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Background: Diagnosing biliary tract cancer is difficult because endoscopic retrograde cholangiopancreatography (ERCP) is performed fluoroscopically, and the sensitivity of bile cytology is low. Liquid biopsy of bile using targeted sequencing is expected to improve diagnosis and treatment, but few studies have been conducted. In this study, we examined whether liquid biopsy of bile improves the diagnostic sensitivity of biliary strictures. Methods: A total of 72 patients with biliary strictures who underwent ERCP at Chiba University Hospital between April 2018 and March 2021 were examined. Of these, 43 and 29 were clinically and pathologically diagnosed as having malignant and benign biliary strictures, respectively. We performed targeted sequencing of bile obtained from these patients, and the sensitivity of this method was compared with that of bile cytology. Detection of at least one oncogenic mutation was defined as having malignancy. Results: The sensitivity of bile cytology was 27.9%, whereas that of genomic analysis was 46.5%. Comparing bile cytology alone with the combination of cytology and genomic analysis, the latter was more sensitive (53.5%, p <.001). Among the 43 patients with malignant biliary strictures, mutations with FDA‐approved drugs were detected in 11 (26%). Conclusions: Liquid biopsy of bile can potentially diagnose malignancy and detect therapeutic targets. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to compare the treatment outcomes of endoscopic papillary large-balloon dilation (EPLBD) with and without mechanical lithotripsy (ML) in removing difficult common bile duct stones. Methods: Patients with difficult common bile duct stones treated with EPLBD, with or without ML, at the Eastern Chiba Medical Center between April 2014 and March 2020, were retrospectively evaluated. The rates of cumulative recurrence and complications were compared between the two groups. Results: Overall, 122 patients (n = 44, EPLBD + ML and n = 78, EPLBD) treated by 12 gastroenterologists were included. Patients in the EPLBD + ML group were older (85 years versus 81.5 years) and had larger maximum stone diameter (15 mm versus 12.5 mm) than those in the EPLBD group. Compared with the EPLBD group, the EPLBD + ML group required more endoscopic retrograde cholangiopancreatography (ERCP) procedures (≥2) (86% versus 67%) and longer total ERCP time after reaching the papilla (78.5 minutes versus 25 minutes). Complication rates were not significantly different (9.1% versus 12.8%); however, the cumulative recurrence rates were higher in the EPLBD + ML group than in the EPLBD group (69.4% versus 23.5% at 4 years). Conclusion: Although there were no differences in complication rates, the long-term recurrence rate was higher in the EPLBD + ML group than in the EPLBD group. This study emphasizes the added burden imposed by performing ML during ERCP and suggests that by appropriate case selection, it is possible to treat cases of difficult biliary stones using EPLBD without ML. [ABSTRACT FROM AUTHOR]

Aim: There are few reports on the safety of endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) in the elderly. In this study, we investigated the safety of EUS‐FNA for pancreatic solid masses in patients aged ≥80 years. Methods: This is a single‐center retrospective study. A total of 600 patients with pancreatic solid masses who underwent EUS‐FNA under midazolam‐based sedation at our institution between September 2016 and December 2022 were enrolled in this study. Eligible patients were divided into two groups: an elderly group aged ≥80 (n = 84), as well as a nonelderly group aged ≤79 (n = 516). These two groups were compared. Results: The elderly group required significantly fewer midazolam doses for sedation (P < 0.001). Adverse events occurred in eight patients (1.3%), including one (1.2%) and seven (1.4%) in the elderly and nonelderly groups, respectively (P = 0.90). There were no cases of early adverse events in the elderly group and six cases (1.2%) in the nonelderly group (P = 0.32). There was one case of late adverse events in both the elderly and nonelderly groups (P = 0.14), and both were needle tract seeding. There was no significant difference between the two groups in the proportion of cases in which percutaneous oxygen saturation decreased to ≤90% during the EUS‐FNA. Conclusions: Our analysis suggests that EUS‐FNA for pancreatic solid masses can be safely performed in patients aged >80 years without increasing the adverse event rate compared to nonelderly patients aged <80 years. Geriatr Gerontol Int 2023; 23: 836–841. [ABSTRACT FROM AUTHOR]

Background: Obtaining sufficient pancreaticobiliary tumor tissue for genomic profiling has limitations. Liquid biopsies using plasma do not provide sufficient sensitivity. Thus, this study aimed to determine the effectiveness of liquid biopsy between bile and plasma for identifying oncogenic and drug‐matched mutations. Methods: This study created a panel of 60 significantly mutated genes specific to pancreaticobiliary cancer (PBCA) and used it for genomic analysis of 212 deoxyribonucleic acid (DNA) samples (87 bile supernatant, 87 bile precipitate, and 38 plasma) from 87 patients with PBCA. The quantity of extracted DNA from bile and plasma was compared, as were genomic profiles of 38 pairs of bile and plasma from 38 patients with PBCA. Finally, we investigated 87 bile and 38 plasma for the ability to detect druggable mutations. Results: The amount of DNA was significantly lower in plasma than in bile (p <.001). Oncogenic mutations were identified in 21 of 38 (55%) patients in bile and nine (24%) in plasma samples (p =.005). Bile was significantly more sensitive than plasma in identifying druggable mutations (p =.032). The authors detected 23 drug‐matched mutations in combined bile and plasma, including five ERBB2, four ATM, three BRAF, three BRCA2, three NF1, two PIK3CA, one BRCA1, one IDH1, and one PALB2. Conclusions: Liquid biopsy using bile may be useful in searching for therapeutic agents, and using the obtained genomic information may improve the prognoses of patients with PBCA. Plain Language Summary: Genomic profiling of formalin‐fixed paraffin‐embedded tissues may provide actionable targets for molecular and immuno‐oncological treatment.However, most pancreaticobiliary malignancies are unresectable and formalin‐fixed paraffin‐embedded tissues cannot be obtained.Although comprehensive genomic profiling tests using plasma have been used in recent years, the utility of those using bile is not clear.Our study revealed that bile identified more drug‐matched mutations than plasma in advanced pancreaticobiliary cancer patients.Bile may help widen the patient population benefiting from targeted drugs. Bile contained a large amount of tumor‐derived DNA in pancreaticobiliary cancer. Liquid biopsy using bile may be useful in searching for therapeutic agents. [ABSTRACT FROM AUTHOR]

Background/Aims: Endoscopic uncovered metal stent (UMS) placement has been widely performed for unresectable hilar malignant biliary stricture (UHMBS). Two stenting methods are used for the two bile duct branches: side-by-side placement (SBS) and partial stent-in-stent placement (PSIS). However, it remains controversial whether SBS or PSIS is superior. This study aimed to compare SBS and PSIS in UHMBS cases with UMS placement in two branches of the IHD. Methods: This retrospective study included 89 cases of UHMBS treated with UMS placement through the SBS or PSIS technique using endoscopic retrograde cholangiopancreatography at our institution. Patients were divided into two groups, SBS (n = 64) and PSIS (n = 25), and compared. Results: Clinical success was achieved in 79.7% and 80.0% in the SBS and PSIS groups, respectively (p = 0.97). The adverse event rate was 20.3% and 12.0% in the SBS and PSIS groups, respectively (p = 0.36). The recurrent biliary obstruction (RBO) rate was 32.8% and 28.0% in the SBS and PSIS groups, respectively (p = 0.66). The median cumulative time to RBO was 224 and 178 days in the SBS and PSIS groups, respectively (p = 0.52). The median procedure time was 43 and 62 min in the SBS and PSIS groups, respectively, which was significantly longer in the PSIS group (p = 0.014). Conclusions: No significant differences were noted in the clinical success rate, adverse event rate, time to RBO, or overall survival between the SBS and PSIS groups, other than the significantly longer procedure time in the PSIS group. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the validity of pathological diagnosis of early CRC (E‐CRC) from the genetic background by comparing data of E‐CRC to colorectal adenoma (CRA) and The Cancer Genome Atlas (TCGA) on advanced CRC (AD‐CRC). Methods: TCGA data on AD‐CRC were studied in silico, whereas by next‐generation sequencer, DNA target sequences were performed for endoscopically obtained CRA and E‐CRC samples. Immunohistochemical staining of mismatch repair genes and methylation of MLH1 was also performed. The presence of oncogenic mutation according to OncoKB for the genes of the Wnt, MAPK, and cell‐cycle–signaling pathways was compared among CRA, E‐CRC, and AD‐CRC. Results: The study included 22 CRA and 30 E‐CRC lesions from the Chiba University Hospital and 212 AD‐CRC lesions from TCGA data. Regarding the number of lesions with driver mutations in the Wnt and cell‐cycle–signaling pathways, E‐CRC was comparable to AD‐CRC, but was significantly greater than CRA. CRA had significantly more lesions with a driver mutation for the Wnt signaling pathway only, versus E‐CRC. Conclusions: In conclusion, the definition of E‐CRC according to the Japanese criteria had a different genetic profile from CRA and was more similar to AD‐CRC. Based on the main pathway, it seemed reasonable to classify E‐CRC as adenocarcinoma. The pathological diagnosis of E‐CRC according to Japanese definition seemed to be valid from a genetic point of view. [ABSTRACT FROM AUTHOR]

Background and objectives: The safety of electrohydraulic lithotripsy (EHL) in older adults remains unclear. We aimed to investigate the efficacy and safety of EHL using peroral cholangioscopy (POCS) under endoscopic retrograde cholangiopancreatography (ERCP) guidance in older adults aged ≥80 years. Materials and Methods: This retrospective clinical study was conducted at a single center. Fifty patients with common bile duct stones who underwent EHL using POCS under ERCP guidance at our institution, between April 2017 and September 2022, were enrolled in this study. The eligible patients were divided into an elderly group (n = 21, age ≥80 years) and a non-elderly group (n = 29, age ≤79 years), and were analyzed. Results: A total of 33 and 40 EHL procedures were performed in the elderly and non-elderly groups, respectively. After excluding cases in which stone removal was performed at other institutions, complete removal of common bile duct stones was confirmed in 93.8% and 100% of the elderly and non-elderly groups, respectively (p = 0.20). The mean number of ERCPs required for complete removal of bile duct stones was 2.9 and 4.3 in the elderly and non-elderly groups, respectively (p = 0.17). In the EHL session, the overall occurrence of adverse events was eight and seven in the elderly (24.2%) and non-elderly (17.5%) groups, respectively; however, the difference was insignificant (p = 0.48). Conclusions: EHL using POCS under ERCP guidance is effective in patients aged ≥80 years and there was no significant increase in adverse event rates compared to those aged ≤79 years. [ABSTRACT FROM AUTHOR]

The position- and energy-sensitive primary particle detectors of a nanodosimetry system are described. They consist of a telescope of silicon strip detectors, which allow the determination of the particle's position from the hit strip address and its energy from the specific energy loss. In our implementation, the energy loss is measured through the time over threshold (TOT). When testing the performance of a single silicon strip detector, it was found that between the energies of 20 and 100 MeV, primary particle energy could be determined to an accuracy of 15%, decreasing to 25% at 250 MeV. Below 20 MeV, we observed TOT saturation. It is concluded that the performance of the tested silicon strip detector is suitable for application in nanodosimetry.

Background/Purpose: There are limitations in obtaining sufficient pancreaticobiliary tumor tissue for genomic profiling of tumors. Herein, we investigated whether archived cytological specimen (ACS) is suitable for genomic profiling to identify oncogenic and drug‐matched mutations. Methods: We constructed a pancreaticobiliary cancer panel for targeted sequencing covering 60 significantly mutated genes (280 220 bp). Eighty DNA samples (19 formalin‐fixed paraffin‐embedded [FFPE] tissues and 61 ACS) from 44 patients with pancreaticobiliary disease were analyzed. We compared genomic profiles of 19 FFPE and 29 ACS from 19 patients with malignancies (Validation Cohort). We tested 32 ACS from 25 patients (15 malignant and 10 benign) for the ability to discriminate between malignant and benign disorders (Testing Cohort). We explored whether actionable and drug‐matched mutations (Validation and Testing Cohorts) could be identified from ACS. Results: Oncogenic mutations observed in ACS were identical to those identified in FFPE specimens (76% consistency). Genomic profiling using only ACS discriminated between malignant and benign disorders with 93% accuracy, 91% sensitivity, and 100% specificity. Actionable and drug‐matched mutations were identified in 74% and 32% of ACS, respectively, and in 79% and 21% in FFPE samples, respectively. Conclusion: Archived cytological specimen may be used to discriminate malignancy and to detect drug‐matched mutations in patients with advanced pancreaticobiliary cancer. [ABSTRACT FROM AUTHOR]

Background: In Western countries, most patients with primary sclerosing cholangitis (PSC) have concurrent ulcerative colitis (UC). The number of patients with UC in East Asia has increased markedly over the past two decades. However, current clinical features of PSC and of PSC associated with UC (PSC-UC) have not yet been clarified in East Asia, particularly in Japan. We aimed to reveal the clinical courses and associations with UC in Japanese patients with PSC from the mutual viewpoint of PSC and UC. Methods: We retrospectively retrieved medical records of patients with PSC (69) and UC (1242) who were diagnosed at Chiba University Hospital between June 1991 and August 2017. Results: In the present cohort, 37 patients had PSC-UC; the cumulative risks of PSC in patients with UC and of UC in patients with PSC were 3.0% and 53.6%, respectively. We confirmed similar distinctive results by a Japanese nationwide survey, noting that younger patients with PSC had a notably high possibility of association with UC. From the viewpoint of the UC cohort, the occurrence of right-sided disease was significantly higher in patients with PSC-UC than in those with UC (16.2% vs. 4.2%, P = 0.003). Pancolitis was more commonly observed in PSC-UC, and proctits/left-sided colitis was less commonly found in patients with UC. The number of patients with young-onset PSC-UC may be increasing similar to an increase in patients with UC in Japan. Conclusions: In our cohort, the comorbidity rate of PSC-UC was higher than that obtained in previous reports. The incidence of PSC-UC and UC may increase in the future in East Asia, particularly in Japan. [ABSTRACT FROM AUTHOR]

Aim: Little is known about the factors that contribute to the occurrence of adverse events in endoscopic retrograde cholangiopancreatography (ERCP) for people aged ≥85 years and safety for the super‐old. Therefore, we decided to identify these factors and to examine whether ERCP is safe in the super‐old. Methods: This was a single‐center retrospective study. A total of 137 patients aged ≥85 years who underwent therapeutic ERCP at Chiba University Hospital from January 2012 to March 2017 were retrospectively reviewed. Results: Four cases of Billroth II reconstruction and two cases of gastrectomy with Roux‐en‐Y reconstruction were excluded, and 131cases in total were examined in the present study. A total of 10 and 121 cases with and without adverse events, respectively, were present. Using univariate analysis, factors significantly contributing to the occurrence of adverse events in therapeutic ERCP were identified as aged ≥90 years (P = 0.0096), duodenal papilla cancer (P = 0.0012), gallbladder carcinoma (P = 0.023), and biliary metal stenting (P = 0.040). In multivariate analysis, only ≥90 years‐of‐age was a significant factor (P = 0.049). In addition, comparison between 25 cases of the super‐old and 106 cases aged 85–89 years was carried out. In the super‐old group, the average value of the American Society of Anesthesiologists physical status classification and Charlson’s Comorbidity Index were significantly better than those in 85–89‐year‐olds (P = 0.0035 and P < 0.0001, respectively). Conclusions: Although the super‐old group had fewer comorbid diseases, they had significantly increased adverse events compared with patients aged 85–89 years. Geriatr Gerontol Int 2018; 18: 1038–1045. [ABSTRACT FROM AUTHOR]

Nonlinearity is the vital factor for stochastic computing. Toward the realization of brain-mimetic function using molecular network, the nonlinear electric properties of molecular systems are investigated in nanoscale with atomic force microscopy and nano-gap electrodes. Nonlinear current–voltage characteristics were observed for {Mo154/152}-ring, cytochromec, and cytochromec/DNA networks where the conduction paths includes electron injection into weakly coupled discrete energy levels, electron tunneling through potential well, and electron hopping via Coulomb-blockade network. Stochastic resonance was observed in cytochromec/DNA network. [ABSTRACT FROM AUTHOR]