommended for patients who present with gallbladder (GB) stones after endoscopic CBDS extraction. However, CBDS can occasionally recur. To date, the occurrence of CBDS after endoscopic CBDS extraction and subsequent cholecystectomy is not fully understood. Hence, the current study aimed to evaluate the incidence of postoperative CBDSs.This retrospective observational study included consecutive patients who underwent postoperative endoscopic retrograde cholangiography after endoscopic CBDS extraction and subsequent cholecystectomy between April 2012 and June 2021 at our institution. After endoscopic CBDS extraction, a biliary plastic stent was inserted to prevent obstructive cholangitis. Endoscopic retrograde cholangiography was performed to evaluate postoperative CBDSs after cholecystectomy until hospital discharge. The outcomes were the incidence of postoperative CBDSs and CBDSs/sludge. Moreover, the predictive factors for postoperative CBDSs were evaluated via univariate and multivariate analyses.Of eligible 204 patients, 52 patients (25.5%) presented with postoperative CBDSs. The incidence rate of CBDS/sludge was 36.8% (n = 75). Based on the univariate analysis, the significant predictive factors for postoperative CBDSs were ≥ 6 CBDSs, presence of cystic duct stones, and ≥ 10 GB stones (P 0.05). Moreover, male sex and 60-mm minor axis in GB might be predictive factors (P 0.10). Based on the multivariate analysis, ≥ 6 CBDSs (odds ratio = 6.65, P 0.01), presence of cystic duct stones (odds ratio = 4.39, P 0.01), and ≥ 10 GB stones (odds ratio = 2.55, P = 0.01) were independent predictive factors for postoperative CBDSs.The incidence of postoperative CBDS was relatively high. Hence, patients with predictive factors for postoperative CBDS must undergo imaging tests or additional endoscopic procedure after cholecystectomy.

Endoscopic dilation for severe benign biliary stricture using mechanical dilation devices is occasionally ineffective. Hence, diathermic dilation has recently been gaining attention as a salvage procedure. We evaluated the short- and long-term outcomes of diathermic dilation for severe benign biliary stricture that could not be dilated using conventional mechanical dilation. Thirteen consecutive cases with severe benign biliary stricture that underwent diathermic dilation using 6-Fr electrocautery dilator were enrolled. Short- and long-term outcomes were analyzed. Diathermic dilation was successful in 13 cases (100%), whereas stent was successfully placed in 12 cases (92.3%). Adverse events occurred in two cases (15.4%): mild hemobilia and cholangitis. Recurrence of bile duct stricture was observed in five out of 12 cases (41. 7%) in the 1115-day median follow-up period. Finally, eight cases achieved stent-free state (61.5%) and have remained stent-free without any episode of cholangitis and abnormal liver function test. Diathermic dilation using 6-Fr electrocautery dilator is a promising salvage procedure for severe benign biliary stricture when the conventional dilation technique has been ineffective.

IntroductionPacing-induced cardiomyopathy occasionally occurs in patients undergoing pacemaker implantation. Although compared with right ventricular (RV) apical pacing, RV septal pacing can attenuate left ventricular dyssynchrony; the success rate of lead placement on the RV septum using the stylet system is low. Additionally, no randomised controlled trial has addressed the issue regarding the accuracy of RV lead placement on the RV septum using the stylet and delivery catheter systems. This study hypothesises that a newly available delivery catheter system can improve the accuracy of RV lead placement on the RV septum.Methods and analysisIn a multicentre, prospective, randomised, single-blind, controlled trial, 70 patients with pacemaker indication owing to atrioventricular block will be randomised to either the delivery catheter or stylet group before the pacemaker implantation procedure. The position of the RV lead tip will be assessed using ECG-gated cardiac CT in all patients within 4 weeks after pacemaker implantation. Lead tip positions are classified into three groups: (1) RV septum, (2) anterior/posterior edge of the RV septal wall and (3) RV free wall. The primary endpoint will be the success rate of RV lead tip placement on the RV septum, which will be evaluated using cardiac CT.Ethics and disseminationThis study will be conducted according to the stipulations of the Helsinki Declaration and the institutional review board of Hamamatsu University School of Medicine. The results of the study will be disseminated at several research conferences and will be published in peer-reviewed journals.Trial registration numberjRCTs042200014; Pre-results.

In an era of ecosystem degradation and climate change, maximizing microbial functions in agroecosystems has become a prerequisite for the future of global agriculture. However, managing species-rich communities of plant-associated microbiomes remains a major challenge. Here, we propose interdisciplinary research strategies to optimize microbiome functions in agroecosystems. Informatics now allows us to identify members and characteristics of 'core microbiomes', which may be deployed to organize otherwise uncontrollable dynamics of resident microbiomes. Integration of microfluidics, robotics and machine learning provides novel ways to capitalize on core microbiomes for increasing resource-efficiency and stress-resistance of agroecosystems.

Purpose To identify risk factors for VNS-associated arrhythmia. Methods A literature review identified 14 papers with 21 patients. We compared patients with VNS associated arrhythmia (arrhythmia group, n = 22) and patients without VNS associated arrhythmia (control group of our VNS implanted patients, n = 29). Results New onset syncopal events following VNS placement were seen in the arrhythmia group (p, Highlights • VNS induced bradycardia was misdiagnosed as new onset epileptic seizure. • Post-VNS new onset syncopal events should be monitored carefully. • Cardiac pacemaker treatment resolved bradycardia.

Ab initio calculations based on the density functional theory (DFT) were performed with respect to the structure and orbital energy values of a simple [HPO3BH]4 cage, and the results were discussed with structural parameters reported for other borophosphonate cages as well as with the calculated orbital energy values of its silsesquioxane analogue, [HSiO1.5]8. In addition, two novel borophosphonate cages capable of use as element-block monomers were prepared from two boronic acid–t-butylphosphonic acid reactions.

OBJECTIVE To elucidate the long-term outcomes of permanent endoscopic biliary stenting (EBS) and risk factors for recurrent biliary obstruction (RBO) in high-risk or elderly patients with common bile duct (CBD) stones. METHODS The electronic database of Hakodate Municipal Hospital was searched to identify elderly or high-risk patients with CBD stones who had undergone permanent EBS using a plastic stent without stone removal and were followed up between April 2011 and May 2019, with no further intervention until symptoms occurred. RESULTS We analyzed a total of 47 patients, of whom 19 (40.4%) were men, with a median age of 86 years (interquartile range 80-90 years). RBO and death without biliary disease occurred in 14 (29.8%) and 19 (40.4%) patients, respectively. The cumulative RBO rates at 20, 40, and 60 months were 22.1%, 31.8%, and 35.5%, respectively. The median time to RBO was 13.0 and 38.0 months in the group with CBD stone ≥15 mm and 11-14 mm in diameter, respectively. The cumulative RBO incidence rate in the group with CBD stone ≤10 mm in diameter did not reach 50%. The cumulative RBO incidence rates were significantly different among the three groups based on the CBD stone diameter (competing risk analysis, P

A covered self-expandable metal stent is an efficient and established tool for solution of biliary obstruction. The use of multiple fully covered self-expandable metal stents (SEMSs) for distal malignant biliary obstruction has never been reported. The first case, a 33-year-old female with pancreatic head cancer had low bifurcation of the hepatic ducts and developed obstructive cholangitis by the first single SEMS. The second case, a-59-year-old female with pancreatic head cancer repeatedly underwent biliary decompression by a single SEMS (10-mm, 12-mm), because placed SEMSs were repeatedly dislocated. For solving these problems, we performed side-by-side placement of covered self-expandable metal stents. Finally, side-by-side placement of SEMSs across the papilla for distal malignant biliary obstruction was feasible and available for the two cases.

No worldwide consensus on the assessment tool for liver functional reserve is currently available. The aim of this study was to evaluate the correlation between liver elasticity of both hepatic lobes and liver functional reserve tests. This prospective observational study comprised 40 patients scheduled for hepatectomy. Liver elasticity was assessed by Virtual Touch Quantification (VTQ). The mean VTQ value for the right and left lobes was defined as the mVTQ. Liver functional reserve was measured with technetium-99m-diethylenetriaminepentaacetic acid-galactosyl-human serum albumin scintigraphy as LHL15 and HH15 and the indocyanine green (ICG) excretion test as ICG-R15 and ICG-K. All examinations were measured after biliary decompression confirmed serum a total bilirubin level

OBJECTIVES: Biliary tract cancer (BTC) is an aggressive malignant tumor, and biomarker-based clinical trials for this cancer are currently ongoing. Endoscopic ultrasound–guided fine needle aspiration (EUS-FNA) is a safe procedure and enables pathological diagnoses; however, it is uncertain whether a tiny tumor sample of BTC obtained through EUS-FNA can be analyzed for diverse genetic alterations in the development and tolerance of BTC. Thus, we aimed to verify the feasibility of genetic analyses with EUS-FNA samples of BTC. METHODS: Targeted amplicon sequencing using a cancer gene panel with 50 genes was performed with tissue samples of 21 BTC patients obtained through EUS-FNA with a novel rapid on-site process compared with paired peripheral blood samples. RESULTS: Pathogenic gene alterations were successfully identified in 20 out of 21 patients (95.2%) with EUS-FNA specimens of BTC, which included 19 adenocarcinomas and 2 adenosquamous carcinomas. Eighty single nucleotide variants and 8 indels in 39 genes were identified in total, and 28 pathogenic alterations in 14 genes were identified (average, 1.4 alterations per patient). The most common alterations were TP53, KRAS, and CDKN2A in gallbladder carcinoma; TP53, KRAS, PIK3CA, and BRAF in intrahepatic cholangiocarcinoma; and TP53 and SMAD4 in extrahepatic cholangiocarcinoma. Actionable gene alterations (BRAF, NRAS, PIK3CA, and IDH1) were identified in 7 out of 21 patients. CONCLUSIONS: A novel approach in genetic analysis using targeted amplicon sequencing with BTC specimens obtained through EUS-FNA was feasible and enabled us to identify genomic alterations.

Weed control is an important practice in the maintenance of grassland and the production of high-quality forage. Weeds usually appear as patches, but often, there are also separate portions of a field that are entirely non-weed. Limiting application of herbicides to only where necessary can generate both environmental and economic benefits. However, weed control is often omitted, because searching for weeds over a field is a laborious process. Therefore, a method to easily obtain weed distribution information is needed to achieve site-specific control. As a first step toward precise weed management, the objective of this study is to develop software to detect curly dock weeds in aerial imagery, and to provide their distribution within a field. A dataset of 9800 images is created by using images of a grassland area taken from an unmanned aerial vehicle (UAV) at an altitude of approximately 10 m, and by cropping each section of weed or grass background from the images. A convolutional neural network (CNN) is trained as a classification model between the weeds and background using the dataset. The trained CNN model is then implemented into a software program. This software successfully detects weeds in extra images with an accuracy of 85.4% and outputs their global coordinates via the image coordinates of the detected weeds and the geo-tag information of the image. Finally, the distribution of weeds within the field can be viewed by mapping the coordinates onto geographic information system (GIS) software.