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DOI： 10.1055/a-2794-7734

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BACKGROUND: The diagnostic performance of clinical diagnostic criteria for IgG4-related sclerosing cholangitis 2020 (IgG4-SC2020) has not been fully validated since its proposal as a revision of the 2012 criteria (IgG4-SC2012). METHODS: We conducted a multicenter validation study to evaluate the diagnostic performance of IgG4-SC2020 using clinical data collected from 1034 patients with IgG4-SC and 447 patients with mimickers, including 143 with pancreatic cancer, 157 with primary sclerosing cholangitis, and 147 with cholangiocarcinoma in Japan. RESULTS: The sensitivity of IgG4-SC2020 was significantly higher than that of IgG4-SC2012 (99.0% vs. 89.1%; p < 0.001). The specificities of both IgG4-SC2020 and IgG4-SC2012 were 100% for pancreatic cancer and cholangiocarcinoma. For primary sclerosing cholangitis, the specificities of IgG4-SC2020 and IgG4-SC2012 were 97.5% and 100%, respectively, with no significant difference (p = 0.123). A total of 113 patients who could not be diagnosed according to the IgG4-SC2012 were successfully diagnosed using IgG4-SC2020. These diagnostic improvements were attributed to the inclusion of MRCP findings (n = 97), the absence of neoplastic cells on histology (n = 15), and the presence of IgG4-related kidney lesions (n = 1). CONCLUSIONS: This Japanese multicenter validation study demonstrated that the diagnostic performance of IgG4-SC2020 was superior to that of IgG4-SC2012. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN-CTR), UMIN000052984.

DOI： 10.1002/jhbp.70056

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BACKGROUND: IgG4-related disease is a rare autoimmune disorder characterised by tissue infiltration of IgG4-positive plasma cells, storiform fibrosis, elevated serum IgG4 concentrations, and increased risk of tumour complications. Previous genetic studies have implicated FCGR2B and HLA loci in susceptibility to IgG4-related disease; however, most relied on microarray-based genotyping and imputation, which have limited resolution in highly polymorphic and structurally complex regions. This study aimed to investigate genetic susceptibility to IgG4-related disease using comprehensive genomic variant analysis, including low-frequency and structural variants not readily captured by microarrays. METHODS: We conducted a genome-wide association study using whole-genome sequencing data in a two-set, subtype-stratified case-control design in the Japanese population. Set 1 included samples (cases) from patients with IgG4-related disease from 50 hospitals across Japan participating in the Japanese IgG4-related disease Working Consortium (recruited between Oct 27, 2008, and March 3, 2016) and previously sequenced Japanese population control samples. Set 2 included samples (cases) from patients with IgG4-related disease from eight hospitals of the Consortium (recruited between Aug 12, 2021, and Dec 20, 2023) and previously sequenced healthy individuals residing in the Tokyo metropolitan area (controls). No specific inclusion or exclusion criteria were applied to either cases and controls. We used whole-genome sequencing at depths of 15× or 30× using HiSeqX and NovaSeq platforms (Illumina; San Diego, CA, USA) to enable the inclusion of previously uncaptured single nucleotide polymorphisms and direct analysis of HLA amino acid residues. We investigated complement component 4 copy number variations using short-read sequencing data and established read-depth-based typing methods. People with lived experience of IgG4-related disease were not involved in the study. FINDINGS: This whole-genome sequencing study comprised of 2 sets. Set 1 included 646 patient samples (172 [26·6%] were female, 474 [73·4%] were male, and the mean age was 64·4 years [SD 11·4]) and 2254 population controls (1348 [59·8%] were female and 906 [40·2%] were male). Set 2 included 223 patient samples (78 [35·0%] were female, 145 [65·0%] were male, and the mean age was 63·5 years [10·9]) and 405 population controls (65 [16·0%] were female and 340 [84·0%] were male). All individuals were of Hondo Japanese ancestry. The average IgG4 concentration at diagnosis was 653·1 mg/dL (SD 596·3) in Set 1 and 543·5 mg/dL (603·5) in Set 2. We validated the FCGR2B (p=9·8 × 10-11) region as the susceptibility locus for IgG4-related disease. PTCH1 (p=3·8 × 10-8) and long non-coding RNA LOC102724227 were found to be specific susceptibility loci for Mikulicz's disease. We also confirmed the association between the HLA amino acid residue DRB1-GB-7 (p=1·1 × 10-19) with IgG4-related disease and identified two additional residues, A-GA2-9 (p=4·1 × 10-6) and DQB1-GB-82 (p=4·7 × 10-9), that were significantly associated with IgG4-related disease. In the joint-association analysis of complement component 4 copy number variation, C4A showed a protective association with IgG4-related disease (β=-0·127, p=7·9 × 10-3), whereas C4B was associated with an increased risk (β=0·151, p=1·9 × 10-2). A low level of linkage disequilibrium (r2<0·15) was observed between the C4A and C4B alleles and the identified HLA amino acid residues in the main island Japanese population. INTERPRETATION: C4 copy number variation, in addition to HLA and FCGR2B, was found to be a distinct genetic factor associated with IgG4-related disease susceptibility, illustrating the complex polygenic nature of the disease. Furthermore, the identification of PTCH1 and the long non-coding RNA LOC102724227 as Mikulicz's disease-specific susceptibility loci suggests that genetic heterogeneity might underlie the clinical diversity of IgG4-related disease, particularly with respect to the affected organs. FUNDING: The Japanese Ministry of Health, Labour, and Welfare, the Japanese Agency of Medical Research and Development, the Kyoto University Grant for Top Global University Japan Project, and the Kyoto University Division of Graduate Studies SPRING Program.

DOI： 10.1016/S2665-9913(25)00195-X

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DOI： 10.1055/a-2616-8452

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INTRODUCTION: Preoperative biliary drainage (PBD) is often required for patients with pancreatic cancer accompanied by biliary obstruction to ensure the safe administration of neoadjuvant chemotherapy or to manage cholangitis and jaundice. Although endoscopic retrograde cholangiopancreatography (ERCP) is the standard approach for PBD, it carries a significant risk of post-ERCP pancreatitis. Endoscopic ultrasound-guided biliary drainage (EUS-BD), particularly via hepaticogastrostomy (EUS-HGS), offers a promising alternative that avoids papillary manipulation. However, the clinical utility of EUS-BD as primary drainage for PBD remains unclear due to a lack of prospective studies. This multicentre prospective trial aims to evaluate the safety and efficacy of EUS-HGS as primary drainage for PBD in patients with resectable or borderline resectable pancreatic cancer. METHODS AND ANALYSIS: This multicentre prospective study involves seven institutions in Japan. Eligible patients will undergo EUS-HGS using a 7Fr plastic stent. The primary endpoint is clinical success, defined by improvements in bilirubin or liver enzyme levels within 14 days postprocedure. Secondary endpoints include technical success rate, adverse event incidence, stent patency and surgical outcomes. A total of 30 patients will be enrolled, considering an expected clinical success rate of 90% and a 10% dropout allowance. ETHICS AND DISSEMINATION: This study has been approved by the National Cancer Center Institutional Review Board (Research No. 2024-084). The results of this study will be reported at an international conference and published in an international peer-reviewed journal. TRIAL REGISTRATION NUMBER: UMIN ID: 000055173.

DOI： 10.1136/bmjopen-2025-106543

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PURPOSE: Diagnosing pancreatic tumors ≤ 10 mm is challenging due to limited visualization and low sampling sensitivity. This study aimed to evaluate the cumulative diagnostic performance of repeated endoscopic ultrasound-guided tissue acquisition (EUS-TA) and surrogate repeated endoscopic retrograde pancreatography (ERP). METHODS: This study analyzed 40 patients with suspected pancreatic tumors ≤ 10 mm who underwent EUS-TA and/or ERP retrospectively. When a diagnosis could not be determined based on the initial EUS-TA or ERP procedure, EUS-TA or ERP was repeated as necessary. The cumulative diagnostic performance of EUS-TA and ERP for pancreatic tumors was evaluated. RESULTS: EUS-TA was performed once for 35 cases, twice for seven cases, and three times for one case. ERP was performed for 15 cases, and the median number of ERP attempts was two (range, 1-8). The cumulative sensitivity of EUS-TA increased from 56.7% to 70.0% after three attempts, while ERP sensitivity increased from 54.5% to 72.7% after two attempts. The cumulative diagnostic performance of repeated EUS-TA and ERP combined by case included sensitivity and accuracy rates of 87.9% and 90.0%. When limited to pancreatic cancer, the sensitivity and accuracy rates were 95.8% and 96.8%, respectively. No severe adverse events occurred. CONCLUSION: Repeated EUS-TA and ERP showed good diagnostic sensitivity for small pancreatic cancers ≤ 10 mm. When malignancy is suspected but not confirmed by a single procedure, repeating both may be an option in selected cases. Performing EUS-TA and ERP at least twice may be reasonable when small pancreatic cancer is suspected.

DOI： 10.1007/s10620-025-09373-5

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DOI： 10.1016/j.clnesp.2025.02.004

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OBJECTIVE: Endoscopic sphincterotomy (EST), especially when anticoagulants are used, carries a significant risk of delayed bleeding. However, the relationship between the use of antithrombotic agents, including direct oral anticoagulants, and post-EST bleeding remains unclear. This study aimed to identify the risk factors for post-EST delayed bleeding when antithrombotic agents were administered according to the guidelines. METHODS: We analyzed cases of patients who underwent endoscopic retrograde cholangiopancreatography and EST between January 2018 and August 2022, focusing on those with normal anatomy and naïve papillae. We examined the incidence of post-EST bleeding, endoscopic retrograde cholangiopancreatography procedure details, severity and timing of post-EST delayed bleeding, hemostatic interventions, and factors related to post-EST delayed bleeding. RESULTS: Among the 502 patients included, 76 (15%) were taking antithrombotic agents. Post-endoscopic retrograde cholangiopancreatography delayed bleeding was noted in seven patients (1.4%). Mild, moderate, and severe delayed bleeding occurred in four, one, and two cases, respectively. Hemostatic injection completely controlled cases of delayed bleeding. Multivariate analysis identified a 1-day direct oral anticoagulants interruption (odds ratio: 20.5, 95% confidence interval: 3.33-125, p = 0.0011) and dialysis (odds ratio: 38.7, 95% confidence interval: 2.4-624, p = 0.0099) as significant risk factors for delayed bleeding. No thromboembolic events related to the discontinuation of antithrombotic drugs were observed. CONCLUSION: A 1-day direct oral anticoagulants interruption and dialysis are independent risk factors for post-EST delayed bleeding, necessitating careful consideration.

DOI： 10.1002/deo2.70060

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BACKGROUND: The choice between 22-gauge endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) and EUS-guided fine-needle aspiration (EUS-FNA) for histological diagnosis of type 1 autoimmune pancreatitis (AIP) is unclear. We retrospectively examined the detection rate of histological findings for AIP using EUS-FNA/FNB. METHODS: Patients diagnosed with type 1 AIP using EUS-FNB (Franseen needle) or EUS-FNA (conventional needle) with 22-gauge needles at our hospital between 2012 and 2023 were included in this study. AIP was diagnosed according to International Consensus Diagnostic Criteria (ICDC). The detection rates of level 1 findings, which included storiform fibrosis and/or obliterative phlebitis, and level 2 histological findings were evaluated according to the ICDC. RESULTS: The EUS-FNB and EUS-FNA groups included 25 and 24 patients, respectively. No significant differences in patient background were noted between the two groups. The detection rates of prominent filtration of lymphocytes and plasma cells along with fibrosis were 56.0% in the EUS-FNB group and 12.5% in the EUS-FNA group (p = .001). The detection rates of more than 10 IgG4-positive plasma cells per high-power microscopic field were 68.0% and 29.2% in the EUS-FNB and EUS-FNA groups, respectively (p = .007). The histological findings for levels 1 and 2 were significantly higher in the EUS-FNB group (56.0% vs. 12.5%; p = .001). Mild pancreatitis was observed in the EUS-FNB group; however, no other serious adverse events occurred. CONCLUSION: The 22-gauge EUS-FNB yielded a higher rate of histological findings than 22-gauge EUS-FNA, suggesting that 22-gauge EUS-FNB is suitable and safe for the histological diagnosis of type 1 AIP.

DOI： 10.1002/jhbp.12095

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DOI： 10.1055/a-2291-9116

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DOI： 10.3390/jcm13216328

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Background/Objectives: The usefulness of dual-energy computed tomography (DECT) for low absorption in the parenchymal phase and contrast effects in the delayed phase for pancreatic cancer is not clear. Therefore, the diagnostic capability of low-KeV images obtained using DECT for pancreatic cancer in the pancreatic parenchymal and delayed phases was evaluated quantitatively and qualitatively. Methods: Twenty-five patients with pancreatic cancer who underwent contrast-enhanced DECT were included. A total of 50 and 70 KeV CT images, classified as low-keV and conventional CT-equivalent images, were produced, respectively. The tumor-to-pancreas contrast (Hounsfield units [HU]) in the pancreatic parenchymal and delayed phases was calculated by subtracting the CT value of the pancreatic tumor from that of normal parenchyma. Results: The median tumor-to-pancreas contrast on 50 KeV CT in the pancreatic parenchymal phase (133 HU) was higher than that on conventional CT (68 HU) (p < 0.001). The median tumor-to-pancreas contrast in the delayed phase was -28 HU for 50 KeV CT and -9 HU for conventional CT (p = 0.545). For tumors < 20 mm, the tumor-to-pancreas contrast of 50 KeV CT (-39 HU) had a significantly clearer contrast effect than that of conventional CT (-16.5 HU), even in the delayed phase (p = 0.034). Conclusions: These 50 KeV CT images may clarify the low-absorption areas of pancreatic cancer in the pancreatic parenchymal phase. A good contrast effect was observed in small pancreatic cancers on 50 KeV delayed-phase images, suggesting that DECT is useful for the visualization of early pancreatic cancer with a small tumor diameter.

DOI： 10.3390/tomography10100117

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BACKGROUND: Patients with isolated IgG4-related sclerosing cholangitis (IgG4-SC) often undergo unnecessary resection. The aim of this study was to validate the revised Japanese diagnostic criteria for isolated IgG-4-SC and to improve awareness about this condition in the population. METHODS: This was a Japanese retrospective multicenter study. We focused on the data and diagnostic yield obtained using the Japanese diagnostic criteria published initially in 2012 and revised later in 2020 for the diagnosis of isolated IgG4-SC. RESULTS: Patients with isolated IgG4-SC could be classified into two groups based on the primary location of the lesion: the hilar type (n = 40) and the extrahepatic type (n = 13). In total, 10 patients with the hilar type had undergone unnecessary resection. The revised 2020 criteria are useful for the diagnosis of extrahepatic lesions, which are not included in the 2012 criteria. The need for a steroid trial was reduced from 37.7% when the diagnosis was based on the 2012 criteria to 7.6% when the diagnosis was based on the revised 2020 criteria. The diagnostic specificity also improved from 58.5% for the 2012 criteria to 88.7% for the revised 2020 criteria. CONCLUSION: Our validation of the 2020 criteria for the diagnosis of IgG4-SC could contribute to avoiding unnecessary resection in patients with isolated IgG4-SC, which can be classified into the hilar and extrahepatic types. The 2020 criteria can enhance the diagnosis rate of isolated IgG4-SC and uncover this tough-to-diagnose entity based on inclusion of the imaging findings and decrease the dependence on a steroid trial.

DOI： 10.1002/jhbp.12053

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BACKGROUND AND AIMS: Fully covered self-expandable metallic stents (SEMS) are laser-cut (L) or braided (B); however, which is more effective for distal malignant biliary obstruction (DMBO) has been unclear. We compared the clinical outcomes of using L- type and B-type stents because we believe that recurrent biliary obstruction (RBO) is less likely to occur with L-type stents. METHODS: Patients diagnosed with unresectable DMBO were randomly assigned to groups L and B in a stratified block fashion, and outcomes were compared. The primary outcome was the rate of RBO within 1 year; secondary outcomes were adverse events, clinical success rate, time to RBO (TRBO), and overall survival. RESULTS: Of the 60 enrolled participants, 56 (group L: 27, group B: 29) were included. The rates of RBO within 1 year were 44.4% and 17.2% in groups L and B, respectively (odds ratio 2.57 [95% confidence interval {CI}: 1.045-6.353]). Early adverse events, which improved with conservative treatment, included pancreatitis (n=4) in group L and pancreatitis (n=3) and cholecystitis (n=1) in group B (p=0.913). The median TRBO (220 days [95% CI: 56-272] versus 418 days [95% CI: 232-454]) was significantly longer in group B than in group L (log-rank test, p=0.0118). The median overall survival (L: 158 days, B: 204 days) after stenting was not significantly different between the groups (p=0.8544). CONCLUSIONS: In the setting of DMBO, braided (B)-type stents are associated with less recurrent obstruction than laser-cut-type (L) stents, although there was no difference in safety.

DOI： 10.1016/j.gie.2023.11.057

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BACKGROUND & AIMS: Despite previously reported treatment strategies for nonfunctioning small (≤20 mm) pancreatic neuroendocrine neoplasms (pNENs), uncertainties persist. We aimed to evaluate the surgically resected cases of nonfunctioning small pNENs (NF-spNENs) in a large Japanese cohort to elucidate an optimal treatment strategy for NF-spNENs. METHODS: In this Japanese multicenter study, data were retrospectively collected from patients who underwent pancreatectomy between January 1996 and December 2019, were pathologically diagnosed with pNEN, and were treated according to the World Health Organization 2019 classification. Overall, 1490 patients met the eligibility criteria, and 1014 were included in the analysis cohort. RESULTS: In the analysis cohort, 606 patients (59.8%) had NF-spNENs, with 82% classified as grade 1 (NET-G1) and 18% as grade 2 (NET-G2) or higher. The incidence of lymph node metastasis (N1) by grade was significantly higher in NET-G2 (G1: 3.1% vs G2: 15.0%). Independent factors contributing to N1 were NET-G2 or higher and tumor diameter ≥15 mm. The predictive ability of tumor size for N1 was high. Independent factors contributing to recurrence included multiple lesions, NET-G2 or higher, tumor diameter ≥15 mm, and N1. However, the independent factor contributing to survival was tumor grade (NET-G2 or higher). The appropriate timing for surgical resection of NET-G1 and NET-G2 or higher was when tumors were >20 and >10 mm, respectively. For neoplasms with unknown preoperative grades, tumor size >15 mm was considered appropriate. CONCLUSIONS: NF-spNENs are heterogeneous with varying levels of malignancy. Therefore, treatment strategies based on tumor size alone can be unreliable; personalized treatment strategies that consider tumor grading are preferable.

DOI： 10.1016/j.cgh.2024.03.029

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BACKGROUND: The risk and prognosis of pancreatobiliary cancer and in patients with autoimmune pancreatitis (AIP) and IgG4-related sclerosing cholangitis (IgG4-SC) remain unclear. Therefore, we retrospectively investigated the risk of pancreatobiliary cancer and prognosis in patients with AIP and IgG4-SC. METHODS: Patients with AIP and IgG4-SC at seven centers between 1998 and 2022 were investigated. The following data were evaluated: (1) the number of cancers diagnosed and standardized incidence ratio (SIR) for pancreatobiliary and other cancers during the observational period and (2) prognosis after diagnosis of AIP and IgG4-SC using standardized mortality ratio (SMR). RESULTS: This study included 201 patients with AIP and IgG4-SC. The mean follow-up period was 5.7 years. Seven cases of pancreatic cancer were diagnosed, and the SIR was 8.11 (95% confidence interval [CI]: 7.29-9.13). Three cases of bile duct cancer were diagnosed, and the SIR was 6.89 (95% CI: 6.20-7.75). The SMR after the diagnosis of AIP and IgG4-SC in cases that developed pancreatobiliary cancer were 4.03 (95% CI: 2.83-6.99). CONCLUSIONS: Patients with autoimmune pancreatitis and IgG4-SC were associated with a high risk of pancreatic and bile duct cancer. Patients with AIP and IgG4-SC have a worse prognosis when they develop pancreatobiliary cancer.

DOI： 10.1002/jhbp.1404

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BACKGROUND/PURPOSE: There is currently no consensus on the use of endoscopic papillectomy (EP) for early stage duodenal ampullary adenocarcinoma. This study aimed to evaluate the feasibility of EP for patients with early stage duodenal ampullary adenocarcinoma. METHODS: Patients who underwent EP for ampullary adenocarcinomas were investigated. Complete and clinical complete resection rates were evaluated. Clinical complete resection was defined as either complete resection or resection with positive or unknown margins but no cancer in the surgically resected specimen, or no recurrence on endoscopy after at least a 1-year follow-up. RESULTS: Adenocarcinoma developed in 30 patients (carcinoma in situ [Tis]: 21, mucosal tumors [T1a(M)]: 4, tumors in the sphincter of Oddi [T1a(OD)]: 5). The complete resection rate was 60.0% (18/30) (Tis: 66.7% [14/21], T1a[M]: 50.0% [2/4], and T1a[OD]: 40.0% [2/5]). The mean follow-up period was 46.8 months. The recurrence rate for all patients was 6.7% (2/30). The clinical complete resection rates of adenocarcinoma were 89.2% (25/28); rates for Tis, T1a(M), and T1a(OD) were 89.4% (17/19), 100% (4/4), and 80% (4/5), respectively. CONCLUSIONS: EP may potentially achieve clinical complete resection of early stage (Tis and T1a) duodenal ampullary adenocarcinomas.

DOI： 10.1002/jhbp.1398

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DOI： 10.1055/a-1960-3363

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BACKGROUND AND AIMS: This study evaluated the impact of the coronavirus disease 2019 (COVID-19) pandemic on pancreatic adenocarcinoma (PA) practice in our region and discussed the effects of our institution's regional collaborative system, the "Early Stage Pancreatic Cancer Diagnosis Project," which was originally unrelated to this study's purpose. METHODS: We retrospectively investigated 150 patients with PA at Yokohama Rosai Hospital by defining three time periods: before (C0), during the first year (C1), and during the second year (C2) of the COVID-19 pandemic. RESULTS: Among the three periods (C0, C1, and C2), there were significantly less patients with stage I PA (14.0%, 0%, and 7.4%, p = 0.032) in C1, and significantly more patients with stage III PA (10.0%, 28.3%, and 9.3%, p = 0.014) in C1. The pandemic significantly prolonged the median durations from disease onset to patients' first visits (28, 49, and 14 days, p = 0.012). In contrast, there was no significant difference in the median durations from referral to first visit to our institution (4, 4, and 6 days, p = 0.391). CONCLUSIONS: The pandemic advanced the stage of PA in our region. Although the pancreatic referral network remained functional during the pandemic, there were delays from disease onset to patients' first visit to healthcare providers, including clinics. While the pandemic caused temporary damage to PA practice, the routine regional collaboration provided by our institution's project allowed for early resilience. A notable limitation is that the impact of the pandemic on PA prognosis was not evaluated.

DOI： 10.1016/j.pan.2023.06.002

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BACKGROUND/PURPOSE: This study aimed to investigate the efficacy of intensive fluid-loading therapy post-endoscopic retrograde cholangiopancreatography (ERCP) for the prevention of post-ERCP pancreatitis (PEP) in at-risk patients. METHODS: In this retrospective study, data of 1200 patients at risk for PEP were investigated. After propensity score matching, 404 patients were included in the normal (n = 202) and hydration (n = 202) groups. On the day of ERCP, patients in both groups were infused with 2000 ml/24 h of fluid before ERCP. Meanwhile, the hydration group received an additional 1000 ml/10 h of lactated Ringer's solution postoperatively. RESULTS: The incidence of PEP was lower in the hydration group (12.4%) than in the normal group (24.3%) (odds ratio [OR]: 0.44; 95% CI: 0.26-0.75, p = .003). The incidence of severe PEP was 2.0% and 6.9% in the hydration and normal groups (OR: 0.27; 95% CI: 0.09-0.84, p = .027), respectively. The incidence of fatal PEP was 0% and 2.0% in the hydration and normal groups (OR: N.A.: p = .123), respectively. CONCLUSIONS: Post-ERCP hydration may be an effective method of preventing PEP, including severe PEP, in at-risk patients.

DOI： 10.1002/jhbp.1267

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

OBJECTIVES: The aim of this study was to evaluate whether low skeletal muscle mass before initial treatment is an independent prognostic factor defining overall survival (OS) and progression-free survival (PFS) in patients diagnosed with stage III cervical cancer. METHODS: Body composition and clinicopathologic data were collected retrospectively. Information was extracted and analyzed from the medical records of 92 patients with stage III cervical cancer and undergoing concurrent chemoradiotherapy. Skeletal muscle mass in the L3 region was measured using cross-sectional computed tomography images and corrected for body surface area to calculate the skeletal muscle index (SMI). The primary outcome was OS, and the secondary outcome was PFS. Statistical analyses were performed using the Mann-Whitney U test. The Kaplan-Meier method was used to determine OS and PFS. Univariate and multivariate analyses were performed with Cox proportional hazard ratios. RESULTS: The optimal cutoff value for predicting 5-y survival was 35.6 cm2/m2, defined based on data derived from 24 patients with a low SMI and 68 patients without a low SMI. A low SMI was significantly associated with shorter OS (hazard ratio [HR], 2.470; 95% confidence interval [CI], 1.208-5.053; P = 0.013), with no significant difference in PFS (HR, 1.651; 95% CI, 0.876-3.110; P = 0.121). Multivariate analysis also identified a low SMI as an independent OS-defining prognostic factor (HR, 2.473; 95% CI, 1.151-5.314; P = 0.020). CONCLUSION: A low pretreatment SMI is an independent prognostic factor for OS in patients diagnosed with stage III cervical cancer and treated with concurrent chemoradiotherapy.

DOI： 10.1016/j.nut.2022.111966

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BACKGROUND: We attempted to determine the indications and limitations of steroid therapy as the first-line therapy in patients with autoimmune pancreatitis (AIP) with cyst formation (ACF). METHODS: This Japanese multicenter survey was conducted to examine the merits/demerits of steroid treatment as the initial therapy for ACF. RESULTS: Data of a total of 115 patients with ACF were analyzed. Complete remission was achieved in 86% (86/100) of patients who had received steroid treatment, but only 33.3% (5/15) of patients who had not received steroids. Relapse after the remission (n = 86) occurred in 7.6% (6/86) of patients who had received steroid therapy, but 40% (2/5) of patients who had not received steroid therapy. Multivariate analysis identified adoption of the wait and watch approach without steroid treatment (odds ratio = 0.126, P < .001) as a significant and independent negative predictor of remission of ACF. As for predictors of relapse, the presence of varix (odds ratio = 5.83, P = .036) was identified as an independent risk factor. CONCLUSION: Steroid therapy plays an important role as first-line therapy in AIP patients with pancreatic cyst formation, however, varix formation, besides the diameter of the cyst(s), is a risk factor for refractoriness to steroid therapy.

DOI： 10.1002/jhbp.1227

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OBJECTIVE: IgG4-related sclerosing cholangitis (IgG4-SC) is recognized as a benign steroid-responsive disease; however, little is known about the risk of development of cancer in patients with IgG4-SC and about how to counter this risk. DESIGN: We conducted a retrospective review of the data of 924 patients with IgG4-SC selected from a Japanese nationwide survey. The incidence, type of malignancy, and risk of malignancy in these patients were examined. Then, the standardized incidence ratio (SIR) of cancer in patients with IgG4-SC was calculated. RESULTS: Relapse was recognized in 19.7% (182/924) of patients, and cancer development was noted in 15% (139/924) of patients. Multivariate analysis identified only relapse as an independent risk factor for the development of cancer. In most of these patients with pancreato-biliary cancer, the cancer developed within 8 years after the diagnosis of IgG4-SC. The SIR for cancer after the diagnosis of IgG4-SC was 12.68 (95% confidence interval [CI] 6.89-8.79). The SIRs of cancers involving the biliary system and pancreas were 27.35 and 18.43, respectively. The cumulative survival rate was significantly better in the group that received maintenance steroid treatment (MST) than in the group that did not; thus, MST influenced the prognosis of these patients. CONCLUSION: Among the cancers, the risk of pancreatic and biliary cancers is the highest in these patients. Because of the elevated cancer risk, surveillance after the diagnosis and management to prevent relapse are important in patients with IgG4-SC to reduce the risk of development of cancer.

DOI： 10.1111/jgh.16066

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BACKGROUND: In IgG4-related sclerosing cholangitis (IgG4-SC), the necessity of biliary drainage (BD) is unclear. In this study, we aimed to retrospectively investigate the improvement of liver damage and jaundice in cases of IgG4-SC with and without BD, before starting steroids. METHODS: Fifty-two patients with IgG4-SC were investigated in the study. The study endpoints were the normalization rate of alkaline phosphatase (ALP)/total bilirubin (T-Bil) after 8 weeks of steroids, with and without BD. RESULTS: Propensity score matching was performed based on ALP and T-Bil, and 28 patients were included. There were 14 patients each in the BD and non-BD groups. Before initiation of steroids, the mean ALP in the BD group and the non-BD group was 378/461 (p = 0.541); the mean T-Bil was 2.5/1.8 (p = 0.401). Eight weeks after initiation of steroids, ALP improvement rate in BD group/non-BD group was 69.2%/61.5% (p = 1.000), and T-Bil improvement rate was 100%/100% (p = Ns). CONCLUSIONS: Steroids for IgG4-SC could prove effective in improving liver damage and jaundice, regardless of the presence or absence of BD. BD for IgG4-SC aimed to improve jaundice may not be necessary.

DOI： 10.1002/jhbp.1230

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Diagnosing distal bile duct obstruction remains challenging. This study aimed to examine the diagnostic ability of artificial intelligence (AI) based on clinical biomarkers in diagnosing malignant distal bile duct obstruction. A total of 206 patients with distal bile duct obstruction were included in this study. Clinical laboratory parameters were collected from the patients and evaluated using AI. All clinical parameters were input into the AI algorithm, and the AI value for malignant distal bile duct obstruction was calculated. The benign and malignant diagnostic capabilities of AI and other factors (alkaline phosphatase [ALP], intrahepatic bile duct [IHBD] diameters, and total bile duct [CBD] diameters) were compared. Benign and malignant bile duct obstruction were diagnosed in 142 and 64 patients, respectively. The median AI value of malignant distal bile duct obstruction was significantly greater than that of benign distal bile duct obstruction (0.991 vs. 0.002, p < 0.001). The area under the receiver operating characteristic curve of AI, ALP, IHBD diameter, and CBD diameter were 0.908, 0.795, 0.794, and 0.775, respectively. AI showed a sensitivity, specificity, and accuracy of 83.1%, 87.2%, and 85.9%. AI-based on clinical biomarkers could serve as an auxiliary for diagnosing malignant bile duct obstruction.

DOI： 10.1038/s41598-023-28058-5

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Objective The effectiveness of everolimus for the management of pancreatic neuroendocrine neoplasms (PNENs), including the G3/NEC types, remains unclear. We therefore investigated the effectiveness of the drug for the management of PNENs. Methods We analyzed the progression-free survival (PFS) and overall survival (OS) associated with everolimus and factors influencing the PFS and OS. Results One hundred patients were evaluated. The PFS associated with the G1/G2 types tended to be significantly longer than that associated with the G3/NEC types (hazard ratio [HR], 0.45; p =0.005). A multivariate analysis showed that the significant factors influencing the PFS were age (<65 years old; HR, 0.44; p =0.002), grade (G1/G2; HR, 0.42; p =0.006), everolimus treatment line (≤2nd; HR, 0.55; p =0.031), and presence of treatment with metformin (yes; HR, 0.29; p =0.044). The median OS was 63.8 months. In the multivariate analysis, the significant factors influencing the OS were grade (G1/G2; HR, 0.21; p <0.001), volume of liver metastasis (≤25%; HR, 0.27; p <0.001), everolimus treatment line (≤2nd; HR, 0.27; p <0.001), and presence of primary tumor resection (yes; HR, 0.33; p =0.005). Conclusions The effectiveness of everolimus in the management of G3/NEC types and prognoses tended to be poorer than those associated with the G1/G2 types. Everolimus combined with metformin and early-line treatment with everolimus may be effective for managing advanced PNENs.

DOI： 10.2169/internalmedicine.9416-22

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A 51-year-old man who had been receiving steroid therapy for type 1 autoimmune pancreatitis (AIP) for 3 years contracted coronavirus disease 2019 (COVID-19). As he had a high-grade fever and dry cough, and because his SpO2 level had dropped below 95% in the supine position, he was considered as being at a high risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); therefore, he received combined REGN-COV2 antibody therapy. The patient's fever resolved immediately after this treatment, and he went into remission. A high cumulative steroid dose is associated with an increased susceptibility to infection. Early antibody cocktail therapy may be effective and rewarding for steroid-dependent type 1 AIP patients with a potential risk for SARS-CoV-2.

DOI： 10.2169/internalmedicine.1421-22

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DOI： 10.11405/nisshoshi.120.297

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DOI： 10.2169/internalmedicine.E002-23

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DOI： 10.1055/a-1847-7745

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BACKGROUND: The clinical outcomes of everolimus rechallenge in patients with pancreatic neuroendocrine neoplasms (PNENs) are unknown. This study aimed to investigate the treatment outcomes and safety of everolimus rechallenge treatment with PNENs. METHODS: Clinical data of everolimus-treated patients with PNENs at two institutions were collected. Patients who underwent everolimus rechallenge were included in the study. We analyzed the progression-free survival (PFS) and treatment response associated with everolimus rechallenge and the adverse events. RESULTS: Between 2008 and 2020, 117 patients received initial treatment with everolimus, of which 14 patients received everolimus rechallenge. With regard to the grade of PNENs, there were 2 cases of G1, 11 cases of G2, and 1 case of G3. The median rechallenge PFS was 5.7 months. The objective response rate was 21.4%. the disease control rate was 71.4%. The only major grade 3 or 4 adverse event was neutropenia (n = 1, 7.1%). No other severe adverse event was observed. CONCLUSION: The outcomes and safety of everolimus rechallenge were verified, and it was deemed an acceptable treatment. Everolimus rechallenge may provide a new drug therapy for patients with advanced PNENs for whom no other drug treatment option is available.

DOI： 10.3390/cancers14225669

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BACKGROUND AND PURPOSE: During endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS), tract dilation is one of the most important steps, and the placement of conventional metal stents with 8.5 Fr delivery devices is difficult due to the large outer shape of the device. Fine-gauge balloon catheters have become popular because of their stricture penetration ability and ease of dilation. This study aimed to evaluate the utility of fine-gauge balloon catheters. PATIENTS AND METHODS: This retrospective study involved 38 patients who underwent conventional metal stent placement. The patients were classified into two groups: those who underwent dilation with a fine-gauge balloon catheter before initial metal stenting (balloon dilation group) and those who underwent bougie dilation only (non-balloon dilation group). We evaluated the stenting success rate after initial dilation and adverse events. RESULTS: Seventeen and twenty-one patients were included in the balloon dilation and non-balloon dilation groups, respectively. The stenting success rate after initial dilation was 100% (17/17) in the balloon dilation group and 71.4% (15/21) in the non-balloon dilation group (p = 0.024). As adverse events, peritonitis was observed in one case (4.8%) in the balloon dilation group, and in three cases (14.3%) in the non-balloon dilation group (p = 0.613). CONCLUSIONS: Dilation using a fine-gauge balloon catheter before conventional metal stent with 8.5 Fr delivery device placement is considered effective in EUS-HGS.

DOI： 10.3390/jcm11195681

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PURPOSE: The diagnosis of gallbladder lesions remains challenging. The efficacy of computed diffusion-weighted imaging (DWI) with high b-values and apparent diffusion coefficient (ADC) for the diagnosis of gallbladder cancer remains unknown. We aimed to investigate the usefulness of computed DWI with high b-values and the combination of computed DWI and ADC in differentiating malignant and benign gallbladder lesions. METHODS: Sixty patients (comprising 30 malignant and 30 benign lesions) who underwent magnetic resonance imaging for gallbladder lesions were included in this retrospective study. Qualitative evaluations were performed using conventional DWI with b1000, computed DWI with b1500, b1000 DWI/ADC, and computed b1500 DWI/ADC, and their diagnostic performances were compared. RESULTS: The sensitivity, specificity, and accuracy of computed b1500 DWI/ADC were 90% (27/30), 80% (24/30), and 85% (51/60), respectively. The accuracy of computed b1500 DWI/ADC was higher than that of conventional b1000 DWI (52%, 31/60, p < 0.001), computed b1500 DWI (72%, 43/60, p = 0.008), and b1000 DWI/ADC (78%, 47/60, p = 0.125). The specificity of computed b1500 DWI/ADC was also higher than that of conventional b1000 DWI (7%, 2/30, p < 0.001), computed b1500 DWI (47%, 14/30, p = 0.002), and b1000 DWI/ADC (67%, 20/30, p = 0.125). No significant difference was observed in the sensitivity between the groups. CONCLUSION: This study shows that computed DWI with high b-values combined with ADC can improve diagnostic performance when differentiating malignant and benign gallbladder lesions. Computed diffusion-weighted magnetic resonance imaging with high b-values in the diagnosis of gallbladder lesions. *Computed DWI with b1500 combined with ADC can improve diagnostic performance when differentiating gallbladder lesions compared with conventional methods (b1000 DWI).

DOI： 10.1007/s00261-022-03586-2

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BACKGROUND/PURPOSE: The detection ability and role of different imaging modalities to detect pancreatic neuroendocrine neoplasms (PNENs) including small lesions is unclear. This study aimed to compare the ability of endoscopic ultrasound (EUS) and computed tomography (CT) to detect PNENs. METHODS: Data of patients who underwent EUS and contrast-enhanced CT and were diagnosed with PNENs were analyzed. The detection rates of pancreatic lesions with EUS and CT based on tumor size and influencing factors were investigated. RESULTS: For 256 PNEN lesions, the detection rate of EUS was better than that of CT (94.5% vs 86.3%; P < .001). EUS was significantly superior to CT for PNENs ≤5 mm (58.3% vs 16.7%; P = .006) and 5-10 mm (97.7% vs 79.5%; P = .008). There was no significant difference in the detection rate between EUS and CT for PNENs >10 mm (98.4% vs 96.4%; P = .375). Size (≤5 mm) and insulinoma were independent factors associated with poor EUS and CT detection rates. CONCLUSIONS: Endoscopic ultrasound exhibited better detection ability than CT, with an excellent detection rate for PNENs >5 mm, except for insulinomas. CT could detect PNENs >10 mm, which are amenable to treatment.

DOI： 10.1002/jhbp.1144

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Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is useful in diagnosing subepithelial lesions (SELs), and adequate tissue sampling is necessary to differentiate between benign and malignant diseases to determine therapeutic strategies. This study aimed to evaluate sampling adequacy and diagnostic performance of EUS-FNA for SELs with Franseen needles. This retrospective study enrolled 130 patients who underwent EUS-FNA with a 22-gauge needle for SELs from January 2010 to March 2021. We compared sampling adequacy and predictive factors influencing the sampling adequacy of EUS-FNA for SELs between Franseen and conventional needles. The sampling adequacy rates were 95.0% (38/40) with Franseen needles and 76.7% (69/90) with conventional needles (p = 0.011). The mean number of punctures with Franseen needles (2.80) was significantly less than that with conventional needles (3.42) (p &lt; 0.001). In the multivariate analysis, the use of Franseen needles (p = 0.029; odds ratio [OR], 5.37; 95% confidence interval [CI], 1.18-23.36) was an independent factor influencing the sampling adequacy. Compared to conventional needles, the Franseen needle could play a vital role in accurately diagnosing SELs by yielding better sampling adequacy and reducing the number of passes.

DOI： 10.3390/diagnostics12071667

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Peptide receptor activation therapy (PRRT) is a promising treatment option for metastatic neuroendocrine tumors (NETs). However, predicting tumor shrinkage before treatment is challenging. We analyzed the shrinkage rate of each metastatic tumor lesion to identify predictive factors related to shrinkage. Patients with metastatic NET who underwent PRRT were included in this retrospective study. For each patient, between one to five metastatic lesions were selected in descending order of size, and the change in the maximum tumor diameter after treatment was defined as the shrinkage rate per lesion (L-SR). We analyzed the relationship between pretreatment clinicopathological factors and L-SR. The median L-SR of all 75 lesions in 20 patients was 20% (95% CI: 4.8-26.1%). While previous treatment with cytotoxic agents (34.4%, p &lt; 0.05) and primary tumor of the pancreas (27.8%, p &lt; 0.05) were significantly favorable factors, a primary tumor of the rectum was significantly more resistant to shrinkage (-20.5%, p &lt; 0.001). Therefore, lesion-based analysis of PRRT for NETs showed that pancreatic NET and previous treatment with cytotoxic agents were favorable factors for tumor shrinkage; however, rectal NET was a factor associated with resistance to shrinkage.

DOI： 10.3390/cancers14143317

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BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) in patients with surgically altered anatomy is technically difficult. Extensive training is required to develop the ability to perform this procedure. AIMS: To investigate the learning curve of single-balloon-assisted enteroscopy ERCP (SBE-ERCP). METHODS: We conducted a retrospective, observational case series at a single center. We evaluated the SBE-ERCP procedures between April 2011 and February 2021. The main outcomes were the rate of reaching the target site and the success rate of the entire procedure. These parameters were additionally expressed as a learning curve. RESULTS: A total of 687 SBE-ERCP procedures were analyzed. The learning curve was analyzed in blocks of 10 cases. In this study, seven endoscopists, experts in conventional ERCP, were included. The overall SBE-ERCP procedural success rate was 92.2% (634/687 cases). Combining all data from individual endoscopists' evaluation periods, the insertion and success rates of the SBE-ERCP procedures gradually increased with increased experience performing SBE-ERCP. The insertion success rates for the number of SBE-ERCP cases (< 20, 21-30, > 30) were 82.9%, 92.9%, and 94.3%, respectively; the procedure success rates were 74.3%, 81.4%, and 92.9%, respectively. The endoscopists who had performed > 30 SBE-ERCP cases had a success rate of ≥ 90%. CONCLUSIONS: Our results suggest that performing > 30 cases is one of the targets for conventional ERCP experts to become competent in performing SBE-ERCP in patients with a surgically altered anatomy.

DOI： 10.1007/s10620-021-07342-2

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Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) is a late-onset, slow-progressing multisystem neurodegenerative disorder. Biallelic AAGGG repeat expansion in RFC1 has been identified as causative of this disease, and repeat conformation heterogeneity (ACAGG repeat) was also recently implied. To molecularly characterize this disease in Japanese patients with adult-onset ataxia, we accumulated and screened 212 candidate families by an integrated approach consisting of flanking PCR, repeat-primed PCR, Southern blotting and long-read sequencing using Sequel II, GridION or PromethION. We identified 16 patients from 11 families, of whom seven had ACAGG expansions [(ACAGG)exp/(ACAGG)exp] (ACAGG homozygotes), two had ACAGG and AAGGG expansions [(ACAGG)exp/(AAGGG)exp] (ACAGG/AAGGG compound heterozygotes) and seven had AAGGG expansions [(AAGGG)exp/(AAGGG)exp] (AAGGG homozygotes). The overall detection rate was 5.2% (11/212 families including one family having two expansion genotypes). Long-read sequencers revealed the entire sequence of both AAGGG and ACAGG repeat expansions at the nucleotide level of resolution. Clinical assessment and neuropathology results suggested that patients with ACAGG expansions have similar clinical features to previously reported patients with homozygous AAGGG expansions, although motor neuron involvement was more notable in patients with ACAGG expansions (even if one allele was involved). Furthermore, a later age of onset and slower clinical progression were implied in patients with ACAGG/AAGGG compound heterozygous expansions compared with either ACAGG or AAGGG homozygotes in our very limited cohort. Our study clearly shows the occurrence of repeat conformation heterogeneity, with possible different impacts on the affected nervous systems. The difference in disease onset and progression between compound heterozygotes and homozygotes might also be suspected but with very limited certainty due to the small sample number of cases in our study. Studies of additional patients are needed to confirm this.

DOI： 10.1093/brain/awab363

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Currently, the same-day polyethylene glycol-electrolyte lavage solution (PEG-ELS) regimen is particularly recommended for afternoon colonoscopy as an alternative to the split-dose regimen in western countries. However, in Japan, the split-dose regimen has never been used as a standard colonoscopy preparation regimen. The aim of this study was to compare the efficacy and tolerability of split-dose PEG containing ascorbic acid (ASC) with same-day single dose PEG-ASC in Japan.This was a single-blinded, non-inferiority, two-center, randomized, controlled study. In-hospital patients were randomized to the same-day regimen or the split regimen using a web-based registry system. The same-day group was instructed to take 5 mL of sodium picosulfate in the evening, and on the day of the colonoscopy, they took 1.5 L of PEG-ASC. The split group was instructed to take 1 L of PEG-ASC before the day of colonoscopy, followed by another 1 L of PEG-ASC on the day of colonoscopy. Bowel cleansing was evaluated by the Boston Bowel Preparation Scale.A total of 153 patients were randomized to either the same-day group (n=78, males 60.0%, mean age 62.7 years) or the split group (n=75, 61.3%, 61.9 years). The rates of successful bowel cleansing were 83.3% in the same-day group vs. 92.0% (83.4%-97.0%) in the split group, P=0.10). No serious adverse events occurred in the study population. However, more patients in the same-day group were willing to repeat the same preparation regimen (P<0.001). The split-dose regimen was not inferior to the same-day regimen with respect to the efficacy of bowel preparation, but the patients preferred the same-day regimen.

DOI： 10.18999/nagjms.83.4.787

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BACKGROUND: The incidence and risk factors of severe anaphylaxis by intravenous anti-cancer drugs are unclear, whereas those of milder reactions have been reported. STUDY DESIGN: Electronic medical charts of cancer patients who have undergone intravenous chemotherapy between January 2013 and October 2020 in a university hospital were retrospectively reviewed. Non-epithelial malignancies were also included in the analysis. "Severe anaphylaxis" was judged using Brown's criteria: typical presentation of anaphylaxis and one or more of hypoxia, shock, and neurologic compromise. (UMIN000042887). RESULTS: Among 5584 patients (2964 males [53.1%], 2620 females [46.9%], median age 66 years), 88,200 person-day anti-cancer drug administrations were performed intravenously, and 27 severe anaphylaxes were observed. The causative drugs included carboplatin (14 cases), paclitaxel (9 cases), and cisplatin, docetaxel, trastuzumab, and cetuximab (1 case each). The person-based lifetime incidence of severe anaphylaxis for patients who received at least one intravenous chemotherapy was 0.48% (27/5584, 95% confidence interval (CI) 0.30%-0.67%) and the administration-based incidence was 0.031% (27/88,200, 95% CI 0.019%-0.043%). Among 124 patients who received at least 10 carboplatin administrations, 10 patients experienced carboplatin-induced severe anaphylaxis (10/124, 8.1%, 95% CI 3.0%-13.1%). Carboplatin caused severe anaphylaxis after at least 9-min interval since the drip started. Thirteen out of 14 patients experienced carboplatin-induced severe anaphylaxis within a 75-day interval from the previous treatment. Paclitaxel infusion caused severe anaphylaxis after a median of 5 min after the first drip of the day at a life-long incidence of 0.93% (9/968, 95% CI 0.27%-1.59%). CONCLUSION: We elucidated the high-risk settings of chemotherapy-induced severe anaphylaxis.

DOI： 10.1002/cam4.4252

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BACKGROUND/PURPOSE: The role of endoscopic preoperative biliary drainage for pancreatic head cancer is controversial because of the high incidence of stent occlusion before surgery. We sought to validate a suitable stent for biliary drainage in patients with pancreatic cancer undergoing neoadjuvant chemotherapy (NAC)/neoadjuvant chemoradiotherapy (NAC-RT). METHODS: We evaluated patients who received preoperative neoadjuvant therapy for pancreatic head cancer between January 2013 and December 2019. A covered metal (CMS) or plastic stent (PS) was inserted in symptomatic patients for biliary drainage. Recurrent biliary obstruction (RBO), success rate of endoscopic drainage, adverse events, and surgical outcomes were compared between the CMS and PS groups. RESULTS: Occurrence rate of RBO was significantly higher with PS (97%) vs CMS (15%, P < .001), and time to RBO was significantly longer with CMS vs PS (not reached vs 40.5 days, P < .001). Delayed schedule associated with RBO for neoadjuvant chemotherapy was significantly lower in CMS vs PS (14% vs 50%, P < .05). There was no difference in postoperative bleeding, operation time, complications, and rate of a microscopically margin-negative resection between groups. CONCLUSIONS: Use of CMS during NAC/NAC-RT allows for safe chemotherapy without causing cholangitis or biliary obstruction and for surgery to be performed.

DOI： 10.1002/jhbp.958

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Cholestatic liver disease is a disease that causes liver damage and fibrosis owing to bile stasis. It is represented by primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), but the pathophysiological pathways that cause bile stasis in both diseases are different. The pathogenesis of the disease is still unclear, although autoimmune mechanisms have been postulated and partially elucidated. Although the disease may progress slowly with only mild liver dysfunction, it may progress to liver cirrhosis or liver failure, which require liver transplantation. As a medical treatment, ursodeoxycholic acid is widely used for PBC and has proved to be very effective against disease progression in cases of PBC. On the other hand, its efficacy is limited in cases of PSC, and the research and development of various drugs are underway. Furthermore, the clinical course of both diseases is quite variable, making the design of clinical trials fairly difficult. In this review, we present the general natural history of PBC and PSC, and provide information on the latest drug therapies currently available and those that are under investigation.

DOI： 10.1007/s40265-021-01545-7

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BACKGROUND/PURPOSE: The relationship between autoimmune pancreatitis (AIP) and malignancy has been reported. However, the potential risk for cancer in patients with immunoglobulin 4 (IgG4)-related sclerosing cholangitis (IgG4-SC) is unclear. The present study aimed to evaluate the incidence of cancer in IgG4-SC patients. METHODS: We retrospectively collected clinical data for 121 patients diagnosed with IgG4-SC from 7 hospitals. We calculated the standardized incidence ratio (SIR) of cancer in IgG4-SC patients based on the national cancer rates. The SIR of the period after the diagnosis of IgG4-SC were calculated. RESULTS: The mean follow-up period was 6.4 years, with 121 IgG4-SC patients. During the follow-up period, 26 patients had cancer, and 29 cancers were diagnosed. The SIR of cancer after the diagnosis of IgG4-SC was 1.90 (95% confidence interval [CI] 1.67-2.21). The SIR of pancreatic and bile duct cancer was 10.30 and 8.88, respectively. The SIR of cancer in <1 year, 1-5 years, and >5 years after diagnosis of IgG4-SC were 2.58, 1.01, and 2.44, respectively. CONCLUSIONS: IgG4-SC patients have a high risk of cancer including pancreatic and bile duct cancer. The risk of cancer was high less <1 year and >5 years after diagnosis of IgG4-SC. Therefore, IgG4-SC patients may require careful long-term follow-up.

DOI： 10.1002/jhbp.957

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Objective Neuroendocrine neoplasms (NENs) are rare and indolent diseases, but the efficacy of treatment without surgical resection is temporary and limited. Targeted immunotherapy is an important treatment strategy in several cancers. However, the tumor and host immune reactions in the NEN microenvironment are poorly understood. Therefore, we investigated the immune checkpoint system and host immune response in pathological NEN specimens. Methods The expression of the mismatch repair proteins MSH2, MSH6, PMS2, and MLH1 was immunohistochemically detected in archival tissue samples obtained from 20 patients with gastroenteropancreatic NENs. We additionally assessed the expression of programmed death (PD)-1, PD-L1, and the tumor-infiltrating lymphocyte (TIL) markers CD8 and family of transcription factor P3 (FOXP3). Results All 20 NENs expressed the mismatch repair proteins MSH2, MSH6, PMS2, and MLH1. The PD-L1 and/or PD-1 expression in the tumor cells and/or TILs was confirmed in 75% of the cases. PD-1-, CD8-, and FOXP3-positive TILs were more frequently associated with PD-L1-positive tumors than with PD-L1 negative tumors (PD-1: 19.5 vs. 7.3, CD8: 18.1 vs. 7.1, FOXP3: 13.2 vs. 3.2, p=0.438, p=0.419, P=0.603, respectively). The number of cells positive for PD-1 tended to gradually increase in increasing grade of NENs but did not reach significance (Grade 1: 5.8, Grade 2: 10.2, NEC: 18.1, p=0.903). Conclusion NENs consistently express mismatch repair proteins but have a high expression of PD-L1 and/or PD-1 in the tumor microenvironment. NEC and PD-L1-positive NENs may be immunologically "hot" tumors, so an immunological approach may be an appropriate treatment strategy for these tumors.

DOI： 10.2169/internalmedicine.5648-20

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DOI： 10.1111/den.13874

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AIM: Sarcopenia affects the treatment of various cancer types but its impact on chemotherapy efficacy and prognosis in biliary tract cancer remains unclear. Thus, we evaluated whether sarcopenia independently affects the outcome of chemotherapy for biliary tract cancer. PATIENTS AND METHODS: Data of 50 patients who underwent chemotherapy for biliary tract cancer at two affiliated centres were retrospectively analysed. The association of clinical factors, including sarcopenia, with overall survival and time to treatment failure was analysed. RESULTS: Sarcopenia was an independent factor negatively influencing overall survival and time to treatment failure in univariate and multivariate analyses (median overall survival, sarcopenic vs. non-sarcopenic patients: 10.6 vs. 16.6 months; hazard ratio=2.19, p=0.018; time to treatment failure: 5.3 vs. 13.1 months, hazard ratio=2.50, p=0.019). CONCLUSION: Sarcopenia may affect the efficacy of chemotherapy and prognosis in biliary tract cancer. Thus, improving sarcopenia may improve the prognosis of patients with biliary tract cancer undergoing chemotherapy.

DOI： 10.21873/invivo.12581

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BACKGROUND/PURPOSE: Placement of uncovered self-expandable metallic stents (U-SEMSs) of patients with unresectable perihilar cholangiocarcinoma (UPHC) is recommended as the treatment of first choice to address bile stasis. The aim of this study was to determine which of the following two endoscopic stents might be the stent of first choice for the treatment of biliary stasis in patients with UPHC: plastic stents (PSs) or U-SEMSs. METHODS: U-SEMSs, deployed as a stent-in-stent, were selected as the stents of first choice from 2013 and 2014, while PSs began to be selected as the stents of first choice from 2015 onward. RESULTS: The median time to recurrent biliary obstruction were 66 days in the PS group (N = 38) and 105 days in the U-SEMS group (N = 37; P = .04). Emergency endoscopy was necessitated in 76.3% (29/38) of patients of the PS group and 54.1% (20/37) of patients of the U-SEMS group (P = .0434). The success rate of the first reintervention was 96.5% (27/29) in the PS group and 55% (11/20) in the U-SEMS group (P = .0002). Sustainable chemotherapy could be carried out in 55.2% of patients in the PS group and 32.4% of patients in the U-SEMS group (P = .0472). Multivariate analysis identified selection of U-SEMS as the stent of first choice as the only independent factor predictive of successful reintervention (P = .0016, odds ratio = 0.058). However, the stent selection was not an independent factor for feasible chemotherapy. CONCLUSIONS: Plastic stent placement could enhance the success rate of reintervention in patients with UPHC and might be facilitated by sustainable chemotherapy. However, stent selection might not have an influence on the prognosis.

DOI： 10.1002/jhbp.804

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BACKGROUND AND AIMS: Although the technique of endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) is becoming standardized, its safety issues have not been sufficiently investigated. Therefore, we aimed to identify factors associated with adverse events and stent patency in EUS-CDS. METHODS: Consecutive patients who underwent EUS-CDS between September 2003 and July 2017 were included. Technical/clinical success, adverse events and stent dysfunctions were analyzed retrospectively. RESULTS: A total of 151 patients underwent EUS-CDS. In nine patients, procedures were discontinued before puncture. Technical and clinical success rates were 96.5% (137/142) and 98.5% (135/137), respectively. The adverse event rate was 20.4% (29/142). As a risk factor for peritonitis, plastic stents (PS) showed a significantly high odds ratio (OR) compared with covered self-expandable metal stents (CSEMS; OR, 4.31; P = 0.030). CSEMS cases showed a significantly longer patency period than PS cases (329 vs 89 days; HR, 0.35; P < 0.001). As a risk factor for early stent dysfunction (within 14 days), stent direction to the oral side showed a significantly high OR (OR, 43.47; P < 0.001). In cases with oblique-viewing EUS, double penetration of the duodenum occurred at significantly higher frequency than in cases with forward-viewing EUS (7.0 vs 0.0%; P = 0.024). CONCLUSIONS: Plastic stents and stent direction to the oral side were risk factors for peritonitis and early stent dysfunction, respectively. Using covered self-expandable metal stents and changing stent direction to the anal side seemed appropriate to prevent peritonitis and early stent dysfunction.

DOI： 10.1111/den.13620

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BACKGROUND: The treatment of small (≤ 2 cm), sporadic localized non-functional pancreatic neuroendocrine neoplasms (PNENs) is often controversial. This study aimed to investigate the clinical outcomes with observation and surgical resection in small PNENs. METHODS: Seventy-five patients with small localized sporadic non-functional PNENs ≤ 2 cm, who underwent observation or surgical resection, were retrospectively reviewed. Changes in tumor size during follow-up in the observation group were also investigated. RESULTS: The median age of the cohort was 61 (range 35-81) years. The tumor grades were G1, G2, and unknown, in 61 (81.3%), 8 (10.7%), and 6 (8.0%) patients, respectively. The mean follow-up periods in the observation (n = 23) and surgical resection groups (n = 52) were 52.3 (range 6.8-133.3) months and 73.0 (range 9.1-179.9) months, respectively. The median overall survival was not reached. During follow-up, no patient died of PNENs, two died of other diseases, three had lymph node metastases, and one experienced recurrence after surgical resection. There was no significant difference in overall survival between the observation and surgical resection groups (hazard ratio: 0.031, P = 0.417). The mean change in tumor size in the observation group was + 0.30 mm (range - 1.6 to + 3.0 mm). No deaths, tumor progression, lymph node metastases, distant metastases, or recurrence were noted in patients with PNENs ≤ 1 cm (n = 36). CONCLUSIONS: The prognosis of small localized PNENs is good. Observation may be an alternative to surgery in high-risk patients and those with small G1 tumors, particularly those measuring ≤ 1 cm.

DOI： 10.1007/s00535-019-01655-w

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BACKGROUND AND AIM: The usefulness of preventive closure of the frenulum after endoscopic papillectomy (EP) could reduce bleeding. The feasibility and safety of clipping were evaluated in this prospective pilot study. METHODS: This study involved 40 consecutive patients who underwent preventive closure of the frenulum by clipping just after EP. The outcome data were compared with those of the previous 40 patients in whom no preemptive closure had been performed (no-closure group) (UMIN000014783). Additionally, the bleeding sites were examined. RESULTS: The clipping procedure was successful in all patients. As compared to the no-closure group, the rate of bleeding (P = 0.026) and period of hospital stay (P < 0.001) were significantly reduced in the closure group. There was no difference in the procedure time between the two groups. Furthermore, the incidence rates of pancreatitis and perforation were comparable in the two groups. The bleeding was noted in the frenulum area rather than at any other site in 90.9% of cases. CONCLUSION: Preventive closure of the frenulum after EP is an effective, safe, rational, and economical method to reduce the incidence of delayed bleeding, without prolonging the procedure time or increasing the risk of post-procedure pancreatitis perforation.

DOI： 10.1111/jgh.14922

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BACKGROUND AND AIM: In chronic pancreatitis (CP) patients, diagnosis of small pancreatic lesions by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is challenging. Thus, the aim of the present study was to investigate whether CP influences the diagnostic ability of EUS-FNA for pancreatic lesions ≤10 mm. METHODS: One hundred and seventeen patients who underwent EUS-FNA for pancreatic lesions ≤10 mm in size were enrolled. Patients were classified into two groups based on features of CP observed by EUS (EUS-CP features) in accordance with the Rosemont classification. The CP group was defined as cases consistent with CP or suggestive of CP, and the non-CP group was defined as cases indeterminate for CP or normal. Factors influencing the diagnostic accuracy of EUS-FNA and CP status in pancreatic tumors were also investigated. RESULTS: Diagnostic ability of EUS-FNA (overall cases, non-CP vs CP) had sensitivity (80.4%, 96.7% vs 57.1%; P < 0.001), specificity (100%, 100% vs 100%; P > 0.05), and accuracy (91.5%, 98.6% vs 80.4%; P = 0.001). In multivariate analysis of factors influencing the accuracy of EUS-FNA, CP significantly lowered the accuracy (P = 0.048; odds ratio [OR] = 9.21). Among pancreatic cancer patients, the number of CP patients was significantly higher than the number of patients with benign lesions (P = 0.023). In multivariate analysis, lobularity without honeycombing was more frequently observed in cases of pancreatic cancer (P = 0.018; OR, 12.65). CONCLUSION: Endoscopic ultrasound-guided FNA offers high accuracy for small pancreatic lesions ≤10 mm. However, in cases with CP, the diagnostic ability of EUS-FNA is significantly reduced.

DOI： 10.1111/den.13497

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Background: Neuroendocrine tumors (NETs) are rare, but their worldwide incidence is gradually increasing. NETs are generally heterogeneous; however, in rare cases, they have been shown to change their phenotype (i.e., nonfunctional to functional or one functional phenotype to the addition of another functional phenotype). Here, we present two cases of liver metastatic NETs with phenotype transformation at the advanced stage that led to life-threatening events. Case presentation: A 73-year-old woman had a small intestinal nonfunctional NET with liver metastasis. After uncontrollable liver metastasis at the advanced stage, she developed duodenal perforation with hypergastremia. The patient was treated with octreotide and proton pump inhibitors and underwent endoscopic closure for duodenal perforation, but her general condition gradually deteriorated, and she died 2 weeks after duodenal perforation. Another patient, a 50-year-old man, had a functional NET (gastrinoma) with liver metastasis and duodenal ulcer. After uncontrollable liver metastasis at the advanced stage, he developed hypoglycemia. Although octoreotide and diazoxide were administrated for hyperalimentation, his hypoglycemia was uncontrollable, and he died after 4 months owing to general deterioration. Conclusion: The present cases show that advanced NETs with treatment-uncontrollable liver metastasis can transform their phenotype, specifically from a nonfunctional NET into a functional NET, and from one functional NET into the addition of another functional NET. These experiences suggest that the presence of treatment-resistant liver metastasis might be a hallmark of the potential to gain novel functions.

DOI： 10.3389/fonc.2020.555963

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The imbalanced redox status in lung has been widely implicated in idiopathic pulmonary fibrosis (IPF) pathogenesis. To regulate redox status, hydrogen peroxide must be adequately reduced to water by glutathione peroxidases (GPx). Among GPx isoforms, GPx4 is a unique antioxidant enzyme that can directly reduce phospholipid hydroperoxide. Increased lipid peroxidation products have been demonstrated in IPF lungs, suggesting the participation of imbalanced lipid peroxidation in IPF pathogenesis, which can be modulated by GPx4. In this study, we sought to examine the involvement of GPx4-modulated lipid peroxidation in regulating TGF-β-induced myofibroblast differentiation. Bleomycin-induced lung fibrosis development in mouse models with genetic manipulation of GPx4 were examined. Immunohistochemical evaluations for GPx4 and lipid peroxidation were performed in IPF lung tissues. Immunohistochemical evaluations showed reduced GPx4 expression levels accompanied by increased 4-hydroxy-2-nonenal in fibroblastic focus in IPF lungs. TGF-β-induced myofibroblast differentiation was enhanced by GPx4 knockdown with concomitantly enhanced lipid peroxidation and SMAD2/SMAD3 signaling. Heterozygous GPx4-deficient mice showed enhancement of bleomycin-induced lung fibrosis, which was attenuated in GPx4-transgenic mice in association with lipid peroxidation and SMAD signaling. Regulating lipid peroxidation by Trolox showed efficient attenuation of bleomycin-induced lung fibrosis development. These findings suggest that increased lipid peroxidation resulting from reduced GPx4 expression levels may be causally associated with lung fibrosis development through enhanced TGF-β signaling linked to myofibroblast accumulation of fibroblastic focus formation during IPF pathogenesis. It is likely that regulating lipid peroxidation caused by reduced GPx4 can be a promising target for an antifibrotic modality of treatment for IPF.

DOI： 10.4049/jimmunol.1801232

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Ferroptosis is a necrotic form of regulated cell death (RCD) mediated by phospholipid peroxidation in association with free iron-mediated Fenton reactions. Disrupted iron homeostasis resulting in excessive oxidative stress has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). Here, we demonstrate the involvement of ferroptosis in COPD pathogenesis. Our in vivo and in vitro models show labile iron accumulation and enhanced lipid peroxidation with concomitant non-apoptotic cell death during cigarette smoke (CS) exposure, which are negatively regulated by GPx4 activity. Treatment with deferoxamine and ferrostatin-1, in addition to GPx4 knockdown, illuminate the role of ferroptosis in CS-treated lung epithelial cells. NCOA4-mediated ferritin selective autophagy (ferritinophagy) is initiated during ferritin degradation in response to CS treatment. CS exposure models, using both GPx4-deficient and overexpressing mice, clarify the pivotal role of GPx4-regulated cell death during COPD. These findings support a role for cigarette smoke-induced ferroptosis in the pathogenesis of COPD.

DOI： 10.1038/s41467-019-10991-7

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Esophageal schwannomas are extremely rare esophageal submucosal tumors. Herein, we report a case of simultaneous resection of left lung cancer and an esophageal schwannoma with video-assisted thoracoscopic surgery. An asymptomatic 74-year-old woman received a diagnosis of an esophageal submucosal tumor during the preoperative assessment of a left lung cancer. The esophageal submucosal tumor arose in the left wall of the lower esophagus, and the patient was diagnosed as having a schwannoma by endoscopic ultrasound-guided fine needle aspiration. She underwent video-assisted thoracoscopic surgery for the simultaneous removal of both tumors. Her postoperative course was uneventful. Thoracoscopic surgery is less invasive than thoracotomy, and this allowed the patient to undergo simultaneous operations for two tumors.

DOI： 10.1111/ases.12643

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Language：Japanese   Publisher：日本消化器病学会-関東支部  

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BACKGROUND AND AIM: Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) presents as isolated proximal-type sclerosing cholangitis (i-SC). The present study sought to clarify the imaging differences between i-SC and Klatskin tumor. Differences between i-SC and IgG4-SC associated with autoimmune pancreatitis (AIP-SC) were also studied. METHODS: Differentiating factors between i-SC and Klatskin tumor were studied. Serum IgG4 level, CA19-9 level, computed tomography (CT) findings, cholangiography findings (symmetrical smooth long stricture extending into the upper bile duct [SSLS]), endosonographic features (continuous symmetrical mucosal lesion to the hilar part [CSML]), endoscopic biopsy results, treatment, relapse, and survival were also compared between patients with i-SC and those with AIP-SC. RESULTS: For a differential diagnosis between i-SC (N = 9) and Klatskin tumor (N = 47), the cut-off value of serum IgG4 level was 150 mg/dL (sensitivity, 0.857, specificity, 0.966). Logistic regression analysis indicated that serum IgG4 level, presence of SSLS, presence of CSML, and presence of swollen ampulla are independent factor for identifying i-SC. Relapse rate was significantly higher in the IgG4-SC with AIP group than in the i-SC group (log rank, P = 0.046). CONCLUSION: Isolated proximal-type sclerosing cholangitis presents as a nodular lesion with SSLS and/or CSML mimicking a Klatskin tumor. Those endoscopic features might provide a diagnostic clue for i-SC. i-SC is likely to have a more favorable prognosis than IgG4-SC with AIP.

DOI： 10.1111/den.13320

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OBJECTIVES: Intraductal papillary mucinous neoplasms (IPMNs) are precursor lesions of pancreatic adenocarcinoma. Artificial intelligence (AI) is a mathematical concept whose implementation automates learning and recognizing data patterns. The aim of this study was to investigate whether AI via deep learning algorithms using endoscopic ultrasonography (EUS) images of IPMNs could predict malignancy. METHODS: This retrospective study involved the analysis of patients who underwent EUS before pancreatectomy and had pathologically confirmed IPMNs in a single cancer center. In total, 3,970 still images were collected and fed as input into the deep learning algorithm. AI value and AI malignant probability were calculated. RESULTS: The mean AI value of malignant IPMNs was significantly greater than benign IPMNs (0.808 vs 0.104, P < 0.001). The area under the receiver operating characteristic curve for the ability to diagnose malignancies of IPMNs via AI malignant probability was 0.98 (P < 0.001). The sensitivity, specificity, and accuracy of AI malignant probability were 95.7%, 92.6%, and 94.0%, respectively; its accuracy was higher than human diagnosis (56.0%) and the mural nodule (68.0%). Multivariate logistic regression analysis showed AI malignant probability to be the only independent factor for IPMN-associated malignancy (odds ratio: 295.16, 95% confidence interval: 14.13-6,165.75, P < 0.001). DISCUSSION: AI via deep learning algorithm may be a more accurate and objective method to diagnose malignancies of IPMNs in comparison to human diagnosis and conventional EUS features.

DOI： 10.14309/ctg.0000000000000045

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The diagnosis of pancreatic cystic lesions remains challenging. This study aimed to investigate the diagnostic ability of carcinoembryonic antigen (CEA), cytology, and artificial intelligence (AI) by deep learning using cyst fluid in differentiating malignant from benign cystic lesions. We retrospectively reviewed 85 patients who underwent pancreatic cyst fluid analysis of surgical specimens or endoscopic ultrasound-guided fine-needle aspiration specimens. AI using deep learning was used to construct a diagnostic algorithm. CEA, carbohydrate antigen 19-9, carbohydrate antigen 125, amylase in the cyst fluid, sex, cyst location, connection of the pancreatic duct and cyst, type of cyst, and cytology were keyed into the AI algorithm, and the malignant predictive value of the output was calculated. Area under receiver-operating characteristics curves for the diagnostic ability of malignant cystic lesions were 0.719 (CEA), 0.739 (cytology), and 0.966 (AI). In the diagnostic ability of malignant cystic lesions, sensitivity, specificity, and accuracy of AI were 95.7%, 91.9%, and 92.9%, respectively. AI sensitivity was higher than that of CEA (60.9%, p = 0.021) and cytology (47.8%, p = 0.001). AI accuracy was also higher than CEA (71.8%, p < 0.001) and cytology (85.9%, p = 0.210). AI may improve the diagnostic ability in differentiating malignant from benign pancreatic cystic lesions.

DOI： 10.1038/s41598-019-43314-3

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Downregulation of lamin B1 has been recognized as a crucial step for development of full senescence. Accelerated cellular senescence linked to mechanistic target of rapamycin kinase (MTOR) signaling and accumulation of mitochondrial damage has been implicated in chronic obstructive pulmonary disease (COPD) pathogenesis. We hypothesized that lamin B1 protein levels are reduced in COPD lungs, contributing to the process of cigarette smoke (CS)-induced cellular senescence via dysregulation of MTOR and mitochondrial integrity. To illuminate the role of lamin B1 in COPD pathogenesis, lamin B1 protein levels, MTOR activation, mitochondrial mass, and cellular senescence were evaluated in CS extract (CSE)-treated human bronchial epithelial cells (HBEC), CS-exposed mice, and COPD lungs. We showed that lamin B1 was reduced by exposure to CSE and that autophagy was responsible for lamin B1 degradation in HBEC. Lamin B1 reduction was linked to MTOR activation through DEP domain-containing MTOR-interacting protein (DEPTOR) downregulation, resulting in accelerated cellular senescence. Aberrant MTOR activation was associated with increased mitochondrial mass, which can be attributed to peroxisome proliferator-activated receptor γ coactivator-1β-mediated mitochondrial biogenesis. CS-exposed mouse lungs and COPD lungs also showed reduced lamin B1 and DEPTOR protein levels, along with MTOR activation accompanied by increased mitochondrial mass and cellular senescence. Antidiabetic metformin prevented CSE-induced HBEC senescence and mitochondrial accumulation via increased DEPTOR expression. These findings suggest that lamin B1 reduction is not only a hallmark of lung aging but is also involved in the progression of cellular senescence during COPD pathogenesis through aberrant MTOR signaling.

DOI： 10.4049/jimmunol.1801293

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Organizing pneumonia (OP) and pulmonary alveolar proteinosis (PAP) are rare complications in patients with hematologic disorders. We herein report a case of PAP that developed during steroid treatment for OP in a patient with atypical chronic myeloid leukemia. Physicians should pay close attention to these complications in patients with hematologic malignancies.

DOI： 10.1002/ccr3.2014

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Fanconi anemia (FA) is a disorder of chromosomal fragility characterized by progression to aplastic anemia, myelodysplastic syndrome, and leukemia. FA patients are also predisposed to solid cancers. A case of FA in an adult patient who developed tongue and superficial esophageal cancers following hematopoietic stem cell transplantation is reported. This case was considered significant because it is the first reported case of superficial esophageal cancer in an FA patient that was treated successfully by endoscopic submucosal resection.

DOI： 10.2169/internalmedicine.1434-18

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BACKGROUND/OBJECTIVES: FOLFIRINOX is the reliable treatments for pancreatic cancer, but it has a relatively high toxicity and the selection of suitable patients for this regimen remains challenge. On the other hand, sarcopenia is one of the important prognostic factors of pancreatic cancer. The aim of this study was to investigate the effect of sarcopenia on overall survival (OS) and time to treatment failure (TTF) in patients with pancreatic cancer who received FOLFIRINOX. METHODS: Clinical data of consecutive patients treated with FOLFIRINOX at our institution from 2011 to 2017 was retrospectively reviewed. Skeletal muscle index (SMI) and adipose tissue index (ATI) at the third lumbar spine level was calculated from computed tomography (CT) images. The association between clinical factors (SMI and ATI), and OS and TTF were determined using univariate and multivariate analyses. RESULTS: We assessed 82 patients. The median OS of sarcopenia and the non-sarcopenia patients were 11.3 and 17.0 months, respectively (hazard ratio [HR], 2.49; 95% confidence interval [CI], 1.43-4.32; p = 0.001). Median TTF was 3.0 and 6.1 months in the sarcopenia and the non-sarcopenia patients, respectively (HR, 1.67; 95% CI, 1.03-2.71; p = 0.032). Multivariate analyses revealed that sarcopenia (HR, 1.37; 95% CI, 1.01-1.87; p = 0.045) was an independent prognostic factor of OS. High ATI (p = 0.022) and sarcopenic obesity (p = 0.008) were significantly associated with hematologic toxicity. CONCLUSIONS: Sarcopenia is an independent indicator of poor prognosis in patients with pancreatic cancer who received FOLFIRINOX, while ATI and sarcopenic obesity predicted severe hematologic toxicity.

DOI： 10.1016/j.pan.2018.11.001

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BACKGROUND: Since pancreatic steatosis is reported as a possible risk factor for pancreatic cancer, the development of a non-invasive method to quantify pancreatic steatosis is needed. Proton density fat fraction (PDFF) measurement is a magnetic resonance imaging (MRI) based method for quantitatively assessing the steatosis of a region of interest (ROI). Although it is commonly used for quantification of hepatic steatosis, pancreatic PDFF can greatly vary depending on the ROI's location because of the patchy nature of pancreatic fat accumulation. In this study, we attempted to quantify pancreatic steatosis by fat-water MRI with improved reproducibility. METHODS: Using the MRI images of 159 patients with nonalcoholic fatty liver disease, we attempted to calculate the average PDFF of whole pancreas. We set ROIs covering the entire area of the pancreas appearing in every slice and calculated the average PDFF from all the voxels included in the pancreas. We named this average value as whole-pancreatic PDFF and evaluated the reproducibility of the measured values. In addition to whole-pancreatic PDFF, we measured the average PDFF of the pancreatic head (head-PDFF) and that of the pancreatic body plus tail separately and analyzed their correlation with the clinical characteristics of the patients. RESULTS: The mean inter-examiner coefficient of variation of the whole-pancreatic PDFF was 11.39%. The whole-pancreatic PDFF was correlated with age (p = 0.039), body mass index (p = 0.0093) and presence/absence of diabetes (p = 0.0055). The serum level of low-density lipoprotein cholesterol was inversely correlated with the head-PDFF. CONCLUSION: We developed a new measurement method of the pancreatic PDFF with greater reproducibility. Using this method, we characterized pancreatic steatosis in detail. This novel measurement method allows accurate estimation of the severity of pancreatic steatosis and is therefore useful for the detailed characterization of pancreatic steatosis.

DOI： 10.1371/journal.pone.0224921

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A 20-year old man was diagnosed with fibrolamellar hepatocellular carcinoma (FLHCC) with multiple lung metastases, and chemotherapy with FOLFOX was administered. Contrast enhanced CT after 3 cycles of FOLFOX showed no disease progression. We therefore performed surgical resection and radiofrequency ablation of the liver lesions and lung metastases, after obtaining the patient's informed consent. The liver lesions and lung metastases tested positive for DNAJB1-PRKACA. The treatment for FLHCC with extrahepatic metastasis has not been established; however, in a few cases, good long-term prognoses were obtained with multidisciplinary therapy. We herein report a case of FLHCC with multiple lung metastases that was treated with multidisciplinary therapies.

DOI： 10.2169/internalmedicine.1243-18

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Aberrant pancreas is defined as pancreatic tissue present outside of the pancreas and is often found incidentally during esophagogastroduodenoscopy. Obtaining sufficient tissue to differentiate aberrant pancreas from other subepithelial lesions is sometimes difficult. Due to the lack of a definitive diagnosis, patients often undergo unnecessary surgery. We herein report the first case of aberrant pancreas in which the concomitant use of needle-based probe confocal laser endomicroscopy and fine-needle aspiration supported the final diagnosis. Needle-based probe confocal laser endomicroscopy provides a real-time in vivo histopathology evaluation and may be a feasible means of diagnosing aberrant pancreas.

DOI： 10.2169/internalmedicine.0449-17

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BACKGROUND: Postoperative pulmonary complications (PPC) in patients with pulmonary diseases remain to be resolved clinical issue. However, most evidence regarding PPC has been established more than 10 years ago. Therefore, it is necessary to evaluate perioperative management using new inhalant drugs in patients with obstructive pulmonary diseases. METHODS: April 2014 through March 2015, 346 adult patients with pulmonary diseases (257 asthma, 89 chronic obstructive pulmonary disease (COPD)) underwent non-pulmonary surgery except cataract surgery in our university hospital. To analyze the risk factors for PPC, we retrospectively evaluated physiological backgrounds, surgical factors and perioperative specific treatment for asthma and COPD. RESULTS: Finally, 29 patients with pulmonary diseases (22 asthma, 7 COPD) had PPC. In patients with asthma, smoking index (≥ 20 pack-years), peripheral blood eosinophil count (≥ 200/mm3) and severity (Global INitiative for Asthma(GINA) STEP ≥ 3) were significantly associated with PPC in the multivariate logistic regression analysis [odds ratio (95% confidence interval) = 5.4(1.4-20.8), 0.31 (0.11-0.84) and 3.2 (1.04-9.9), respectively]. In patients with COPD, age, introducing treatment for COPD, upper abdominal surgery and operation time (≥ 5 h) were significantly associated with PPC [1.18 (1.00-1.40), 0.09 (0.01-0.81), 21.2 (1.3-349) and 9.5 (1.2-77.4), respectively]. CONCLUSIONS: History of smoking or severe asthma is a risk factor of PPC in patients with asthma, and age, upper abdominal surgery, or long operation time is a risk factor of PPC in patients with COPD. Adequate inhaled corticosteroids treatment in patients with eosinophilic asthma and introducing treatment for COPD in patients with COPD could reduce PPCs.

DOI： 10.1186/s12890-017-0570-8

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

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BACKGROUND AND AIMS: The barrier function of the small intestinal mucosa prevents the introduction of undesired pathogens into the body. Breakdown of this barrier function increases intestinal permeability. This has been proposed to induce not only gastrointestinal diseases, including inflammatory bowel disease and irritable bowel syndrome, but also various other diseases, including allergies, diabetes mellitus, liver diseases, and collagen diseases, which are associated with this so called "leaky gut syndrome." As such, a method to prevent leaky gut syndrome would have substantial clinical value. However, no drugs have been demonstrated to improve disturbed intestinal permeability in humans to date. Therefore, we investigated whether a drug used to treat chronic constipation, lubiprostone, was effective for this purpose. METHODS: Healthy male volunteers were treated with lubiprostone (24 μg/day) for 28 days. Intestinal permeability was evaluated by measuring the lactulose-mannitol ratio (LMR) after administration of diclofenac and compared with an untreated group. The examination was conducted three times in total, i.e., at baseline before diclofenac administration and after 14 and 28 days of lubiprostone treatment. Blood endotoxin activity was also evaluated at the same time points. RESULTS: The final analysis was conducted on 28 subjects (14 in the lubiprostone group and 14 in the untreated group). The LMR after 28 days of treatment was significantly lower in the lubiprostone group than that in the untreated group (0.017 vs. 0.028, respectively; 95% confidence interval, -0.022--0.0001; p = 0.049). Blood endotoxin activity exhibited almost no change over time in the lubiprostone and untreated groups and displayed no significant differences at any time point of examination. CONCLUSIONS: This study is the first to report an improvement in leaky gut using an available drug in humans. The result suggests that lubiprostone may prevent and ameliorate "leaky gut syndrome". However, a pivotal trial is needed to confirm our finding.

DOI： 10.1371/journal.pone.0175626

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BACKGROUND: Malignant bowel obstruction affect a patient's quality of life, but, management of MBO is controversial. CASE PRESENTATION: A 51-year-old woman who had been diagnosed as uterine cervix cancer 2 years ago and had undergone surgery, chemotherapy and radiotherapy, was admitted to our hospital. She was diagnosed as having a recurrence of peritoneal metastasis and bowel obstruction. For her nasal pain, we considered insertion of a postpyloric decompression tube through the gastrostomy instead of via the nasal cavity. After insertion of a percutaneous gastrostomy tube was performed endoscopically, we introduced a postpyloric decompression tube through her gastrostomy. She could be discharged home, and 91 days later, she died in her home under hospice care, as she had wished. CONCLUSIONS: Insertion of a postpyloric decompression tube through a gastrostomy might be useful in the management of advanced cancer patients with bowel obstruction.

DOI： 10.1186/1756-0500-6-217

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

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

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Language：Japanese   Publisher：(一社)日本皮膚悪性腫瘍学会  

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

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

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Language：Japanese   Publisher：日本消化器病学会-関東支部  

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Language：Japanese  

J-GLOBAL

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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：横浜市立大学医学会  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2024&ichushi_jid=J01499&link_issn=&doc_id=20250124430009&doc_link_id=https%3A%2F%2Fycu.repo.nii.ac.jp%2Frecords%2F2003372&url=https%3A%2F%2Fycu.repo.nii.ac.jp%2Frecords%2F2003372&type=%E6%A8%AA%E6%B5%9C%E5%B8%82%E7%AB%8B%E5%A4%A7%E5%AD%A6%EF%BC%9A%E6%A8%AA%E6%B5%9C%E5%B8%82%E7%AB%8B%E5%A4%A7%E5%AD%A6%E5%AD%A6%E8%A1%93%E6%A9%9F%E9%96%A2%E3%83%AA%E3%83%9D%E3%82%B8%E3%83%88%E3%83%AA&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F80205_3.gif

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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Language：Japanese   Publisher：Japan Biliary Association  

In addition to endoscopic biliary drainage (EBD: Endoscopic Biliary Drainage), endoscopic ultrasound-guided biliary drainage (EUS-BD: EUS guided Biliary Drainage) is being performed mainly at high volume centers. Although both EBD and EUS-BD have been reported to have good success rates at high volume centers, they sometimes cause serious complications, so drainage should be performed with an understanding of how to prevent and deal with complications. In particular, EUS-BD should be performed by or under the supervision of a endoscopist who is familiar with biliary endoscopy and EUS.

DOI： 10.11210/tando.38.205

CiNii Research

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2024&ichushi_jid=J02149&link_issn=&doc_id=20240614280011&doc_link_id=10.11210%2Ftando.38.205&url=https%3A%2F%2Fdoi.org%2F10.11210%2Ftando.38.205&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

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

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

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

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

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

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

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

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

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

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

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

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

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

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Language：Japanese   Publisher：(株)日本メディカルセンター  

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Language：Japanese   Publisher：(株)日本メディカルセンター  

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J-GLOBAL

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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：医学図書出版(株)  

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

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

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

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

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

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

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

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

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

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Language：Japanese   Publisher：日本消化器病学会-関東支部  

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

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

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

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

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

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

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

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

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

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

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Language：Japanese   Publisher：(公社)日本婦人科腫瘍学会  

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

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

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

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Language：Japanese   Publisher：(公社)日本婦人科腫瘍学会  

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

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

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

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

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

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J00192&link_issn=&doc_id=20230629350002&doc_link_id=10.11280%2Fgee.65.1102&url=https%3A%2F%2Fdoi.org%2F10.11280%2Fgee.65.1102&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

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

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

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

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

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

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

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

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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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：(一財)日本消化器病学会  

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

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

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

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

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

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

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

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

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

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

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

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

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

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Language：Japanese   Publisher：日本消化器病学会-関東支部  

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

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Language：Japanese   Publisher：(株)日本メディカルセンター  

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Language：Japanese   Publisher：(株)南江堂  

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2022&ichushi_jid=J00974&link_issn=&doc_id=20220624060019&doc_link_id=issn%3D0022-1961%26volume%3D130%26issue%3D1%26spage%3D91&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0022-1961%26volume%3D130%26issue%3D1%26spage%3D91&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

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

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

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

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

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

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

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Language：Japanese   Publisher：日本消化器病学会-関東支部  

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

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J-GLOBAL

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J-GLOBAL

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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Language：Japanese   Publisher：日本消化器病学会-関東支部  

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

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Language：Japanese   Publisher：(株)日本メディカルセンター  

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

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

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

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

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

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

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

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J-GLOBAL

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J-GLOBAL

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

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

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

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

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

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Language：Japanese   Publisher：肝胆膵治療研究会  

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

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

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

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

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

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

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

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

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

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Language：Japanese   Publisher：(株)医学出版  

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Language：Japanese   Publisher：日本消化器病学会-関東支部  

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J-GLOBAL

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J-GLOBAL

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

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

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

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

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

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

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J02025&link_issn=&doc_id=20190729330004&doc_link_id=1390564238097312000&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390564238097312000&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

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

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

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

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Language：Japanese   Publisher：(一社)日本消化器がん検診学会  

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

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

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

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Language：Japanese   Publisher：日本消化器病学会-東海支部  

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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Language：Japanese   Publisher：(一社)日本消化器がん検診学会  

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

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

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

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

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

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

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

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

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J02025&link_issn=&doc_id=20170516130006&doc_link_id=%2Fcq0pancr%2F2017%2F003202%2F006%2F0168-0177%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcq0pancr%2F2017%2F003202%2F006%2F0168-0177%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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

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

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J-GLOBAL

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

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

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

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

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Language：Japanese   Publisher：日本胆道学会  

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

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

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Language：Japanese   Publisher：日本胆道学会