Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVES: Accurate diagnosis of biliary strictures remains challenging. This study aimed to develop an artificial intelligence (AI) system for peroral cholangioscopy (POCS) using a Vision Transformer (ViT) architecture and to evaluate its performance compared to different vendor devices, conventional convolutional neural networks (CNNs), and endoscopists. METHODS: We retrospectively analyzed 125 patients with indeterminate biliary strictures who underwent POCS between 2012 and 2024. AI models including the ViT architecture and two established CNN architectures were developed using images from CHF-B260 or B290 (CHF group; Olympus Medical) and SpyScope DS or DS II (Spy group; Boston Scientific) systems via a patient-level, 3-fold cross-validation. For a direct comparison against endoscopists, a balanced 440-image test set, containing an equal number of images from each vendor, was used for a blinded evaluation. RESULTS: The 3-fold cross-validation on the entire 2062-image dataset yielded a robust accuracy of 83.9% (95% confidence interval (CI), 80.9-86.7) for the ViT model. The model's accuracy was consistent between CHF (82.7%) and Spy (86.8%, p = 0.198) groups, and its performance was comparable to the evaluated conventional CNNs. On the 440-image test set, the ViT's accuracy of 78.4% (95% CI, 72.5-83.8) was comparable to that of expert endoscopists (82.0%, p = 0.148) and non-experts (73.0%, p = 0.066), with no statistically significant differences observed. CONCLUSIONS: The novel ViT-based AI model demonstrated high vendor-agnostic diagnostic accuracy across multiple POCS systems, achieving performance comparable to conventional CNNs and endoscopists evaluated in this study.

DOI： 10.1111/den.70028

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Background: Biliary strictures are diagnosed using endoscopic retrograde cholangiopancreatography (ERCP) with brush cytology and biopsy. However, brush cytology shows a sensitivity of 9-56.1% and a diagnostic accuracy of 43-65.4%, while biopsy demonstrates a sensitivity of 48%. Both methods exhibit high specificity but limited sensitivity. While rapid on-site evaluation (ROSE) is effective in endoscopic ultrasound-guided fine needle aspiration (EUS-FNA), its application in ERCP-obtained samples remains underexplored. Methods: This prospective pilot study was conducted at Okayama University Hospital from April 2019 to July 2024. Patients requiring ERCP-guided sampling for bile duct strictures were included. ROSE was applied to brush cytology with up to three additional attempts and to imprint cytology from biopsy samples with up to two attempts. Diagnostic accuracy was assessed based on pathology and clinical course. Results: Among 37 patients (median age: 73 years, add range, and male-female ratio: 27:10), 18 had hilar and 19 had distal bile duct strictures. Brush cytology required one, two, or three attempts in twenty-six, six, and five cases, respectively, whereas biopsy required one or two attempts in thirty-five and two cases, respectively. Among the thirty-seven cases, thirty-five were malignant and two were benign. The B-ROSE group showed a sensitivity, specificity, and accuracy of 71.4%, 100.0%, and 73.0%, respectively, compared to lower accuracy in the conventional group, where single brush cytology attempts yielded a sensitivity of 48.6% and an accuracy of 48.6%, and single biopsy attempts showed a sensitivity of 68.6% and an accuracy of 70.3%. Conclusions: B-ROSE improves diagnostic accuracy, reduces repeat sampling, and minimizes patient burden in ERCP-based diagnosis of bile duct strictures, making it a valuable addition to current diagnostic protocols.

DOI： 10.3390/jcm14176207

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Language：Japanese   Publisher：(一社)日本胆道学会  

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Language：Japanese   Publisher：(株)東京医学社  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2025&ichushi_jid=J02312&link_issn=&doc_id=20250728040014&doc_link_id=%2Faq9syokd%2F2025%2F003707%2F011%2F0934-0938%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faq9syokd%2F2025%2F003707%2F011%2F0934-0938%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：日本消化器病学会-中国支部  

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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Language：Japanese   Publisher：日本消化器病学会-中国支部  

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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Language：English   Publishing type：Research paper (scientific journal)  

Background: Endoscopic treatment is one of the first-line treatments for bile leaks after hepatic surgery. However, detailed reports of endoscopic treatment for bile leaks after hepatic resection (HR) or liver transplantation (LT) are scarce. The outcomes of endoscopic treatment for bile leaks after hepatic surgery were examined, and factors related to successful treatment were identified. Methods: A total of 122 patients underwent endoscopic treatment for bile leaks after hepatic surgery. The diagnosis of a bile leak is based on the ISGLS criteria. The decision to perform endoscopic retrograde cholangiography (ERC) is made based on the amount of drainage output, laboratory data, clinical symptoms, and CT scan findings. In our study, the site of the bile leak was assessed using ERC. Endoscopic stents were placed to bridge across the bile leak site as much as possible. Otherwise, stents were placed near the leak site. Endoscopic stents were replaced every 2-3 months until an improvement in the bile leak was observed with or without biliary strictures. The outcomes of endoscopic treatment and the factors related to clinical success were evaluated. Results: Seventy-four patients with HR and forty-eight patients with LT were treated endoscopically. Technical and clinical success was achieved in 89% (109/122) and 82% (100/122) of patients, respectively. Three (2%) patients died from uncontrollable bile leaks. Bridging stent placement (p < 0.001), coexistent percutaneous drainage (p = 0.0025), and leak severity (p = 0.015) were identified as independent factors related to the clinical success of endoscopic treatment. During a median observation period of 1162 days after the achievement of clinical success, bile leak recurrence was observed in only three cases (3%). Conclusions: Endoscopic treatment is safe and effective for bile leaks after hepatic surgery. Bridging stent placement across the leak site is the most crucial factor for clinical success.

DOI： 10.3390/jcm14103381

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Intrahepatic cholangiocarcinoma has a poor prognosis. In unresectable cases, the survival period is short despite combination therapy with cytotoxic anticancer agents and immune checkpoint inhibitors. The usefulness of immune checkpoint inhibitors against malignant tumors with microsatellite instability-high (MSI-H) mutations was shown in the KEYNOTE158 study; however, data for intrahepatic cholangiocarcinoma are insufficient. In the present case, a 65-year-old man with intrahepatic cholangiocarcinoma and lymph node metastasis could not be treated with a combination of gemcitabine, CDDP, and S-1. A comprehensive cancer genomic profiling (CGP) test showed MLH1 pathogenic mutation and MSI-H. When pembrolizumab was administered, the tumor shrinkage effect was rapidly observed, which was sustained even after 30 months. No pathogenic mutations were observed in the germline test, and MSI-high was considered to be due to the MLH1 pathogenic mutation occurring sporadically in somatic cells. MSI-H intrahepatic cholangiocarcinoma is extremely rare. However, because pembrolizumab is expected to be effective, CGP testing should be actively performed.

DOI： 10.1007/s12328-025-02103-4

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We herein report a case of pancreatic ductal adenocarcinoma (PDAC) that developed within the pancreatic duct and was initially diagnosed as an intraductal tubulopapillary neoplasm (ITPN). A 76-year-old man presented with weight loss and main pancreatic duct dilation. The imaging studies revealed a 30-mm hypovascular tumor within the main duct of the pancreatic head. An endoscopic examination with a biopsy revealed high-grade atypical epithelial cells with immunostaining patterns suggestive of ITPN. Following robot-assisted pancreaticoduodenectomy, postoperative pathology revealed conflicting features: nodular/cribriform infiltrations typical of ITPN and non-lobular replacement with scattered infiltrations characteristic of PDAC. A comprehensive genomic profiling test detected KRAS and TP53 mutations, leading to the final diagnosis of PDAC (fT3N1aM0, stage IIB). The patient received adjuvant S-1 chemotherapy and remained recurrence-free for 15 months post-surgery. This case highlights the diagnostic challenges of differentiating intraductal pancreatic tumors and demonstrates the utility of integrating genetic testing with conventional diagnostic modalities for an accurate diagnosis and appropriate treatment selection.

DOI： 10.1007/s12328-025-02098-y

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OBJECTIVES: Endoscopic ultrasonography (EUS)-guided radiofrequency ablation has recently been introduced as one of the management strategies for small pancreatic neuroendocrine neoplasms (PNENs). However, prospective data on its safety and efficacy remain limited. METHODS: This prospective pilot study was conducted at Okayama University Hospital from May 2023 to December 2024. Patients with grade 1 PNENs ≤15 mm, confirmed by EUS-guided fine-needle aspiration, were included. The primary endpoint was safety (adverse events [AEs] evaluated according to the 2010 guidelines of the American Society for Gastrointestinal Endoscopy. Severe AEs were defined as moderate or higher in American Society for Gastrointestinal Endoscopy grading and grade ≥3. Secondary endpoints included efficacy (complete response on contrast-enhanced computed tomography at 1 and 6 months), treatment details, device failure, diabetes mellitus exacerbation, and overall survival at 6 months. RESULTS: Five patients with non-functional PNENs (median age: 64 years; median tumor size: 10 mm) were treated. AEs occurred in two patients (40%, 2/5), although none was severe. Both patients developed asymptomatic pseudocysts, one experienced mild pancreatitis, and both resolved with conservative treatment. The complete response rates on contrast-enhanced computed tomography at one and 6 months were 100%. The median procedure time was 16 min without any device failure, and the median hospitalization was 5 days. None of the patients developed new-onset or worsening diabetes mellitus. The 6-month overall survival rate was 100%. CONCLUSION: EUS-guided radiofrequency ablation demonstrated a high complete response rate with no severe AEs in this pilot study, suggesting a minimally invasive option for small, low-grade PNENs (jRCTs062230014).

DOI： 10.1002/deo2.70073

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A 64-year-old woman had undergone subtotal stomach-preserving pancreaticoduodenectomy for locally advanced pancreatic head cancer. She had an uneventful postoperative course with no recurrence. However, approximately 18 months after surgery, she presented with recurrent abdominal pain. Although contrast-enhanced computed tomography abdominal radiographs showed internal stent migration to the residual pancreas, dilatation of the tail side of the pancreatic duct was observed. The impaired internal stent was considered to be the cause of the abdominal pain. An attempt to remove the stent via balloon-assisted endoscopy was unsuccessful as the pancreaticojejunostomy site could not be reached. Consequently, endoscopic ultrasonography-guided pancreatic duct drainage was performed, and a plastic stent was placed through the jejunal site to the stomach. Two months later, the endosonographically/endoscopic ultrasonography-guided created route was dilated, and an endoscopic introducer was inserted into the pancreatic duct. Biopsy forceps were advanced through the sheath, allowing the successful removal of the stent by direct grasping. The symptoms of the patient improved, and she was discharged without complications.

DOI： 10.1002/deo2.70096

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Language：English   Publishing type：Research paper (scientific journal)  

Objective: The sedation method used in double-balloon endoscopic retrograde cholangiopancreatography (DB-ERCP) varies across countries and between healthcare facilities. No previous studies have compared the effects of different benzodiazepines on sedation during endoscopic procedures. This study aimed to compare the effects of midazolam and diazepam sedation on DB-ERCP outcomes. Methods: This retrospective cohort study analyzed consecutive patients who underwent DB-ERCP between January 2017 and February 2024. A total of 203 patients who were sedated with diazepam (n = 94) or midazolam (n = 109) were analyzed. Propensity score matching was applied to adjust for baseline group differences. The primary outcome was the incidence of sedation-related adverse events (AEs). Secondary outcomes included inadequate sedation requiring additional sedatives and risk factors for sedation-related AEs. Results: Sedation-related AEs were more frequent with diazepam (28% [21/75]) than with midazolam (14% [11/75]; p = 0.046). Hypoxia occurred more frequently with diazepam (19% [14/75]) than with midazolam (5% [4/75]; p = 0.012). However, no significant differences were observed between the two groups for hypotension (p = 0.41) and bradycardia (p = 1.0). Poor sedation requiring other sedatives occurred significantly more often with diazepam (8% [6/75]) compared with midazolam sedation (0% [0/75], p = 0.012). Multivariate analysis identified diazepam sedation (odds ratio, 2.3; 95% confidence interval, 1.0-5.3; p = 0.048) as the sole risk factor for sedation-related AEs. Conclusions: Midazolam is safer and more effective than diazepam sedation in patients undergoing DB-ERCP.

DOI： 10.3390/jcm14072287

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BACKGROUND: Bleeding is a serious and frequent adverse event that occurs during and after endoscopic papillectomy (EP). Previous studies have highlighted the effectiveness of preventive clipping closure of the resection site in preventing post-EP bleeding. However, the optimal length of closure remained unclear. OBJECTIVES: We aimed to clarify the optimal clipping length at the post-EP resection site to prevent delayed bleeding. DESIGN: This study was a multicenter retrospective cohort study. METHODS: We retrospectively analyzed patients who were consecutively admitted to nine high-volume centers for EP between November 2003 and October 2023. The primary outcome was the frequency of delayed bleeding based on the closure length. The optimal closure length rate of the resected site to prevent delayed bleeding was determined using a receiver operating characteristic curve. Secondary outcomes were the incidence, treatment outcomes, and risk factors for post-EP delayed bleeding. RESULTS: A total of 130 patients who underwent EP were analyzed. Delayed bleeding was observed in 22 (17%) patients, occurring more frequently in cases without clipping closure than in those with clipping closure (28% (13/47) vs 11% (9/83); p = 0.014). Among 83 patients who underwent clipping closure, delayed bleeding occurred more frequently with a closure length rate <65% than in those with a closure rate ⩾65% (25% (5/20) vs 6% (4/63); p = 0.019). Multivariate analysis showed that a closure rate <65% was the risk factor for delayed bleeding (odds ratio, 6.3; 95% confidence interval, 1.2-33; p = 0.030) in cases with clipping. CONCLUSION: Clipping closure was effective in preventing delayed bleeding, and closure length rate ⩾65% of the resected site significantly reduced post-EP delayed bleeding.

DOI： 10.1177/17562848251326450

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Language：Japanese   Publisher：日本消化器病学会-中国支部  

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Language：Japanese   Publisher：日本消化器病学会-中国支部  

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Language：Japanese   Publisher：日本消化器病学会-中国支部  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：English   Publishing type：Research paper (scientific journal)  

Rapid on-site cytopathology evaluation (ROSE) has been considered an effective method to increase the diagnostic ability of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA); however, ROSE is unavailable in most institutes worldwide due to the shortage of cytopathologists. To overcome this situation, we created an artificial intelligence (AI)-based system (the ROSE-AI system), which was trained with the augmented data to evaluate the slide images acquired by EUS-FNA. This study aimed to clarify the effects of such data-augmentation on establishing an effective ROSE-AI system by comparing the efficacy of various data-augmentation techniques. The ROSE-AI system was trained with increased data obtained by the various data-augmentation techniques, including geometric transformation, color space transformation, and kernel filtering. By performing five-fold cross-validation, we compared the efficacy of each data-augmentation technique on the increasing diagnostic abilities of the ROSE-AI system. We collected 4059 divided EUS-FNA slide images from 36 patients with pancreatic cancer and nine patients with non-pancreatic cancer. The diagnostic ability of the ROSE-AI system without data augmentation had a sensitivity, specificity, and accuracy of 87.5%, 79.7%, and 83.7%, respectively. While, some data-augmentation techniques decreased diagnostic ability, the ROSE-AI system trained only with the augmented data using the geometric transformation technique had the highest diagnostic accuracy (88.2%). We successfully developed a prototype ROSE-AI system with high diagnostic ability. Each data-augmentation technique may have various compatibilities with AI-mediated diagnostics, and the geometric transformation was the most effective for the ROSE-AI system.

DOI： 10.1038/s41598-024-72312-3

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Language：Japanese   Publisher：(株)アークメディア  

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Language：Japanese   Publisher：(一社)日本胆道学会  

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND AND AIMS: Accurately diagnosing biliary strictures is crucial for surgical decisions, and although peroral cholangioscopy (POCS) aids in visual diagnosis, diagnosing malignancies or determining lesion margins via this route remains challenging. Indigo carmine is commonly used to evaluate lesions during gastrointestinal endoscopy. We aimed to establish the utility of virtual indigo carmine chromoendoscopy (VICI) converted from POCS images using artificial intelligence. METHODS: This single-center, retrospective study analyzed 40 patients with biliary strictures who underwent POCS using white light imaging (WLI) and narrow-band imaging (NBI). A "cycle-consistent adversarial network" (CycleGAN) was used to convert the WLI into VICI of POCS images. Three experienced endoscopists evaluated WLI, NBI, and VICI via POCS in all patients. The primary outcome was the visualization quality of surface structures, surface microvessels, and lesion margins. The secondary outcome was diagnostic accuracy. RESULTS: VICI showed superior visualization of the surface structures and lesion margins compared with WLI (P<0.001) and NBI (P<0.001). The diagnostic accuracies were 72.5%, 87.5%, and 90.0% in WLI alone, WLI and VICI simultaneously, and WLI and NBI simultaneously, respectively. WLI and VICI simultaneously tended to result in higher accuracy than WLI alone (P=0.083) and the results were not significantly different from WLI and NBI simultaneously (P=0.65). CONCLUSIONS: VICI in POCS proved valuable for visualizing surface structures and lesion margins and contributed to higher diagnostic accuracy comparable to NBI. In addition to NBI, VICI may be a novel supportive modality for POCS.

DOI： 10.1016/j.gie.2024.06.013

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Language：Japanese   Publisher：日本消化器内視鏡学会-中国支部  

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Language：Japanese   Publisher：日本消化器病学会-中国支部  

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Language：Japanese   Publisher：日本消化器内視鏡学会-中国支部  

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Language：Japanese   Publisher：日本消化器病学会-中国支部  

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BACKGROUND AND AIMS: The difficulty of radiographic confirmation of the presence of stones remains a challenge in the treatment of intrahepatic bile duct (IHBD) stones in patients after hepaticojejunostomy (HJ). Peroral direct cholangioscopy (PDCS) enables direct observation of the bile duct and is useful for detecting and removing residual stones; however, its effectiveness is not clearly established in this clinical context. METHODS: This single-center, single-arm, prospective study included 44 patients with IHBD who underwent bowel reconstruction with HJ during the study period. Stone removal was performed by short-type double-balloon enteroscopy (DBE). Following balloon-occluded cholangiography, the DBE was exchanged for an ultraslim endoscope through the balloon overtube for PDCS. The primary endpoint was the rate of residual stones detected by PDCS. Secondary endpoints were success rate of PDCS, residual stone removal with PDCS, procedure time for PDCS, procedure-related adverse events, and stone recurrence rate. RESULTS: PDCS was successful in 39/44 patients (89%), among whom residual stones were detected in 16 (41%) (95% CI: 28%-54%). Twelve patients (75%) had residual stones <5 mm. Stone removal was successful in 15 (94%) patients and median procedure time for PDCS was 16 (IQR: 10-26) min. The rate of procedure-related adverse events was 7% (3/44), all of which improved with conservative treatment. During median follow-up of 2.1 years (IQR: 1.4-3.3), the overall probability of recurrence-free status at 1, 2, and 3 years was 100%, 92%, and 86%, respectively. CONCLUSIONS: PDCS is a safe and effective procedure for complete stone removal in patients with IHBD stones after HJ.

DOI： 10.1016/j.gie.2024.04.014

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Gallbladder cancer incidence has been increasing globally, and it remains challenging to expect long prognosis with the current systemic chemotherapy. We identified a novel nucleic acid-mediated therapeutic target against gallbladder cancer by using innovative organoid-based gallbladder cancer models generated from KrasLSL-G12D/+; Trp53f/f mice. Using comprehensive microRNA expression analyses and a bioinformatics approach, we identified significant microRNA-34a-5p downregulation in both murine gallbladder cancer organoids and resected human gallbladder cancer specimens. In three different human gallbladder cancer cell lines, forced microRNA-34a-5p expression inhibited cell proliferation and induced cell-cycle arrest at the G1 phase by suppressing direct target (CDK6) expression. Furthermore, comprehensive RNA sequencing revealed the significant enrichment of gene sets related to the cell-cycle regulators after microRNA-34a-5p expression in gallbladder cancer cells. In a murine xenograft model, locally injected microRNA-34a-5p mimics significantly inhibited gallbladder cancer progression and downregulated CDK6 expression. These results provide a rationale for promising therapeutics against gallbladder cancer by microRNA-34a-5p injection, as well as a strategy to explore therapeutic targets against cancers using organoid-based models, especially for those lacking useful genetically engineered murine models, such as gallbladder cancer.

DOI： 10.1016/j.omton.2024.200765

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：English   Publishing type：Research paper (scientific journal)  

Gemcitabine is an effective chemotherapeutic agent for biliary tract cancers (BTCs), including gallbladder cancer (GBC) and cholangiocarcinoma (CCA). However, few other effective agents are currently available, particularly for GEM-refractory BTCs. We previously identified microRNA-451a (miR-451a) as a potential therapeutic target in GBC. To elucidate the antineoplastic effects of miR-451a and its underlying mechanisms, we transfected miR-451a into GBC, gemcitabine-resistant GBC (GR-GBC), and gemcitabine-resistant CCA (GR-CCA) cell lines. Furthermore, mimicking in vivo conditions, tumorigenic GBC organoids and three-dimensional (3D) cell culture systems were employed to investigate the anti-proliferative effects of miR-451a on BTCs, and its effect on stem cell properties. We found that miR-451a significantly inhibited cell proliferation, induced apoptosis, and reduced chemoresistant phenotypes, such as epithelial-mesenchymal transition, in both GBC and GR-GBC. The principal mechanism is probably the negative regulation of the phosphatidylinositol 3-kinase/AKT pathway, partially accomplished by directly downregulating macrophage migration inhibitory factor. The Gene Expression Omnibus database revealed that miR-451a was the most significantly downregulated microRNA in CCA tissues. The introduction of miR-451a resulted in similar antineoplastic effects in GR-CCA. Furthermore, miR-451a reduced cell viability in 3D spheroid models and tumorigenic GBC organoids. These findings suggest that the supplementation of miR-451a is a potential treatment strategy for GEM-refractory BTCs.

DOI： 10.1016/j.omtn.2023.102054

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DOI： 10.1055/a-2063-3408

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1055/a-1966-0534

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1055/a-2142-4555

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Language：Japanese   Publisher：日本消化器病学会-中国支部  

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Language：Japanese   Publisher：日本消化器病学会-中国支部  

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: EUS-FNA/B for pancreatic ductal adenocarcinoma (PDAC) is generally considered to be safe; however, while the incidence is low, there are occurrences of complications. Among these complications, there are serious ones like needle tract seeding (NTS), and it is not known than which types of tumors have the risks of EUS-FNA/B complications. This study aimed to evaluate the risk of EUS-FNA/B complications in patients with PDAC, focusing on morphological features. METHODS: Overall, 442 patients who underwent EUS-FNA/B for solid pancreatic masses between January 2018 and May 2022 in four institutions were retrospectively surveyed. Finally, 361 patients histopathologically diagnosed with PDAC were analyzed. Among these patients, 79 tumors with cysts or necrotic components were compared with 282 tumors without cysts or necrotic components. The incidence and risk of EUS-FNA/B complications including NTS were evaluated. RESULTS: There were 9 (2.4 %) of total EUS-FNA/B complications and 3 (0.8 %) of NTS. The incidence of total complication rate and NTS in tumors with cysts or necrotic components were significantly higher than in those without cysts or necrotic components (total complication 6.3 % vs. 1.4 %, p = 0.026, NTS 3.7 % vs. 0 %, p = 0.01). The transgastric route of puncture (OR: 93.3, 95 % CI: 3.81-2284.23) and the existence of cysts or necrotic components (OR: 7.3, 95 % CI: 1.47-36.19) were risk factors for EUS-FNA/B complications identified by the multivariate analysis. CONCLUSIONS: We should pay attention to the risks of EUS-FNA/B complications, including NTS, when the tumor has cysts or necrotic components.

DOI： 10.1016/j.pan.2023.10.018

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We investigated the effect of modified FOLFIRINOX (mFFX) in unresectable pancreatic cancer by retrospectively analyzing the cases of 43 patients who underwent BRCA testing (germline, n=11; somatic, n=26; both germline and somatic, n=6). The association between BRCA mutations and therapeutic effect was clarified. Six patients tested positive for germline pathogenic variants. Familial pancreatic cancer (33% vs. 3%, p=0.006) and peritoneal disseminated lesions (66% vs. 8%, p<0.001) were significantly more common in patients with germline pathogenic variants. The partial response (PR) rate was 100% in the germline BRCA-positive patients, and 27% in the germline BRCA-negative patients (p<0.001). The median progression-free survival (PFS) was not reached for any germline BRCA-positive patients but was 9.0 months for the germline BRCA-negative patients (p=0.042). Patients with stage IV BRCA-associated pancreatic cancer had better overall survival than those with non-BRCA-associated pancreatic cancer, although the difference was nonsignificant (not reached vs. 655 days, p=0.061). Our results demonstrate that a PR and prolonged PFS can be expected in germline BRCA-positive patients after treatment with mFFX. Our findings also suggest that germline BRCA pathogenic variants may be useful as biomarkers for the therapeutic effect of mFFX in patients with pancreatic cancer.

DOI： 10.18926/AMO/65974

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BACKGROUND: The sedation method used during double-balloon endoscopic retrograde cholangiopancreatography (DB-ERCP) differs among countries and/or facilities, and there is no established method. This study aimed to evaluate the efficacy of non-anesthesiologist-administered propofol (NAAP) sedation using a target-controlled infusion (TCI) system during DB-ERCP. METHODS: This retrospective study was conducted between May 2017 and December 2020 at an academic center. One hundred and fifty-six consecutive patients who underwent DB-ERCP were sedated by gastroenterologists using diazepam (n = 77) or propofol with a TCI system (n = 79), depending on the period. The primary endpoint was a comparison of poor sedation rates between the two groups. Poor sedation was defined as a condition requiring the use of other sedative agents or discontinuation of the procedure. Secondary endpoints were sedation-related adverse events and risk factors for poor sedation. RESULTS: Poor sedation occurred significantly more often in the diazepam sedation group (diazepam sedation, n = 12 [16%] vs. propofol sedation, n = 1 [1%]; P = 0.001). Vigorous body movements (3 or 4) (diazepam sedation, n = 40 [52%] vs. propofol sedation, n = 28 [35%]; P = 0.038) and hypoxemia (< 85%) (diazepam sedation, n = 7 [9%] vs. propofol sedation, n = 1 [1%]; P = 0.027) occurred significantly more often in the diazepam sedation group. In the multivariate analysis, age < 70 years old (OR, 10.26; 95% CI, 1.57-66.98; P = 0.015), BMI ≥ 25 kg/m2 (OR, 11.96; 95% CI, 1.67-85.69; P = 0.014), and propofol sedation (OR, 0.06; 95% CI, 0.01-0.58; P = 0.015) were associated factors for poor sedation. CONCLUSIONS: NAAP sedation with the TCI system during DB-ERCP was safer and more effective than diazepam sedation.

DOI： 10.1186/s12876-023-02936-8

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Language：Japanese   Publisher：日本膵・胆管合流異常研究会  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J05229&link_issn=&doc_id=20231002360049&doc_link_id=10.34410%2Fjspbm.46.0_76&url=https%3A%2F%2Fdoi.org%2F10.34410%2Fjspbm.46.0_76&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：English   Publisher：(一社)日本癌学会  

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Language：Japanese   Publisher：(一社)日本胆道学会  

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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Language：English   Publishing type：Research paper (scientific journal)  

We investigated the efficacy and safety of endoscopic plastic stent (PS) placement for hilar benign biliary strictures (BBSs) and compared cases with PS placement above (inside stent, IS) and across (usual stent, US) the sphincter of Oddi. Patients who underwent initial endoscopic PS placement for hilar BBSs between August 2012 and December 2021 were retrospectively analyzed. Hilar BBSs in 88 patients were investigated. Clinical success was achieved in 81 of these cases (92.0%), including 38 patients in the IS group and 43 patients in the US group. Unexpected stent exchange (uSE) before the first scheduled PS exchange occurred in 18 cases (22.2%). The median time from first stent placement to uSE was 35 days. There was no significant difference in the rate and median time to uSE between the two groups. The rates of adverse events such as pancreatitis or cholangitis in the two groups did not significantly differ. However, the rate of difficult stent removal in the IS group (15.8%) was significantly higher than that in the US group (0%) (p=0.0019). US placement is preferable to IS placement for scheduled stent exchange, as it offers the same effectiveness and risk of adverse events with easier stent removal.

DOI： 10.18926/AMO/65494

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Language：Japanese   Publisher：日本消化器病学会-中国支部  

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Language：Japanese   Publisher：日本消化器病学会-中国支部  

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Language：Japanese   Publisher：日本消化器内視鏡学会-中国支部  

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Language：Japanese   Publisher：日本消化器内視鏡学会-中国支部  

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Language：Japanese   Publisher：日本消化器内視鏡学会-中国支部  

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Language：Japanese   Publisher：日本消化器病学会-中国支部  

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Language：Japanese   Publisher：日本消化器内視鏡学会-中国支部  

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Language：Japanese   Publisher：日本消化器病学会-中国支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：English   Publishing type：Research paper (scientific journal)  

INTRODUCTION: Ceftriaxone (CTRX) is known to occasionally cause pseudolithiasis. This condition is often observed in children; however, few studies have reported the incidence and risk factors for CTRX-associated pseudolithiasis. METHODS: In this single-center retrospective study, we investigated the incidence of and risk factors for CTRX-associated pseudolithiasis in adults. All patients underwent computed tomography to confirm pseudolithiasis before and after CTRX administration. RESULTS: The study included 523 patients. Pseudolithiasis was detected in 89 patients (17%). Data analysis showed that abdominal area-related biliary diseases at the site of infection (odds ratio [OR] 0.19, 95% confidence interval [CI] 0.064-0.53, p = 0.0017), CTRX administration for >3 days (OR 5.0, 95% CI: 2.5-9.9, p < 0.0001), CTRX dose of 2 mg (OR 5.2, 95% CI: 2.8-9.6, p < 0.0001), fasting period >2 days (OR 3.2, 95% CI: 1.6-6.4, p = 0.0010), and estimated glomerular filtration rate <30 mL/min/1.73 m2 (OR 3.4, 95% CI: 1.6-7.5, p = 0.0022) were independent factors for pseudolithiasis. CONCLUSIONS: CTRX-associated pseudolithiasis may occur in adults and should be considered in the differential diagnosis in patients who develop abdominal pain or liver enzyme elevation after CTRX administration, particularly in patients with chronic kidney disease, in those who are fasting, in and those who receive high-dose CTRX therapy.

DOI： 10.1159/000529522

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一社)日本消化管学会  

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Drainage exceeding 50% of total liver volume is a beneficial prognostic factor in patients with unresectable malignant hilar biliary obstruction (UMHBO). However, it is unclear what threshold percentage of total liver volume drained ('liver drainage rate') significantly improves survival in patients with UMHBO who received systemic chemotherapy. OBJECTIVES: We aimed to assess the optimal liver drainage rate that improves survival in patients with UMHBO receiving chemotherapy using a three-dimensional (3D)-image volume analyzer. DESIGN: This study was a single-center retrospective cohort study. METHODS: Data from 90 patients with UMHBO who received chemotherapy after endoscopic biliary drainage using metal stents at Okayama University Hospital from January 2003 to December 2020 were reviewed. The liver drainage rate was calculated by dividing the drained liver volume by the total liver volume using a 3D-image volume analyzer. The primary endpoint was overall survival by liver drainage rate. The secondary endpoints were time to recurrent biliary obstruction (TRBO) and prognostic factors. RESULTS: The median total liver volume was 1172 (range: 673-2032) mL, and the median liver drainage rate was 83% (range: 50-100). Overall survival was 376 (95% CI: 271-450) days, and patients with >80% drainage (n = 67) had significantly longer survival than those with <80% drainage (n = 23) (450 days versus 224 days, p = 0.0033, log-rank test). TRBO was 201 (95% CI: 155-327) days and did not differ significantly by liver drainage rate. Multivariate Cox proportional hazards regression analysis revealed >80% liver drainage [hazard ratio (HR): 0.35, 95% CI: 0.20-0.62, p = 0.0003] and hilar cholangiocarcinoma (HR: 0.30, 95% CI: 0.17-0.50, p < 0.0001) as significant prognostic factors. CONCLUSION: In patients with UMHBO scheduled for chemotherapy, >80% drainage is associated with improved survival. Further prospective multicenter studies are needed to verify the results of this study. TRAIL REGISTRATION: Okayama University Hospital, IRB number: 2108-011.

DOI： 10.1177/17562848231206980

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Language：English   Publishing type：Research paper (scientific journal)  

RATIONALE: Duodenal wall perforation by a dislocated biliary stent placed for biliary structure is rare but can be life-threatening. There are few reports on the management of stent-related duodenal perforation. PATIENT CONCERNS: Three cases included in this study had undergone endoscopic retrograde cholangiopancreatography with placement of a plastic stent for biliary stricture. Two cases had symptoms (fever or abdominal pain), while other case showed no symptom after biliary stent placement. DIAGNOSES: Dislocation of plastic stents was revealed on computed tomography or endoscopic images. Two patients were diagnosed with duodenal perforation due to distal migration of long stents with a straight shape on the distal side. One patient was diagnosed with fistula formation between the intrahepatic bile duct and duodenum due to perforation of a pigtail stent. INTERVENTIONS: All cases could successfully be managed endoscopically with closure by hemoclips or stent replacement. OUTCOMES: All 3 cases were improved after endoscopic treatment without any subsequent intervention. LESSONS: Longer stents with a straight distal side are associated with a higher risk of duodenal perforation. Endoscopic management is appropriate as a first-line approach for a clinically stable patient. At the time of stent placement, we should pay attention to the length and type of stent.

DOI： 10.1097/MD.0000000000031868

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Language：Japanese   Publisher：(株)東京医学社  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J02312&link_issn=&doc_id=20230213140021&doc_link_id=10.24479%2Fendo.0000000572&url=https%3A%2F%2Fdoi.org%2F10.24479%2Fendo.0000000572&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Language：English  

BACKGROUND: Gastric linitis plastica (GLP) is a subset of gastric cancer with a poor prognosis. It is difficult to obtain a definitive diagnosis by endoscopic mucosal biopsies, and the usefulness of an endoscopic ultrasonography-guided fine-needle biopsy (EUS-FNB) for GLP has been recently reported. Meanwhile, autoimmune diseases are occasionally known to coexist with malignant tumors as paraneoplastic syndrome. We herein report the usefulness of an EUS-FNB for detecting GLP and the possibility of paraneoplastic syndrome coexisting with GLP. CASE SUMMARY: An 81-year-old man was admitted to our hospital for a 1-mo history of epigastric pain that increased after eating. His laboratory data revealed high levels of serum carbohydrate antigen 19-9 and immunoglobulin-G4. Endoscopic examinations showed giant gastric folds and reddish mucosa; however, no epithelial changes were observed. The gastric lumen was not distensible by air inflation, suggesting GLP. Computed tomography showed the thickened gastric wall, the diffuse enlargement of the pancreas, and the peripancreatic rim, which suggested autoimmune pancreatitis (AIP) coexisting with GLP. Because the pathological findings of the endoscopic biopsy showed no malignancy, he underwent an EUS-FNB and was diagnosed with GLP. He received chemotherapy for unresectable gastric cancer due to peritoneal metastasis, after which both the gastric wall thickening and diffuse enlargement of the pancreas were improved. CONCLUSION: An EUS-FNB for GLP with a negative endoscopic biopsy is useful, and AIP may develop as a paraneoplastic syndrome.

DOI： 10.12998/wjcc.v10.i31.11607

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Language：Japanese   Publisher：日本消化器病学会-中国支部  

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Language：Japanese   Publisher：日本消化器病学会-中国支部  

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Language：Japanese   Publisher：日本消化器病学会-中国支部  

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Language：Japanese   Publisher：日本消化器病学会-中国支部  

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Language：Japanese   Publisher：日本消化器病学会-中国支部  

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUNDS: Pancreatic juice (PJ) is directly associated with pancreatic lesions, including pancreatic ductal cancer and intraductal papillary mucinous neoplasm-derived cancer. Therefore, EVs secreted from these lesions into PJ can be promising biomarkers for early diagnosis. However, there are limited data from analysis of EVs in PJ samples. AIMS AND METHODS: We aimed to determine the stability of EVs in PJ collected using endoscopic naso-pancreatic drainage (ENPD) tubes as well as catheter during endoscopic retrograde cholangiography (ERCP), with or without the impact of positive protease activity, and optimize the EV isolation method. RESULTS: Size exclusion chromatography was found to be an optimal isolation method for EVs in PJ as it achieved higher recovery and purity of EVs compared with differential ultracentrifugation and polymer-based precipitation. Approximately 40% of the PJ samples collected during ERCP and more than 90% of those collected using ENPD tubes had positive protease activity. In vitro exposure to room temperature for less than 3 h was harmless to the structure of double-membrane EVs in PJ and the expression levels of TSG101, even with positive protease activity. CONCLUSIONS: We clarified the physiobiological status of EVs in PJ and optimized the EV isolation method using suitable PJ samples; these findings can be utilized to discover biomarkers for cancer diagnosis and elucidate their function.

DOI： 10.1007/s10620-021-07339-x

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：English   Publishing type：Research paper (scientific journal)  

We herein report a 78-year-old man who underwent endoscopic retrograde cholangiopancreatography (ERCP) to examine main pancreatic duct (MPD) stenosis. During ERCP, MPD perforation occurred due to the cytology brush maneuver. Endoscopic pancreatic stenting to bridge the perforated site failed because the MPD was bent and formed a loop. Thus, we placed the stent at the proximal perforated side. The patient developed retroperitoneal perforation and pancreatic fistula with infection, showing a worsening condition. Pancreatic duct drainage was not effective, so we performed endoscopic ultrasonography-guided pancreatic duct drainage. Subsequently, he gradually improved and was discharged 3 months after initial ERCP.

DOI： 10.1007/s12328-022-01699-1

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Language：Japanese   Publisher：(一社)日本胆道学会  

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Language：Japanese   Publisher：(一社)日本胆道学会  

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1055/a-1893-5644

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND AND AIMS: Endoscopic ultrasonography-guided hepaticogastrostomy (EUS-HGS) is often performed using a single guidewire (SGW), but the efficacy of the double guidewire (DGW) technique during endoscopic ultrasonography-guided biliary drainage has been reported. We evaluated the efficacy of the DGW technique for EUS-HGS, focusing on the guidewire angle at the insertion site. METHODS: This retrospective cohort study included consecutive patients who underwent EUS-HGS between April 2012 and March 2021. We measured the guidewire angle at the insertion site using still fluoroscopic imaging. We compared the clinical outcomes of EUS-HGS with the DGW and SGW techniques. The factors associated with successful cannula insertion, need for additional fistula dilation and adverse event rate were assessed by a logistic regression multivariable analysis. RESULTS: The DGW group showed higher technical (p = 0.020) and clinical success rates (p = 0.016) than the SGW group, which showed more adverse events (p = 0.017) than the DGW group. Successful cannula insertion was associated with a guidewire angle > 137° and an uneven double-lumen cannula. The DGW technique made the guidewire angle obtuse at the insertion site (p < 0.0001). A guidewire angle ≤ 137° (OR, 35.6; 95% CI, 1.70-744; p = 0.0045) and intrahepatic bile duct diameter of the puncture site ≤ 3.0 mm (OR, 14.4; 95% CI, 1.37-152; p = 0.0056) were risk factors for needing additional fistula dilation in a multivariate analysis, and additional dilation was a significant predictive factor for adverse events (OR, 8.3; 95% CI, 0.9-77; p = 0.026). CONCLUSIONS: The DGW technique can modify the guidewire angle at the insertion site and facilitate stent deployment with few adverse events.

DOI： 10.1007/s00464-022-09350-3

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Language：Japanese   Publisher：(NPO)日本高齢消化器病学会  

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DOI： 10.1055/a-1838-3553

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Language：Japanese   Publisher：日本消化器病学会-中国支部  

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Language：Japanese   Publisher：日本消化器病学会-中国支部  

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Language：Japanese   Publisher：日本消化器内視鏡学会-中国支部  

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Language：Japanese   Publisher：日本消化器内視鏡学会-中国支部  

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: The interaction between cancer cells and laminin (Ln) is a key event in tumor invasion and metastasis. Previously, we determined the effect of full-length Ln511 on gastric cancer cells. However, the interactions between the Ln511-E8 fragment, a truncated protein of Ln511, and gastric cancer cells have not been investigated. METHODS: We investigated the adhesion properties of gastric cancer cells to full-length Ln511 and Ln511-E8 fragments. RESULTS: The proliferation of four gastric cancer cell lines (SH-10-TC, MKN74, SC-6-JCK, and MKN45) was highest on the Ln511-E8 fragment. Further, a larger cytoplasm was observed in SH-10-TC and MKN74 cells cultured on full-length Ln511 or Ln511-E8 fragments. The percentage of adhesive cells was highest on the Ln511-E8 fragment in all four cell lines. Moreover, adhesion of the gastric cancer cells to Ln511-E8 fragment-coated plates was reduced by the Cdc42 GTPase inhibitor in a dose-dependent manner, suggesting the involvement of Cdc42 in the Ln511-E8 fragment-induced enhanced adhesion of gastric cancer cells. CONCLUSIONS: The Ln511-E8 fragment had a greater impact on the adhesion, morphology, and proliferation of gastric cancer cells than full-length laminin. Thus, the Ln511-E8 fragment is suitable for investigating the interaction between gastric cancer cells and extracellular matrices in tumor invasion and metastasis.

DOI： 10.3390/cimb44040105

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Language：English  

Endoscopic migrated stent removal using a balloon-assisted enteroscope is technically difficult in patients with bowel reconstruction. We report the treatment outcomes and endoscopic removal methods for migrated stents using a double-balloon enteroscope (DBE). We retrospectively studied 12 patients with stent migration into the main pancreatic duct (MPD) or bile duct who underwent bowel reconstruction between January 2012 and June 2020. The successful removal rates in the MPD (n = 3) and the bile duct (n = 9) were 66.7% (2/3) and 88.9% (8/9), respectively. The removal techniques included the indirect method (n = 3), the direct method (n = 4), and a combination of indirect and direct methods (n = 3). The removal devices included an extraction balloon catheter (n = 7), basket catheter (n = 5), biopsy forceps (n = 3), and snare (n = 2). Stent removal using a DBE was feasible and useful as the first treatment for patients with bowel reconstruction. The choice of the direct and/or indirect method according to the situation of the migrated stent is important.

DOI： 10.1002/deo2.32

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Mixed neuroendocrine-non-neuroendocrine neoplasm (MINEN) is a rare disease and there is scarce literature on its diagnosis, treatment, and prognosis. We encountered two unusual cases of MINEN in the biliary tract, one in the ampulla of Vater and the other in the distal bile duct. In this report, we describe the clinical course of these two cases in detail. CASE PRESENTATION: Case 1: A 69-year-old woman presented with a chief complaint of epigastric pain. When endoscopic sphincterotomy and retrograde biliary drainage were performed for gallstone pancreatitis, an ulcerated lesion was found in the ampulla of the Vater. Based on the biopsy results, the lesion was diagnosed as the ampulla of Vater carcinoma and subtotal stomach-preserving pancreatoduodenectomy (SSPPD) was performed. Postoperative histopathological examination revealed the coexistence of adenocarcinoma and neuroendocrine carcinoma components, consistent with the diagnosis of MINEN. In addition, lymph node metastasis was found on the dorsal side of the pancreas and the metastatic component was adenocarcinoma. Adjuvant chemotherapy with etoposide and cisplatin was administered for 6 months, and presently the patient is alive without recurrence 64 months after surgery. Case 2: A 79-year-old man presented with a chief complaint of anorexia. Cholangiography showed severe stenosis of the distal bile duct. A biopsy was conducted from the stenotic lesion and it revealed the lesion to be adenocarcinoma. A diagnosis of distal bile duct carcinoma was made, and SSPPD was performed. Histopathological examination revealed the coexistence of adenocarcinoma and neuroendocrine carcinoma components, and the tumor was confirmed as MINEN of the distal bile duct. No adjuvant chemotherapy was administered due to the poor performance status. 7 months later, the patient was found to have a liver metastasis. CONCLUSION: We experienced two valuable cases of biliary MINEN. To identify better treatments, it is important to consider the diversity of individual cases and to continue sharing a variety of cases with different presentations.

DOI： 10.1186/s40792-022-01386-w

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: The number of patients with non-functional neuroendocrine tumors (NETs) has increased recently, and the rate of liver metastasis of NETs is about 20% in patients at the first diagnosis. Transcatheter arterial embolization (TAE) and everolimus are therapies with reported efficacy, but few reports have described their combined treatment. We therefore aim to evaluate the efficacy and safety of combination therapy with everolimus and TAE in patients with liver metastasis of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in a prospective study. METHODS: We design a single-arm, open-label, prospective study to evaluate the efficacy and safety of combination therapy with everolimus and TAE in patients with liver metastases of GEP-NETs. The study started in June 2021 at Okayama University Hospital and is expected to enroll 18 patients over a 2-year period. DISCUSSION: This study is a prospective study investigating a new treatment method for a rare disease called GEP-NETs. We may obtain useful information that contributes to the treatment guidelines in this study. However, NET is a rare disease, and although the number of cases is statistically established, it may not be possible to accurately assess causality.TRIAL REGISTRATION NUMBER: jRCT1061210015.

DOI： 10.1177/11795549221127750

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1055/a-1694-3794

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Language：English   Publishing type：Research paper (scientific journal)  

A 71-year-old man who had undergone total gastrectomy, partial pancreatectomy, and splenectomy with Roux-en-Y reconstruction for gastric cancer was referred for a possible pancreatic tail tumor. Contrast-enhanced computed tomography showed mold-like, poor contrast lesion in the dilated main pancreatic duct in the pancreatic tail. Endoscopic ultrasonography revealed a slightly hyperechoic solid lesion that occupied the lumen of the main pancreatic duct. Linear calcification was observed in the lesions on both computed tomography and endoscopic ultrasonography, and endoscopic ultrasound-guided fine-needle biopsy was performed. Histopathology revealed sulfur grains and inflammatory infiltrates with no malignant findings. We also performed an anaerobic culture using fine-needle biopsy specimens, and Actinomyces meyeri was detected in the culture results. After confirming susceptibility, oral administration of amoxicillin was initiated. After 8 months of treatment, the size of the lesion slightly decreased, and the antibiotics treatment is still ongoing. This shows that such cases could be diagnosed based on histological findings and anaerobic culture using a fine-needle biopsy specimen, and unnecessary surgery may be avoided. In the case of tumors developed in the residual pancreas without typical malignant imaging findings, pancreatic actinomycosis should be considered as a differential diagnosis.

DOI： 10.1007/s12328-021-01523-2

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Objective Strict follow-up is recommended for branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) to avoid missing the development of high-risk stigmata (HRS) at a premalignant stage. This study explored the risk factors associated with the development of HRS during follow-up. Methods We performed a retrospective analysis of 283 patients with BD-IPMN, treated at Okayama University Hospital in Japan between January 2009 and December 2016. Only patients with imaging studies indicative of classical features of BD-IPMN without HRS and followed for over one year were included in the study. We performed radiological follow-up every six months and collected patients' demographic data, cyst characteristics, and clinical outcomes and used univariate logistic regression models to determine the odds of developing HRS. Results Ten patients (3.5%) developed HRS after a median surveillance period of 55.8 months. The main pancreatic duct (MPD) size (5-9 mm) and cyst growth rate (>2.5 mm/year) were both suggested to be possible risk factors for the development of HRS [odds ratio, 14.2; 95% confidence interval (CI), 3.1-65.2, p=0.0006, and odds ratio, 6.1; 95% CI 1.5-25.5, p=0.014]. Regarding the number of worrisome features (WFs), the rate of HRS development was 2.0% (4/199) in cases with no WF, 1.6% (1/62) in cases with single WF and 22.7% (5/22) in cases with multiple WFs, respectively. The rate of HRS development was significantly higher in cases with multiple WFs than in the other cases (p<0.0001). Conclusion MPD dilation, rapid cyst growth, and multiple WFs were significant risk factors for the development of HRS. In the presence of such features, it is necessary to closely follow the development of HRS and avoid missing the best opportunity to perform surgical intervention.

DOI： 10.2169/internalmedicine.7168-21

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BACKGROUND: The technique to analyze circulating tumor DNA (ctDNA) in body fluid (so-called "liquid biopsy") is recently developed. AIMS: Our aim was to assess the utility of liquid biopsy for predicting progression of pancreatic ductal adenocarcinoma (PDAC) after surgical resection or chemotherapy. METHODS: A total of 72 patients with PDAC were retrospectively enrolled for this study, 33 treated surgically and 39 given chemotherapy, either FOLFIRINOX (oxaliplatin/irinotecan/fluorouracil/leucovorin) or gemcitabine plus nab-paclitaxel. Prior to treatment, patients were screened for the presence of KRAS mutations (G12D and G12V) in plasma using droplet digital polymerase chain reaction, and outcomes were compared. RESULTS: KRAS mutations were identified in plasma samples of 12 patients (36%) underwent surgical resection. Patients with plasma KRAS mutations had significantly shorter disease-free survival (DFS) and overall survival (p < .01 and p = .01, respectively). Of 10 clinical variables analyzed, plasma KRAS mutation was the factor predictive of DFS in multivariate analysis (RR = 3.58, 95% CI: 1.36-9.60; p = .01). Although 12 patients (31%) given chemotherapy tested positive for plasma KRAS mutations, there was no demonstrable relation between plasma KRAS mutations and progression-free survival (PFS) or overall survival (OS) (p = .35 and p = .68, respectively). CONCLUSIONS: In patients with PDAC, detection of KRAS mutations in plasma proved independently predictive of early recurrence after surgical resection but did not correlate with PFS following chemotherapy.

DOI： 10.1080/15384047.2021.1980312

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Language：Japanese   Publisher：(株)東京医学社  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2021&ichushi_jid=J02312&link_issn=&doc_id=20211008090012&doc_link_id=%2Faq9syokd%2F2021%2F003309%2F013%2F1437-1444%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faq9syokd%2F2021%2F003309%2F013%2F1437-1444%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

BACKGROUND: The effects of the Franseen needle size in endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) of solid pancreatic masses remain unclear. This study aimed to compare 25G and 22G Franseen needles in terms of adequate tissue acquisition from solid pancreatic masses. METHODS: In this single-center, crossover, randomized noninferiority trial, eligible patients underwent EUS-FNB with both 25G and 22G Franseen needles in a randomized order between November 2018 and August 2020. Tissue specimens from each pass were separately evaluated based on the cellularity scoring system. The primary outcome was the proportion of acquired specimens allowing adequate histological assessment (cellularity score ≥3). A -15% noninferiority margin was assumed. RESULTS: Data from 88 patients were analyzed, which showed malignant and benign lesions in 84 (95.5%) and four (4.5%) patients, respectively. Of the 88 specimens, 62 (70.5%) and 69 (78.4%) acquired using 25G and 22G needles, respectively, allowed adequate histological assessment. The adjusted proportion difference was -6.6% (95% confidence interval -8.8% to -4.5%), indicating noninferiority of the 25G Franseen needle (P < 0.001). The diagnostic accuracies of the 25G and 22G needles were 86.4% and 89.8%, respectively, with no significant difference (P = 0.180). Adverse events occurred in one patient. CONCLUSIONS: The 25G Franseen needle showed a noninferior adequate tissue acquisition and similar diagnostic performance compared to that of the 22G Franseen needle. However, a 15% noninferiority margin was high for clinical use; thus, further consideration is needed (Clinical Trial Registry no. UMIN000034596).

DOI： 10.1111/den.14079

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/den.14079

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BACKGROUND: Hepaticojejunostomy anastomotic stricture (HJAS) is a significant complication of biliary reconstruction surgery. Endoscopic management of HJAS using double-balloon enteroscopy has expanded; however, retrospective reports in this setting are limited. This study aimed to evaluate the efficacy of endoscopic balloon dilatation combined with stent deployment for HJAS. METHODS: This was a single-arm prospective clinical trial involving 40 patients with treatment-naïve HJAS enrolled between March 2016 and August 2019 at four endoscopy units in Japan. For HJAS, plastic stents combined with balloon dilatation were placed for 6 months after initial stenting. The primary outcome was HJ anastomosis patency 12 months after stent removal. RESULTS: The technical success rate was 97.5% (39/40). The failed case required percutaneous transhepatic biliary drainage using the rendezvous technique. All cases achieved successful endoscopic treatment. During the treatment period, four of 40 patients (10%) ended the study protocol due to unrelated causes and were excluded from the primary analysis. Among the 36 patients, clinical success was achieved in 34 (94.4%) patients. The remaining two patients achieved HJAS resolution after an additional 3 months. All 36 patients achieved HJAS resolution. Adverse events were observed in two patients (5.0%) who developed moderate cholangitis. During a median follow-up of 21.3 months, HJAS recurrence was observed in 8.3% (3/36) with a median time to recurrence of 4.3 months and HJ anastomosis patency at 12 months was 94.4%. CONCLUSIONS: Endoscopic balloon dilatation combined with plastic stent deployment for 6 months was a safe and effective strategy for HJAS. (Clinical Trial Registry no. UMIN000020613).

DOI： 10.1111/den.14097

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BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) for extraction of common bile duct (CBD) stones in patients with Roux-en-Y gastrectomy (RYG) remains technically challenging. METHODS: Seventy-nine RYG patients (median 79 years old) underwent short-type double-balloon enteroscopy-assisted ERCP (sDBE-ERCP) for CBD stones at three referral hospitals from 2011-2020. We retrospectively investigated the treatment outcomes and potential factors affecting complete stone extraction. RESULTS: The initial success rates of reaching the papilla of Vater, biliary cannulation, and biliary intervention, including complete stone extraction or biliary stent placement, were 92%, 81%, and 78%, respectively. Of 57 patients with attempted stone extraction, complete stone extraction was successful in 74% for the first session and ultimately in 88%. The adverse events rate was 5%. The multivariate analysis indicated that the largest CBD diameter ≥ 14 mm (odds ratio (OR), 0.04; 95% confidence interval (CI), 0.01-0.58; p = 0.018) and retroflex position (OR, 6.43; 95% CI, 1.12-36.81; p = 0.037) were independent predictive factors affecting complete stone extraction achievement. CONCLUSIONS: Therapeutic sDBE-ERCP for CBD stones in a relatively elderly RYG cohort, was effective and safe. A larger CBD diameter negatively affected complete stone extraction, but using the retroflex position may be useful for achieving complete stone clearance.

DOI： 10.3390/jcm10153314

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A 76-year-old woman with branch duct intraductal papillary mucinous neoplasm (IPMN) was admitted with epigastric pain and vomiting. She had received warfarin due to a history of deep vein thrombosis. A blood test showed decreased serum hemoglobin and elevated serum amylase. Contrast-enhanced computed tomography revealed acute pancreatitis and formation of a pseudoaneurysm in the IPMN. We suspected rupture of a pseudoaneurysm and performed trans-catheter angiography. Angiography showed extravasation from the posterior superior pancreaticoduodenal artery, and coil embolization was performed. It is important to be alert for the formation of pseudoaneurysm in patients with cystic neoplasms.

DOI： 10.2169/internalmedicine.6445-20

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Circulating microRNAs (miRNAs) in serum extracellular vesicles (EVs) are a promising biomarker in cancer. We aimed to elucidate the serum EVs miRNA biomarkers to identify patients with gallbladder cancer (GBC) and to clarify their potential roles. One hundred nineteen serum EVs from GBC and non-GBC individuals were isolated by pure-EVs-yieldable size-exclusion chromatography, and then were analyzed using a comprehensive miRNAs array and RT-qPCR-based validation. The functional roles of the identified miRNAs were also investigated using GBC cell lines. Serum EVs miR-1246 and miR-451a were significantly upregulated and downregulated, respectively in GBC patients (P = 0.005 and P = 0.001), in line with their expression levels in cancer tissue according to an in silico analysis. The combination of CEA and CA19-9 with miR-1246 showed the highest diagnostic power (AUC, 0.816; Sensitivity, 72.0%; Specificity, 90.8%), and miR-1246 was an independent prognostic marker of GBC (Hazard ratio, 3.05; P = 0.017) according to a Cox proportional hazards model. In vitro, miR-1246 promoted cell proliferation and invasion, while miR-451a inhibited cell proliferation and induced apoptosis with the targeting of MIF, PSMB8 and CDKN2D. Taken together, miR-1246 in serum EVs has potential application as a diagnostic and prognostic marker and miR-451a may be a novel therapeutic target in GBC.

DOI： 10.1038/s41598-021-91804-0

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Laminins (Ln), a type of extracellular matrix glycoprotein, are key regulators of cellular behavior. Recent work revealed that in various tumor cell lines, laminin isoforms influence specific responses, such as cell anchorage, survival, proliferation, migration, organization, and specialization. The contribution of laminin isoforms to the function of gastric cancer cells, however, remain unclear. Here, we revealed that in gastric cancer, laminin isoforms Ln411, Ln421, Ln511, and Ln521 promote cellular proliferation; Ln511 and Ln521 increase cell cytoplasmic volume; Ln511 hampers invadopodia formation in some cells, Ln511 enables prompt adhesion of cells to plates, and Ln411 and Ln511 do not alter the gastric cancer stem cell markers CD44 and Lgr5. These results indicate that Ln411 and Ln511 dynamically modulate the proliferation, adhesion, and morphology of gastric cancer cells in different ways that are independent of stem cell properties. In particular, Ln511 showed a high affinity for gastric cancer cells. Our observations broaden the possible options for controlling cancer cell progression and metastasis by modulating laminin-integrin interactions.

DOI： 10.1007/s12013-021-00972-3

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BACKGROUND: Acute pancreatitis is a major adverse event of endoscopic retrograde cholangiopancreatography (ERCP). Rectal administration of non-steroidal anti-inflammatory drugs (NSAIDs) decreases the incidence of post-ERCP pancreatitis (PEP). However, the efficacy of low dose rectal NSAIDs for preventing PEP remains controversial. METHODS: We performed a retrospective study of 301 patients with native papilla and a body weight of <50 kg who underwent ERCP between September 2010 and October 2019. After July 2016, a 25 mg dose of rectal diclofenac was routinely administered within 15 min before ERCP (NSAIDs group, n = 72) and the control group (n = 229) consisted of patients undergoing ERCP before this date without treatment. We compared the incidence of PEP between the two groups using propensity score matching. RESULTS: A total of 66 pairs of patients in each group were selected. The patients and procedural-related factors were similar in both groups. In total, 15 patients (11.4%) developed PEP: 12.1% (8/66) in the NSAIDs group and 10.6% (7/66) in the control group (Odds ratio (OR) 1.2; 95% confidence interval (CI) 0.4-3.5; P = 0.78). There was no significant difference in incidence of other adverse events related to ERCP between the two groups. CONCLUSIONS: Prophylactic administration of a 25 mg dose of rectal diclofenac did not reduce the incidence of PEP in patients with a native papilla and a body weight of <50 kg in this study and a certain dose of rectal NSAIDs, such as a 100-mg dose, should be administered regardless of body weight to prevent PEP.

DOI： 10.1111/den.13828

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BACKGROUND: Endoscopic papillectomy is increasingly performed as an alternative to surgery for early ampullary tumors. AIM: This retrospective study aimed to evaluate the long-term results of endoscopic papillectomy, the management of cases with incomplete endoscopic resection, and the long-term recurrence rates. METHODS: All 46 patients who underwent endoscopic papillectomy for ampullary tumors between November 2003 and March 2018 were retrospectively evaluated. RESULTS: The final pathological diagnoses were adenoma (n = 44) and adenocarcinoma (n = 2). Histopathological evaluations after endoscopic papillectomy revealed that complete resection was achieved in 19 patients (19/46, 41.3%). Among the 27 patients with incomplete resection, the margin was histopathologically positive in 14 patients and difficult to evaluate in 13. Additional surgery was performed for 2 of the 14 patients with positive margins. Excluding 2 patients who received additional surgery, 7 of the 25 patients with incomplete resection had recurrence, and 18 had no recurrence during the follow-up period. Ten (77%) of the 13 patients in whom the margin was difficult to evaluate had no recurrence. CONCLUSION: Approximately 80% of the patients in whom the histopathological evaluation of the resected margin was difficult had no recurrence even after approximately 5 years of follow-up. Thus, careful observation may be considered for these patients.

DOI： 10.1007/s11605-020-04532-7

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BACKGROUND AND AIMS: The subtypes of intraductal papillary mucinous neoplasms (IPMNs) are closely associated with the clinicopathological behavior and recurrence after surgical resection. However, there are no established non-invasive methods to confirm the subtypes of IPMNs without surgery. The aim of this study is to predict the subtypes of IPMNs using the findings of endoscopic ultrasonography (EUS). METHODS: Sixty-two consecutive patients with IPMNs who underwent EUS before surgery were retrospectively reviewed. The following EUS findings were analyzed and their relationship with the subtypes was evaluated: diameter of the main pancreatic duct, cyst size, number of cysts, height of mural nodule, early chronic pancreatitis (CP) finding, fatty parenchyma and atrophic parenchyma. RESULTS: The subtypes of IPMNs were as follows: gastric (G)-type 38 (61%), intestinal (I) -type 14 (23%) and pancreatobiliary (PB) -type 10 (16%). Fatty parenchyma was significantly associated with G-type (P < 0.0001). Early CP findings ≥2 and atrophic parenchyma were significantly correlated with I-type (P < 0.0001). PB-type was significantly associated with pancreatic parenchyma without early CP findings or fatty degeneration in comparison to the other subtypes (P < 0.0001). Using the above characteristic EUS findings, the sensitivity, specificity, and accuracy were as follows: 63%, 92% and 74%, respectively, in G-type, 57%, 96% and 87% in I-type, and 90%, 94% and 94% in PB-type. CONCLUSIONS: The evaluation of EUS findings, especially focused on the pancreatic parenchyma, has the potential to predict the subtypes of IPMN.

DOI： 10.1016/j.pan.2021.01.026

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BACKGROUND AND STUDY AIMS: Endoscopic treatment outcomes for hepatolithiasis in patients with altered anatomy are not well known. The aim of this study was to evaluate the treatment outcomes of hepatolithiasis in patients with hepaticojejunostomy (HJ) using short-type double-balloon endoscopy (sDBE) and to assess the risk factors for stone recurrence. PATIENTS AND METHODS: This was a retrospective cohort study that consisted of 73 patients with hepatolithiasis who underwent bowel reconstruction with HJ at an academic center. Stone removal was performed using sDBE. After balloon-occluded cholangiography using sDBE, peroral direct cholangioscopy (PDCS) using ultraslim endoscopy was performed to check for residual stones, depending on the bowel reconstruction method. Recurrence was defined as the development of cholangitis from stones. RESULTS: The success rate of reaching the HJ site was 92% (67/73), and the complete stone removal rate was 93% (62/67) with multiple sessions (mean number 1.5 ± 0.9). The occurrence rate of procedure-related adverse events was 6.8%. Among 58 patients evaluated for stone recurrence, 13 (22%) developed recurrence during a median follow-up period of 2.7 years (interquartile range: 1.5-4.8). Multivariate analyses determined that a stone diameter ≥ 8 mm [odds ratio (OR), 5.57; 95% confidence interval (CI), 1.39-37.2; p = 0.013] and performing PDCS (OR, 0.16; 95% CI, 0.0084-0.90; p = 0.036) were significant factors for stone recurrence. CONCLUSIONS: Endoscopic treatment using sDBE for hepatolithiasis was effective and safe. PDCS might reduce the rate of stone recurrence by detecting stones that are too small to confirm on fluoroscopic images.

DOI： 10.1007/s00464-020-08139-6

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OBJECTIVES: The aim of this multicenter retrospective study was to identify the optimal chemotherapeutic regimen for advanced pancreatic acinar cell carcinoma (PACC). METHODS: Fifty-eight patients with histopathologically confirmed advanced PACC who had received chemotherapy between 1996 and 2013 were enrolled. The clinical characteristics of the patients and the treatment efficacy data were collected from the medical records at 16 Japanese institutions, using standardized data collection instrument. RESULTS: The most commonly selected treatment regimens were gemcitabine-, fluoropyrimidine-, platinum-, and irinotecan-containing regimens. The overall response rate in the patients who received first-line chemotherapy were 7% and 38%, respectively, and the median overall survival was 13.2 months. When the data for all the treatment lines were aggregated, the response rates to gemcitabine-, fluoropyrimidine-, platinum-, and irinotecan-containing regimens were 7%, 18%, 40%, and 29%, respectively. The overall survival tended to be better in patients who had received a platinum-containing regimen (hazard ratio, 0.50; 95% confidence interval, 0.23-1.11; P = 0.08) or irinotecan-containing regimen (hazard ratio, 0.42; 95% confidence interval, 0.15-1.19; P = 0.09) at least once in the treatment course as compared with those who had not. CONCLUSIONS: Our findings suggested that platinum- and irinotecan-containing regimens exhibited some potential efficacy in patients with advanced PACC.

DOI： 10.1097/MPA.0000000000001718

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BACKGROUND: Cutting needles are thought to be effective as biopsy needles. A few types of cutting needles are available for endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), and the Menghini-type needle is an end-type cutting needle. AIMS: A prospective randomized controlled trial was conducted to compare the results of EUS-FNA using a Menghini-type needle (needle M) versus a conventional needle (needle S). METHODS: The main eligibility criteria were as follows: patients with a pancreatic mass referred for EUS-FNA, ≥ 20 years old, and a performance status < 4. The primary outcome was the sample quality. The secondary outcomes were factors associated with the sample quality, diagnostic accuracy, and adverse events. RESULTS: A total of 97 patients were enrolled in this study. The sample quality for total puncture with needle M (92.8%) was significantly higher than that with needle S (81.4%) (p = 0.0305). The tumor size (p = 0.033) and type of needle (p = 0.031) were significant factors associated with adequate tissue collection in univariate and multivariate analyses (odds ratio [OR] 2.71; 95% confidence interval [CI] 1.12-6.54; p = 0.027 for tumor size, and OR 2.93; 95% CI 1.23-8.21; p = 0.0153 for type of needle). The diagnostic accuracy of each needle was 88.7% (86/97) with needle M and 73.2% (71/97) with needle S. Adverse events occurred in 2 of the 97 patients (0.02%). CONCLUSION: A Menghini-type needle was able to obtain core tissue for histology more effectively than a conventional aspiration needle. TRIAL REGISTRATION NUMBERS: UMIN registration number of 000020668.

DOI： 10.1007/s10620-020-06628-1

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BACKGROUND AND AIMS: The sensitivity of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for diagnosing the recurrence of pancreatic cancer is usually low because of difficulties in obtaining adequate samples for pathological examinations. We evaluated the efficacy of highly sensitive KRAS mutation analysis using EUS-FNA washes to detect cancer recurrence. METHODS: Nineteen consecutive patients with suspected pancreatic cancer recurrence after surgical resection were enrolled. All underwent EUS-FNA, and samples were obtained for pathological examination. After the first session, the inside of the FNA needle was washed with saline for DNA extraction. KRAS mutations were examined using digital droplet PCR (dPCR). RESULTS: The median needle puncture number used to obtain adequate pathological samples was two (range 1-6). In ten patients pathologically diagnosed with malignant pancreatic cancer, nine patients tested positive for a KRAS mutation. All patients who were not diagnosed with a malignant pancreatic cancer tested negative for a KRAS mutation. About half of surgically resected primary cancers (9/19) showed double KRAS mutations (G12V and G12D); however, all but one wash sample showed a single KRAS mutation, G12D. After including one patient who showed a malignant recurrence during follow-up, the sensitivities of a pathological diagnosis and KRAS analysis to detect recurrence were 90.9% and 81.8%, respectively. CONCLUSIONS: KRAS mutation analysis of needle wash samples using dPCR is a new methodology for the diagnosis of the local recurrence of pancreatic cancer. The diagnostic ability of dPCR with a one-time needle wash sample was comparable to a pathological diagnosis with multiple samplings.

DOI： 10.1007/s10620-019-06006-6

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BACKGROUND: Pancreatic juice cytology (PJC) is a tool for diagnosing malignant intraductal papillary mucinous neoplasm (IPMN); however, the accuracy is insufficient using the conventional method. Liquid-based cytology (LBC) improves the cell recovery rate, and almost all cells can be evaluated. We evaluated the efficacy of PJC with LBC for malignant IPMN. METHODS: We retrospectively analyzed 90 patients with suspected malignant IPMN who underwent PJC before pancreatectomy. PJC with smear and LBC methods was conducted in 52 patients (between June 2003 to December 2011) and 38 patients (between January 2012 to December 2018). Based on the imaging studies, all of the patients were classified according to the international consensus guidelines for IPMN revised in 2017. RESULTS: Of the 90 patients, 43 (48%) had malignant IPMN (high-grade dysplasia or invasive carcinoma), and the remaining patients had non-malignant IPMN (intermediate- or low-grade dysplasia). LBC increased the accuracy of PJC for the diagnosis of malignant IPMN (smear method: 56% [29/52] vs. LBC method: 76% [29/38]; P = 0.044). In a multivariate analysis, LBC was a significant factor influencing the accurate diagnosis of PJC (odds ratio: 3.52; P = 0.021). Furthermore, LBC increased the accuracy of PJC for malignant IPMN in patients with worrisome features (smear method: 66% [19/29] vs. LBC method: 93% [14/15]; P = 0.043). CONCLUSIONS: LBC increases the accuracy of PJC for diagnosing malignant IPMN compared with the conventional smear method.

DOI： 10.1186/s12876-020-01465-y

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Background/Aims: Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA; EUS-FNA) allows for diagnostic tissue specimens from various regions to be analyzed. However, diagnosing recurrent pancreaticobiliary cancer after surgery is sometimes difficult. We evaluated the efficacy of EUS-FNA in the diagnosis of local recurrence of pancreaticobiliary cancer and analyzed the factors associated with falsenegative results. Methods: Fifty-one consecutive patients who underwent EUS-FNA due to suspected recurrence of pancreaticobiliary cancer after surgery in an academic center were retrospectively analyzed. The criteria for EUS-FNA were a resected margin or remnant pancreas mass, round swollen lymph node (≥10 mm in diameter), and soft-tissue enhancement around a major artery. Patients with suspected liver metastasis or malignant ascites were excluded. Results: Thirty-nine of the 51 patients had pancreatic cancer; the remaining 12 had biliary cancer. The target sites for EUS-FNA were the soft tissue around a major artery (n=22, 43%), the resected margin or remnant pancreas (n=12, 24%), and the lymph nodes (n=17, 33%). The median size of the suspected recurrent lesions was 15 mm (range, 8 to 40 mm). The overall sensitivity, specificity and accuracy of EUS-FNA for the diagnosis of recurrence was 84% (32/38), 100% (13/13), and 88% (45/51), respectively. FNA of the soft tissue around major arteries (odds ratio, 8.23; 95% confidence interval, 1.2 to 166.7; p=0.033) was significantly associated with a falsenegative diagnosis in the multivariate analysis. Conclusions: EUS-FNA is useful for diagnosing recurrent cancer, even after pancreaticobiliary surgery. The diagnoses of recurrence at soft-tissue sites should be interpreted with caution.

DOI： 10.5009/gnl19200

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Language：Japanese   Publisher：日本胆道学会  

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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The physiological role of the reduced expression of immortalized cells (REIC)/Dickkopf-3 (Dkk-3) protein in patients with hepatocellular carcinoma (HCC) remains unclear. In this study, we evaluated the effect of the REIC/Dkk-3 protein on HCC cell proliferation and assessed the relationship between the serum REIC/Dkk-3 protein level and the prognosis in patients with HCC. We evaluated the REIC/Dkk-3 protein-induced anticancer effects on Huh7 and Hep3B cells (HCC cell lines) in the presence of peripheral blood mononuclear cells (PBMCs), and found that combination treatment with REIC/Dkk-3 protein and PBMCs reduced the proliferation of HCC cells (Hep3B: 82.0%±16.3%; Huh7: 72.6%±9.1%). We also studied 194 HCC patients who underwent primary liver resection or primary radiofrequency ablation from 2008 to 2017. Serum REIC/Dkk-3 protein levels were measured by an enzyme-linked immunosorbent assay and compared to the prognostic data. The 3-year disease-free survival of the REIC/Dkk-3 high group was significantly higher than that in the REIC/Dkk-3 low group. In conclusion, this is the first study investigating the relationship between HCC patient survival and serum REIC/Dkk-3 protein levels in a large population. Based on the results, the serum REIC/Dkk-3 protein level should be considered a new prognostic marker for patients with HCC.

DOI： 10.18926/AMO/59957

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There are several places where the P-value and Odds ratio in Table 3 are incorrect: these are shown in the corrected Table 3 below.

DOI： 10.1007/s00464-020-07399-6

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BACKGROUND: To evaluate the outcomes of endoscopic retrograde cholangiopancreatography (ERCP) for malignant biliary obstruction (MBO) using short-type double-balloon enteroscope (sDBE) in patients with surgically altered anatomy. METHODS: A total of 45 patients with surgically altered anatomy underwent ERCP using sDBE for the treatment of MBO between April 2011 and March 2019. We retrospectively evaluated the clinical and technical success (insertion and biliary intervention success), adverse events, and risk factors for clinical failure. RESULTS: The scope was successfully inserted in the target site in 82.2% of patients (37/45), and among them, biliary intervention success was achieved in 86.4% (32/37). The overall technical success rate was 71.1% (32/45) and clinical success rate was 68.9% (31/45), with an adverse event rate of 11.1%. In multivariate analysis, the presence of peritoneal dissemination (odds ratio, 7.3; 95% confidence interval, 1.5-43.5, p = 0.02) was as an independent risk factor for clinical failure. The clinical success rate was 38.5% in patients with peritoneal dissemination and 81.3% in those without peritoneal dissemination. CONCLUSION: Endoscopic treatment using sDBE in patients without peritoneal dissemination provided favorable outcomes, and it can be an initial treatment for MBO in patients with surgically altered anatomy.

DOI： 10.1007/s00464-020-07385-y

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BACKGROUND: Endoscopic ultrasound is useful for obtaining high-resolution images of pancreaticobiliary diseases, but is not readily available for physical checkups. In this study, we evaluated the safety and efficacy of single-session esophagogastroduodenoscopy and endoscopic ultrasound in the detection of upper-gastrointestinal and pancreaticobiliary diseases using a forward-viewing radial scan ultrasonic endoscope. METHODS: A total of 148 patients who were scheduled for upper-gastrointestinal screening using an endoscope were prospectively included. All patients were examined by EUS in combination with EGD using a forward-viewing radial scan ultrasonic endoscope. The primary endpoint was the safety of the procedures. The secondary endpoints were the prevalence of diseases, the basal imaging capability of EUS, the procedure time, total dose of propofol, and the correlation between background factors and the prevalence of pancreatic disease. The imaging capability at each region was scored as 0 (invisible) to 2 (sufficient visualization to evaluate the organs). RESULTS: Intraoperative hypotension occurred as an adverse event of intravenous anesthesia in one patient. There were 82 pancreaticobiliary findings and 165 upper-gastrointestinal findings (malignancy not included). Follicular lymphoma of the intra-abdominal lymph nodes was detected in one patient. The mean imaging scores of each section were 1.95 (pancreatic head and papilla), 2.0 (pancreatic body), 1.99 (pancreatic tail), and 1.89 (common bile duct and gallbladder). Age, history of diabetes mellitus, and smoking history were significantly associated with the prevalence of pancreatic diseases. CONCLUSION: The simultaneous performance of EGD and EUS using a new ultrasonic endoscope is tolerable and safe for upper-gastrointestinal and pancreaticobiliary screening.

DOI： 10.1186/s12876-019-1141-7

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BACKGROUND: Recently, therapeutic antibodies against programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) have shown promising clinical results for several solid tumors, including pancreatic cancer. In this study, we evaluated the relationship between the PD-L1 expression of surgical resected and fine-needle aspiration (FNA) specimens for patients with pancreatic cancer. METHODS: Of 121 patients who underwent endoscopic ultrasound-guided (EUS)-FNA before surgery for pancreatic cancer in an academic center, the 94 (78%) with adequate FNA specimens for a histological evaluation were retrospectively analyzed. All the patients had undergone upfront surgery without any chemotherapy or radiotherapy. We performed immunohistochemistry (IHC) staining to investigate the PD-L1 expression in both resected and FNA specimens. The positive-stained cells were counted, and their percentage was used for the investigation. RESULTS: Of the 94 patients, 16 (17%) and 11 (10%) were defined as positive on resected cancer specimens using cutoff points of 5% and 10% positively stained cancer cell counts, respectively. The concordance rates for the positive frequency of PD-L1 expression between resected and FNA specimens were 44% (7/16) and 55% (6/11) when the positivity was set to ≥ 5% and ≥ 10%, respectively. The concordance rates for the negative frequency of PD-L1 expression between two specimens were 97% (76/78) and 99% (82/83) when the positivity was set to ≥ 5% and ≥ 10%, respectively. CONCLUSIONS: Approximately, half of the patients with PD-L1 expression positive and almost all the patients with PD-L1 expression negative could be diagnosed on FNA specimens.

DOI： 10.1007/s00535-019-01586-6

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PURPOSE: Histological grading is important for the treatment algorithm in pancreatic neuroendocrine neoplasms (PNEN). The present study examined the efficacy of contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) and time-intensity curve (TIC) analysis of PNEN diagnosis and grading. METHODS: TIC analysis was performed in 30 patients using data obtained from CH-EUS, and a histopathological diagnosis was made via EUS-guided fine-needle aspiration or surgical resection. The TIC parameters were analyzed by dividing them into G1/G2 and G3/NEC groups. Then, patients were classified into non-aggressive and aggressive groups and evaluated. RESULTS: Twenty-six patients were classified as G1/G2, and four as G3/NEC. From the TIC analysis, five parameters were obtained (I: echo intensity change, II: time for peak enhancement, III: speed of contrast, IV: decrease rate for enhancement, and V: enhancement ratio for node/pancreatic parenchyma). Three of these parameters (I, IV, and V) showed high diagnostic performance. Using the cutoff value obtained from the receiver-operating characteristic (ROC) analysis, the correct diagnostic rates of parameters I, IV, and V were 96.7%, 100%, and 100%, respectively, between G1/G2 and G3/NEC. A total of 21 patients were classified into the non-aggressive group, and nine into the aggressive group. Using the cutoff value obtained from the ROC analysis, the accurate diagnostic rates of I, IV, and V were 86.7%, 86.7%, and 88.5%, respectively, between the non-aggressive and aggressive groups. CONCLUSION: CH-EUS and TIC analysis showed high diagnostic accuracy for grade diagnosis of PNEN. Quantitative perfusion analysis is useful to predict PNEN grade diagnosis preoperatively.

DOI： 10.1007/s10396-019-00967-x

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BACKGROUND: Short-type double-balloon endoscope (DBE)-assisted endoscopic retrograde cholangiopancreatography (ERCP) has been developed as an alternative approach for cases with a surgically altered gastrointestinal anatomy. However, this technique is sometimes technically challenging and carries a risk of severe adverse events. AIMS: To evaluate the factors affecting the technical success rate and adverse events of DBE-ERCP. METHODS: A total of 319 patients (805 procedures) with a surgically altered gastrointestinal anatomy underwent short DBE-ERCP. The factors affecting the technical success rate and adverse events, and the learning curve of the trainees were retrospectively evaluated. RESULTS: The technical success rate of all procedures was 90.7%. Adverse events occurred in 44 (5.5%) procedures. A multivariate analysis indicated that Roux-en-Y reconstruction and first-time short DBE-ERCP were factors affecting the technical failure and adverse event rates, while the modified Child method after subtotal stomach-preserving pancreaticoduodenectomy reconstruction was a non-risk factor for adverse events. The trainee caseload did not affect the technical success or adverse event rates significantly; however, trainees tended to perform cases involving the modified Child method after subtotal stomach-preserving pancreaticoduodenectomy reconstruction. The success rate of scope insertion increased according to experience; however, the overall success rate did not differ to a statistically significant extent. CONCLUSION: Short DBE-ERCP was useful and safe for managing cases with a surgically altered anatomy; however, trainees should concentrate on accumulating experience with easy cases, such as those with the modified Child method after subtotal stomach-preserving pancreaticoduodenectomy reconstruction or a history of DBE-ERCP.

DOI： 10.1007/s10620-019-05857-3

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DOI： 10.1055/a-0896-2498

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BACKGROUND/AIMS: This study aimed to examine the diagnostic ability of endoscopic ultrasonography (EUS) for major vascular invasion in pancreatic cancer and to evaluate the relationship between EUS findings and pathological distance. METHODS: In total, 57 consecutive patients who underwent EUS for pancreatic cancer before surgery were retrospectively reviewed. EUS image findings were divided into four types according to the relationship between the tumor and major vessel (types 1 and 2: invasion, types 3 and 4: non-invasion). We also compared the EUS findings and pathologically measured distances between the tumors and evaluated vessels. RESULTS: The sensitivity, specificity, and accuracy of EUS diagnosis for vascular invasion were 89%, 92%, and 91%, respectively, in the veins and 83%, 94%, and 93%, respectively, in the arteries. The pathologically evaluated distances of cases with type 2 EUS findings were significantly shorter than those of cases with type 3 EUS findings in both the major veins (median [interquartile range], 96 [0-742] µm vs. 2,833 [1,076-5,694] µm, p=0.012) and arteries (623 [0-854] µm vs. 3,097 [1,396-6,000] µm, p=0.0061). All cases with a distance of ≥1,000 µm between the tumors and main vessels were correctly diagnosed. CONCLUSION: Tumors at a distance ≥1,000 µm from the main vessels were correctly diagnosed by EUS.

DOI： 10.5946/ce.2018.163

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BACKGROUND/AIMS: We applied a back light system (BLS) with a magnifying glass to improve the ability to assess the adequacy of specimen sampling using endosonography. We conducted this study to evaluate the efficacy of the BLS in sampling of specimens by endoscopic ultrasound-guided fine needle aspiration of solid pancreatic masses. METHODS: This was a prospective, randomized, crossover, single-center clinical trial. An endosonographer evaluated adequacy on gross visual inspection and identified whitish specimen sampling sites with and without the BLS according to a randomization sequence in the first and second passes with a 25-G needle. On cytological evaluation, the presence of well-defined pancreatic ductal epithelium was evaluated by a cytopathologist who was blinded to any clinical information. RESULTS: A total of 80 consecutive patients were eligible during the study period. Adequacy was observed for 52 specimens (65%) with the BLS and 54 (68%) without the BLS (p=0.88). In assessment of specimen adequacy on gross examination, only fair agreement was observed both with and without BLS (kappa score 0.40 and 0.29, respectively). CONCLUSION: The BLS did not influence the ability to identify specimen sampling sites or reliable assessment of specimen site adequacy using gross visual inspection.

DOI： 10.5946/ce.2019.004

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BACKGROUND: Hepaticojejunostomy anastomotic stricture (HJAS) is an important complication of biliary reconstructive surgery but has no standard treatment. We aimed to evaluate the outcomes of endoscopic treatment for benign HJAS and identify the risk factors for its recurrence. METHODS: This study retrospectively analyzed 176 patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) for HJAS between April 2008 and March 2016. The outcome of endoscopic biliary stenting combined with balloon dilation (EBS group) and balloon dilation alone (balloon group) was evaluated. RESULTS: The scope was successfully inserted into the HJ site in 93.8% patients (165/176), and 139 patients underwent endoscopic treatment after HJAS was confirmed. Successful biliary drainage was achieved in 137 patients by using ERCP and rendezvous procedures. Among these, 103 patients were included in balloon group and 34 patients were in EBS group. HJAS was resolved in 132 patients; five died from recurrence of primary disease. The 1 (3)-year bile duct patency rates in the balloon and EBS groups were 62.5% (46.6%) and 89.4% (84.7%), respectively (p = 0.015). Univariate analysis showed that balloon dilation (p = 0.009) and early HJAS formation (time from surgery to ERCP < 1 year) (p = 0.02) were risk factors for HJAS recurrence. In the multivariate analysis, balloon dilatation was identified as independent risk factors for HJAS recurrence. CONCLUSIONS: Balloon dilation without stent deployment and early HJAS formation are risk factors for HJAS recurrence after endoscopic treatment. Stent deployment might be recommended for definite resolution of HJAS.

DOI： 10.1007/s11605-019-04297-8

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DOI： 10.1055/a-0800-8178

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In recent years, liquid biopsy for blood and body fluid in cancer patients has attracted attention. However, there have been few reports of liquid biopsy focusing on urine of pancreatic ductal adenocarcinoma (PDAC). In 56 patients with PDAC, DNA was extracted from urine and plasma prior to treatment, and KRAS mutations were analyzed with droplet digital PCR to examine the mutation detection rate. Our study showed that KRAS mutations were found in 27 cases (48%) in urine and 27 cases (48%) in plasma. The detection rate of urine KRAS mutations varied by renal functions. The rates were 70% (14/20) and 36% (13/36) in the creatinine clearance rate (CCr) < 70 mL/min group and in the CCr ≥ 70 mL/min group, respectively (P = .024). Whereas, no influence of the CCr was observed in the detection rates of plasma KRAS mutations. The rates were 50% (10/20) and 47% (17/36) in cases with the CCr < 70 mL/min group and the CCr ≥ 70 mL/min group, respectively. Although the sample size was small, this study clearly indicated a new possibility of less invasive urine liquid biopsy in PDAC patients.

DOI： 10.1080/15384047.2019.1638685

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BACKGROUND: Advanced pancreatic cancer is accompanied not only by bile duct obstruction, but also occasionally by duodenal obstruction. With new advances in chemotherapy and improvement in the management of stent dysfunction, the life expectancy of patients with pancreatic cancer has increased. This study aimed to evaluate the efficacy and safety of chemotherapy for advanced pancreatic cancer, as well as to analyze the prognostic factors, following endoscopic double stenting. METHODS: This retrospective study was conducted from January 1, 2007 to October 31, 2015 at an academic center. Fifty consecutive patients with pancreatic cancer who had undergone endoscopic double stenting, comprising duodenal and biliary stenting, were analyzed. We reviewed the patients records and analyzed the data of stent dysfunction rates after double stenting, reintervention for stent dysfunction, chemotherapy after double stenting, adverse events associated with chemotherapy after double stenting, survival times following double stenting, and overall survival times. The hospital's institutional review board for human research approved this study. RESULTS: The overall survival time and the survival time following double stenting were 10.9 months (IQR 6.0-18.4 months) and 2.4 months (IQR 1.4-5.2 months), respectively. After double stenting, duodenal stent dysfunction occurred in 6 patients (12%), and biliary stent dysfunction occurred in 12 patients (24%), respectively. All patients who experienced stent dysfunction underwent endoscopic reintervention, and all of the procedures were successful. Twenty-one (42%) patients were treated with chemotherapy post double stenting; 9 patients received chemotherapy as a first-line treatment, 9 as a second-line treatment, and 3 as a third-line treatment. During chemotherapy, 8 (38%) patients had grade 3-4 adverse events, which were manageable. Chemotherapy post double stenting (OR, 0.19; 95% CI, 0.059-0.60; P = .0051), reintervention for biliary stent dysfunction (OR, 0.21; 95% CI, 0.081-0.50; P = .0002), and performance status (< 2) (OR, 0.28; 95% CI, 0.098-0.71; P = .0064) were significant prognostic factors after double stenting. CONCLUSIONS: Systemic chemotherapy was manageable, even in patients with double stenting. Chemotherapy after double stenting and appropriate reintervention for stent obstructions potentially prolonged the survival of patients with advance pancreatic cancer.

DOI： 10.1186/s12876-018-0886-8

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The γ-secretase inhibitor blocks Notch activity by preventing its cleavage at the cell surface. In the present study, the effect of the γ-secretase inhibitor on the viability of gastric cancer cells when administered in combination with cisplatin was investigated, with particular focus on CD44highLgr-5high cancer cells. The four gastric cancer cell lines, MKN45, MKN74, SC-6-JCK and SH-10-TC, were used for the experiments. In the MTT assay, treatment with 25 µM dipeptide γ-secretase inhibitor (DAPT) alone did not affect cell proliferation in any of the four cell lines. Gastric cancer cells subjected to combination treatment with DAPT and cisplatin exhibited decreased viability when compared with those treated with cisplatin alone. Flow cytometry was performed to evaluate the expression of cluster of differentiation (CD)-44 and leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr-5), two cancer stem cell markers in gastric cancers. Treatment with cisplatin alone significantly increased the proportion of CD44highLgr-5high cells. However, the addition of DAPT to cisplatin reduced the CD44highLgr-5high fraction, suggesting that DAPT reduced the number of gastric cancer cells. In conclusion, the present study demonstrated the synergistic effects of DAPT in combination with cisplatin by decreasing the survival of gastric cancer cells. In addition, combination treatment with DAPT reduced the number of CD44highLgr-5high cells, which are thought to exhibit cancer stem cell properties. These results highlight the therapeutic potential of DAPT in gastric cancer treatment.

DOI： 10.3892/ol.2018.9301

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PURPOSE: Streptozocin (STZ) is a key agent for treating advanced pancreatic neuroendocrine tumors (pNET). Most STZ regimens for pNET are daily and also include 5-fluorouracil (5FU), whereas STZ monotherapy and weekly regimens have also been applied in daily practice in Japan. The present study aimed to evaluate responses to weekly regimens and to STZ monotherapy, and to identify a predictive marker of a response to STZ. METHODS: Clinical data regarding STZ-based chemotherapy for pNET were collected between 2015 and 2017 at 25 facilities. We analyzed the effects, safety, progression-free survival (PFS), and factors that correlate with responses to STZ. RESULTS: The overall objective response rate (ORR) of 110 patients who underwent STZ-based chemotherapy (monotherapy, 81.8%; weekly regimen 46.4%) was 21.8%, and PFS was 9.8 months. The ORR of weekly vs. daily regimens was 21.6 vs. 22.0% (P = 1.000), and that of monotherapy vs. combination therapy was 21.1 vs. 25.0% (P = 0.766). A Ki67 proliferation index (Ki67) of > 5% was a predictive marker of a response to STZ (P = 0.017), whereas regimen type, mono- or combination therapy, treatment line and liver tumor burden were not associated with responses. The frequencies of Grade ≥ 3 nausea and hematological adverse events were significantly lower for monotherapy than combination therapy (P = 0.032). CONCLUSIONS: The effects of weekly STZ monotherapy on pNET are comparable to those previously reported and the toxicity profile was acceptable. Ki67 > 5% was the sole predictive marker of an objective response.

DOI： 10.1007/s00280-018-3656-y

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We conducted a multicenter retrospective analysis to evaluate the efficacy of systemic chemotherapy for unresectable combined hepatocellular and cholangiocarcinoma. We enrolled 36 patients with pathologically proven, unresectable combined hepatocellular and cholangiocarcinoma treated with systemic chemotherapy. The log-rank test determined the significance of each prognostic factor. Elevated alpha-fetoprotein, carcinoembryonic antigen and carbohydrate antigen 19-9 levels were observed in 58.3%, 16.7% and 38.9% of patients, respectively. First-line chemotherapy included platinum-containing regimens consisting of gemcitabine/cisplatin (n = 12) and fluorouracil/cisplatin (n = 11), sorafenib (n = 5) and others (n = 8). The median overall and progression-free survival times were 8.9 and 2.8 months, respectively, with an overall response rate of 5.6%. Prognostic factors associated with negative outcomes included poor performance status, no prior primary tumor resection, a Child-Pugh class of B, and elevated carcinoembryonic antigen levels with a hazard ratio of 2.25, 2.48, 3.25 and 2.84 by univariate analysis, respectively. The median overall survival times of the gemcitabine/cisplatin, fluorouracil/cisplatin, sorafenib and other groups were 11.9, 10.2, 3.5 and 8.1 months, respectively. Multivariate analysis revealed that the overall survival of patients within the sorafenib monotherapy group was poor compared with platinum-containing regimens (HR: 15.83 [95% CI: 2.25-111.43], P = .006). All 7 patients in the sorafenib group had progressive disease, including 2 patients with second-line therapy. In conclusion, the platinum-containing regimens such as gemcitabine/cisplatin were associated with more favorable outcomes than sorafenib monotherapy for unresectable combined hepatocellular and cholangiocarcinoma.

DOI： 10.1111/cas.13656

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PURPOSE: Although EUS-guided hepaticogastrostomy (EUS-HGS) with a covered self-expandable metal stent (SEMS) is a useful procedure, it is associated with severe adverse events, including stent migration. We, therefore, developed an intra-conduit release method, and investigated whether the technique yields a safer and more stable procedure. METHODS: The intra-conduit release method is a procedure to release the SEMS in the working channel conduit of the scope for anchoring between the liver and stomach to avoid stent migration. Forty-three patients who underwent EUS-HGS at two high-volume centers in Japan were enrolled in this retrospective study, and the safety and usefulness of this method were evaluated retrospectively. RESULTS: The intra-conduit release method was applied in 36 cases. The technical success rate of EUS-HGS with the intra-conduit release method was significantly higher in comparison with the conventional method. Additionally, the rate of early adverse events was significantly lower than that for the conventional method. CONCLUSION: The intra-conduit release method during EUS-HGS is useful for a stable procedure that avoids early adverse events.

DOI： 10.1007/s10396-017-0846-x

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Background and study aims  Endoscopic treatment for post-operative bile is technically challenging in patients with altered gastrointestinal anatomy. This study evaluated the effectiveness of using a short-type double-balloon enteroscope to treat postoperative bile leakage after hepaticojejunostomy.

DOI： 10.1055/s-0043-125143

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Language：Japanese   Publisher：(一社)日本内科学会  

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BACKGROUND: Endoscopic retrograde cholangiography using a short double-balloon endoscope (DB-ERC) is a promising minimally-invasive method for accessing hepaticojejunostomy (HJ) anastomosis in patients with surgically altered anatomy. We aimed to evaluate the immediate and long-term outcomes of balloon dilatation for benign HJ anastomotic stricture (HJAS) in patients who had previously undergone Whipple's procedure using a DB-ERC. METHODS: We conducted a retrospective analysis of 46 patients who underwent balloon dilatation alone with a DB-ERC for benign HJAS between November 2008 and November 2014. The median follow-up duration was 3.5 (interquartile range [IQR], 1.9-5.1) years. RESULTS: The technical and clinical success rates were 100%, and adverse events occurred in 7% (3/46, cholangitis). The median hospitalization period was seven (IQR, 5-10) days. Of 42 patients (91%) followed-up for > 1 year, 24 (51%) had recurrent HJAS at a median of 1.2 (IQR, 0.6-2.9) years after balloon dilatation. The cumulative anastomotic patency rates at 1, 2, and 3 years were 73, 55, and 49%, respectively. In univariate analysis, early stricture formation (< 1 year) was a risk factor for recurrent stenosis, although no statistically significant risk factors were observed in multivariate analysis. CONCLUSIONS: Endoscopic balloon dilatation with DB-ERC for benign HJAS is effective and safe, having good immediate technical success and few adverse events. Further improvements to this procedure are needed to prevent recurrent HJAS.

DOI： 10.1186/s12876-018-0742-x

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We report the cases of two patients who underwent endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) using metallic stents (MS) for recurrent cholangitis due to benign biliary stenosis. The patients had repeatedly undergone double-balloon endoscopy and anastomotic stenosis. Thus, EUS-HGS was performed. The procedures were successful, and placement of a covered metallic stent (C-MS) relieved cholangitis. The occurrence of cholangitis was subsequently considerably reduced. For patients with postoperative recurrent cholangitis, EUS-HGS with MS should be considered because of its efficacy and safety.

DOI： 10.1155/2018/7201967

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Background and Aims: Biliary stenting for the treatment of biliary stricture is the most common indication of ERCP, but the procedure is sometimes unsuccessful because of severe strictures. The Swing Tip is useful for passing through severe strictures because it has a manually operable tip. The efficacy of using a Swing Tip was retrospectively evaluated. Methods: The 2353 patients who underwent ERCP for biliary stenting at our facility between January 2012 and July 2018 were enrolled. In all patients, procedures were begun using tapered tip-catheters, and Swing Tips were used if the procedure was found to be difficult with other devices. The indication for switching to the Swing Tip and the technical success rate were retrospectively evaluated. Results: A total of 99 patients (4.2%) underwent ERCP using the Swing Tip, including 49 patients for the selection of biliary branches and 50 for exchanging guidewires for rigid ones. In these patients, biliary stenting was successful in 22 patients (44.9%) and 45 patients (90%), respectively. The other 32 patients with failed endoscopic biliary drainage were treated via alternative approaches, such as percutaneous procedures, surgeries, or conservative treatments. There were no adverse events associated with the Swing Tip. Conclusion: The Swing Tip was technically feasible especially for exchanging guidewires during ERCP. Percutaneous procedures or surgical treatments can be avoided by using the Swing Tip. Ethical Statements: This study was approved by the institutional review board of Okayama University. All subjects provided informed consent. The study was registered in the UMIN protocol registration system (identification number UMIN 000033692).

DOI： 10.1155/2018/7125714

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Background and Aims: Recurrent pancreatitis associated with pancreatic strictures requires treatment with endoscopic retrograde pancreatography (ERP), but it is sometimes technically unsuccessful. Endoscopic ultrasound-guided pancreatic drainage (EUS-PD) was developed as an alternative to a surgical approach after failed ERP; however, the indications for EUS-PD are unclear. In this study, we evaluated the outcomes of EUS-PD and established the indications for EUS-PD. Methods: A total of 15 patients had indications for EUS-PD for recurrent pancreatitis due to pancreatic strictures. There were eight patients with benign pancreatic strictures and seven with malignant pancreatic strictures. The success rate, adverse events, and long-term outcomes were evaluated. Results: The technical success rates of benign and malignant strictures were 75% (6/8) and 100% (7/7), respectively, and clinical success was achieved in 100% (6/6) and 87.5% of cases (6/7), respectively. Rendezvous procedures were performed in two patients with benign strictures. The adverse event (AE) rate was 26.7% (4/15) and included cases of peritonitis, bleeding, and stent migration. Reinterventions were performed in three patients with benign strictures and two with malignant strictures. Conclusions: EUS-PD was an appropriate treatment for not only benign strictures but also malignant strictures with recurrent pancreatitis after failed ERP. However, the AE rate was high, and reinterventions were required in some cases during long-term follow-up. The indications for EUS-PD should be considered carefully, and careful follow-up is needed.

DOI： 10.1155/2018/8216109

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Background and study aims No standard procedure for endoscopic retrograde cholangiopancreatography is available for patients with Roux-en-Y hepaticojejunostomy (RYHJ) with side-to-end hepaticojejunostomy. We therefore explored methods of efficient scope insertion at a hepaticojejunostomy site. Patients and methods Patients with suspected biliary disease were prospectively enrolled. Based on two fluoroscopic images obtained on scope insertion into each lumen of a two-pronged Roux-en-Y anastomosis, we selected the lumen in which the distal end of the scope progressed toward the patient's liver or head. The accuracy of this method for selecting the correct lumen leading to the hepaticojejunostomy site was investigated. Results Of the 33 included patients, successful insertion to the hepaticojejunostomy site was achieved in 32 (97 %), 26 (81 %) of whom had undergone the imaging method. The accuracy of the method was 88 % (23/26). The time required for insertion between the anastomotic site and the hepaticojejunostomy site was shorter when the lumen selection had been correct (13 minutes [7 - 30] (n = 23) vs. 18 minutes [8 - 28] (n = 9); P = 0.95). Conclusion This method based on two fluoroscopic images was useful for achieving efficient scope insertion in patients with RYHJ.Trial registered at University Hospital Medical Information Network Clinical Trials Registry (UMIN000014183).

DOI： 10.1055/s-0043-117406

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Background and study aims We designed a new 7-Fr plastic stent for treating self-expandable metal stent (SEMS) obstruction in patients with malignant hilar biliary obstruction (MHBO) via endoscopic re-intervention with the stent-in-stent (SIS) method and evaluated its efficacy. Patients and methods A total of 33 consecutive patients who underwent endoscopic re-intervention for metal stent obstruction after multi-branched SEMS placement were enrolled. The initial SEMSs were placed in two or three biliary branches in 14 and 19 patients, respectively. We retrospectively evaluated the technical and clinical success, and adverse events. Technical success was defined as successful plastic stent placement into all target branches through the lumen of the SEMS. Results The technical success rates were 85.7 % (12/14) and 78.9 % (15/19) in patients who underwent two- or three-branched biliary drainage, respectively. The clinical success rate was 100 % in the 27 patients in whom technical success was achieved. We achieved successful plastic stent placement in more than two branches, using the new plastic stent combined with a conventional plastic stent, in 97.0 % (32/33). Conclusions This new plastic stent was technically feasible for treating stent obstruction via re-intervention with SIS methods.

DOI： 10.1055/s-0043-116215

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DOI： 10.1111/jgh.13757

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DOI： 10.1055/s-0043-108543

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japan Gastroenterological Endoscopy Society  

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Acute pancreatitis is the major complication of endoscopic retrograde cholangiopancreatography(ERCP). A preliminary research suggested that the administration of nonsteroidal anti-inflammatory drugs (NSAIDs) with nitrate might reduce the incidence of post-ERCP pancreatitis (PEP) more effectively than NSAIDs alone. We conduct a two-arm, multicenter, prospective, randomized, superiority trial to evaluate the additional effect of nitrate for prevention of PEP. A total of 900 patients randomly receive 50 mg diclofenac suppository either alone or with 5 mg isosorbide dinitrate sublingual tablet. The primary endpoint is the occurrence of PEP. This study will clarify whether NSAIDs plus nitrate can prevent PEP.

DOI： 10.18926/AMO/55314

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japan Gastroenterological Endoscopy Society  

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BACKGROUND AND AIM: Few reports describe the endoscopic double-stenting procedure for malignant biliary and duodenal obstructions. We evaluated the clinical outcomes from double stenting, and analyzed the risk factors for biliary stent dysfunction following double stenting. METHODS: Eighty-one patients who underwent endoscopic double stenting for malignant biliary and duodenal obstructions were retrospectively analyzed. We determined the stent dysfunction rate and the biliary stent dysfunction risk factors, and analyzed the endoscopic reintervention results. RESULTS: Overall survival time and survival time following double stenting were 365 (38-1673) days and 73 (20-954) days, respectively. After double stenting, the 3-month and 6-month duodenal stent dysfunction rates were 14% and 41%, respectively. Reintervention technical success rate was 100% (10/10), and mean gastric outlet obstruction scoring system scores improved from 0.7 to 2.4 points (P < 0.001). The 3-month and 6-month biliary stent dysfunction rates were 26% and 41%, respectively. The reintervention technical and clinical success rates were 95% (20/21) and 81% (17/21), respectively. Risk factors for biliary stent dysfunction following double stenting were events associated with duodenal stent dysfunction (odds ratio [OR], 11.1; 95% confidence interval [CI], 2.09-87.4; P = 0.0044) and the biliary stent end's location (OR, 6.93; 95% CI, 1.37-40.2; P = 0.0019). CONCLUSIONS: Some patients had stent dysfunction irrespective of the survival period after double stenting. Endoscopic reintervention was technically feasible and clinically effective even after double stenting. Duodenal stent dysfunction and biliary stent end's location were risk factors for biliary stent dysfunction.

DOI： 10.1111/den.12830

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BACKGROUND AND AIM: Endoscopic procedures are used as first-line treatment for bile leak after hepatobiliary surgery. Advances have been made in endoscopic techniques and devices, but few reports have described the effectiveness of endoscopic procedures and the management principles based on severity of bile leak. We evaluated the effectiveness of an endoscopic procedure for the treatment of bile leak after hepatobiliary surgery. METHODS: Fifty-eight patients underwent an endoscopic procedure for suspected bile leak after hepatobiliary surgery; the presence of bile leak on endoscopic retrograde cholangiopancreatography (ERCP) was evaluated retrospectively. Two groups were created based on bile leak severity at ERCP. We defined success as follows: technical, successful placement of the plastic stent at the intended bile duct; clinical, improvement in symptoms of bile leak; and eventual, disappearance of bile leak at ERCP. We evaluated several factors that influenced the success of the endoscopic procedure and the differences between bile leak severity. RESULTS: Success rates were as follows: technical, 90%; clinical, 79%; and eventual, 71%. Median interval between first endoscopic procedure and achievement of eventual success was 135 days (IQR, 86-257 days). Bile leak severity was the only independent factor associated with eventual success (P = 0.01). CONCLUSIONS: Endoscopic therapy is safe and effective for postoperative bile leak. Bile leak severity is the most important factor influencing successful endoscopic therapy.

DOI： 10.1111/den.12798

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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BACKGROUND AND AIM: Pathological grading is important in defining the therapeutic strategy in pancreatic neuroendocrine neoplasm (PNEN) but is difficult for unresectable cases. Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) is useful in the diagnosis of PNEN, but its usefulness for pathological grading is not well established. No studies have examined the diagnostic ability of dynamic computed tomography (CT) for pathological grading of PNEN. We investigated the usefulness of EUS-FNA and dynamic CT in the diagnosis and pathological grading of PNEN. METHODS: In this retrospective study, 39 PNEN patients finally diagnosed via EUS-FNA and/or surgical resection underwent dynamic CT. Pathological samples were diagnosed based on WHO2010; staging was based on the European Neuroendocrine Tumor Society classification. The proportion of the quantification value in the tumor to the pancreatic parenchyma in arterial phase was defined as the CT ratio. Immunohistochemical staining with CD31 was performed to evaluate microvessel density (MVD). We evaluated the relationship between pathological grade, CT ratio, and MVD. RESULTS: By using EUS-FNA, 35 of 39 (90%) cases were diagnosed as PNEN. As for pathological grade, 15 of 35 (43%) cases could be identified correctly. CT ratio could predict pathological Grade 3 disease. The sensitivity, specificity, and diagnostic accuracy were 100%, 94%, and 95%. MVD was significantly correlated with CT ratio (r = 0.83, P < 0.0001) and pathological grade (P = 0.0074). CONCLUSIONS: Computed tomography ratio has a relationship with pathological grade in PNEN, which would help decide therapeutic strategy in unresectable cases and cases in which pathological grading is difficult.

DOI： 10.1111/jgh.13594

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier {BV}  

DOI： 10.1016/s0016-5085(17)31819-x

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DOI： 10.1016/j.pan.2016.12.011

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DOI： 10.1177/1756283X16674633

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BACKGROUND AND AIMS: To evaluate the outcomes of management for biliary stricture (BS) after living donor liver transplantation (LDLT) using short-type double-balloon enteroscopy. METHODS: This study retrospectively evaluated 20 patients who underwent endoscopic retrograde cholangiography using short-type double-balloon enteroscopy (sDB-ERC) upon suspicion of BS after LDLT with hepaticojejunal (HJ) reconstruction at Okayama University Hospital. RESULTS: Scope insertion to the HJ site and sDB-ERC succeeded in 85 % (17/20) and 82.4 % (14/17) of patients, respectively. Of 14 patients who required treatment for BS, 11 were successfully treated using sDB-ERC, and 3 were successfully treated using sDB-ERC and rendezvous procedures. Adverse events occurred in 2.9 % of all sessions (2/68). After resolution of BS, 7 patients (50 %) experienced a recurrence. Of these, 6 (85.7 %) were treated with only balloon dilation, and 1 (14.3 %) was treated with both balloon dilation and stent deployment (P = 0.029). CONCLUSIONS: sDB-ERC is a useful procedure for diagnosis and treatment for BS after LDLT with HJ reconstruction. Balloon dilation combined with stent deployment might be recommended for definite resolution of BS.

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Language：Japanese   Publisher：(公社)日本超音波医学会  

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Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is a standard procedure for precise histological diagnosis of pancreas tumors, but it is sometimes difficult to obtain adequate specimens. EUS Sonopsy CY® is a newly designed needle with original features. This randomized study will compare the tissue collection rate of EUS Sonopsy CY® to that of a conventional needle in EUS-FNA. The major eligibility criteria are as follows: Patients with a pancreatic mass referred for EUSFNA; age 20 years, and performance status＜4. The primary outcome is the tissue collection rate. This study will elucidate the efficacy of EUS Sonopsy CY®.

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Recently, endoscopic ultrasonography (EUS)-guided ethanol ablation for small pancreatic neuroendocrine tumors (p-NETs) has been reported. However, the efficacy and safety of the technique remain unclear. We have launched a prospective pilot study of EUS-guided ethanol ablation for p-NETs. The major eligibility criteria are the presence of a pathologically diagnosed grade (G) 1 or G2 p-NET, a tumor size of 2cm, and being a poor candidate for surgery. A total of 5 patients will be treated. The primary endpoint will be the complete ablation rate at 1 month after treatment.

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Contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) with contrast agent enabled us to assess the hemodynamics closely, despite limited data in pancreatic tumors. We have initiated a prospective, single arm, and non-randomized study to clarify the accuracy and safety of CH-EUS with Sonazoid and time-intensity curve (TIC) analysis for diagnosing benign or malignant pancreatic tumors. A total of 200 patients will undergo CH-EUS and TIC analysis. Receiver operating characteristic (ROC) analysis will be used to determine the optimal parameter cutoff values for TIC analysis. This will clarify whether CH-EUS and TIC can further improve the diagnosis of pancreatic tumors over conventional EUS.

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Language：Japanese   Publisher：日本胆道学会  

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BACKGROUND: To evaluate the outcomes and investigate the factors associated with restricture after endoscopic treatment. METHODS: Between April 2001 and July 2014, 98 patients experienced biliary anastomotic stricture (BAS) after living donor liver transplantation (LDLT) with duct-to-duct reconstruction, and all were first referred to Okayama University Hospital for endoscopic stent deployment. When deployment was unsuccessful, a percutaneous transhepatic procedure was used. Treatment outcomes, including stricture resolution, BAS recurrence, and risk factors of BAS recurrence, were evaluated retrospectively. RESULTS: Successful stent deployment was achieved in 90 of 98 patients (91.8%) by both procedures. Among the 90 patients, stricture resolution was eventually observed in 72. The median number of endoscopic retrograde cholangiographies performed was 5. After a median follow-up period of 48.8 months from stent removal, BAS recurrence that required intervention occurred in 22 patients (30.6%). In multivariate analysis, portal vein stenosis after LDLT was associated with BAS recurrence after endoscopic treatment (P = 0.03). Among the 22 patients who required reintervention, 16 (73%) had their stents removed, and recurrence after retreatment occurred in 3 patients (18.8%). CONCLUSIONS: Endoscopic treatment is a useful procedure for the treatment for BAS after LDLT with duct-to-duct reconstruction. Portal vein stenosis may be one of the risks associated with the recurrence of BAS.

DOI： 10.1097/TP.0000000000001187

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DOI： 10.1111/jgh.13259

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DOI： 10.3892/or.2016.4681

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BACKGROUND: Hepatolithiasis is a postoperative complication of hepaticojejunostomy (HJ) performed for various pancreatobiliary diseases. Hepatolithiasis can cause repeated cholangitis. Complete stone removal and bile stasis elimination are therefore necessary. Here, we evaluated the effectiveness of peroral direct cholangioscopy (PDCS) using an ultraslim endoscope for treating hepatolithiasis in HJ patients. METHODS: We studied 14 patients with hepatolithiasis who underwent bowel reconstruction with HJ between April 2012 and May 2014. Diagnostic and therapeutic endoscopic retrograde cholangiography using a short double-balloon enteroscope (DBE) was initially performed. Following stone removal, the DBE was exchanged for an ultraslim endoscope through the balloon overtube for PDCS. RESULTS: The success rate of PDCS procedure was 85.7% (12/14). In 5 of 12 (41.7%) patients with successful PDCS, the residual stones were detected and removed completely using a 5-Fr basket catheter and suction after normal saline irrigation. In the remaining 7 (58.3%) patients, no residual stone was detected. The median procedure time was 14 min (range 8-36) with no serious postoperative complications. The median follow-up time after PDCS was 21 months (range 5-26), and only 1 patient (8.3%) had IHBD stone recurrence with an anastomotic stricture. CONCLUSIONS: PDCS using an ultraslim endoscope appears to be useful for detecting and removing residual stones following hepatolithiasis treatment using a DBE. The combined use of a DBE and PDCS may reduce the risk of hepatolithiasis recurrence in HJ patients.

DOI： 10.1007/s00464-015-4323-6

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BACKGROUND AND STUDY AIMS: Preoperative diagnosis of the pathological grade of intraductal papillary mucinous neoplasms (IPMNs) is difficult. This study aimed to evaluate the accuracy of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) with time - intensity curve analysis in differentiating between low or intermediate grade dysplasia (LGD/IGD) and high grade dysplasia or invasive carcinoma (HGD/invasive carcinoma) in IPMNs and to assess correlation between the time - intensity curve parameters and tumor microvessel density. PATIENTS AND METHODS: Data from 30 patients with resected IPMNs (14 LGD/IGD, 16 HGD/invasive carcinoma) who underwent CH-EUS with time - intensity curve analysis were evaluated retrospectively. Time - intensity curve parameters and the microvessel density of the mural nodule were compared between the HGD/invasive carcinoma and LGD/IGD groups; the diagnostic accuracy of the time - intensity curve parameters was evaluated. RESULTS: The echo intensity change and echo intensity reduction rate of the mural nodule, and the nodule/pancreatic parenchyma contrast ratio were significantly higher in the HGD/invasive carcinoma group than in the LGD/IGD group (P < 0.05); the accuracies of these parameters were 80 %, 86.7 %, and 93.3 %, respectively. The microvessel density of the mural nodule was significantly higher in the HGD/invasive carcinoma group (P = 0.002). There was a strong positive, linear correlation between the echo intensity change of the mural nodule and the microvessel density (r = 0.803, P < 0.001). CONCLUSIONS: CH-EUS with time - intensity curve analysis is potentially useful for quantitatively evaluating the blood flow of IPMN microvasculature, and for differentiating between HGD/invasive carcinoma and LGD/IGD.

DOI： 10.1055/s-0034-1393563

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DOI： 10.1016/j.pan.2015.11.002

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BACKGROUND: Ethanol, a commonly available agent, has been used to successfully ablate cystic and solid lesions in the pancreas. The aim of this study is to investigate the effects of an ethanol injection into the porcine pancreas and observe the time-dependent image changes in the pancreatic parenchyma. METHODS: Pure ethanol was injected into the pancreatic tail using a 25-gauge EUS needle with direct ultrasound guidance under celiotomy: 1 mL and 2 mL were injected, respectively. The abdomen was closed after the injection. MRI was performed before the procedure, immediately after, and on postoperative day (POD) seven. Blood samples were taken before the procedure and on PODs one, three, five, and seven. The pigs were euthanised on POD seven. RESULTS: Immediately after the injection, linear high signal areas in the pancreatic tail on T2 and rounded speckled high signal areas on DWI images were detected in both animals, measuring 35 × 32 mm in the 1 mL injected pig and 42 × 38mm in the 2 mL injected pig. After POD seven, rounded high signal areas were noted on T2 images, measuring 22 × 18 mm and 36 × 28 mm respectively. On POD one, the 1 mL injected animal had a 53% elevation in serum amylase while the 2 mL injected animal had a 66% elevation. Histologically, cystic and necrotic changes in the parenchyma were observed, measuring 23 × 22 mm and 40 × 35 mm respectively. CONCLUSIONS: Our results, which are limited to normal pancreas, suggested that a 1 mL injection caused localised changes within the pancreas while a 2 mL injection induced more widespread changes beyond the pancreas. The effective area of ethanol was widespread immediately after injection, and then the area was reduced with cystic and necrosis changes.

DOI： 10.3332/ecancer.2016.663

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DOI： 10.2169/internalmedicine.55.6741

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A 52-year-old woman was admitted to our hospital with right upper quadrant pain with gallbladder wall thickening and multiple liver tumors. Endoscopic ultrasound-guided biopsy revealed small cell carcinomas of both the gallbladder and liver. After 10 cycles of chemotherapy with etoposide and cisplatin, marked shrinkage of the tumors was evident on computed tomography. The patient subsequently underwent hepatectomy and resection of the extrahepatic bile duct and gallbladder with curative intent. Although no viable tumor cells were found in the resected specimens, we confirmed phagocytosis of tumor cells killed by chemotherapy in the resected liver specimen. Therefore, we suspected that the patient had primary small cell carcinoma of the liver that had been successfully treated. This is a rare case of primary small cell carcinoma of the liver that showed pathological complete response to chemotherapy with etoposide and cisplatin.

DOI： 10.11405/nisshoshi.112.2024

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Language：Japanese   Publisher：(一社)日本移植学会  

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DOI： 10.3892/or.2015.4126

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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There are few reports on endoscopic ultrasonography (EUS)-guided transjejunal drainage. Here, we report a case with postoperative pancreatic fistula treated by endoscopic transjejunal drainage using a forward-viewing (FV) echoendoscope. A 69-year-old woman who had undergone pancreaticoduodenectomy was admitted because of pancreatic fistula. Placement of plastic stents into the pancreatic duct using a double-balloon enteroscope and EUS-guided transgastric drainage failed. We attempted EUS-guided transjejunal drainage using an FV echoendoscope that can advance through the acute-angled intestinal tract safely, and drainage was performed. There were no complications, and follow-up computed tomography showed complete resolution.

DOI： 10.1007/s12328-015-0580-0

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BACKGROUND: The treatment of biliary stricture is crucially important for continuing stable chemotherapy for unresectable biliary carcinoma; however, there is no consensus regarding the use of hilar biliary drainage. In this study, we examined the efficacy of endoscopic over 3-branched biliary drainage using self-expandable metallic stents (SEMSs) in patients with unresectable malignant hilar biliary stricture (HBS). METHODS: A total of 77 patients with unresectable HBS treated with a SEMS and chemotherapy were retrospectively reviewed. There were 59 patients with cholangiocarcinoma and 18 patients with gallbladder carcinoma. The patients were divided into 2 groups (4- or 3-branched group and 2- or 1-branched group) and compared with respect to the duration of stent patency and overall survival. RESULTS: A comparison of the patients' baseline characteristics showed no significant differences between the 4- or 3-branched group and the 2- or 1-branched group. Neither the duration of patency nor survival time exhibited significant differences between the 2 groups, although, among the patients achieving disease control , the duration of patency period and survival time of the 4- or 3-branched group were significantly higher than those observed in the 2- or 1-branched group (P=0.0231 and 0.0466). CONCLUSIONS: The use of endoscopic over 3-branched biliary drainage with a SEMS may improve the duration of patency in patients with HBS.

DOI： 10.1097/MCG.0000000000000213

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BACKGROUND: In endoscopic retrograde cholangiopancreatography (ERCP) for patients who have undergone a pancreatoduodenectomy (PD) with a Braun anastomosis, two different approaches are available: the afferent-limb route and the efferent-limb route. This study was to clarify the usefulness of a short double-balloon enteroscope (DBE) in ERCP for prior-PD patients, and to reveal which route was optimal for ERCP. METHODS: Seventy-two consecutive patients with a prior PD underwent diagnostic or therapeutic ERCP using the DBE. This retrospective study evaluated the outcome of the ERCP and assessed the shape of the DBE by fluoroscopic imaging to compare the maneuverability of the two routes. RESULTS: In 71 patients (99%) the bilioenteric anastomosis was reached and cholangiography was performed. Treatment was required in 59 patients (83%) and was performed successfully in all. Complications occurred in two patients (3%) with cholangitis. In three patients, the afferent-limb route had to be changed to the efferent-limb route in the procedure. A gentler arc-shaped angulation of the DBE was induced using the efferent-limb route compared to the afferent-limb route (128° (n = 42) vs. 113° (n = 15); p = 0.037), and that was also revealed in 11 patients (15%) who underwent repeated ERCP by each route (123° vs. 96°; p = 0.003). CONCLUSIONS: The short DBE facilitates ERCP in prior-PD patients. Particularly, ERCP using the efferent-limb route can achieve a maneuverable procedure without unnecessary stress, such as scope insertion to the sharp-angled afferent limb and the handling of various accessories through the narrow scope channel with a sense of resistance.

DOI： 10.1007/s00464-014-3889-8

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DOI： 10.3748/wjg.v21.i24.7594

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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BACKGROUND AND AIM: There have been few reports on the success rate of balloon dilation and stent deployment using endoscopic retrograde cholangiopancreatography by double-balloon enteroscopy (DBE-ERCP) or on the follow-up period after stent removal in patients with a reconstructed digestive tract and stenosis of choledochojejunal anastomosis. The present study was designed to evaluate the usefulness of DBE-ERCP in patients with a reconstructed digestive tract and stenosis of choledochojejunal anastomosis. METHODS: Forty-four patients with stenosis of choledochojejunal anastomosis underwent DBE-ERCP at Okayama University Hospital between April 2008 and January 2012 (107 procedures). Rates of reaching choledochojejunal anastomosis, stent deployment, and restenosis after stent removal were retrospectively evaluated. RESULTS: Insertion of DBE into the choledochojejunal anastomotic site succeeded in 38 of 44 patients (86.4%), and anastomotic dilation and stent deployment succeeded in 36 of 44 patients (81.8%). In 32 of 44 patients (72.7%), their anastomotic stenoses were improved, and they achieved stent removal. After stent removal, restenosis of choledochojejunal anastomosis was detected in seven of 32 patients; however, the resolution of restenosis was achieved in all seven of those patients. CONCLUSION: Dilation of choledochojejunal anastomosis combined with stent deployment using DBE-ERCP seems to be a viable first-line treatment for patients with stenosis of choledochojejunal anastomosis.

DOI： 10.1111/den.12332

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BACKGROUND/AIMS: There have been limited studies evaluating single-session EUS-FNA and ERCP for evaluation of pancreatic masses. The aim of this study was to determine the safety of single-session EUS-FNA and ERCP, and to compare the diagnostic accuracies of cytodiagnosis by EUS-FNA, ERCP, and their combination. METHODOLOGY: A total of 100 patients with pancreatic masses were prospectively enrolled. All patients underwent single-session EUS-FNA and ERCP. The main outcome measurement was frequency of post-procedural complications. Another measurement was diagnostic accuracy of cytodiagnosis by EUS-FNA, ERCP, and their combination. RESULTS: Procedure-related pancreatitis occurred in 10 patients, but all patients were conservatively managed. Cytodiagnosis by EUS-FNA was significantly superior to ERCP in accuracy. In patients with a pancreatic head mass, 3 cases of false negative EUS-FNA were positive on ERCP. The combination procedures improved accuracy compared with EUS-FNA alone. By contrast, in the subgroup of the pancreatic body or tail mass, the combination of EUS-FNA and ERCP did not improve cytodiagnosis compared to that with EUS-FNA alone. CONCLUSIONS: Single-session EUS-FNA and ERCP appears to be as safe as performing each procedure separately. EUS-FNA should be considered the principal procedure for cytodiagnosis. ERCP has only a complementary role in patients with pancreatic head mass.

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OBJECTIVE: Rapid on-site evaluation (ROSE) of cytologic adequacy improves the diagnostic yield of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). However, on-site advice from a cytotechnologist or cytopathologist is not always available during EUS-FNA. To enhance endosonographers' ability to assess the adequacy of EUS-FNA specimens, we designed an intensive, 2-h interactive training program. The aim of this study was to determine the usefulness of the program. METHODS: Four cytological pictures were selected by a trained cytotechnologist and board-certified cytopathologist from each of the seven patients who underwent EUS-FNA for pancreatic mass in Okayama University Hospital. In total, 28 pictures were used in this study. Twenty endosonographers and 14 cytologists with different levels of EUS-FNA experience evaluated cytological pictures independently before and after the training program. RESULTS: Endosonographers' skill in evaluating the adequacy of EUS-FNA specimens was significantly improved after the completion of the training program (p < 0.001). In contrast, almost all cytologists correctly judged the adequacy of the specimens before taking the training program. CONCLUSIONS: This intensive, 2-h interactive training program is useful for endosonographers and capable of improving ROSE of EUS-FNA specimens.

DOI： 10.3109/00365521.2014.915051

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DOI： 10.1111/jgh.12501

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：John Wiley and Sons Ltd  

DOI： 10.1016/j.molonc.2013.04.004

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DOI： 10.1002/ijc.27575

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Herein, a case of immunoglobulin G4 (IgG4)-related sclerosing cholangitis is reported. IgG4 was diagnosed based on observations from peroral cholangioscopy and laparoscopy, and these methods are proposed for definitive and precise diagnosis of this disease. A 76-year-old male patient with inguinal Paget's disease had intrahepatic bile duct dilatations detected with computed tomography at his periodic check-up. Magnetic resonance cholangiography showed stenosis of the upper common bile duct and poststenotic dilatation of left intrahepatic bile ducts. The portal tract and bilateral intrahepatic bile ducts were surrounded by a low-density area, facing a tumor-like lesion at segment 2. Cytological examinations of the stenotic and dilated lesions revealed no cellular atypia. Histological examination of the tumor showed normal liver tissue with infiltration of lymphocytes, indicating an inflammatory pseudotumor. Peroral cholangioscopy excluded the possibility of biliary cancer and indicated that the stenotic legion was of submucosal, not mucosal, origin. Laparoscopic observations showed discoloration with wide yellowish-white lobular markings and wide depressed lesions at segments 2 and 7. Liver histology showed mild cholangitis with infiltration of IgG4-positive plasma cells around the bile ducts. Serum IgG4 levels were elevated. From these findings, the patient was diagnosed with IgG4-related sclerosing cholangitis. After treatment with prednisolone, blood liver enzymes and IgG4 rapidly normalized, bile duct dilatations improved, and the hepatic pseudotumor disappeared. The cholangitis did not recur. In this case, biliary cancer was ruled out by observation with peroral cholangioscopy, and the spread of cholangitis in the liver periphery was verified with laparoscopy; this information could not be obtained with other modalities.

DOI： 10.1111/j.1443-1661.2012.01300.x

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DOI： 10.3892/or.2011.1336

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DOI： 10.1186/1471-2407-11-3

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OBJECTIVES: One or more patterns of 6 K-ras mutations are detected in cells from the pancreatic juice of patients with intraductal papillary mucinous neoplasms (IPMNs). We investigated whether these mutations are associated with malignant progression. METHODS: Between January 2002 and December 2007, 53 patients with IPMN were subjected to collection of pure pancreatic juice to evaluate K-ras mutation. According to the histological and radiological findings, the IPMNs were classified into 4 groups: carcinoma group, adenoma group, high-risk group, and low-risk group. We retrospectively investigated the mutation with these groups. RESULTS: In patients with a positive K-ras mutation, a single pattern of K-ras mutation was observed in 80% (8/10) of the carcinoma group, in 71% (5/7) of the adenoma group, in 40% (2/5) of the high-risk group, and in 38% (8/21) of the low-risk group. The rate of a single pattern of K-ras mutation decreased in a stepwise order (P = 0.017). The incidence of a single pattern of K-ras mutation was significantly higher in the patients who received surgical therapy (75%, 12/16) than in those who did not (38%, 10/26; P = 0.033). CONCLUSIONS: The present study suggests that the single-clonal convergence of K-ras mutation is associated with the malignant progression of IPMNs.

DOI： 10.1097/MPA.0b013e3181c75d9b

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Language：Japanese   Publisher：(有)科学評論社  

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Language：Japanese   Publisher：日本消化器病学会-中国支部  

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DOI： 10.1200/JCO.2018.36.15_suppl.TPS3119

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Language：Japanese   Publisher：(一社)日本医療薬学会  

治癒切除不能膵がんと診断され、化学療法としてゲムシタビン/nab-パクリタキセル併用療法(GN療法)を施行した52例(男性61.5%、平均65.7±9.4歳)を対象とした。一次治療群26例、二次治療群26例であった。PSは0および1が全体で86.5%、一次治療群で84.6%、二次治療群で88.5%であった。GN療法1コース施行前後の好中球数平均値は、一次治療群と二次治療群での有意差は認めなかった。一次治療群と二次治療群を比較して、貧血のみ重篤な副作用の発現頻度に有意差を認めた。全例を対象として、重篤な好中球減少の発現リスクとなる因子の解析を行い、性別、年齢、PS、がん発症部位、手術歴、転移の有無との関連は認めなかった。血液検査値から、WBC、HT、ANCは低値を、AST、ALTは高値をリスク因子とした。単変量解析の結果では、WBCまたはANCとPLTが低値で、AST、ALTが高値であることによって、重篤な好中球減少症の発現リスクが上昇することが示された。多重ロジスティック回帰分析を行い、重篤な好中球減少症の発現と関連性の強い因子として、WBC、ANC、ALTが抽出された。

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Language：Japanese   Publisher：(一社)日本医療薬学会  

治癒切除不能膵がんと診断され、化学療法としてゲムシタビン/nab-パクリタキセル併用療法(GN療法)を施行した52例(男性61.5%、平均65.7±9.4歳)を対象とした。一次治療群26例、二次治療群26例であった。PSは0および1が全体で86.5%、一次治療群で84.6%、二次治療群で88.5%であった。GN療法1コース施行前後の好中球数平均値は、一次治療群と二次治療群での有意差は認めなかった。一次治療群と二次治療群を比較して、貧血のみ重篤な副作用の発現頻度に有意差を認めた。全例を対象として、重篤な好中球減少の発現リスクとなる因子の解析を行い、性別、年齢、PS、がん発症部位、手術歴、転移の有無との関連は認めなかった。血液検査値から、WBC、HT、ANCは低値を、AST、ALTは高値をリスク因子とした。単変量解析の結果では、WBCまたはANCとPLTが低値で、AST、ALTが高値であることによって、重篤な好中球減少症の発現リスクが上昇することが示された。多重ロジスティック回帰分析を行い、重篤な好中球減少症の発現と関連性の強い因子として、WBC、ANC、ALTが抽出された。

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Language：Japanese   Publisher：(公社)日本薬学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J00192&link_issn=&doc_id=20170912190007&doc_link_id=10.11280%2Fgee.59.1644&url=https%3A%2F%2Fdoi.org%2F10.11280%2Fgee.59.1644&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J00192&link_issn=&doc_id=20170727260008&doc_link_id=10.11280%2Fgee.59.1524&url=https%3A%2F%2Fdoi.org%2F10.11280%2Fgee.59.1524&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

Language：Japanese   Publisher：(一社)日本膵臓学会  

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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Language：Japanese   Publisher：(株)東京医学社  

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DOI： 10.3892/or.2017.5419

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：English   Publishing type：Research paper, summary (international conference)  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2016&ichushi_jid=J02149&link_issn=&doc_id=20160620040016&doc_link_id=%2Fdw1tando%2F2016%2F003002%2F016%2F0290-0297%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdw1tando%2F2016%2F003002%2F016%2F0290-0297%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：English   Publishing type：Research paper, summary (international conference)  

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Language：Japanese   Publisher：日本膵臓学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2016&ichushi_jid=J02025&link_issn=&doc_id=20160513040002&doc_link_id=%2Fcq0pancr%2F2016%2F003102%2F003%2F0135-0144%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcq0pancr%2F2016%2F003102%2F003%2F0135-0144%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2016&ichushi_jid=J02025&link_issn=&doc_id=20160304110004&doc_link_id=%2Fcq0pancr%2F2016%2F003101%2F005%2F0025-0031%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcq0pancr%2F2016%2F003101%2F005%2F0025-0031%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：English   Publishing type：Research paper, summary (international conference)  

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Language：English   Publishing type：Research paper, summary (international conference)  

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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DOI： 10.1016/j.molonc.2014.03.007

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Language：Japanese   Publisher：日本膵臓学会  

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Language：Japanese   Publisher：日本膵臓学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：English   Publishing type：Research paper, summary (international conference)  

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