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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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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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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 GI 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 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 < .001) and NBI (P < .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 = .083), and the results were not significantly different from WLI and NBI simultaneously (P = .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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Endoscopic ultrasound (EUS) was developed in the 1990s and has significantly transformed pancreatic tumor diagnosis. Subsequently, EUS has rapidly shifted from being a purely diagnostic procedure to being used in a wide range of interventional procedures. Recently, new therapeutic techniques, such as EUS-guided fine needle injection (EUS-FNI) or radiofrequency ablation (RFA), have been developed to deliver various antitumor agents. Despite technological advancements, pancreatic cancer (PC) has a poor prognosis and improvements in treatment outcomes are urgently required. One of the reasons for the limited response to antitumor agents in PC is the abundant desmoplasia and hypovascular nature of the tumor, complicating drug delivery into the tumor. Thus, changing the tumor microenvironment may be important to enhance the effectiveness of chemotherapy, and direct injection of antitumor agents into the tumor under EUS guidance can help overcome treatment challenges in PC. Treatment approaches using the EUS-FNI or RFA technique are expected to further improve the prognosis of PC. Therefore, this study reviewed the existing literature on EUS-guided antitumor therapy, specifically highlighting its application in PC to address the current challenges and to identify potential advancements in the field.

DOI： 10.1111/den.14815

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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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BACKGROUND: Advances in upper gastrointestinal endoscopic technology have enabled early detection and treatment of hypopharyngeal cancer. However, in-depth pharyngeal observations require sedation and are invasive. It is important to establish a minimally invasive and simple evaluation method to identify high-risk patients. METHODS: Eighty-seven patients with superficial hypopharyngeal cancer and 51 healthy controls were recruited. We assessed the methylation status of DCC, PTGDR1, EDNRB, and ECAD, in tissue and saliva samples and verified the diagnostic accuracy by methylation analyses of their promoter regions using quantitative methylation-specific PCR. RESULTS: Significant differences between cancer and their surrounding non-cancerous tissues were observed in the methylation values of DCC (p = 0.003), EDNRB (p = 0.001), and ECAD (p = 0.043). Using receiver operating characteristic analyses of the methylation values in saliva samples, DCC showed the highest area under the curve values for the detection of superficial hypopharyngeal cancer (0.917, 95% confidence interval = 0.864-0.970), compared with those for EDNRB (0.680) and ECAD (0.639). When the cutoff for the methylation values of DCC was set at ≥0.163, the sensitivity to detect hypopharyngeal cancer was 82.8% and the specificity was 90.2%. CONCLUSIONS: DCC methylation in saliva samples could be a non-invasive and efficient tool for early detection of hypopharyngeal cancer in high-risk patients.

DOI： 10.1038/s41416-024-02654-2

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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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DOI： 10.1016/j.gastha.2024.07.018

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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-1966-0534

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DOI： 10.1055/a-2063-3408

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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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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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DOI： 10.1002/ctd2.177

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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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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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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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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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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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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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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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DOI： 10.1055/a-1838-3553

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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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DOI： 10.1055/a-1694-3794

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

An 89-year-old woman underwent examinations for leg edema. Blood tests indicated low nutrition and low pancreatic enzymes, and a stool examination indicated fatty stool. Computed tomography showed pleural effusion, ascites, and cystic lesions in the pancreatic head and mural nodules within the cysts. Pancreatic juice cytology revealed adenocarcinoma. The diagnosis was pancreatic exocrine insufficiency caused by intraductal papillary mucinous carcinoma. The patient did not wish to undergo surgery. Therefore, diuretics, component nutrients, and pancreatic exocrine replacement therapy using pancrelipase were initiated. After starting treatment, her leg edema, pleural effusion, and ascites disappeared, and her activities of daily living improved markedly.

DOI： 10.2169/internalmedicine.8611-21

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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 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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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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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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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 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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BACKGROUND: The histological diagnosis of autoimmune pancreatitis (AIP) by an endoscopic ultrasound (EUS)-guided approach is still challenging. METHODS: We investigated the utility of the 21-gauge Menghini-type biopsy needle with the rolling method for the histological diagnosis of AIP, in comparison with conventional 22-gauge needles. Among total 28 patients, rate of definitive histological diagnosis, acquired sample area of tissue, rate of histopathological diagnosis of AIP, and adverse events were retrospectively analyzed. RESULTS: Definitive histological diagnoses were successfully accomplished in all 14 patients (100%) treated with a Menghini-type needle, and in 57% of cases (8/14) treated with conventional 22-gauge needles (P < 0.001). The median sample area of the tissue, except for blood contamination, was remarkably larger by the Menghini-type needle than by conventional-type needles (6.2 [IQR, 4.5-8.8] versus 0.7 [IQR, 0.2-2.0] mm2, P < 0.001), and the area per punctures was approximately 4 times larger (1.4 [IQR: 0.9-2.9] versus 0.3 [IQR: 0.1-0.6] mm2/puncture, P < 0.001). Based on the International Consensus Diagnostic Criteria, lymphoplasmacytic infiltration, abundant IgG4-postive cells, storiform fibrosis, and obliterative phlebitis were found in 86%/29%, 64%/0%, 36%/0%, and 7%/0% patients who were treated with the Menghini-type needle and conventional-type needles, respectively. Consequently, histopathological diagnosis with type 1 AIP (lever 1 or 2) was achieved in 9 patients (64%) treated with the Menghini-type needle and in no patient treated with conventional-type needles (P < 0.001). Two patients who had mild post-procedural pancreatitis improved with conservative treatment, and no bleeding occurred in patients treated with the Menghini-type needle. CONCLUSION: EUS-guided rolling method with the 21-gauge Menghini-type biopsy needle is useful for the histopathological diagnosis of AIP, due to its abundant acquisition of good-quality tissue from the pancreas.

DOI： 10.1186/s12876-020-01590-8

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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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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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Language：Japanese  

A 68-year-old woman with an 11-day history of sudden abdominal pain and severe watery diarrhea was transferred to our hospital due to an exacerbation of renal function despite hydration. After treatment for dehydration and acidemia was provided in our intensive care unit, patient's renal function improved. Contrast-enhanced abdominal computed tomography was finally performed, revealing a hypervascular pancreatic mass with multiple hepatic masses. This imaging finding along with her clinical symptoms indicated watery diarrhea hypokalemia achlorhydria (WDHA) syndrome caused by a pancreatic VIPoma. Somatostatin analog was administered immediately leading to the improvement of her diarrhea and her general condition. As a result, endoscopic ultrasonography-guided fine-needle aspiration could be performed. Consequently, she was diagnosed with a pancreatic neuroendocrine tumor. She then underwent surgical resection of the pancreatic tumor and liver metastasis. As revealed in the immunohistochemical analysis of the excised tumor tissue, VIP was highly expressed, resulting in the final diagnosis of pancreatic VIPoma. Therefore, the immediate use of a somatostatin analog is crucial for improving the patient's general condition and achieving a definitive diagnosis pathologically when a patient is suspected of having a pancreatic VIPoma.

DOI： 10.11405/nisshoshi.117.84

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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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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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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: 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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Accessory spleen (AS) is common anomaly, and 20% of AS cases occur in the pancreatic tail. An intrapancreatic AS can be difficult to distinguish from pancreatic neoplasms. In most cases, an AS is described as a hypervascular and solitary tumor, but an AS sometimes takes other forms. We herein report a rare case of an intrapancreatic AS with temporal changes in its appearance after splenectomy, which mimicked aspects of pancreatic cancer. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and 99mTc sulfur colloid scintigraphy were useful for the diagnosis.

DOI： 10.2169/internalmedicine.9271-17

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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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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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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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BACKGROUND AND AIM: Reduced expression in immortalized cells (REIC)/dickkopf-3 (Dkk-3) is a tumor suppressor gene that is downregulated in various cancers. In our previous study of prostate cancer, the REIC/Dkk-3-expressing adenoviral vector (Ad-REIC) was found to induce cancer-selective apoptosis. This study recently developed a novel super gene expression (SGE) system and used this system to re-construct an Ad-REIC vector, termed the Ad-SGE-REIC, to achieve more effective therapeutic outcomes. In this study, the therapeutic effects of Ad-SGE-REIC on hepatocellular carcinoma (HCC) was assessed. METHODS: Human HCC cell lines (HLE, Huh7, HepG2, HLF, SK-Hep1, and PLC), human HCC tissues, and mouse HCC cell line (Hepa1-6) were used in this study. REIC/Dkk-3 expression was assessed by immunoblotting and immunohistochemistry. The relative cell viability and the apoptotic effect were examined in vitro, and the anti-tumor effects of Ad-SGE-REIC treatment were analyzed in the mouse xenograft model. This study additionally assessed anti-tumor immunological effects on the immunocompetent mice. RESULTS: REIC/Dkk-3 expression was decreased in HCC cell lines and HCC tissues. Ad-SGE-REIC reduced cell viability and induced apoptosis in HCC cell lines (HLE and Huh7), inhibited tumor growth in the mouse xenograft model, and demonstrated in vivo anti-cancer immunostimulatory effects on the HCC cell line (Hepa1-6). CONCLUSIONS: Ad-SGE-REIC treatment not only enhanced cell killing effects in vitro but also elicited significant therapeutic effects, with tumor growth suppression, in vivo. REIC/Dkk-3 gene therapy using Ad-SGE-REIC potentially represents an innovative new therapeutic tool for HCC.

DOI： 10.1111/jgh.13757

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DOI： 10.1055/s-0043-108543

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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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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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DOI： 10.1111/den.12881

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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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Several studies have indicated that periodontitis is a risk factor for cancer. However, the association between periodontitis and the prognosis of pancreatobiliary tract cancer remains unclear. The aim of this pilot study was to investigate the association between periodontitis and prognosis of pancreatobiliary tract cancer. A total of 22 patients diagnosed with pancreatobiliary tract cancer were analyzed. Oral health status, including severity of periodontitis, general health status and biochemical serum markers were evaluated. The Kaplan-Meier method and Cox proportional hazards model were used to assess factors affecting the prognosis of pancreatobiliary tract cancer. The Kaplan-Meier analysis demonstrated that low body mass index, high concentration of serum C-reactive protein (CRP) and severe periodontitis were significant prognostic factors for survival rate. The Cox proportional hazards model revealed that serum carbohydrate antigen 19-9 concentration [hazard ratio (HR)=1.002; 95% confidence interval (CI): 1.000-1.004] and serum CRP concentration (HR=2.57; 95% CI: 1.15-5.74) were significantly associated with the prognosis of pancreatobiliary tract cancer. In addition, cancer patients with severe periodontitis had higher serum CRP concentrations compared with those without severe periodontitis. Therefore, severe periodontitis indirectly affected the prognosis of pancreatobiliary tract cancer through promoting systemic inflammation.

DOI： 10.3892/mco.2017.1220

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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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Gastric outlet obstruction (GOO) is one of severe comorbidities caused by many kinds of malignant diseases and is associated with not only degradation of patients' quality of life but also mortality. Although surgical bypass is one of the main therapies for malignant GOO, it is often difficult to perform in end-stage patients. The deployment of self-expandable metallic stents (SEMSs) has recently become a viable alternative to surgical bypass for malignant GOO. This technique is less invasive and more effective, particularly in patients with poor prognoses. Many reports have referred to the feasibility, effectiveness, and safety of the placement of SEMSs for malignant GOO. According to these reports, the rates of technical and clinical success were reported to be relatively high and the rate of adverse events to be acceptable. However, precautions against severe adverse events such as massive bleeding and perforation are necessary. Several reports have described the differences in clinical results among different kinds of SEMSs. The presence of a covered design for SEMSs may affect the patency of SEMSs and the rate of stent dysfunction. Selection of the SEMS according to axial force may affect successful achievement of long patency of SEMSs and avoidance of gastroduodenal perforation at the bending site of the duodenum. Compared with high technical success rates nearing 100%, clinical success rates were usually lower than technical success. Therefore, determination of predictive factors for failure of clinical success is important. Several papers reported that low performance status could be associated with failure of clinical success. However, the association of clinical success with other factors such as carcinomatosa and ascites remains controversial, which is a problem to be solved. Reintervention with SEMS using the stent-in-stent method after stent dysfunction can be performed effectively as well as placement of the first SEMS.

DOI： 10.21037/atm.2017.02.11

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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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A newly developed short double-balloon enteroscope with a working channel enlarged to a diameter of 3.2 mm is a novel innovation in stent placement for patients with surgically altered anatomies. Herein, we report three patients in whom this new scope contributed to an efficient technique and ideal treatment. In the first case, the double guidewire technique was efficient and effective for multiple stent placements. In the second case, covered self-expandable metal stent (SEMS) placement, which is the standard treatment for malignant biliary obstruction, could be performed in a technologically sound and safe manner. In the third case, SEMS placement was performed as palliative treatment for malignant afferent-loop obstruction; this procedure could be performed soundly and safely using the through-the-scope technique. The wider working channel of this new scope also facilitates a smoother accessory insertion and high suction performance, which reduces procedure time and stress on endoscopists. Furthermore, this new scope, which has advanced force transmission, adaptive bending, and a smaller turning radius, is expected to be highly successful in both diagnosis and therapy for various digestive diseases in patients with surgically altered anatomies.

DOI： 10.5009/gnl16441

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DOI： 10.1016/j.cgh.2016.09.142

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BACKGROUND: Bile duct stones after hepaticojejunostomy are considered a troublesome adverse event. Although percutaneous transhepatic procedures using a cholangioscopy is performed to treat these bile duct stones, a peroral endoscopic procedure using a short, double-balloon enteroscope (sDBE) is an alternative. This study aimed to compare the immediate and long-term outcomes of both treatments for bile duct stones in patients who underwent prior hepaticojejunostomy. METHODS: Between October 2001 and May 2013, 40 consecutive patients were treated for bile duct stones after hepaticojejunostomy at a tertiary care hospital. Initial success with biliary access, biliary intervention-related technical success, clinical success, adverse events, hospitalization duration, and stone-free survival were retrospectively evaluated. RESULTS: The initial success rates for biliary access were 100% (8/8) with percutaneous transhepatic cholangioscopy (PTCS) and 91% (29/32) with sDBE. In three patients in whom biliary access during initial sDBE failed, successful access with subsequent PTCS was achieved, and biliary intervention-related technical success and clinical success were eventually achieved in all 40 patients. The rate of adverse events was significantly lower with sDBE than with PTCS (10% versus 45%; p = 0.025). The median hospitalization duration for complete stone clearance was significantly shorter with sDBE than with PTCS (10 versus 35 days; p < 0.001). During the median 7.2 year or 3.1 year follow up, the probabilities of being stone-free at 1, 2, and 3 years were 100%, 73%, and 64% for PTCS and 85%, 65%, and 59% for sDBE, respectively (p = 0.919). CONCLUSIONS: sDBE was useful, with few adverse events and short hospitalization; therefore, experienced endoscopists can consider it as first-line treatment for bile duct stones in patients with prior hepaticojejunostomy.

DOI： 10.1177/1756283X16674633

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DOI： 10.1016/j.gie.2016.07.010

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OBJECTIVES: To evaluate the utility and safety of a short-type double-balloon endoscope (DBE) in the treatment of biliary disease in patients with surgically altered gastrointestinal (GI) anatomy. METHODS: This study was conducted as a multicenter, single-arm, prospective trial at five tertiary academic care centers and three community-based hospitals in Japan. Consecutive patients with biliary disease with altered GI anatomy were prospectively included in this study. RESULTS: A total of 311 patients underwent double-balloon endoscopic retrograde cholangiography (ERC). The success rate of reaching the target site, the primary end point, was 97.7% (95% confidence interval (CI): 95.4-99.1). The success rate of biliary cannulation and contrast injection of the targeted duct, the secondary end point, was 96.4% (95% CI: 93.6-98.2), and the therapeutic success rate was 97.9% (95% CI: 95.4-99.2). Adverse events occurred in 33 patients (10.6%, 95% CI: 7.1-14.0) and were managed conservatively in all patients with the exception of 1 in whom a perforation developed, requiring emergency surgery. CONCLUSIONS: ERC using a short-type DBE resulted in an excellent therapeutic success rate and a low rate of adverse events. This treatment can be a first-line treatment for biliary disease in patients with surgically altered GI anatomy.

DOI： 10.1038/ajg.2016.420

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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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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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Pancreatobiliary tract cancer is a highly fatal cancer. Detection of pancreatobiliary tract cancer is difficult because it lacks typical clinical symptoms and because of its anatomical location. Biomarker discovery is therefore important to detect pancreatobiliary tract cancer in its early stage. A study demonstrated that expression levels of miR‑1246, miR‑3976, miR‑4306, and miR‑4644 in serum exosomes were higher in pancreatic cancer patients than these levels in healthy control participants. Supposing that microRNA (miRNA) expression profiles in saliva are similar to those in serum, four miRNAs (miR‑1246, miR‑3976, miR‑4306, and miR‑4644) in salivary exosomes may also be useful for detection of pancreatobiliary tract cancer. In this study, it was examined whether these miRNAs could be used as biomarkers for pancreatobiliary tract cancer. Twelve pancreatobiliary tract cancer patients and 13 healthy control participants were analyzed as a cancer and a control group, respectively. Unstimulated whole saliva was collected, salivary exosomes were isolated, and total RNA was extracted. Using quantitative real‑time PCR (RT‑qPCR), the relative expression ratios of miR‑1246 and miR‑4644 were significantly higher in the cancer group than these ratios in the control group. Receiver operating characteristic (ROC) curves were constructed to analyze the discrimination power of these miRNAs. For miR‑1246, the results yielded an area under the curve (AUC) of 0.814 (P=0.008). For miR‑4644, the results yielded an AUC of 0.763 (P=0.026). For the combination of miR‑1246 and miR‑4644, the results yielded an increased AUC of 0.833 (P=0.005). This pilot study suggests that miR‑1246 and miR‑4644 in salivary exosomes could be candidate biomarkers for pancreatobiliary tract cancer.

DOI： 10.3892/or.2016.5021

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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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OBJECTIVES: Several studies report on the outcomes of self-expandable metallic stents (SEMSs) deployment for malignant gastric outlet obstruction (GOO). However, data was mostly based on the analysis of single-center studies including only a small number of patients. This study aimed to evaluate clinical outcomes after the deployment of SEMS in patients with malignant GOO and to compare the clinical outcomes of two metallic stents with different designs. METHODS: Altogether 125 consecutive patients from five institutions were included. Clinical outcomes were evaluated according to technical success, clinical success, stent patency period, survival period and complications. A comparison of clinical outcomes between Niti-S pyloric/duodenal and WallFlex duodenal stents was also undertaken. RESULTS: Rates for clinical and technical success were 100% and 92.0%, respectively. The median stent patency and survival periods were 72.0 days (range 3-775 days) and 75.0 days (range 3-775 days), respectively. The rate of overall adverse events was 28.8%. The rate of stent dysfunction was 16.8%, and that of adverse events, except stent dysfunction was 12.0%. Massive bleeding occurred in two patients as a late complication. The clinical success rate for Niti-S stent was significantly higher than that for WallFlex stent (96.2% vs 84.8%, P = 0.023). CONCLUSIONS: We successfully deployed a SEMS in malignant GOO. The selection of a SEMS with a lower axial force may be important for patients to resume the oral food intake. Additionally, consideration must be given to the appropriate management of fatal bleeding as a late complication.

DOI： 10.1111/1751-2980.12377

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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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BACKGROUND: Pancreatico-biliary malignancies exhibit similar characteristics, including obesity-related features and poor prognosis, and require new treatment strategies. Oxidative stress is known to induce DNA damage and carcinogenesis, and its reduction is viewed as being favorable. However, it also has anti-infection and anti-cancer functions that need to be maintained. To reveal the effect of oxidative stress on cancer progression, we evaluated oxidative stress and anti-oxidative balance in pancreatic cancer (PC) and cholangiocarcinoma (CC) patients, as well as the effect of add-on antioxidant treatment to chemotherapy in a mouse cholangiocarcinoma model. METHODS: We recruited 84 CC and 80 PC patients who were admitted to our hospital. Serum levels of reactive oxygen metabolites (ROM) and the anti-oxidative OXY-adsorbent test were determined and the balance of these tests was defined as an oxidative index. A diabetic mouse-based cholangiocarcinoma model was utilized to evaluate the effects of add-on antioxidant therapy on cholangiocarcinoma chemotherapy. RESULTS: Serum ROM was higher and anti-oxidant OXY was lower in CC patients with poor outcomes. These parameters were not significantly different in PC patients. In mice, vitamin E administration induced antioxidant hemeoxygenase (HO)-1 protein expression in cancer tissue, while the number of stem-like cells increased. l-carnitine administration improved intestinal microbiome and biliary acid balance, upregulated the hepatic mitochondrial membrane uptake related gene Cpt1 in non-cancerous tissue, and did not alter stem-like cell numbers. CONCLUSION: Oxidative stress balance was dysregulated in cholangiocarcinoma with poor outcome. The mitochondrial function-supporting agent l-carnitine is a good candidate to control oxidative stress conditions.

DOI： 10.3109/10715762.2016.1172071

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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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Intra-abdominal fluid collection associated with infection is a major complication after liver transplantation (LT). However, post-LT recipients are at high risk for requiring various interventions and surgeries, due to their poor, immunosuppressed conditions. We herein describe six patients with symptomatic or growing intra-abdominal fluid collection after LT who underwent endoscopic ultrasonography (EUS)-guided drainage. There were five males and one female, and the median age was 47 years (24-60 years). All procedures were technically and clinically successful in all patients. The median number of endoscopic sessions was 2.5 (1-4 sessions) until resolution. Procedure-related adverse events occurred in two patients and included peritonitis, bleeding, and stent migration, which improved conservatively or endoscopically. During the median follow-up period of 63 months (17-110 months), recurrence occurred in one patient. EUS-guided drainage is an effective and safe treatment for intra-abdominal fluid collection even in post-LT recipients.

DOI： 10.1007/s10396-016-0720-2

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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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DOI： 10.2169/internalmedicine.55.6790

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A 59-year-old man was admitted to our hospital for treatment of a 45 mm pancreatic mass found during a medical examination. Endoscopic ultrasound-guided fine-needle aspiration cytology showed polygonal cells with pseudopapillary structures. The tumor cells were positive for nuclear/cytoplasmic β-catenin and CD10, and negative for chromogranin A. After a tentative diagnosis of a solid pseudopapillary neoplasm, middle pancreatectomy was performed. Histologically, polygonal cells with abundant eosinophilic cytoplasm formed in the trabeculae and were immunohistochemically positive for HepPar1 and protein induced by vitamin K absence or antagonist-II. The tumor was finally diagnosed to be pancreatic hepatoid carcinoma. No recurrence occurred for 12 months, even without adjuvant chemotherapy.

DOI： 10.2169/internalmedicine.55.6741

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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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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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DOI： 10.1111/den.12509

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DOI： 10.1111/den.12487

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The management of jaundice and cholangitis is important for improving the prognosis and quality of life of patients with unresectable malignant hilar biliary strictures (UMHBS). In addition, effective chemotherapy, such as a combination of gemcitabine and cisplatin, requires the successful control of jaundice and cholangitis. However, endoscopic drainage for UMHBS is technical demanding, and continuing controversies exist in the selection of the most appropriate devices and techniques for stent deployment. Although metallic stents (MS) are superior to the usual plastic stents in terms of patency, an extensive comparison between MS and "inside stents", which are deployed above the sphincter of Oddi, is necessary. Which techniques are preferred remains as yet unresolved: for instance, whether to use a unilateral or bilateral drainage, or a stent-in-stent or side-by-side method for the deployment of bilateral MS, although a new cell design and thin delivery system for MS allowed us to accomplish successful deployments of bilateral MS. The development of techniques and devices for re-intervention after stent occlusion is also imperative. Further critical investigations of more effective devices and techniques, and increased randomized controlled trials are warranted to resolve these important issues.

DOI： 10.4253/wjge.v7.i11.1032

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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: Cell-free circulating tumor DNA (ctDNA) in serum has been considered to be a useful candidate for noninvasive cancer diagnosis. The current study was designed to estimate the clinical usefulness of genetic analysis for ctDNA by digital polymerase chain reaction in patients with pancreatic cancer. METHODS: The authors compared K-ras mutations detected in endoscopic ultrasound-guided fine-needle aspiration biopsy tissue DNA and in ctDNA from 75 patients with pancreatic cancer. K-ras mutations in the serum of 66 independent, consecutive patients with pancreatic cancer were also analyzed and the authors compared the results with survival rates. RESULTS: The frequencies of the mutations in tissue samples at G12V, G12D, and G12R in codon 12 were 28 of 75 samples (37.3%), 22 of 75 samples (29.3%), and 6 of 75 samples (8.0%), respectively. Conversely, the rates of the mutations in ctDNA were 26 of 75 samples (34.6%), 29 of 75 samples (38.6%), and 4 of 75 samples (5.3%), respectively. Overall, the K-ras mutation rates in tissue and ctDNA were 74.7% and 62.6%, respectively, and the concordance rate between them was 58 of 75 samples (77.3%). Survival did not appear to differ by the presence of K-ras mutations in tissue DNA, but the survival of patients with K-ras mutations in ctDNA was significantly shorter than that of patients without mutations in both a development set (P = .006) and an independent validation set (P = .002). The difference was especially evident in cases with a G12V mutation. CONCLUSIONS: Analysis of ctDNA is a new useful procedure for detecting mutations in patients with pancreatic cancer. This noninvasive method may have great potential as a new strategy for the diagnosis of pancreatic cancer as well as for predicting survival.

DOI： 10.1002/cncr.29364

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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： 10.1016/j.pan.2015.05.470

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We report a case of biliary drainage for malignant stricture using a metal stent with an ultrathin endoscope through the gastric stoma. A 78-year-old female was referred to our hospital for jaundice and fever. She had undergone percutaneous endoscopic gastrostomy (PEG) for esophageal obstruction after radiation therapy for cancer of the pharynx. Abdominal contrast-enhanced computed tomography showed a 3-cm enhanced mass in the middle bile duct and dilatation of the intra-hepatic bile duct. We initially performed endoscopic retrograde cholangiopancreatography (ERCP) with a trans-oral approach. However, neither the side-viewing endoscope nor the ultrathin endoscope passed through the esophageal orifice. Thus, we eventually performed ERCP via the PEG stoma using an ultrathin endoscope. We performed biliary drainage with a 6F introducer self-expanding metal stent. The cytology findings obtained by brush cytology showed malignancy. Her laboratory results were restored to normal levels after drainage and no complication occurred.

DOI： 10.3748/wjg.v21.i24.7594

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OBJECTIVES: The objectives of this study were to examine the whole-serum N-glycan profile of patients with unresectable pancreatic cancer and to evaluate the ability of glycans to predict gemcitabine treatment efficacy and patient survival. METHODS: We collected serum from 52 patients with advanced pancreatic cancer before they began gemcitabine monotherapy. The serum glycan profile was measured through comprehensive quantitative high-throughput glycome analysis and compared with the treatment efficacy and patient survival. RESULTS: Of the 61 glycans detected, the serum levels of glycan 4310 (molecular weight [m/z] 1549.566), 6301 (m/z 2032.724), and 9200 (m/z 2010.692) were high in patients with a short time to tumor progression (TTP). Multivariate analysis revealed that a high glycan 9200 concentration was an independent risk factor for shorter TTP (hazard ratio, 2.11; 95% confidence interval, 1.07-4.17) and poor overall survival (hazard ratio, 2.56; 95% confidence interval, 1.08-6.19). The median TTP of patients with up-regulation of 9200 after gemcitabine treatment was shorter than for the remaining patients (91 vs 301 days; P = 0.0005). A similar relationship was observed for overall survival (median, 181 vs 561 days; P = 0.001). CONCLUSIONS: Glycan 9200 is a possible biomarker predicting gemcitabine efficacy survival in patients with unresectable pancreatic cancer.

DOI： 10.1097/MPA.0000000000000321

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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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DOI： 10.1055/s-0034-1393138

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BACKGROUND/AIMS: Recently, we found the presence of anti-60S ribosomal protein L29 antibody (anti-RPL29) in human sera, inhibiting the proliferation of pancreatic cancer cells in vitro. We aimed to estimate the association of serum anti- RPL29 levels with clinical features in patients affected with unresectable pancreatic cancer. METHODS: We retrospectively reviewed 105 patients with unresectable pancreatic cancer. Serum anti-RPL29 levels were measured by the indirect enzyme-linked immunosorbent assay. The cut-off was represented by the 95th percentile in 62 healthy volunteers. RESULTS: Median survival time (MST) was 11.1 months in 49 patients showing serum anti-RPL29 level >cut-off and 7.4 months in 56 patients showing serum anti-RPL29 level ≤ cutoff. In locally advanced disease, MST was 17.9 months in 22 patients showing serum anti-RPL29 level >cut-off and 10.0 months in 19 patients showing serum anti-RPL29 level ≤ cutoff. In metastatic disease, MST was 8.7 months in 27 patients showing serum anti-RPL29 level >cut-off and 5.9 months in 37 patients showing serum anti-RPL29 level ≤ cut-off. In the multivariate Cox proportional hazard model, serum anti- RPL29 level >cut-off, abdominal or back pain, performance status, and metastatic disease were identified as independent prognostic factors. CONCLUSION: Serum anti-RPL29 levels may be a novel candidate for a prognostic marker for unresectable pancreatic cancer.

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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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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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Endoscopic retrograde cholangiopancreatography (ERCP) for patients with digestive tract reconstruction is a difficult procedure from an anatomical point of view. A short-type double-balloon enteroscope has a 2.8-mm working channel and a 152-cm working length, and its advantage is that it can accommodate most conventional devices for ERCP. Although the shorter length compared with the long-type balloon-assisted enteroscope (BAE) was suspected of making it difficult or impossible to reach the blind end, in fact, the success rate of reaching the blind end with the short type is similar to that with the long- type BAE. In addition, the success rate of ERCP-related procedures with the short type is satisfactory. However, it remains controversial as to which BAE is more suitable for this procedure. Further randomized controlled trials by high-volume centers are warranted.

DOI： 10.1111/den.12251

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DOI： 10.1055/s-0034-1390732

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DOI： 10.1055/s-0034-1390754

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DOI： 10.1055/s-0034-1377408

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We report our experience with two cases of lymphoepithelial cysts (LECs) of the pancreas. Both patients were in their sixties. Contrast-enhanced computed tomography revealed masses in the pancreas with multilocular cystic lesions. Endoscopic ultrasound (EUS) findings presented highly echo-dense structures in the cystic masses; however, contrast-enhanced EUS revealed only the septum inside each mass without enhancing the dense structures. Contrast-enhanced EUS was useful for defining the contents in the cystic lesions; therefore, it may be useful for the diagnosis of LEC.

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BACKGROUND: Most of the glycan changes reported in cancers were based on the examinations of a small number of patients or particular proteins. The aim of this study was to determine the changes of the serum N-glycan profile comprehensively in a large number of pancreatic cancer patients and investigate its clinical utility. METHODS: Glycan levels in the serum of 92 pancreatic cancer patients and 243 healthy volunteers (HLT) were examined by comprehensive quantitative high-throughput glycome analysis and were compared with clinical parameters. RESULTS: Out of 66 glycans detected, 15 were differentially expressed in pancreatic cancer, and 10 out of the 15 glycans were significantly up-regulated in cases with distant metastasis. There was a clear increase in overall expression of serum glycans, especially highly-branched glycans with fucose moieties, in pancreatic cancer. Among these 15 glycans, a tri-antennary complex type glycan (m/z 3195) showed the highest area under the receiver operating characteristic curve (AUROC = 0.799) for the diagnosis of pancreatic cancer. The ratio of pairs of glycans on the same path of the biosynthesis pathway (m/z 3195/1914) was found to be significantly higher in pancreatic cancer than in HLT (median = 1.11 and 0.41, respectively; p < 0.0001, AUROC = 0.831). For this pair ratio, the hazard ratio for survival (2.60, 95 % CI = 1.44-4.79) was higher than that of any single glycan and 1-year survival of patients with a high and low ratio was 36.9 and 69.2 %, respectively, (p = 0.001). CONCLUSIONS: Comprehensive glycome analysis can be used to know the presence of pancreatic cancer, distant metastasis, and patient prognosis, simultaneously.

DOI： 10.1007/s00535-012-0732-7

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Bilioenteric or pancreatoenteric anastomotic strictures often occur after surgery for a pancreaticobiliary disorder. Therapeutic endoscopic retrograde cholangiopancreatography using balloon enteroscopy has been shown to be feasible and effective in patients with such strictures. However, when a benign anastomotic stricture is severe, a dilation catheter cannot pass through the stricture despite successful insertion of the guidewire. We report on the usefulness of the Soehendra Stent Retriever over a guidewire for dilating a severe bilioenteric or pancreatoenteric anastomotic stricture under short double-balloon enteroscopy, in two patients with surgically altered anatomies.

DOI： 10.4253/wjge.v5.i8.412

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BACKGROUND/AIMS: Little is known about the management of occluded multiple metallic stent (MS) deployed in malignant hilar biliary strictures (HBS). The purpose of this study was to evaluate the endoscopic management of occluded multiple MSs deployed in HBS. METHODOLOGY: Fifty-five patients with unresectable biliary tract carcinoma had multiple MSs inserted due to HBS. The endoscopic intervention through the duodenal papilla was performed on 30 cases that had MS occlusion. The procedure success rate, the survival time after the procedure and the number of endoscopic interventions before death were analyzed, retrospectively. RESULTS: The causes of MS obstruction were tissue ingrowth (n=20), sludge (n=7), tumor overgrowth (n=2), and hemobilia (n=1). Endoscopic cleaning or deployment of plastic stents or metallic stents was performed on these patients and was successfully accomplished only via the transpapillary approach. The survival time after MS obstruction was 219 days. The median number of endoscopic interventions before death was 3. The median interval of endoscopic intervention after the first plastic stent occlusion was 84 days. CONCLUSIONS: Our long-term data regarding the endoscopic management of occluded MSs deployed in malignant hilar biliary strictures are acceptable although the patency time of plastic stents deployed after MS occlusion was relatively short.

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Jaundice and cholangitis are associated with morbidity and mortality for patients with malignant hilar biliary strictures. Endoscopic biliary drainage is considered a useful procedure for palliation of unresectable malignant hilar biliary strictures. However, even today, the devices and methods to effectively achieve the drainage of these strictures are under debate. Endoscopic bilateral deployment of multiple metallic stents for malignant hilar biliary strictures is a feasible and useful procedure, providing long-term patency and the preservation of functional liver volume. We report the cases of two patients who underwent endoscopic bilateral deployment of multiple metallic stents using the partial stent-in-stent method. Both of the patients had malignant hilar biliary stricture due to biliary tract cancer. The cancers were unresectable and the patients decided to receive chemotherapy. Before the chemotherapy, bilateral deployment of metallic stents was carried out and each patient has been receiving chemotherapy without occlusion of the metallic stents for several months.

DOI： 10.1111/den.12061

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DOI： 10.5754/hge11325

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DOI： 10.1016/j.gie.2012.09.016

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Endoscopic intervention is less invasive than percutaneous or surgical approaches and should be considered the primary drainage procedure in most cases with obstructive jaundice. Recently, therapeutic endoscopic retrograde cholangiopancreatography (ERCP) using double-balloon enteroscopy (DBE) has been shown to be feasible and effective, even in patients with surgically altered anatomies. On the other hand, endoscopic partial stent-in-stent (PSIS) placement of self-expandable metallic stents (SEMSs) for malignant hilar biliary obstruction in conventional ERCP has also been shown to be feasible, safe and effective. We performed PSIS placement of SEMSs for malignant hilar biliary obstruction due to liver metastasis using a short DBE in a patient with Roux-en-Y anastomosis and achieved technical and clinical success. This procedure can result in quick relief from obstructive jaundice in a single session and with short-term hospitalization, even in patients with surgically altered anatomies.

DOI： 10.3748/wjg.v18.i45.6674

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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： 10.1016/j.gie.2012.03.1398

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OBJECTIVES: The purpose of this study is to evaluate the feasibility of contrast-enhanced ultrasonography (CE-US) to differentiate between benign and malignant intraductal papillary mucinous neoplasms (IPMN). PATIENTS AND METHODS: Contrast-enhanced ultrasonography with a contrast agent was performed on 22 consecutive patients with IPMN suspected of being malignant. This revealed 10 carcinomas, 1 borderline lesion and 11 adenomas. All patients underwent surgery, and the histological diagnosis was confirmed by examination of resected specimens. CE-US was performed using a contrast agent. The detection rates of mural nodules were compared between CE-US and contrast-enhanced computed tomography (CE-CT), and the imaging of mural nodules depicted under CE-US was analyzed. RESULTS: Seventeen of 22 resected specimens (77.3%) had mural nodules. There was no significant difference in the detection rate between CE-US (n=15; 88.2%) and CE-CT (n=12; 70.6%). In 12 (80.0%) of these patients, CE-US revealed small vessels in the mural nodule. The spotty or linear-shaped pattern was detected in 4 patients and the branch-shaped pattern in 8. The branch-shaped pattern lesion was associated with carcinoma. These mural nodules were 10mm or more in height. In the perfusion image phase, cystic walls and mural nodules were also enhanced in all cases. CONCLUSION: The vessel shapes of the mural nodules depicted under CE-US were associated with size and pathological findings. These results suggested that CE-US with a contrast agent is a powerful modality with which to evaluate the malignant potential of IPMN.

DOI： 10.1016/j.ejrad.2010.11.027

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DOI： 10.1016/j.pan.2012.07.009

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BACKGROUND: This randomized phase II study compared the efficacy and toxicity between 4-week and 3-week schedules of gemcitabine monotherapy in advanced pancreatic cancer. METHODS: Patients with advanced pancreatic cancer were randomly assigned to either a 4-week schedule (gemcitabine at 1000 mg/m² as a 30-min infusion weekly for 3 consecutive weeks every 4 weeks) or a 3-week schedule (gemcitabine at 1000 mg/m² as a 30-min infusion weekly for 2 consecutive weeks every 3 weeks). The primary endpoint was the compliance rate during the first 8 weeks between the two groups. RESULTS: A total of 90 patients were enrolled. The compliance rate during the first 8 weeks was the same (53.3%). For the 4- and 3-week schedules, the tumor response rates were 14.2 and 17.1% (p = 0.92), median progression free survival was 112 and 114 days (p = 0.82), and median overall survival was 206 and 250 days (p = 0.84), respectively. Grade 3-4 neutropenia was the major adverse event in both schedules: 37.7 and 35.5% (p = 0.82). In contrast, thrombocytopenia (platelet count <70000/mm³) was significantly higher for the 4-week schedule: 26.6 and 4.4% (p = 0.008). The mean received dose intensity was equal: 588 and 550 mg/m²/week (p = 0.14). CONCLUSIONS: The 3-week schedule of gemcitabine did not improve the compliance rate during 8 weeks compared with the 4-week schedule, but it attained a comparable efficacy with lower toxicity. Further investigation will be needed to introduce it into daily practice. CLINICAL TRIAL REGISTRATION NUMBER: UMIN ID 974.

DOI： 10.1007/s10147-011-0237-z

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DOI： 10.1016/j.gie.2011.03.1124

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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

PubMed

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BACKGROUND AND STUDY AIMS: Biliary stricture after radiofrequency ablation (RFA) for nodules of hepatocellular carcinoma (HCC) close to major bile ducts sometimes causes septic complications and liver failure. Therefore, it may require interventional drainage for decompression during the follow-up period. The purpose of this study is to clarify the feasibility and safety of bile duct cooling using an endoscopic nasobiliary drainage (ENBD) tube in RFA for HCC close to major bile ducts. PATIENTS AND METHODS: Between August 2003 and July 2007, 14 consecutive patients (14 nodules) undergoing RFA with cooling by an ENBD tube for HCCs close to major bile ducts were enrolled in this study. We infused chilled saline solution via the ENBD tube at 1ml/s to prevent heat damage during RFA. As controls, 11 patients (13 nodules) undergoing RFA without cooling close to major bile ducts between April 2001 and August 2003 were reviewed. The major outcomes for evaluation were biliary complications and the secondary outcome was local tumor recurrence. RESULTS: There were no significant differences in tumor recurrence between the two groups. However, the rate of biliary complications was significantly lower in the cooling group than in the non-cooling group (0% vs. 39%, P=0.02). CONCLUSIONS: Cooling of bile ducts via an ENBD tube can prevent biliary complications induced by RFA of HCC close to major bile ducts without increasing local recurrence. This technique increases indication of RFA in difficult cases.

DOI： 10.1016/j.ejrad.2008.10.021

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Biliary strictures after living donor liver transplantation (LDLT) with duct-to-duct (D-D) reconstruction are associated with postoperative morbidity and mortality. The aims of this study were to evaluate the long-term outcomes of endoscopic deployment of plastic stents, and to investigate factors associated with the stent deployment failure. Between April 2001 and May 2007, 96 patients received LDLT with D-D reconstruction at Okayama University Hospital. Among them, 41 patients (43%) had anastomotic biliary strictures, and all were referred first for endoscopic retrograde cholangiography (ERC). When deployment was unsuccessful, a percutaneous transhepatic procedure was employed. Successful stent deployment was achieved in 35 out of total 41 patients (85%) by both procedures. Among the 35 patients, 28 had their stents removed as a result of strictures resolution. Eight patients underwent ERC and repeated stent deployment as a result of recurrence of the strictures. Finally, 21 out of 41 (51%) patients with biliary stricture were completely treated by endoscopic therapy during the observation period (median 873 days: range 77-2060). By multivariate analysis, biliary leakage was associated with stent deployment failure. Endoscopic deployment of plastic stents is a first-line therapy for patients with biliary stricture after LDLT.

DOI： 10.1111/j.1432-2277.2009.00895.x

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BACKGROUND: Although needle-knife precut papillotomy (NKPP) is considered a useful alternative for achieving selective biliary cannulation, controversy remains regarding the technical proficiency needed to perform the procedure and its safety. This study evaluated whether procedural experience with NKPP predicted either successful cannulation or the development of complications. METHODS: This study retrospectively investigated 104 patients, out of 589 consecutive patients with native papillary, who underwent NKPP performed by a single endoscopist between October 2002 and July 2006. To demonstrate changes in NKPP, the 104 patients were divided chronologically into two groups according to periods: period A (October 2002 to September 2004) and period B (October 2004 to July 2006). RESULTS: Of the 104 consecutive patients who underwent NKPP, 41 (41/267, 15%) were treated in period A and 63 (63/322, 20%) in period B. There was no significant difference in the overall success rate between periods A (90%) and B (98%) (p = 0.08). However, the initial success rate was higher in period B (95%) than in period A (80%) (p < 0.05). The complication rates were not significantly different between the two groups (10% vs 16%; p = 0.56). Although all complications involved pancreatitis, severe pancreatitis was not observed. CONCLUSION: Whereas the initial success rate for NKPP can increase with procedural experience, the complication rate does not seem to decrease. Furthermore, the need for NKPP does not appear to decrease with increasing endoscopic retrograde cholangiopancreatography (ERCP) experience.

DOI： 10.1007/s00464-008-9969-x

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DOI： 10.1016/j.gie.2007.12.031

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BACKGROUND & AIMS: For the treatment of unresectable biliary tract carcinoma with hilar biliary stricture, antitumor therapy and biliary stenting should be addressed in terms of prolonged survival with a good quality of life. However, the endoscopic management of malignant hilar biliary strictures is difficult even for an expert endoscopist. We evaluated the efficacy and safety of the endoscopic deployment of multiple JOSTENT SelfX units in patients with hilar biliary strictures treated with or without chemotherapy. METHODS: Between November 2003 and December 2006, endoscopic deployment of multiple JOSTENT SelfX units in hilar biliary strictures by using a partial stent-in-stent procedure was performed on 41 consecutive patients with primary cholangiocarcinoma (n = 34) and gallbladder carcinoma (n = 7) at a gastroenterologic center of Okayama University Hospital. Thirty-three patients were treated with gemcitabine (n = 25) or S-1 (n = 8). RESULTS: Metallic stent deployment was successfully accomplished in all cases via only endoscopic procedures. During the follow-up period (mean, 210 days), mean patency time was 150 days, and metallic stent obstruction occurred in 15 cases (37%). Although a repeat intervention was required in all metallic stent obstructed cases, the deployment of the second metallic or plastic stent was completed successfully. The remaining 26 cases (63%) required no interventions. The median overall survival period was only 235 days. However, that of the patients receiving chemotherapy was 392 days. CONCLUSIONS: Endoscopic partial stent-in-stent deployment with multiple JOSTENT SelfX prostheses is effective and safe for the treatment of malignant hilar biliary stricture even in patients receiving chemotherapy.

DOI： 10.1016/j.cgh.2007.12.036

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A santorinicele is defined as a focal cystic dilatation of the terminal portion of the dorsal pancreatic duct at the minor papilla; most cases have been reported in patients with pancreas divisum. It has been suggested that a santorinicele results from a combination of a minor papilla obstruction which prevents the flow of pancreatic juice and a weakness of the duodenal wall where the dorsal pancreatic duct terminates. However, these conditions can occur in patients with invasive ductal cancer in the pancreatic head. We encountered a rare case of a santorinicele with unresectable adenocarcinoma of the pancreatic head in an 81-year-old woman.

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BACKGROUND: In view of the recent advancement in endoscopic devices for biliary endoscopic intervention, the expert endoscopist can address complex morbidity. However, endoscopic 3-branched partial stent-in-stent deployment of metallic stents (MS) in patients with malignant hilar biliary stricture is technically demanding. OBJECTIVES: To evaluate the efficacy and safety of endoscopic 3-branched partial stent-in-stent deployment of MS. DESIGN: Case study. SETTING: Gastroenterological Center, Okayama University Hospital. PATIENTS: Nine consecutive patients (mean age 63 years, range 52-84 years, mean follow-up period 5 months) with malignant hilar biliary stricture were enrolled. They had cytologically or histologically proven unresectable biliary-tract carcinoma with hilar biliary stricture type IIIa or IV according to Bismuth's classification. INTERVENTIONS: Endoscopic 3-branched partial stent-in-stent deployment of MS in hilar biliary strictures by using a JOSTENT SelfX stent. MAIN OUTCOME MEASUREMENTS: The success rate of the procedure, stent patency time, reinterventions, and complications. RESULTS: Endoscopic 3-branched partial stent-in-stent deployment was successfully accomplished in all cases. The MS became obstructed in 3 cases (33%), mean 1.5 months, range 1.4 to 2.7 months. However, no MS obstruction occurred in the other 6 patients (67%), mean 11 months, range 4.7 to 16.4 months. In the obstructed cases, the deployment of 2 or 3 tube stents was completed successfully. One case of cholecystitis was observed as a short-term complication. LIMITATION: The small number of cases. CONCLUSIONS: Endoscopic 3-branched partial stent-in-stent deployment of a JOSTENT SelfX stent was effective in selected patients with high-grade malignant hilar biliary stricture.

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We report two cases of patients with hepatocellular carcinoma (HCC) that developed in cryptogenic cirrhosis suggestive of nonalcoholic steatohepatitis (NASH) as background liver disease. Case 1 was a 68-year-old woman, and case 2 was a 46-year-old man. They were admitted to our department for evaluation and treatment of HCC. The causes of the underlying liver disease were not determined from blood tests. However, histological analysis of non-tumor tissues of the liver revealed cirrhosis with few fat droplets. Both patients had undergone liver biopsy 26 years before the treatment of HCC. Histological review of the biopsy specimens revealed NASH (case 1) and fatty liver (case 2), respectively. It was suggested that these cases progressed from NASH and fatty liver, respectively, to NASH-related cirrhosis (so called burned-out NASH), eventually, developing HCC. These findings suggest that substantial number of burned-out NASH cases may be included in those with cryptogenic cirrhosis. These two patients are indicative cases that may reveal the long-term natural course of fatty liver and NASH.

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DOI： 10.1055/s-2006-945068

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DOI： 10.1055/s-2007-966612

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

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

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01118&link_issn=&doc_id=20200128570009&doc_link_id=130007784877&url=https%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F130007784877&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

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DOI： 10.11280/gee.54.281

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

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DOI： 10.1055/s-0030-1256318

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DOI： 10.1055/s-2006-945159

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Language：Japanese   Publisher：岡山済生会総合病院  

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Language：Japanese   Publisher：いわき市医療センター  

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