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Aim: Pancreatic fluid collections (PFCs) are common local complications of pancreatitis that may require interventional therapy. Endoscopic ultrasound (EUS)-guided transluminal drainage from the digestive tract, particularly with lumen-apposing metal stents (LAMS), is the first-line therapy due to its safety and efficacy. However, adverse events and post-removal courses remain uncertain. This study aimed to clarify the characteristics of LAMS placement and its removal, comparing pancreatic pseudocysts (PPC) and walled-off necrosis (WON)., Methods: This single-center retrospective study included 23 patients who underwent transgastric LAMS placement for PFCs under EUS guidance. The patients were categorized into the PPC group (n = 14) and the WON group (n = 9). Backgrounds and clinical outcomes were analyzed and compared., Results: The mean procedure time was 19 minutes in the PPC group and 25 minutes in the WON group, with no significant difference (p = 0.11). The overall incidence of adverse events during LAMS placement was 14.3% in the PPC group and 33.3% in the WON group, with no significant difference (p = 0.28), but the incidence of infection of noninfected fluid collections was 0% in the PPC group and 55.5% in the WON group, significantly higher in the WON group (p = 0.0016). At the time of LAMS removal, a double-pigtail plastic stent (DPS) was replaced in 53.8% of the PPC group and 57.1% of the WON group. Within one year, 57.1% of the replaced DPS in the PPC group and 25.0% in the WON group became dislocated. There were no adverse events due to the dislocation of the replaced DPS. Adverse events occurred in one patient in each group after LAMS removal: 7.7% in the PPC group and 14.3% in the WON group (p = 0.64), which consisted of peritonitis in the PPC group and recurrent infection of fluid collection in the WON group, and both of these events occurred when the replaced DPS was still in place after LAMS removal., Conclusions: Although there was no significant difference in the overall incidence of adverse events between PPC and WON, the incidence of infection after LAMS placement was significantly higher in WON. Regarding the replaced DPS, there were some cases of dislocation within one year, but there were no related adverse events. Adverse events occurred even after the removal of LAMS and replacement with DPS, so careful follow-up is required., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Review Board of Chiba University Hospital issued approval HK202403-12. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Takahashi et al.)

Background and Aim: Endoscopic retrograde cholangiopancreatography (ERCP) may help detect cholangiocarcinoma in patients with primary sclerosing cholangitis (PSC), but it may be associated with complications. This study was aimed at determining the prognostic impact of ERCP on patients with PSC without cholangitis., Methods: Patients with PSC without cholangitis were divided into two groups: those who underwent ERCP within three years after diagnosis (ERCP-performed group) and those who did not (non-ERCP group). These groups were compared in terms of clinical outcomes (liver-related death or liver transplantation, endoscopic treatment requirement and repeated cholangitis) and the composite outcome., Results: Of 99 patients with PSC with detailed medical history, 49 were included in the ERCP-performed group and 21 in the non-ERCP group. In Kaplan-Meier analysis, the non-ERCP group was less likely to achieve the three outcomes and the composite outcome, showing statistical significance (endoscopic treatment requirement; p = 0.017 and composite outcome; p = 0.014). A Cox proportional hazards model indicated that ERCP in the asymptomatic state was a significant predictor of endoscopic treatment requirement (hazard ratio [HR]: 4.37, 95% confidence interval [CI]: 1.03-18.59) and the composite outcome (HR: 4.54, 95% CI: 1.07-19.28)., Conclusion: ERCP in patients with PSC without cholangitis is likely to require further endoscopic treatment and may be associated with poor prognosis., (© 2024. The Author(s).)

Hereditary spastic paraplegia (HSP) is a heterogeneous group of neurological disorders that are characterized by progressive spasticity and weakness in the lower limbs. SPG26 is a complicated form of HSP, which includes not only weakness in the lower limbs, but also cognitive impairment, developmental delay, cerebellar ataxia, dysarthria, and peripheral neuropathy, and is caused by biallelic mutations in the B4GALNT1 (beta-1,4- N -acetylgalactosaminyltransferase 1) gene. The B4GALNT1 gene encodes ganglioside GM2/GD2 synthase (GM2S), which catalyzes the transfer of N -acetylgalactosamine to lactosylceramide, GM3, and GD3 to generate GA2, GM2, and GD2, respectively. The present study attempted to characterize a novel B4GALNT1 variant (NM_001478.5:c.937G>A p.Asp313Asn) detected in a patient with progressive multi-system neurodegeneration as well as deleterious variants found in the general population in Japan. Peripheral blood T cells from our patient lacked the ability for activation-induced ganglioside expression assessed by cell surface cholera toxin binding. Structural predictions suggested that the amino acid substitution, p.Asp313Asn, impaired binding to the donor substrate UDP-GalNAc. An in vitro enzyme assay demonstrated that the variant protein did not exhibit GM2S activity, leading to the diagnosis of HSP26. This is the first case diagnosed with SPG26 in Japan. We then extracted 10 novel missense variants of B4GALNT1 from the whole-genome reference panel jMorp (8.3KJPN) of the Tohoku medical megabank organization, which were predicted to be deleterious by Polyphen-2 and SIFT programs. We performed a functional evaluation of these variants and demonstrated that many showed perturbed subcellular localization. Five of these variants exhibited no or significantly decreased GM2S activity with less than 10% activity of the wild-type protein, indicating that they are carrier variants for HSP26. These results provide the basis for molecular analyses of B4GALNT1 variants present in the Japanese population and will help improve the molecular diagnosis of patients suspected of having HSP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Inamori, Nakamura, Shishido, Hsu, Nagafuku, Nitta, Ikeda, Yoshimura, Kodaira, Tsuchida, Matsumoto, Uemura, Ohno, Manabe, Yamaguchi, Togayachi, Aoki-Kinoshita, Nishihara, Furukawa, Kaname, Nakamura, Shimohata, Tadaka, Shirota, Kinoshita, Nakamura, Ohno, Sekijima and Inokuchi.)

Background: Salivary gland-type cancers (SGTCs) are histologically heterogeneous and can affect organs other than the salivary glands. Some tumors outside the salivary glands are diagnosed on their unique histological characteristics. Comprehensive cross-organ studies on SGTCs are limited., Methods: We retrospectively analyzed the data of patients with salivary duct carcinoma (SDC), adenoid cystic carcinoma (AdCC), mucoepidermoid carcinoma (MEC), epithelial-myoepithelial carcinoma (EMC), acinic cell carcinoma (AcCC), and polymorphous adenocarcinoma (PAC) who visited our institution between 2009 and 2019. The primary tumor sites were classified into four categories; major salivary glands, head/neck (H/N) excluding (exc) major salivary glands (MSG) regions, broncho-pulmonary regions, and "others". H/N exc MSG was further divided into three subcategories, nasal/paranasal sinus, oral and pharynx/larynx., Results: We identified 173 patients with SGTCs, with SDC, AdCC, MEC, EMC, AcCC, and PAC accounting for 20%, 42%, 27%, 3%, 8%, and 1% of the cases, respectively. The most frequent primary site was the major salivary glands (64%), followed by H/N exc MSG regions (27%), broncho-pulmonary regions, and "others", thus non-salivary gland origins accounted for 9% of all cases. Patients with SDC, MEC, AcCC, or SGTC of the major salivary glands and broncho-pulmonary regions were more frequently treated by surgery. The overall survival time of the patients with MEC was significantly better than that of patients with SDC or EMC., Conclusions: This cross-organ study highlights the clinical significance of SGTCs, underscoring the need for developing novel therapies for this rare disease entity., (© 2024. The Author(s).)

Endoscopic ultrasound-guided hepaticogastrostomy is performed when transpapillary biliary drainage using endoscopic retrograde cholangiopancreatography is difficult due to surgically altered anatomy, an inaccessible papilla, or difficult biliary cannulation. This procedure consists of puncturing the intrahepatic bile duct from the stomach, inserting a guidewire into the bile duct, dilating the puncture tract, and placing a stent. Recently, a novel partially covered self-expandable metal stent with a super-slim stent delivery system of 5.9 Fr has become available. With this stent, endoscopic ultrasound-guided hepaticogastrostomy can be performed without using a dilator to expand the puncture tract. Herein, we describe a technique for dilator-free stent deployment for endoscopic ultrasound-guided hepaticogastrostomy using this novel stent. We performed an endoscopic ultrasound-guided hepaticogastrostomy with this stent in a 65-year-old patient with obstructive jaundice due to pancreatic head cancer without adverse events and with satisfactory improvement in jaundice. This procedure is expected to reduce bile leakage into the abdominal cavity and shorten the procedure time., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Takahashi et al.)

Here, we report a case of tardive peritonitis after endoscopic ultrasound (EUS)-guided transmural pancreatic pseudocyst drainage. A 50-year-old man was diagnosed with acute pancreatitis and a pancreatic pseudocyst measuring 5 cm. Ten months later, his pancreatic pseudocyst was 10 cm. We performed EUS-guided transmural drainage using a lumen-apposing metal stent. After two months, the stent was replaced with a double-pigtail plastic stent. Two months later, the patient developed fever and abdominal pain, and computed tomography revealed abdominal free air. He was diagnosed with peritonitis due to free air caused by a fistula rupture. The double-pigtail plastic stent was removed, and clipping was performed at the fistula site to achieve closure. The patient's symptoms subsequently improved. Long-term placement of a plastic stent for pancreatic pseudocysts makes recurrence less likely, but late adverse events due to stent placement can occur. Notably, fistula rupture can occur even when the fistula is well-formed several months after the initial drainage., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Takahashi et al.)

Because scaffold diversity has a pronounced impact on biological screening, the efficient and expedient construction of skeletally diverse compound collections is a fundamental demand in drug discovery. In this regard, we report here an asymmetric tandem conjugate addition-elimination reaction of pyrroline esters with nitroallyl acetates and its application to the construction of various types of fused or spirocyclic pyrrolidines. A AgOAc/( R , S p )-ThioClickFerrophos (TCF) catalyst efficiently promotes the addition-elimination reaction, setting vicinal chiral stereocenters featuring a tetrasubstituted carbon with excellent enantio- and diastereoselectivity while leaving the versatile nitroolefin moiety. The broad substrate scope of this reaction and the transformability of the resulting nitroolefin, imine, and ester moieties allow for the construction of diverse pyrrolidine-based fused or spiro bicyclic skeletons in optically active forms by various intramolecular cyclization processes.

Duchenne muscular dystrophy (DMD) is an intractable X-linked myopathy caused by dystrophin gene mutations. Patients with DMD suffer from progressive muscle weakness, inevitable cardiomyopathy, increased heart rate (HR), and decreased blood pressure (BP). The aim of this study was to clarify the efficacy and tolerability of ivabradine treatment for DMD cardiomyopathy.A retrospective analysis was performed in 11 patients with DMD, who received ivabradine treatment for more than 1 year. Clinical results were analyzed before (baseline), 6 months after, and 12 months after the ivabradine administration.The initial ivabradine dose was 2.0 ± 1.2 mg/day and the final dose was 5.6 ± 4.0 mg/day. The baseline BP was 95/64 mmHg. A non-significant BP decrease to 90/57 mmHg was observed at 1 month but it recovered to 97/62 mmHg at 12 months after ivabradine administration. The baseline HR was 93 ± 6 bpm and it decreased to 74 ± 12 bpm at 6 months (P = 0.011), and to 77 ± 10 bpm at 12 months (P = 0.008). A linear correlation (y = 2.2x + 5.1) was also observed between the ivabradine dose (x mg/day) and HR decrease (y bpm). The baseline LVEF was 38 ± 12% and it significantly increased to 42 ± 9% at 6 months (P = 0.011) and to 41 ± 11% at 12 months (P = 0.038). Only 1 patient with the lowest BMI of 11.0 kg/m 2 and BP of 79/58 mmHg discontinued ivabradine treatment at 6 months, while 1-year administration was well-tolerated in the other 10 patients.Ivabradine decreased HR and increased LVEF without lowering BP, suggesting it can be a treatment option for DMD cardiomyopathy.

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., (© 2023 Japan Geriatrics Society.)

Fidget spinners are said to be a very successful toy, and it's said that it has a good impact on attention for children with ADHD and hand motor control. However, there is limited scientific evidence to support these claims, and there is a lack of data on neurobiological responses to rotating fidget spinners. To better understand the mechanism whereby fidget spinners affect motor behavior, we tried to identify the neural correlates of rotating fidget spinners using functional magnetic resonance imaging and non-magnetic fidget spinners with five types of ease of rotation. As a result, we confirmed that the pre/postcentral gyrus, middle temporal gyrus, supplementary motor area (SMA), cerebellum, and striatum are activated when rotating spinners. Furthermore, the SMA was activated more with easier-to-rotate spinners. Additionally, a psychophysiological interaction analysis revealed increased functional connectivity between the SMA and the caudate while rotating fidget spinners compared to just holding them. These results suggest that the fine motor control associate with spinning a fidget spinner is supported by the cortico-striatal circuits involved in planning and reward., (© 2023. Springer Nature Limited.)

Severe drug-induced lung injury (DLI) has been reported to be associated with sequential administration of osimertinib, a third-generation tyrosine kinase inhibitor, following a programmed cell death ligand 1 (PD-L1) inhibitor. However, the relationship of sequential treatment with an anti-epidermal growth factor receptor (EGFR) antibody and PD-1 inhibitor with the risk of DLI remains to be elucidated. The present study conducted a retrospective review of the medical records of a total of 179 patients with head and neck cancer who had received treatment with cetuximab and/or a PD-1 inhibitor (nivolumab or pembrolizumab) at Chiba University Hospital (Chiba, Japan) between September 2014 and December 2020. The incidence of pneumonia and the clinical background characteristics of the patients were analyzed. The patients were classified into subgroups for analysis of the outcomes in this study: Patients who had received sequential, but not concurrent, cetuximab and PD-1 inhibitor treatment (Group C+P; n=43); patients who had received cetuximab-containing chemotherapy, but not a PD-1 inhibitor (Group C; n=101); and patients who had received PD-1 inhibitor-containing chemotherapy, but not cetuximab (Group P; n=35). The rates of DLI in the three groups were: Group C+P, 18.6%; Group C, 7.9%; and Group P, 11.4%. Prior use of ICI was not associated with any increase in the risk of DLI. DLI is seen frequently in patients receiving sequential PD-1 inhibitor and anti-EGFR antibody therapy., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Arai et al.)

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.

Background: ST3GAL5 encodes GM3 synthase (ST3 beta-galactoside alpha-2,3-sialyltransferase 5; ST3GAL5), which synthesizes GM3 by transferring sialic acid to lactosylceramide. GM3, a sialic acid-containing glycosphingolipid known as ganglioside, is a precursor to the biosynthesis of various more complex gangliosides that are active in the brain. Biallelic variants in ST3GAL5 cause GM3 synthase deficiency (GM3SD), a rare congenital disorder of glycosylation. GM3SD was first identified in the Amish population in 2004., Case: We report two siblings diagnosed with GM3SD due to novel compound heterozygous ST3GAL5 variants. The novel ST3GAL5 variants, detected by whole-exome sequencing in the patients, were confirmed to be pathogenic by GM3 synthase assay. The clinical courses of these patients, which began in infancy with irritability and growth failure, followed by developmental delay and hearing loss, were consistent with previous case reports of GM3SD. The older sibling underwent deep brain stimulation for severe involuntary movements at the age of 9 years. The younger sibling suffered from acute encephalopathy at the age of 9 months and subsequently developed refractory epilepsy., Discussion: Reports of GM3SD outside the Amish population are rare, and whole-exome sequencing may be required to diagnose GM3SD in non-Amish patients. Since an effective treatment for GM3SD has not yet been established, we might select deep brain stimulation as a symptomatic treatment for involuntary movements in GM3SD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

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.

Background Acute cholangitis is caused by cholestasis and bacterial infection, and if exacerbated, sepsis may occur and be fatal. Biliary drainage is recommended for acute cholangitis regardless of severity, except in some cases of mild acute cholangitis, in which antibiotics are effective. A novel integrated device comprising a biliary drainage stent and a nasobiliary drainage tube, called the UMIDAS NB stent (UMIDAS Inc., Kanagawa, Japan), was developed. In this study, we evaluated the efficacy and safety of biliary drainage using the UMIDAS NB stent outside type for acute cholangitis in clinical practice. Methods Patients with acute cholangitis with common bile duct stones or distal biliary strictures who underwent biliary drainage with the UMIDAS NB stent outside type at our institution between January 2022 and December 2022 were examined retrospectively. The UMIDAS NB stent outside type was placed transpapillary using endoscopic retrograde cholangiopancreatography (ERCP). Patients with biliary drainage stent placement other than the UMIDAS NB stent outside type on the same ERCP session and patients with acute cholecystitis were excluded. Results A total of 13 patients were included in this study. The severity of cholangitis was mild in four cases, moderate in five, and severe in four. There were eight cases of common bile duct stones and five cases of pancreatic cancer. The stent diameter was 7 French scale (Fr) in five cases and 8.5 Fr in eight cases. The median procedure time was 20 minutes. Clinical success was achieved in all 13 patients (100%). No treatment-related adverse events were observed. Unintended removal of the nasobiliary drainage tube was not observed. There were no cases of biliary drainage stent dislocation with nasobiliary drainage tube removal. Conclusions Although the sample size was small, our study demonstrated that biliary drainage with the UMIDAS NB stent outside type was effective and safe for patients with acute cholangitis who had common bile duct stones or distal biliary strictures, regardless of the severity of cholangitis., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Takahashi et al.)

Nasal pressure signal is commonly used to evaluate obstructive sleep apnea. This study aimed to assess its safety for respiratory monitoring during sedation. A total of 45 adult patients undergoing sedation with propofol and fentanyl for invasive endoscopic procedures were enrolled. While both nasal pressure and capnograph signals were continuously recorded, only the nasal pressure signal was displayed. The primary outcome was the incidence of oxygen desaturation below 90%. The secondary outcomes were the ability to predict the desaturation and incidence of harmful events and false alarms, defined as an apnea waveform lasting more than 3 min without desaturation. Of the 45 participants, 43 completed the study. At least one desaturation event occurred in 12 patients (27.9%; 95% confidence interval 15.3-43.7%). In these 12 patients, more than half of the desaturation events were predictable in 9 patients by capnography and 11 patients by nasal pressure monitoring (p = 0.59). In the 43 patients, false alarms were detected in 7 patients with capnography and 11 patients with nasal pressure monitoring (p = 0.427). Harmful events unrelated to nasal pressure monitoring occurred in 2 patients. Nasal pressure monitoring is safe and possibly useful for respiratory monitoring despite false alarms during sedation., (© 2023. The Author(s).)

GM3 synthase (GM3S) is a sialyltransferase that transfers sialic acid from CMP-sialic acid to lactosylceramide. This reaction results in formation of ganglioside GM3 and is essential for biosynthesis of its downstream derivatives, which include a- and b-series gangliosides. Here, we describe a method for GM3S enzymatic assay using fluorescence-labeled alkyl lactoside as acceptor substrate, followed by HPLC for separation of enzymatic product. The method allows quantitative assay of GM3S sialyltransferase activity in cultured cells and mouse brain tissues., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

This study aimed to evaluate the feasibility of performing endoscopic ultrasound-guided hepaticogastrostomy using a 22-gauge fine-needle aspiration needle. This was a single-center retrospective study. Fourteen patients who underwent endoscopic ultrasound-guided hepaticogastrostomy with a 22-gauge fine-needle aspiration needle were examined. Fourteen eligible patients were included in this study. The age of patients ranged from 55 to 93 years, with a median of 76 years. Of patients with existing underlying diseases, there were 8 cases of pancreatic cancer (57.1%), 2 cases of metastatic liver tumor (14.3%), 2 cases of bile duct stones (14.3%), 1 case of hilar cholangiocarcinoma (7.1%), and 1 case of gallbladder cancer (7.1%). Regarding gastrointestinal anatomy, there were 11 cases (78.6%) of normal and 3 cases (21.4%) of gastric resection with Roux-en-Y. Reasons for endoscopic ultrasound-guided hepaticogastrostomy were duodenal obstruction in 7 cases (50.0%), surgically altered anatomy in 3 cases (21.4%), and 4 cases (28.6%) of failed endoscopic retrograde cholangiopancreatography. Technical success was achieved in 11 cases (78.6%). Subsequently, 11 cases of technical success were analyzed. There were 5 cases of puncturing B2 (45.5%). The puncture bile duct diameter ranged from 3.1 to 5.7 mm, with a median of 4.4 mm. endoscopic ultrasound-guided antegrade procedures was combined with endoscopic ultrasound-guided hepaticogastrostomy in 2 cases (18.2%). Clinical success was achieved in all the cases. The procedure time ranged from 15 to 93 minutes, with a median duration of 35 minutes. Regarding the type of stent placed in hepaticogastrostomy, a plastic stent was placed in 10 cases (90.9%) and a metal stent was placed in 1 case (9.1%). Early adverse events occurred in 4 cases (36.4%), and all of these cases developed biliary peritonitis, late adverse events occurred in 1 case (9.1%), this was biloma. A change to a 0.025-inch guidewire during the procedure was required in 8 cases (72.7%). Esophageal puncture was not performed. endoscopic ultrasound-guided hepaticogastrostomy using a 22-gauge fine-needle aspiration needle is effective. However, in 72.7% of the cases started using the 0.018-inch guidewire, the guidewire was exchanged for a 0.025-inch guidewire during procedure., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: This study assessed whether neoadjuvant chemoradiotherapy (CRT) with S-1 increases the R0 resection rate in BRPC., Summary of Background Data: Although a multidisciplinary approach that includes neoadjuvant treatment has been shown to be a better strategy for BRPC than upfront resection, a standard treatment for BRPC has not been established., Methods: A multicenter, single-arm, phase II study was performed. Patients who fulfilled the criteria for BRPC received S-1 (40 mg/m 2 bid) and concurrent radiotherapy (50.4 Gy in 28 fractions) before surgery. The primary endpoint was the R0 resection rate. At least 40 patients were required, with a 1-sided α = 0.05 and β = 0.05 and expected and threshold values for the primary endpoint of 30% and 10%, respectively., Results: Fifty-two patients were eligible, and 41 were confirmed to have definitive BRPC by a central review. CRT was completed in 50 (96%) patients and was well tolerated. The rate of grade 3/4 toxicity with CRT was 43%. The R0 resection rate was 52% among the 52 eligible patients and 63% among the 41 patients who were centrally confirmed to have BRPC. Postoperative grade III/IV adverse events according to the Clavien-Dindo classification were observed in 7.5%. Among the 41 centrally confirmed BRPC patients, the 2-year overall survival rate and median overall survival duration were 58% and 30.8 months, respectively., Conclusions: S-1 and concurrent radiotherapy seem to be feasible and effective at increasing the R0 resection rate and improving survival in patients with BRPC., Trial Registration: UMIN000009172., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

A 77-year-old woman with obstructive jaundice due to pancreatic head tumor was admitted to our hospital for biliary drainage. Transpapillary biliary drainage was attempted using endoscopic retrograde cholangiopancreatography; however, the catheter could not be inserted into the bile duct. Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) was conducted using a 7-Fr plastic stent. Fever and cognitive dysfunction were observed 73 days after EUS-HGS. Abdominal-computed tomography (CT) showed a huge biloma and a liver abscess. On admission, an uncovered metal stent was applied to the biliary obstruction site of the distal bile duct using an antegrade stenting technique, and the plastic hepaticogastrostomy stent was substituted with a new one. On the second day, two double-pigtail plastic stents were inserted into the biloma, and one into the liver abscess. Head CT and magnetic resonance imaging revealed a brain abscess in the right cerebral frontal lobe. Serum white blood cell count and C-reactive protein level, and the state of consciousness, improved with antibiotic administration. Biloma and liver abscess almost disappeared on CT 38 days after admission. The brain abscess also improved, and the patient was discharged from the hospital 48 days after admission. Endoscopic ultrasound-guided biloma drainage is helpful because self-removal of the drainage tube and reduced activities of daily living are unlikely to occur., (© 2022. Japanese Society of Gastroenterology.)

Although the efficacy and safety of salvage techniques for biliary cannulation in endoscopic retrograde cholangiopancreatography (ERCP) have been reported, few reports analyzed the choice of techniques and their clinical outcomes in large cohorts. This study aimed to evaluate the outcomes of biliary cannulation in patients with native papillae. We retrospectively identified 1021 patients who underwent initial ERCP from January 2013 to March 2020. We investigated background factors, treatment details, cannulation success rates, and adverse event rates. Then we analyzed a series of treatment processes, including salvage techniques such as double guidewire technique (DGT), needle knife pre-cutting (NKP), and transpancreatic pre-cut papillotomy (TPPP). The initial ERCP success rate using standard technique alone was 62.8%, which increased to 94.3% including salvage techniques. Salvage techniques were frequently required in patients with long oral protrusions (OR 2.38; 95% CI 1.80-3.15; p < 0.001). A total of 503 cases (49.3%) had long oral protrusions, 47.5% of which required the salvage techniques, much higher than 27.5% of not-long cases. Patients with long oral protrusions had a higher frequency of NKP. In conclusion, patients with long oral protrusions frequently required salvage techniques. Salvage techniques may help to overcome many difficult biliary cannulation cases., (© 2022. The Author(s).)

Objective: To evaluate changes in the learning attitudes of primary care physicians., Design: Qualitative study through one focus group interview with the programme's participants. Analysis of the focus group content using the Steps for Coding and Theorization method., Setting: Japan., Participants: Eight primary care physicians who completed a 2-year continuing professional development (CPD) programme using a problem-based learning (PBL) approach, focused on acquiring the skills needed to practise as primary care physicians in the community., Results: Participants described positive changes in their attitudes and behaviours as a result of the training programme. These changes were grouped into three main themes: 'changes in learning methods regarding medical practice', 'encounters with diverse perspectives and values, and confidence gained from those encounters', and 'showing one's attitude towards learning and its influence on others'. The experienced practitioners participating in this study reported that the programme helped them apply their skills more broadly; for example, searching the literature for psychosocial aspects of practice and engaging more comfortably with diverse perspectives. They reported the positive impact of their learning on their coworkers., Conclusion: A 2-year CPD programme using PBL can influence primary care physicians' attitudes and learning-related behaviours. Further research is needed to determine which specific aspects of the programme are the most effective and whether the changes in attitudes and behaviours described affect patient care., Competing Interests: Competing interests: MM received lecture fees and lecture travel fees from the Centre for Family Medicine Development of the Japanese Health and Welfare Co-operative Federation. MM is an adviser for the Centre for Family Medicine Development Practice-Based Research Network. The other authors report no conflicts of interest., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Retrieval is challenging once prophylactic pancreatic stents migrate deep into the pancreatic duct. Herein, we describe a case of successful endoscopic retrieval of a migrated prophylactic pancreatic stent using a basket catheter through a biliary plastic stent pusher tube. Patient: A 71 year-old man was referred to our hospital for removal of a straight-shaped migrated 5-Fr 3-cm prophylactic pancreatic stent with a flap on the duodenal side. There were no subjective symptoms at the time of the hospital visit. Results: During endoscopic retrograde cholangiopancreatography, we inserted an 8.5-Fr plastic biliary stent pusher tube in front of the migrated pancreatic stent. The stent was then grasped using a basket catheter for peroral cholangioscopy through the biliary stent pusher tube. The stent was pulled into the pusher tube and was successfully retrieved from the pancreatic duct. No complications were associated with endoscopic retrograde cholangiopancreatography. Conclusion: Although rare, prophylactic pancreatic duct stent migration after pancreatic duct guidewire placement should be noted. In our case, endoscopic retrieval of a migrated prophylactic pancreatic stent using a basket catheter for peroral cholangioscopy through the biliary plastic stent pusher tube was successful., Competing Interests: The authors declare no conflicts of interest regarding the publication of this paper., (©2022 The Japanese Association of Rural Medicine.)

Objective: To describe the case of a patient with intraperitoneal bleeding from the gastroepiploic artery by endoscopic ultrasound who was successfully treated with transcatheter arterial coil embolization. Patient and Methods: An 87-year-old man was referred to our hospital for examination of a gallbladder tumor. Endoscopic ultrasonography was performed using an oblique-view echoendoscope. After the endoscopic ultrasound, the patient went into shock. Computed tomography revealed a huge intraperitoneal hematoma and an aneurysm in the right gastroepiploic artery that were not seen on previous computed tomography images. Thus, urgent catheter angiography was performed, which showed a pseudoaneurysm of the right gastroepiploic artery and extravasation of the contrast medium from the pseudoaneurysm. Results: Transcatheter arterial coil embolization was subsequently performed, and the bleeding stopped. Thereafter, his hemodynamics stabilized and his general condition improved. The patient was discharged 22 days post-treatment with an uneventful course. Conclusion: Observation-only endoscopic ultrasound without invasive procedures can cause intraperitoneal bleeding due to a ruptured splanchnic artery. Thus, endoscopic ultrasonography should be performed more carefully in elderly patients., (©2022 The Japanese Association of Rural Medicine.)

Background and objective In this study, we aimed to evaluate the efficacy and safety of a single pigtail stent made by cutting a nasobiliary drainage tube (NBD stent) by comparing the clinical outcomes of using an NBD stent and those of using a ready-made double pigtail stent (RDP stent) in endoscopic gallbladder stenting (EGBS) for acute cholecystitis. Materials and methods This was a single-center retrospective study involving 20 cases that had technical success with EGBS for acute cholecystitis; the patients were divided into two groups: those using NBD stent (NBD group) and those using RDP stent (RDP group). The baseline characteristics and clinical outcomes were compared between the two groups. Results There were 13 patients in the NBD group and seven in the RDP group. The rates of clinical success (NBD group: 92% vs. RDP group: 100%, p=0.45) did not differ significantly between the groups. Regarding adverse events, gallbladder perforation occurred in one case in the NBD group; however, no other adverse events occurred in either group (NBD group: 7.7% vs. RDP group: 0%, p=0.45). The stent patency periods did not differ significantly between the groups [NBD group: 43 (12-64) days vs. RDP group: 97 (58-215) days, p=0.17]. The stent patency period in cases of long-term stent placement after EGBS was 1,381 days and 1,579 days in the NBD group and 305 days in the RDP group, respectively. Conclusion NBD stents are considered as effective as RDP stents in EGBS for acute cholecystitis. They are highly versatile and can be used for both bridging to surgery and long-term stent placement., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Takahashi et al.)

Introduction and Objectives: Acute cholangitis, which is characterized by biliary infection and acute liver injury, may impact cirrhosis prognosis. However, the prognosis itself remains unclear., Materials and Methods: This multicenter retrospective cohort study compared the mortality and liver function change between patients with and without cirrhosis who underwent endoscopic treatment for acute cholangitis caused by choledocholithiasis between January 2004 and December 2019., Results: We analyzed 699 patients, 44 of whom had cirrhosis. The cirrhotic group had a significantly higher 30-day mortality rate than the noncirrhotic group (14% vs. 1%; P < 0.001). The cirrhotic group also had significantly lower total bilirubin and albumin recovery. However, all patients with cirrhosis who survived achieved total-bilirubin recovery, and 91% achieved albumin recovery within 90 days. In multivariable Cox regression analysis, the independent risk factors for total-bilirubin recovery included cirrhosis (hazard ratio, 0.37; 95%CI, 0.24‒0.58; P < 0.001) and high total-bilirubin level (0.46; 95%CI, 0.34‒0.60; P < 0.001), whereas those for albumin recovery were cirrhosis (0.51; 95%CI, 0.33‒0.79; P = 0.002), high age (0.62; 95%CI, 0.47‒0.82; P < 0.001), organ dysfunction (0.62; 95%CI, 0.39‒0.96; P = 0.03), low albumin level (0.57; 95%CI, 0.36‒0.91; P = 0.02), and high C-reactive protein level (0.73; 95%CI, 0.56‒0.95; P = 0.02)., Conclusions: Patients with cirrhosis complicated with acute cholangitis had poor prognosis. Recovery of liver function after endoscopic treatment was slow; nevertheless, most patients who survived could recover within 90 days., Competing Interests: Conflicts of interest None., (Copyright © 2022 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Peroral cholangioscopy (POCS) has been used to overcome the difficulty in diagnosing indeterminate biliary stricture or tumor spread. However, the value of adding POCS to computed tomography (CT) remains unclear. Our aim was to evaluate the diagnostic value of adding POCS to CT for indeterminate biliary stricture and tumor spread by interpretation of images focusing on the high diagnostic accuracy of visual findings in POCS., Methods: We retrospectively identified 52 patients with biliary stricture who underwent endoscopic retrograde cholangiography (ERC) at our institution between January 2013 and December 2018. Two teams, each composed of an expert endoscopist and surgeon, performed the interpretation independently, referring to the CT findings of the radiologist. The CT + ERC + POCS images (POCS group) were evaluated 4 weeks after the evaluation of CT + ERC images (CT group). A 5-point scale (1: definitely benign to 5: definitely malignant) was used to determine the confident diagnosis rate, which was defined as an evaluation value of 1 or 5. Tumor spread was also evaluated., Results: In the evaluation of 45 malignant diagnoses, the score was significantly closer to 5 in the POCS group than in the CT group in both teams (P < 0.001). The confident diagnosis rate was significantly higher for the POCS group (92% and 73%) than for the CT group (25% and 12%) in teams 1 and 2, respectively (P < 0.001). We found no significant difference in diagnostic accuracy for tumor spread between the groups., Conclusion: Visual POCS findings confirmed the diagnosis of biliary strictures. POCS was useful in cases of indefinite diagnosis of biliary strictures by CT., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Sex is considered an important risk factor for asthma onset and exacerbation. The prevalence of asthma is higher in boys than in girls during childhood, which shows a reverse trend after puberty-it becomes higher in adult females than in adult males. In addition, asthma severity, characterized by the rate of hospitalization and relapse after discharge from the emergency department, is higher in female patients. Basic research indicates that female sex hormones enhance type 2 adaptive immune responses, and male sex hormones negatively regulate type 2 innate immune responses. However, whether hormone replacement therapy in postmenopausal women increases the risk of current asthma and asthma onset remains controversial in clinical settings. Recently, sex has also been shown to influence the pathophysiology of asthma in its relationship with genetic or other environmental factors, which modulate asthmatic immune responses in the airway mucosa. In this narrative review, we highlight the role of sex in the continuity of the asthmatic immune response from sensing allergens to Th2 cell activation based on our own data. In addition, we elucidate the interactive role of sex with genetic or environmental factors in asthma exacerbation in women.

Background: Although population studies have implicated emotional burden in asthma severity, the underlying genetic risk factors are not completely understood. We aimed to evaluate the genetic influence of a functional single-nucleotide polymorphism (SNP) in the stress-related μ-opioid receptor gene (OPRM1; A118G SNP, rs1799971) on asthma severity., Methods: We initially assessed disease severity in asthmatic outpatients carrying A118G. Using an ovalbumin-induced experimental asthma rodent model harboring the functionally equivalent SNP, we investigated the mechanism by which this SNP influences the allergic immune response., Results: Among 292 outpatients, 168 underwent airway hyperresponsiveness (AHR) to methacholine testing. Compared with patients carrying the AA and AG genotypes, those carrying the GG genotype exhibited enhanced AHR. The stress levels were presumed to be moderate among patients and were comparable among genotypes. Compared with Oprm1 AA mice, GG mice demonstrated aggravated asthma-related features and increased pulmonary interleukin-4 + CD4 + effector and effector memory T cells under everyday life stress conditions. Intraperitoneal naloxone methiodide injection reduced effector CD4 + T cell elevation associated with increased eosinophil numbers in bronchoalveolar lavage fluid of GG mice to the levels in AA mice, suggesting that elevated Th2 cell generation in the bronchial lymph node (BLN) of GG mice induces enhanced eosinophilic inflammation., Conclusions: Without forced stress exposure, patients with asthma carrying the OPRM1 GG genotype exhibit enhanced AHR, attributable to enhanced Th2 cell differentiation in the regional lymph node. Further research is necessary to elucidate the role of the OPRM1 A118G genotype in the Th2 cell differentiation pathway in the BLN., (Copyright © 2021 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Background: According to a questionnaire sent to Designated Cancer Care Hospitals in Japan in 2013, only 39.4% of the institutes had medical oncology departments. Furthermore, most of these medical oncology departments were primarily responsible for the treatment of limited disease categories and the administration of newly developed therapeutic modalities, including molecular-targeted therapy. The aim of the present study was to update these previous findings and to clarify the changes over the intervening 7-year period., Methods: The questionnaire was sent to all 393 Designated Cancer Care Hospitals on 13 March 2020. Similar to the previous questionnaires, questions were asked regarding the presence of a medical oncology department, the number of physicians in the department and the degrees of responsibility for drug therapies provided by medical oncologists to adult patients with solid cancers., Results: In total, 270 institutions (68.7%) responded. Overall, 145 of these 270 institutions (53.7%) had medical oncology departments, representing a significant increase compared with the results of the previous study (P < 0.01). Among the institutions with a medical oncology department, these departments were responsible for the administration of over 30% of all cytotoxic and molecular-targeted drug therapies for extragonadal germ cell tumors, cancers of unknown primary site, soft tissues, head and neck, esophagus, stomach, colon and rectum, and pancreas as well as the administration of immune checkpoint inhibitors (ICI) for microsatellite instability-high tumors, cancers of the stomach, esophagus and head and neck, and melanoma., Conclusion: The proportion of institutes with medical oncology departments in Japan has increased. In addition, the responsibility of medical oncology departments has expanded to include newly emerging drugs, such as ICIs., (© The Author(s) 2021. Published by Oxford University Press.)