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

BACKGROUND AND AIMS: Gastroduodenal and biliary obstruction may occur synchronously or asynchronously in advanced pancreatic cancer, and endoscopic double stent placement may be required. EUS-guided biliary drainage (EUS-BD) often is performed after unsuccessful placement of an endoscopic transpapillary stent (ETS), and EUS-BD may be beneficial in double stent placement. This retrospective multicenter cohort study compared the outcomes of ETS placement and EUS-BD in patients with an indwelling gastroduodenal stent (GDS). METHODS: We recorded the clinical outcomes of patients at 5 tertiary-care medical centers who required biliary drainage after GDS placement between March 2009 and March 2014. RESULTS: Thirty-nine patients were included in this study. Patients' mean age was 68.5 years; 23 (59.0%) were men. The GDS overlay the papilla in 23 patients (59.0%). The overall technical success rate was significantly higher with EUS-BD (95.2%) than with ETS placement (56.0%; P < .01). Furthermore, the technical success rate was significantly higher with EUS-BD (93.3%) than with ETS placement (22.2%; P < .01) when the GDS overlies the papilla. The overall clinical success rate of EUS-BD also was significantly higher than for ETS placement (90.5% vs 52.0%, respectively; P = .01), and there was no significant difference in the incidence of adverse events (ETS, 32.0% vs EUS-BD, 42.9%; P = .65). CONCLUSION: Endoscopic double stent placement with EUS-BD is technically and clinically superior to ETS placement in patients with an indwelling GDS. EUS-BD should be considered the first-line treatment option for patients with an indwelling GDS that overlies the papilla. ETS placement remains a reasonable alternative when the papilla is not covered by the GDS.

DOI： 10.1016/j.gie.2018.01.021

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：S. Karger AG  

DOI： 10.1159/000481237

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MOSBY-ELSEVIER  

BACKGROUND AND AIMS: Endoscopic gastroduodenal stenting for malignant gastric outlet obstruction recently has become more effective, but the factors that predict gastroduodenal stenting outcomes are poorly defined. This multicenter retrospective cohort study evaluated the clinical outcomes of gastroduodenal stenting in malignant gastroduodenal obstruction and identified factors predicting clinical ineffectiveness, stent dysfunction, and adverse events. METHODS: All consecutive patients with malignant gastroduodenal obstruction who underwent through-the-scope gastroduodenal stenting from 2009 to 2014 at 4 tertiary-care medical centers were identified. Clinically ineffective stenting was defined as symptom recurrence and a gastric outlet obstruction scoring system (GOOSS) score <2. RESULTS: Of the 278 patients (mean age ± standard deviation [SD] 71.7 ± 11.4 years), 121 (43.5%) and 87 (31.3%) had pancreatic and gastric cancer, respectively. Technical success was achieved in 277 patients (99.6%). GOOSS scores rose from 0.5 ± 0.6 to 2.6 ± 0.8. Stenting was ineffective in 32 patients (12.6%). Stent dysfunction that caused symptom recurrence during follow-up developed in 46 patients (16.6%). Adverse events occurred in 49 patients (17.7%). Three or more stenosis sites (odds ratio [OR] = 6.11; P < .01) and Karnofsky performance scores ≤50 (OR = 6.63; P < .01) predicted clinical ineffectiveness. Karnofsky performance scores ≤50 predicted stent dysfunction (hazard ratio [HR] = 3.63; P < .01). Bile duct stenosis (HR = 9.55; P = .02) and liver metastasis (HR = 9.42; P < .01) predicted stent overgrowth. Covered stent predicted stent migration (HR = 12.63; P < .01). Deployment of 2 stents predicted perforation (HR = 854.88; P < .01). CONCLUSIONS: Through-the-scope gastroduodenal stenting tended to be ineffective in patients with poor performance status and long stenosis sites. Stent dysfunction occurred more frequently in patients with poorer performance status. Deployment of 2 stents was a risk factor for perforation. Identification of these risk variables may help yield better gastroduodenal stenting outcomes.

DOI： 10.1016/j.gie.2016.03.1498

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Language：English   Publisher：GEORG THIEME VERLAG KG  

DOI： 10.1055/s-0034-1393649

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Language：Japanese   Publisher：Japan Pancreas Society  

<p>One characteristic of pancreatic cancer, considered incurable, is fibrosis in the interstitium and associated tissue sclerosis. Tissue stiffness is known to induce increased intrastromal pressure and vascular collapse, inhibiting the penetration of anticancer drugs into the interstitium with delivery to cancer cells. Cancer-associated fibroblasts (CAFs) play a central role in the development of fibrosis in the stroma. Various therapies targeting CAFs have been developed but have not yet been successful. In this study, we demonstrated that inducing the expression of Meflin, a marker and functional molecule of tumor suppressive CAFs, in CAFs improves the sensitivity to chemotherapy of pancreatic cancer. Furthermore, a compound library screening revealed that AM80, a synthetic retinoid, effectively induces the expression of Meflin in CAFs and improves sensitivity to chemotherapy with improved drug delivery. Based on these results, the authors are conducting a clinical trial of AM80 in combination with conventional anticancer agents to treat patients with unresectable pancreatic cancer to evaluate the efficacy of AM80.</p>

DOI： 10.2958/suizo.38.37

CiNii Research

Language：English   Publisher：Journal of Gastroenterology and Hepatology (Australia)  

Background and Aim: Double-balloon endoscopic retrograde cholangiography (DBERC) is a valuable procedure for patients with altered gastrointestinal anatomy. Nonetheless, it is time-consuming and burdensome for both patients and endoscopists, partly because route selection in the reconstructed bowel with complicating loop is challenging. Carbon dioxide insufflation enterography is reportedly useful for route selection in the blind loop. This prospective randomized clinical trial investigated the usefulness of carbon dioxide insufflation enterography for route selection by comparing it with conventional observation. Methods: Patients scheduled to undergo DBERC were consecutively registered. They were divided into carbon dioxide insufflation enterography and conventional groups via randomization according to stratification factors, type of reconstruction methods, and experience with DBERC. The primary endpoint was the correct rate of initial route selection. The secondary endpoints were the insertion time, examination time, amount of anesthesia drugs, and complications. Results: The correct rate of route selection was significantly higher in the carbon dioxide insufflation enterography group (23/25, 92%) than in the visual method (15/25, 60%) (P = 0.018). The insertion time was significantly shorter in the carbon dioxide insufflation enterography group than in the visual group (10.8 ± 11.1 min vs 29.8 ± 15.7 min; P < 0.001). No significant differences in complications were noted between the two groups. The amounts of sedatives and analgesics used were significantly lower in the carbon dioxide insufflation enterography group (P < 0.001 and P < 0.001, respectively). Conclusions: Carbon dioxide insufflation enterography can reduce the burden of DBERC on patients and endoscopists by shortening the examination time and reducing the amount of medication.

DOI： 10.1111/jgh.16112

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Publisher：日本メディカルセンター  

DOI： 10.19020/cg.0000002511

CiNii Research

Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media SA  

Background

Pancreatic neuroendocrine carcinoma (PanNEC) is a rare disease entity with rapid progression and poor prognosis. Here, we report a PanNEC case with unique morphological features mimicking intraductal papillary mucinous carcinoma.

Case presentation

A 69-year-old Japanese man was referred to our hospital for further evaluation of weight loss and deterioration of diabetes mellitus. Contrast-enhanced computed tomography showed a solid and cystic mass with hypo-enhancement at the tail of the pancreas. The main pancreatic duct (MPD) was diffusely dilated without obstruction, accompanied by marked parenchymal atrophy. Multiple peritoneal and omental nodules were observed, suggesting tumor dissemination. Endoscopic retrograde cholangiopancreatography revealed that the mass correlated with the dilated MPD. During pancreatography, a large amount of mucus was extruded from the pancreatic orifice of the ampulla. Based on these imaging findings, intraductal papillary mucinous carcinoma was suspected. Per-oral pancreatoscopy (POPS)-guided tumor biopsies were conducted for the lesion's solid components. Histopathological examination of the biopsied material confirmed small-cell-type PanNEC with a Ki-67 labeling index of 90%. Due to his condition's rapid decline, the patient was given the best supportive care and died 28 days after diagnosis.

Conclusion

Although rare, PanNEC, which correlates with the MPD and is accompanied by marked dilation of the MPD, does exist as one phenotype. In such cases, POPS-guided biopsy could be a useful diagnostic modality.

DOI： 10.3389/fmed.2022.951834

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Background/Aims: Bispectral index (BIS) monitors process and display electroencephalographic data and are used to assess the depth of anesthesia. This study retrospectively evaluated the usefulness of BIS monitoring during endoscopic ultrasonography (EUS). Methods: This study included 725 consecutive patients who underwent EUS under sedation with propofol. BIS monitoring was used in 364 patients and was not used in 361. The following parameters were evaluated: (1) median dose of propofol; (2) respiratory and circulatory depression; (3) occurrence of body movements; (4) awakening score >8 at the time; and (5) awakening score 2 hours after leaving the endoscopy room. Results: The BIS group received a significantly lower median dose of propofol than the non-BIS group (159.2 mg vs. 167.5 mg; p=0.015) in all age groups. For patients aged ≥75 years, the reduction in heart rate was significantly lower in the BIS group than in the non-BIS group (1.2% vs. 9.1%; p=0.023). Moreover, the occurrence of body movements was markedly lower in the BIS group than in the non-BIS group (8.5% vs. 39.4%; p<0.001). Conclusions: During EUS examination, BIS monitoring is useful for maintaining a constant depth of anesthesia, especially in patients 75 years of age or older.

DOI： 10.5946/ce.2022.001

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Background: The value of contrast-enhanced harmonic EUS (CH-EUS) for diagnosis of portal vein invasion in patients with pancreatic cancer was evaluated. Patients and Methods: This single-center, retrospective study included consecutive patients with pancreatic cancer who underwent both surgical resection after preoperative EUS, CH-EUS, and contrast-enhanced computed tomography (CE-CT) examinations between April 2015 and August 2017. CH-EUS evaluation was performed during the late phase. Portal vein invasion on EUS and CH-EUS was defined as no continuity in the line of the vessel wall. Definition of portal vein invasion on CE-CT was based on the Loyer's criteria. The accuracy of three modalities for diagnosis of invasion into the portal vein was compared using the McNemar's test. Results: Eighty-eight patients (mean age: 71.0 years, ratio of male to female: 48:40) were eligible. Postoperative pathological results were as follows: seven cases of portal vein invasion; 81 cases without. Diagnostic accuracy of EUS, CH-EUS, and CE-CT for diagnosing invasion into the portal vein was 72.7%, 93.2%, and 81.8%, respectively. The differences between CH-EUS and CE-CT (P = 0.0094) and CH-EUS and EUS (P = 0.0022) were significant. EUS and CE-CT were comparable. Conclusion: CH-EUS is useful for diagnosis of portal vein invasion by pancreatic cancer.

DOI： 10.4103/EUS-D-21-00185

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Language：English   Publisher：Canadian Journal of Gastroenterology and Hepatology  

Background. There is a need for a more tolerable preoperative biliary drainage (PBD) method for perihilar cholangiocarcinoma (PHCC). In recent years, inside stents (ISs) have attracted attention as a less suffering PBD method. Few studies have compared IS with a fully covered self-expandable metallic stent (FCSEMS) as PBD for resectable PHCC. The aim of this study is to compare them. Methods. This study involved 86 consecutive patients (IS: 51; FCSEMS: 35). The recurrent biliary obstruction (RBO) rate until undergoing surgery or being diagnosed as unresectable, time to RBO, factors related to RBO, incidence of adverse events related to endoscopic retrograde cholangiography, and postoperative complications associated with each stent were evaluated retrospectively. Results. There was no significant difference between the two groups in the incidence of adverse events after stent insertion. After propensity score matching, the mean (SD) time to RBO was 37.9 (30.2) days in the IS group and 45.1 (35.1) days in the FCSEMS group, with no significant difference (P=0.912, log-rank test). A total of 7/51 patients in the IS group and 3/35 patients in the FCSEMS group developed RBO. The only risk factor for RBO was bile duct obstruction of the future excisional liver lobe(s) due to stenting (HR 29.8, P=0.008) in the FCSEMS group, but risk factors could not be indicated in the IS group. There was no significant difference in the incidence of bile leakage or liver failure. In contrast, pancreatic fistula was significantly more common in the FCSEMS group (13/23 patients) than in the IS group (3/28 patients) (P<0.001), especially in patients who did not undergo pancreatectomy (P=0.001). Conclusions. As PBD, both IS and FCSEMS achieved low RBO rates. Compared with FCSEMS, IS shows no difference in RBO rate, is associated with fewer postoperative complications, and is considered an appropriate means of PBD for resectable PHCC. This trail is registered with UMIN000025631.

DOI： 10.1155/2022/3005210

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Language：English   Publisher：BMC Gastroenterology  

Background: The pathological evaluation of tissues with cholangitis is considered difficult, which can often occur after endoscopic sphincterotomy (EST) and endoscopic biliary stenting (EBS). This study aimed to evaluate the influence of a history of EST and EBS on the sensitivity of transpapillary forceps bile duct biopsy (TB) for bile duct adenocarcinoma. Methods: This retrospective study included consecutive cases of bile duct adenocarcinoma in which TB was performed before July 2020 until the number exceeded that required to support statistical and noninferiority analyses of the sensitivity of TB between patients with and without each variable. The incidence of postprocedural adverse events related to each factor was also investigated. Results: Overall, 280 samples were required in each group, and 437 subjects (792 samples) were included. The sensitivity of TB was 63.6% for the subjects and 59.6% for the biopsy samples. For the biopsy samples, the sensitivity did not differ significantly between samples from patients with and without a history of EST (59.1% vs. 58.9%, P = 0.952) and EBS (62.1% vs. 55.4%, P = 0.065). The sensitivity was significantly higher for samples from patients with jaundice (67.9% vs. 57.0%, P = 0.008). There were significantly fewer procedure-related adverse events in patients with a history of EST (10.8% vs. 19.0%, P = 0.017) and EBS (12.0% vs. 21.7%, P = 0.005). Conclusions: A history of EST or EBS did not influence sensitivity of TB but significantly decreased the incidence of adverse events. To safely and reliably perform TB to diagnose bile duct adenocarcinoma, planning, including for EST and EBS, is necessary.

DOI： 10.1186/s12876-022-02402-x

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Language：Japanese   Publisher：(株)南江堂  

＜文献概要＞▼膵がんは予後不良ながん腫であり,その改善のためには早期診断・早期治療が必須である.▼早期膵がんを疑う画像所見としては「尾側膵管拡張を伴う限局性主膵管狭窄」がその代表である.しかしながらこの所見は慢性膵炎などの良性膵疾患でも認められる.▼近年,早期膵がん症例のCTにおける「主膵管狭窄部周囲の限局性膵実質萎縮」が良悪性診断に有用との報告が散見される.この所見を認めた場合は早期膵がんの可能性を考慮し,胆膵専門医へ紹介することが推奨される.

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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=20220624060014&doc_link_id=10.15106%2Fj_naika130_69&url=https%3A%2F%2Fdoi.org%2F10.15106%2Fj_naika130_69&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

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

Objectives: The endoscopic bilateral stent-in-stent (SIS) deployment is a challenging procedure. Such difficulty is mainly caused by sticking of the tip of the delivery sheath into the self-expandable metal stents (SEMSs) mesh, requiring an additional dilating procedure. Herein, we assessed the clinical results of using cross-wired metal stent for endoscopic bilateral SIS deployment (BONASTENT M-Hilar) in patients with malignant hilar biliary obstruction (MHBO) in both high-volume and non-high-volume centers. Methods: We prospectively enrolled consecutive patients with MHBO between February 2016 and December 2018 at eight centers. Results: Forty-six patients were enrolled during the study period. The proportions of technical success were 93.5% (43/46) and clinical success (CS) on intention-to-treat and per-protocol analyses were 91.3% (42/46) and 93.0% (40/43), respectively. The proportion of an additional dilating procedure during the primary procedure was 50.0% (23/46). Recurrent biliary obstruction (RBO) on intention-to-treat analysis occurred in 32.6% (15/46) of cases. Almost all of the events were caused by stent ingrowth (14/15). The median survival time and time to RBO were 255 and 349 days, respectively. The probability of stent patency at 3, 6, and 12 months was 86.5%, 63.9%, and 47.6%, respectively. Conclusions: The cross-wired metal stent had excellent technical and CS, although non-high-volume centers were included in this study (UMIN000021441).

DOI： 10.1002/deo2.20

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/deo2.20

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DOI： 10.3390/jcm11061705

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DOI： 10.1111/jgh.15780

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1007/s00464-021-08637-1

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Other Link： https://link.springer.com/article/10.1007/s00464-021-08637-1/fulltext.html

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

Due to the tendency of gastric linitis plastica (GLP) to cause extensive submucosal infiltration, a superficial endoscopic biopsy sometimes yields no evidence of malignancy, hindering definite diagnosis. The present study was a single-center retrospective analysis of 54 consecutive patients diagnosed with GLP between 2016 and 2020 to evaluate EUS-guided fine-needle aspiration (EUS-FNA) biopsy outcomes in patients with negative endoscopic biopsy findings. A pathological GLP diagnosis was achieved by endoscopic biopsy in 40 patients (74.1%). EUS-FNA biopsy with a 22-gauge needle was performed in 13 of the remaining 14 patients, and GLP diagnosis was confirmed in 10 patients, with a median of three needle passes. The remaining four patients were laparoscopically diagnosed with GLP. The diagnostic ability of EUS-FNA biopsy for GLP was 76.9%, and EUS-FNA biopsy contributed to GLP diagnosis in 18.5% (10/54) of all cases. None of the 13 patients exhibited EUS-FNA biopsy-related adverse events. Univariable and multivariable analyses revealed an absence of superficial ulcerations as a predictor of false-negative endoscopic biopsy findings in patients with GLP. These results suggest EUS-FNA biopsy as a minimally invasive and safe alternative diagnostic modality for GLP in cases where conventional endoscopic biopsy fails to verify malignancy, although prospective studies with larger cohorts are warranted to confirm these findings.

DOI： 10.3390/jcm10163716

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BACKGROUND AND AIMS: Pancreatic neuroendocrine neoplasms (PanNENs), including Grade 1 (G1) or G2 tumors, can have a poor prognosis. This study investigated the value of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) for predicting the prognosis of PanNENs. METHODS: This single-center, retrospective study included 47 consecutive patients who underwent CH-EUS and were diagnosed with PanNEN by surgical resection or EUS-guided fine needle aspiration between December 2011 and February 2016. Patients were divided into aggressive and non-aggressive groups according to the degree of clinical malignancy. CH-EUS was assessed regarding its capacity for diagnosing aggressive PanNEN, the correspondence between contrast patterns and pathological features, and its ability to predict the prognosis of PanNEN. RESULTS: There were 19 cases of aggressive PanNEN and 28 cases of non-aggressive PanNEN. The aggressive group included three G1, four G2, three G3 tumors, three mixed neuroendocrine non-neuroendocrine neoplasms, and six neuroendocrine carcinomas. CH-EUS was superior to contrast-enhanced computed tomography for the diagnosis of aggressive PanNEN (P < 0.001): hypo-enhancement on CH-EUS was an indicator of aggressive PanNEN, with sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 94.7%, 100%, 100%, 96.6%, and 97.9%, respectively. Among G1/G2 PanNENs, cases with hypo-enhancement on CH-EUS had a poorer prognosis than those with hyper/iso-enhancement (P = 0.0009). Assessment of 36 resected specimens showed that hypo-enhancement on CH-EUS was associated with smaller and fewer vessels and greater degree of fibrosis. CONCLUSION: Contrast-enhanced harmonic endoscopic ultrasonography may be useful for predicting the prognosis of PanNENs.

DOI： 10.1111/den.13862

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Unsuccessful stent replacement in transpapillary biliary drainage with plastic stents (PSs) has a significant impact on patient prognosis; thus, a safe and reliable replacement method is required. We aimed to compare the snare-over-the-guidewire (SOG) method, wherein the PS lumen is used as an access route to the biliary tract and the PS is removed with a snare inserted via the inserted guidewire, with the conventional side-of-stent (SOS) method, wherein the biliary approach is performed from the side of the PS. This retrospective single-center study included 244 consecutive patients who underwent biliary PS replacement between January 2018 and July 2020. The procedural success rates were compared between the two methods. A predictive analysis of unsuccessful PS replacement was also performed. The procedural success rate in the SOG group was significantly higher than that in the SOS group (p = 0.026). In the proximal biliary stenosis lesion, the same trend was observed (p = 0.025). Multivariate analysis also showed that the SOS method (p = 0.0038), the presence of proximal biliary stenosis (p < 0.0001), and parapapillary diverticulum (p = 0.0007) were predictors of unsuccessful PS replacement. The SOG method may be useful for biliary PS replacement, especially in cases of proximal hilar bile duct stenosis.

DOI： 10.3390/jcm10132858

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OBJECTIVES: The transpapillary drainage by endoscopic retrograde cholangiopancreatography (ERCP-D) cannot be performed without fluoroscopy, and there are many situations in which fluoroscopy is required even in endoscopic ultrasound-guided drainage (EUS-D). Previous studies have compared the efficacy, but not the radiation exposure of EUS-D and ERCP-D. While radiation exposure in ERCP-D has been previously evaluated, there is a paucity of information regarding radiation doses in EUS-D. This study aimed to assess radiation exposure in EUS-D compared with that in ERCP-D. METHODS: This retrospective single-center cohort study included consecutive patients who underwent EUS-D and ERCP-D between October 2017 and March 2019. The air kerma (AK: mGy), kerma-area product (KAP: Gycm2 ), fluoroscopy time (FT: min), and procedure time (PT: min) were assessed. The invasive probability weighting method was used to qualify the comparisons. RESULTS: We enrolled 372 and 105 patients who underwent ERCP-D and EUS-D, respectively. The mean AK, KAP, and FT in the EUS-D group were higher by 53%, 28%, and 27%, respectively, than those in the ERCP-D group, whereas PT was shorter by approximately 11% (AK; 135.0 vs. 88.4, KAP; 28.1 vs. 21.9, FT; 20.4 vs. 16.0, PT; 38.7 vs. 43.5). The sub-analysis limited to biliary drainage cases showed the same trend (AK; 128.3 vs. 90.9, KAP; 27.0 vs. 22.2, FT; 16.4 vs. 16.1, PT; 32.5 vs. 44.4). CONCLUSIONS: This is the first study to assess radiation exposure in EUS-D compared with that in ERCP-D. Radiation exposure was significantly higher in EUS-D than in ERCP-D, despite the shorter procedure time.

DOI： 10.1111/den.14060

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This study aimed to investigate whether the incorporation of contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) into the international consensus guidelines (ICG) for the management of intraductal papillary mucinous neoplasm (IPMN) could improve its malignancy diagnostic value. In this single-center retrospective study, 109 patients diagnosed with IPMN who underwent preoperative CH-EUS between March 2010 and December 2018 were enrolled. We analyzed each malignancy diagnostic value (sensitivity (Se), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV)) by replacing fundamental B-mode EUS with CH-EUS as the recommended test for patients with worrisome features (WF) (the CH-EUS incorporation ICG) and comparing the results to those obtained using the 2017 ICG. The malignancy diagnostic values as per the 2017 ICG were 78.9%, 42.3%, 60.0%, and 64.7% for Se, Sp, PPV, and NPV, respectively. The CH-EUS incorporation ICG plan improved the malignancy diagnostic values (Se 78.9%/Sp, 53.8%/PPV, 65.2%/NPV 70.0%). CH-EUS may be useful in determining the appropriate treatment strategies for IPMN.

DOI： 10.3390/jcm10091818

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DOI： 10.1053/j.gastro.2021.03.056

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Pancreatic ductal adenocarcinoma (PDAC) arises from precursor lesions, such as pancreatic intra-epithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN). The prognosis of high-grade precancerous lesions, including high-grade PanIN and high-grade IPMN, without invasive carcinoma is good, despite the overall poor prognosis of PDAC. High-grade PanIN, as a lesion preceding invasive PDAC, is therefore a primary target for intervention. However, detection of localized high-grade PanIN is difficult when using standard radiological approaches. Therefore, most studies of high-grade PanIN have been conducted using specimens that harbor invasive PDAC. Recently, imaging characteristics of high-grade PanIN have been revealed. Obstruction of the pancreatic duct due to high-grade PanIN may induce a loss of acinar cells replaced by fibrosis and lobular parenchymal atrophy. These changes and additional inflammation around the branch pancreatic ducts (BPDs) result in main pancreatic duct (MPD) stenosis, dilation, retention cysts (BPD dilation), focal pancreatic parenchymal atrophy, and/or hypoechoic changes around the MPD. These indirect imaging findings have become important clues for localized, high-grade PanIN detection. To obtain pre-operative histopathological confirmation of suspected cases, serial pancreatic-juice aspiration cytologic examination is effective. In this review, we outline current knowledge on imaging characteristics of high-grade PanIN.

DOI： 10.3390/cancers13050945

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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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BACKGROUND: Pancreatic pleural effusion and ascites are defined as fluid accumulation in the thoracic and abdominal cavity, respectively, due to direct leakage of the pancreatic juice. They usually occur in patients with acute or chronic pancreatitis but are rarely associated with pancreatic neoplasm. We present here an extremely rare case of pancreatic neuroendocrine tumor with stenosis of the main pancreatic duct, leading to pancreatic pleural effusion. CASE PRESENTATION: A 51-year-old man complained of dyspnea. Left-sided pleural effusion was detected on the chest X-ray. Pleural puncture was performed, and the pleural fluid indicated a high amylase content (36,854 IU/L). Hence, the patient was diagnosed with pancreatic pleural effusion. Although no tumor was detected, the computed tomography (CT) scan showed a pseudocyst and dilation of the main pancreatic duct in the pancreatic tail. Magnetic resonance cholangiopancreatography showed a fistula from the pseudocyst into the left thoracic cavity. Endoscopic retrograde pancreatic drainage was attempted; however, it failed due to stenosis in the main pancreatic duct in the pancreatic body. Endoscopic ultrasound revealed a hypoechoic mass measuring 15 × 15 mm in the pancreatic body that was not enhanced in the late phase of contrast perfusion and was thus suspected to be an invasive ductal carcinoma. The patient underwent distal pancreatectomy with splenectomy and the postoperative course was uneventful. Histopathological examination confirmed a neuroendocrine tumor of the pancreas (NET G2). The main pancreatic duct was compressed by the tumor. Increased pressure on the distal pancreatic duct by the tumor might have caused formation of the pseudocyst and pleural effusion. To the best of our knowledge, this is the first case report of pancreatic pleural effusion associated with a neuroendocrine tumor. CONCLUSIONS: Differential diagnosis of a pancreatic neoplasm should be considered, especially when a patient without a history of pancreatitis presents with pleural effusion.

DOI： 10.1186/s40792-020-00987-7

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IgG4-related disease (IgG4-RD) is a multi-organ autoimmune disease characterized by elevated serum IgG4 concentration. Although serum IgG4 concentration is widely used as a biomarker for IgG4-RD and type 1 autoimmune pancreatitis (AIP), a pancreatic manifestation of IgG4-RD, a significant number of patients have normal serum IgG4 levels, even in the active phase of the disease. Recently, we reported that the development of experimental AIP and human type 1 AIP is associated with increased expression of IFN-α and IL-33 in the pancreas. In this study, we assessed the utility of serum IFN-α and IL-33 levels as biomarkers for type 1 AIP and IgG4-RD. Serum IFN-α and IL-33 concentrations in patients who met the diagnostic criteria for definite type 1 AIP and/or IgG4-RD were significantly higher than in those with chronic pancreatitis or in healthy controls. Strong correlations between serum IFN-α, IL-33, and IgG4 concentrations were observed. Diagnostic performance of serum IFN-α and IL-33 concentrations as markers of type 1 AIP and/or IgG4-RD was comparable to that of serum IgG4 concentration, as calculated by the receiver operating characteristic curve analysis. Induction of remission by prednisolone treatment markedly decreased the serum concentration of these cytokines. We conclude that serum IFN-α and IL-33 concentrations can be useful as biomarkers for type 1 AIP and IgG4-RD.

DOI： 10.1038/s41598-020-71848-4

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DOI： 10.1016/j.vgie.2020.04.015

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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：(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)日本膵臓学会  

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Language：Japanese   Publisher：PLoS ONE  

Despite recent advances in clinical treatment, pancreatic cancer remains a highly lethal malignancy. In order to improve the survival rate of patients with pancreatic cancer, the development of non-invasive diagnostic methods using effective biomarkers is urgently needed. Here, we developed a highly sensitive method to detect DNA methylation in cellfree (cf)DNA samples based on the enrichment of methyl-CpG binding (MBD) protein coupled with a digital PCR method (MBD-ddPCR). Five DNA methylation markers for the diagnosis of pancreatic cancer were identified through DNA methylation microarray analysis in 37 pancreatic cancers. The sensitivity and specificity of the five markers were validated in another independent cohort of pancreatic cancers (100% and 100%, respectively; n = 46) as well as in The Cancer Genome Atlas data set (96% and 90%, respectively; n = 137). MBD-ddPCR analysis revealed that DNA methylation in at least one of the five markers was detected in 23 (49%) samples of cfDNA from 47 patients with pancreatic cancer. Further, a combination of DNA methylation markers and the KRAS mutation status improved the diagnostic capability of this method (sensitivity and specificity, 68% and 86%, respectively). Genome-wide MBD-sequencing analysis in cancer tissues and corresponding cfDNA revealed that more than 80% of methylated regions were overlapping; DNA methylation profiles of cancerous tissues and cfDNA significantly correlated with each other (R = 0.97). Our data indicate that newly developed MBD-ddPCR is a sensitive method to detect cfDNA methylation and that using five marker genes plus KRAS mutations may be useful for the detection of pancreatic cancers.

DOI： 10.1371/journal.pone.0233782

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Language：Japanese   Publisher：Diseases of the Esophagus  

Page 4 Left 38th line (original) On magnified observation of NBI, when we observe the lesion at maximum magnification, the length of the corner of the screen is about 0.5 mm, and the length of one side is about 3 mm (Fig. 3).Using this standard, the size of the AVA can be estimated. (revised) On magnified observation of NBI, when we observe the lesion at maximum magnification, the length of one side is about 3 mm, and the length of the corner of the screen is about 0.5 mm (Fig. 3).Using this standard, the size of the AVA can be estimated. Page 4 Right Fig 3. figure legend (original) Fig 3. Estimate the size of AVA. In magnified observation of NBI, when we observe the lesion by the maximum magnification, the length of the corner of the screen is about 0.5mm[A], and the length of one side is about 3mm [B]. Using this standard, we can estimate the size of AVA. (1 scale is equivalent to 1mm.). NBI, narrow band images; AVA, avascular area. (revised) Fig 3. Estimate the size of AVA. On magnified observation of NBI, when we observe the lesion at maximum magnification, the length of one side is about 3 mm [A], and the length of the corner of the screen is about 0.5 mm [B]. Using this standard, the size of the AVA can be estimated. (1 scale is equivalent to 1mm.). NBI, narrow band images; AVA, avascular area.

DOI： 10.1093/dote/doaa040

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

DOI： 10.1016/j.gie.2020.06.051

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DOI： 10.1055/a-1107-2629

PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Internal Medicine  

DOI： 10.2169/internalmedicine.3958-19

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BACKGROUND: Although several techniques for endoscopic ultrasound-guided biliary drainage (EUS-BD) are available at present, an optimal treatment algorithm of EUS-BD has not yet been established. AIM: To evaluate the clinical utility of treatment method conversion during single endoscopic sessions for difficult cases in initially planned EUS-BD. METHODS: This was a single-center retrospective analysis using a prospectively accumulated database. Patients with biliary obstruction undergoing EUS-BD between May 2008 and April 2016 were included. The primary outcome was to evaluate the improvement in EUS-BD success rates by converting the treatment methods during a single endoscopic session. Secondary outcomes were clarification of the factors leading to the conversion from the initial EUS-BD and the assessment of efficacy and safety of the conversion as judged by technical success, clinical success, and adverse events (AEs). RESULTS: A total of 208 patients underwent EUS-BD during the study period. For 18.8% (39/208) of the patients, the treatment methods were converted to another EUS-BD technique from the initial plan. Biliary obstruction was caused by pancreatobiliary malignancies, other malignant lesions, biliary stones, and other benign lesions in 22, 11, 4, and 2 patients, respectively. The reasons for the difficulty with the initial EUS-BD were classified into the following 3 procedures: Target puncture (n = 13), guidewire manipulation (n = 18), and puncture tract dilation (n = 8). Technical success was achieved in 97.4% (38/39) of the cases and clinical success was achieved in 89.5% of patients (34/38). AEs occurred in 10.3% of patients, including bile leakage (n = 2), bleeding (n = 1), and cholecystitis (n = 1). The puncture target and drainage technique were altered in subsequent EUS-BD procedures in 25 and 14 patients, respectively. The final technical success rate with 95%CI for all 208 cases was 97.1% (95%CI: 93.8%-98.9%), while that of the initially planned EUS-BD was 78.8% (95%CI: 72.6%-84.2%). CONCLUSION: Among multi-step procedures in EUS-BD, guidewire manipulation appeared to be the most technically challenging. When initially planned EUS-BD is technically difficult, treatment method conversion in a single endoscopic session may result in successful EUS-BD without leading to severe AEs.

DOI： 10.3748/wjg.v26.i9.947

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

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

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BACKGROUND: Balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography (BE-ERCP) has been reported to be effective for patients with surgically altered gastrointestinal anatomy. However, selective biliary cannulation remains difficult in BE-ERCP. We examined the usefulness of a modified double-guidewire technique using an uneven double lumen cannula (the uneven method) for BE-ERCP in patients with surgically altered gastrointestinal anatomy. METHODS: To clarify the usefulness of the uneven method for selective biliary cannulation in BE-ERCP in comparison to the pancreatic guidewire (PGW) method, 40 patients with surgically altered gastrointestinal anatomy who underwent BE-ERCP with successful placement of a guidewire in the pancreatic duct were evaluated. The uneven method was used in 18 cases (uneven group) and the PGW method was used in the remaining 22 cases (PGW group). RESULTS: The technical success rate of biliary cannulation was higher in the uneven group than in the PGW group (83.3 vs. 59.0%; P = 0.165). In addition, the time to biliary cannulation were significantly shorter in the uneven group than in the PGW group (6 vs. 18 min; P = 0.004; respectively). In the PGW group, post-ERCP pancreatitis (PEP) occurred in 3 of 22 cases (13.6%). No adverse events, including PEP, occurred in the uneven group. CONCLUSIONS: The uneven method may be a useful option of selective biliary cannulation in BE-ERCP for the patients with surgically altered gastrointestinal anatomy.

DOI： 10.1007/s00464-019-07228-5

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DOI： 10.5946/ce.2019.204

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DOI： 10.1055/a-1032-8272

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DOI： 10.19020/cg.0000000968

CiNii Research

J-GLOBAL

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

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DOI： 10.1016/j.gie.2019.03.1193

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DOI： 10.1016/j.gie.2019.03.1247

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DOI： 10.1055/a-0858-9831

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DOI： 10.1016/j.gie.2019.03.1006

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DOI： 10.1016/j.gie.2019.03.217

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DOI： 10.1016/j.gie.2019.03.1041

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DOI： 10.1055/a-0890-3220

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DOI： 10.11405/nisshoshi.116.1053

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Immunotherapy targeting programmed cell death-1 (PD-1) signaling is becoming the standard of care for advanced gastric cancer. We herein report a patient with gastric adenocarcinoma with peritoneal dissemination who was treated with nab-paclitaxel and ramucirumab following nivolumab and developed sclerosing cholangitis. Endoscopic retrograde cholangiography showed irregular narrowing and widening of the entire intrahepatic biliary system. Intriguingly, the patient receiving second-line chemotherapy with nab-paclitaxel plus ramucirumab prior to being administered nivolumab, however, he had experienced progressive disease. Thereafter, the administration of fourth-line chemotherapy with nab-paclitaxel and ramucirumab following nivolumab resulted in a clinical response. Nivolumab may enhance the efficacy of the subsequent chemotherapy regimens but also induce sclerosing cholangitis.

DOI： 10.2169/internalmedicine.1981-18

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Language：Japanese   Publisher：Investigational New Drugs  

In the original publication of this article, the license subtype should be CC BYand not CC BY-NC. The original article has been corrected.

DOI： 10.1007/s10637-019-00757-9

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

BACKGROUND AND AIMS: Contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) is used for the diagnosis of pancreatic cancer (PC). Here, we examined the usefulness of CH-EUS for evaluating therapeutic responses in PC. METHODS: The study included 23 patients with PC who received chemotherapy. Patients underwent contrast-enhanced computed tomography (CE-CT) and CH-EUS before chemotherapy and at the time of evaluation of the therapeutic response. Patients with a ≧50% reduction in serum carbohydrate antigen 19-9 levels after chemotherapy were defined as "super responders". The incidence of an avascular area in the tumor on CH-EUS after chemotherapy was compared between "super responders" and non-super responders. RESULTS: Nine patients were included in the "super responders" group.Tumor reduction rates did not differ significantly between CE-CT and CH-EUS in the "super responders". The appearance of an avascular area was detected in 7 of 9 super responders (77.8%) and in 4 of 14 non-super responders (28.6%), and the difference was significant (P = 0.036). The mean survival time of patients with an avascular area after chemotherapy was longer than that of without an avascular area. CONCLUSIONS: Detection of avascular areas by CH-EUS after chemotherapy may predict long-term survival of patients with PC.

DOI： 10.1016/j.dld.2019.03.015

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BACKGROUND: Although Gankyrin is overexpressed in many malignancies, the role of Gankyrin for tumorigenesis and chemoresistance remains to be elucidated in sporadic colorectal cancer (CRC). AIMS: We investigate whether Gankyrin affects Adenomatous polyposis coli (Apc) inactivation-induced tumorigenesis and therapeutic response to anti-angiogenic agents. METHODS: Epithelial cell-specific APC and/or Gankyrin-deficient mice were used. The patients with metastatic CRC (n = 53) who were enrolled in this study underwent resection of primary cancer followed by systemic chemotherapy containing bevacizumab. We determined whether gene expression in CRC tissues before chemotherapy is associated with radiological responses. RESULTS: Deletion of Gankyrin in epithelial cell reduced the expression of c-Myc, a critical mediator of the APC signaling pathway, and interleukin-6. Gankyrin deficiency decreased the expression of Bmi1, a downstream molecule of c-Myc, and the activity of V-Akt murine thymoma viral oncogene homolog and extracellular signal-regulated protein kinase, leading to reduced Apc inactivation-induced tumorigenesis. Of 53 patients, 38 (72%) had increased Gankyrin expression in tumor cells. The enhanced Gankyrin expression in tumor cells was associated with unfavorable progression-free survival (log-rank test p = 0.026). CONCLUSION: Gankyrin in epithelial cell contributes to the development of sporadic CRC and the expression could serve as a biomarker to predict therapeutic response in patients with metastatic CRC.

DOI： 10.1159/000494969

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Language：Japanese   Publisher：American Journal of Case Reports  

Objective: Rare co-existance of disease or pathology Background: Mucinous cystic neoplasm (MCN) of the pancreas is a rare mucin-producing cystic neoplasm that has a characteristic histological feature referred to as ovarian-type stroma (OS) underlying the epithelium. Pancreatic ductal carcinoma arises from MCN as a precursor lesion, but data on progression pathways are limited. Case Report: A 40-year-old female was referred to our hospital for further investigation of a pancreatic cyst. Further examination showed a 7.0 cm multilocular cyst in the pancreatic tail and a solid mass in the thick septum of the cystic tumor. Distal pancreatectomy and splenectomy were performed. Histological examination revealed a moderately differentiated invasive ductal carcinoma (IDC) with a diameter of 0.5 cm in the thick septum of the cystic lesion and a cyst wall composed of epithelium with low-grade to severe dysplasia. The epithelium covered an OS. Pathological diagnosis was IDC arising in MCN of the pancreas. Immunohistochemical examination showed that MUC1 expression was negative in MCN but positive in IDC. KRAS mutation was observed in both MCN and IDC regions. Conclusions: We present a rare case of moderately differentiated pancreatic IDC arising in MCN. To elucidate the underlying progression pathway, we explored the correlation between KRAS mutation and MUC expression as a clinicopathological parameter.

DOI： 10.12659/AJCR.914092

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

Autoimmune pancreatitis (AIP) is a pancreatic manifestation of a newly proposed disease entity, IgG4-related disease (IgG4-RD), characterized by enhanced IgG4 antibody responses and involvement of multiple organs. We have previously reported that innate immune activation contributes to the development of AIP and IgG4-RD, as these diseases are characterized by the production of IFN-α and IL-33 by plasmacytoid dendritic cells (pDCs) that mediate chronic fibroinflammatory responses. In this study, we investigated the roles played by innate immunity against intestinal microflora in experimental AIP induced in MRL/MpJ mice by repeated administrations of 100 µg of polyinosinic-polycytidylic acid [poly (I:C)]. Bowel sterilization with a broad spectrum of antibiotics inhibited pancreatic accumulation of pDCs producing IFN-α and IL-33, and thereby suppressed the development of AIP. Mice treated with 10 µg of poly (I:C) developed severe AIP equivalent to that induced by 100 µg of poly (I:C) upon co-housing with mice treated with 100 µg of poly (I:C). Fecal microbiota transplantation (FMT) from donor mice treated with 100 µg of poly (I:C) led to the development of severe AIP in the recipient mice upon injection with 10 µg of poly (I:C). Induction of severe AIP in mice with 10 µg of poly (I:C) was associated with pancreatic accumulation of pDCs producing IFN-α and IL-33 in the co-housing and FMT experiments. These data collectively suggest that innate immune responses against intestinal microflora are involved in the development of experimental AIP, and that intestinal dysbiosis increases sensitivity to experimental AIP via activation of pDCs.

DOI： 10.1093/intimm/dxz050

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Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞EUSは上部消化管粘膜下腫瘍(SMT)の診断に用いられているが,上部消化管SMTの良悪性鑑別には限界がある.本稿では,造影ハーモニックEUSによる上部消化管粘膜下腫瘍の診断に関する前向き研究1報と後ろ向き研究6報の合計7報の研究をもとに上部消化管SMTの鑑別診断について調べた.造影ハーモニックEUSによるGISTとそれ以外の上部消化管SMTの鑑別診断に関する3つの報告では,hyper-enhancementがGISTの造影ハーモニックEUS所見であり,診断能は感度84.5〜100%,特異度73.3〜100%であった.一方,low-grade malignancy GISTとhigh-grade malignancy GISTの鑑別診断に関する4つの報告では,造影ハーモニックEUSによるhigh-grade malignancy GISTの診断能は感度53.8〜100%,特異度63〜100%であった.またhigh-grade malignancy GISTでは造影ハーモニックEUSにおいてirregular vesselsが高率に認められた.hyper-enhancementか否かおよびirregular vesselsの有無を確認することで上部消化管SMTの鑑別診断が可能であることが示唆された.

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DOI： 10.1055/a-0767-6143

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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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DOI： 10.3390/cancers10100367

PubMed

Copyright© 2018 Japan Gastroenterological Endoscopy Society. All rights reserved. Background and Aim: Differential diagnosis of localized gallbladder lesions is challenging. The aim of the present study was to evaluate the utility of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) for diagnosis of localized gallbladder lesions. Methods: One hundred and twenty-five patients with localized gallbladder lesions were evaluated by CH-EUS between March 2007 and February 2014. This was a single-center retrospective study. Utilities of fundamental B-mode EUS (FB-EUS) and CH-EUS in the differentiation of gallbladder lesions and sludge plug were initially compared. Thereafter, these two examinations were compared with respect to their accuracy in the diagnosis of malignant lesions. Five reviewers blinded to the clinicopathological results evaluated microcirculation patterns in the vascular and perfusion images. Results: In the differentiation between gallbladder lesions and sludge plug, FB-EUS had a sensitivity, specificity, and accuracy of 82％, 100％, and 95％, respectively, whereas CH-EUS had a sensitivity, specificity, and accuracy of 100％, 99％, and 99％, respectively. FB-EUS-based diagnosis of carcinomas based on tumor size and/or shape had a sensitivity, specificity, and accuracy of 61-87％, 71-88％, and 74-86％, respectively. Additional information regarding irregular vessel patterns in the vascular image and/or heterogeneous enhancement in the perfusion image on CH-EUS increased the sensitivity, specificity, and accuracy for the diagnosis of carcinomas to 90％, 98 ％, and 96％, respectively. There was a significant difference between FB-EUS and CH-EUS in terms of carcinoma diagnosis. Conclusion: CH-EUS was useful for the evaluation of localized gallbladder lesions.

DOI： 10.11280/gee.60.1611

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DOI： 10.4103/eus.eus_91_17

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DOI： 10.1111/den.13253

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Neurilemmomas are benign tumors arising from the sheaths of peripheral nerves. They appear rarely in the abdominal cavity. We herein report an 80-year-old man with a multilocular cystic neurilemmoma mimicking a liver lesion. Preoperative images showed a lesion in the porta hepatis. Although a preoperative diagnosis was difficult, surgery was undertaken because of the possibility of malignancy. Histologically, the tumor consisted of spindle-shaped cells with positivity for S-100 protein. The final diagnosis was a neurilemmoma. Porta hepatic neurilemmomas are rare. When we encounter a multilocular cystic lesion of the liver, neurilemmoma should be considered in the differential diagnosis.

DOI： 10.2169/internalmedicine.0881-18

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Language：Japanese   Publisher：日本胆道学会  

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DOI： 10.1158/1538-7445.AM2018-3331

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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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DOI： 10.1007/s10620-018-4908-8

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DOI： 10.1111/den.12976

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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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The most common symptom in patients with advanced pancreatic cancer is abdominal pain. This has traditionally been treated with nonsteroidal anti-inflammatory drugs and opioid analgesics. However, these treatments result in inadequate pain control or drug-related adverse effects in some patients. An alternative pain-relief modality is celiac plexus neurolysis, in which the celiac plexus is chemically ablated. This procedure was performed percutaneously or intraoperatively until 1996, when endoscopic ultrasound (EUS)-guided celiac plexus neurolysis was first described. In this transgastric anterior approach, a neurolytic agent is injected around the celiac trunk under EUS guidance. The procedure gained popularity as a minimally invasive approach and is currently widely used to treat pancreatic cancer-associated pain. We focus on two relatively new techniques of EUS-guided neurolysis: EUS-guided celiac ganglia neurolysis and EUS-guided broad plexus neurolysis, which have been developed to improve efficacy. Although the techniques are safe and effective in general, some serious adverse events including ischemic and infectious complications have been reported as the procedure has gained widespread popularity. We summarize reported clinical outcomes of EUS-guided neurolysis in pancreatic cancer (from the PubMed and Embase databases) with a goal of providing information useful in developing strategies for pancreatic cancer-associated pain alleviation.

DOI： 10.3390/cancers10020050

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We report a case of successful transluminal drainage of walled-off necrosis (WON) under contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) guidance. Recently, EUS-guided transluminal drainage (EUS-TD) of WON has been increasingly used as a minimally invasive treatment option with reportedly high technical and clinical success rates; however, B-mode EUS occasionally fails to depict the target lesion and its margins, particularly in cases where the target shows a heterogeneous echogenicity. In our case, EUS-TD was attempted for infected WON, but visualization using B-mode EUS imaging was poor. Thus, CH-EUS was performed to enhance the contrast between the targeted WON and its surrounding tissues. Immediately after injecting a sonographic contrast agent, WON and its margins were clearly identified as an avascular area and were punctured under CH-EUS guidance. CH-EUS enables the assessment of the microvasculature and hemodynamics of the target lesion in real time. It may also provide valuable information and could be a useful modality for EUS-TD to clearly visualize target lesions and their margins and to decisively puncture them, even when they could not be identified using B-mode EUS.

DOI： 10.1007/s10396-017-0784-7

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Cap polyposis is a rare gastrointestinal disease characterized by multiple inflammatory polyps located between the distal colon and the rectum. Despite the lack of clarity regarding its pathogenesis, mucosal prolapse, chronic inflammatory responses, and Helicobacter pylori infection are considered key contributors to the development of this disease entity. Although it is now generally accepted that dysbiosis of gut microbiota is associated with intestinal and extra-intestinal diseases, alterations of intestinal microbiota have been poorly defined in cap polyposis. Here, we report a patient with H. pylori-negative cap polyposis who was successfully treated with antibiotics and exhibited dramatic alterations in intestinal microbiota composition after antibiotic treatment. The patient was treated with oral administration of ampicillin and metronidazole and showed regression of cap polyposis 6 months after antibiotic treatment. Fecal microbiota analysis using the next-generation sequencing technology revealed a significant alteration in the intestinal microbiota composition following antibiotic treatment-a marked reduction of Blautia, Dorea, and Sutterella was observed concomitant with a marked increase in Fusobacterium. These data suggest that cap polyposis may originate from dysbiosis and that microbiome-targeted therapy may be useful in this disorder.

DOI： 10.3389/fimmu.2018.00918

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DOI： 10.4103/eus.eus_91_17.

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A 27-year-old man bearing an erythropoietic protoporphyria (EPP)-associated ferrochelatase (FECH) mutation was admitted to our hospital for general malaise and marked elevation of the serum levels of hepatobiliary enzymes and bilirubin. Initial treatment with plasma exchange did not reduce the blood protoporphyrin or serum liver enzyme levels, so phlebotomy was started. Surprisingly, weekly phlebotomy normalized the serum levels of liver enzymes, accompanied by a marked reduction in the blood protoporphyrin levels. The clinical course of this case strongly suggests that phlebotomy may be a suitable treatment option for EPP-related hepatopathy.

DOI： 10.2169/internalmedicine.0673-17

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DOI： 10.3390/cancers10100367.

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BACKGROUND AND AIM: This study evaluated the utility of endoscopic ultrasonography (EUS) combined with contrast-enhanced harmonic EUS (CH-EUS) for surveillance of the remnant pancreas after surgery for intraductal papillary mucinous neoplasm (IPMN). METHODS: This was a single-center, retrospective, descriptive study. A total of 134 consecutive patients who underwent surgical resection for IPMN between April 2009 and March 2015 were evaluated. Rates of recurrence and development of IPMN-concomitant pancreatic ductal adenocarcinoma (PDAC) during follow up were assessed. Clinical findings of patients with recurrence or development of PDAC were also evaluated. RESULTS: Of 134 resected IPMN 56 (41.8%) and 78 (58.2%) were classified as benign and malignant, respectively. Patients were followed up for a median of 29 months, 33 (24.6%) by both contrast-enhanced computed tomography (CE-CT) and EUS, and 101 (75.4%) by computed tomography (CT) alone. Thirteen patients (9.7%) showed tumor recurrence, five with intra-pancreatic recurrence and eight with extra-pancreatic metastases. An enhancing mural nodule within the dilated main pancreatic duct was successfully detected by EUS in one patient, but not by CE-CT. Two patients developed IPMN-concomitant PDAC during follow up. EUS combined with CH-EUS successfully detected small IPMN-concomitant PDAC in two patients, whereas these lesions were not detected by CT. CH-EUS was useful for better visualization of the margins of IPMN-concomitant PDAC in one of these two patients. CONCLUSION: Endoscopic ultrasonography combined with CH-EUS may improve follow up of patients with resected IPMN.

DOI： 10.1111/den.13176

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DOI： 10.1007/s10396-017-0850-1

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Language：Japanese   Publisher：Diseases of the Esophagus  

A new classification of magnifying endoscopy with narrow band imaging (ME-NBI) for diagnosing and staging superficial esophageal squamous cell carcinoma (SESCC) was proposed by the Japan Esophageal Society in 2011. This study aimed to compare the new classification with the conventional classifications (Inoue's classification and Arima's classification). This was a prospective analysis of data from a single cancer center involving 151 consecutive patients with 156 SESCCs that were endoscopically or surgically resected. Initially, only ME-NBI images were selected and reviewed independently by three experienced endoscopists. White light imaging (WLI) was then evaluated separately after an interval. The diagnostic performance of each classification and interobserver agreement were assessed, and the WLI findings that affect the diagnosis by the new classification were identified. The specificity for classifying invasive depth as epithelium (EP)/lamina propria mucosae (LPM) confined was higher with the new classification than with Inoue's classification (0.512 vs. 0.349; P = 0.02) and Arima's classification (0.512 vs. 0.279; P < 0.01). However, the sensitivity was lower (0.902 vs. 1.000; P < 0.01) compared with Arima's classification. The concordance rates of three evaluators (κ values) were 0.52 for the new classification, 0.50 for Inoue's classification, and 0.23 for Arima's classification. On multivariate analysis, thickness on WLI independently affected the accuracy of diagnosis with the new classification (OR 3.23; 95%CI, 1.30-8.03). The new classification is superior to conventional classifications with respect to specificity for diagnosing SESCC with depth EP/LPM. Thickness on WLI was a factor negatively affecting the diagnostic performance of the new classification.

DOI： 10.1093/dote/dox037

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DOI： 10.1055/s-0043-117939

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DOI： 10.4103/eus.eus_9_17

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BACKGROUND AND AIM: Differential diagnosis of localized gallbladder lesions is challenging. The aim of the present study was to evaluate the utility of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) for diagnosis of localized gallbladder lesions. METHODS: One hundred and twenty-five patients with localized gallbladder lesions were evaluated by CH-EUS between March 2007 and February 2014. This was a single-center retrospective study. Utilities of fundamental B-mode EUS (FB-EUS) and CH-EUS in the differentiation of gallbladder lesions and sludge plug were initially compared. Thereafter, these two examinations were compared with respect to their accuracy in the diagnosis of malignant lesions. Five reviewers blinded to the clinicopathological results evaluated microcirculation patterns in the vascular and perfusion images. RESULTS: In the differentiation between gallbladder lesions and sludge plug, FB-EUS had a sensitivity, specificity, and accuracy of 82%, 100%, and 95%, respectively, whereas CH-EUS had a sensitivity, specificity, and accuracy of 100%, 99%, and 99%, respectively. FB-EUS-based diagnosis of carcinomas based on tumor size and/or shape had a sensitivity, specificity, and accuracy of 61-87%, 71-88%, and 74-86%, respectively. Additional information regarding irregular vessel patterns in the vascular image and/or heterogeneous enhancement in the perfusion image on CH-EUS increased the sensitivity, specificity, and accuracy for the diagnosis of carcinomas to 90%, 98%, and 96%, respectively. There was a significant difference between FB-EUS and CH-EUS in terms of carcinoma diagnosis. CONCLUSION: CH-EUS was useful for the evaluation of localized gallbladder lesions.

DOI： 10.1111/den.12900

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Language：Japanese   Publisher：和歌山医学会  

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EUS-guided hepaticogastrostomy (EUS-HGS) is useful for treating obstructive jaundice. However, stent migration may sometimes occur both during and after the procedure. This report describes a patient with pancreatic cancer and massive ascites who underwent EUS-HGS combined with EUS-guided antegrade stenting (EUS-AS), with additional EUS-AS playing a role in troubleshooting for stent migration during EUS-HGS.

DOI： 10.1016/j.ajg.2017.05.016

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DOI： 10.1055/s-0043-106185

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BACKGROUND AND AIMS: EUS-guided FNA (EUS-FNA) is used for the diagnosis of pancreatic adenocarcinoma, but sometimes the method results in a false negative. Occasionally, an avascular area may be observed within the pancreatic adenocarcinoma tumor during contrast-enhanced harmonic EUS (CH-EUS). The aim of this study was to evaluate whether the diagnostic sensitivity of EUS-FNA for pancreatic adenocarcinoma was affected by the presence of avascularity on CH-EUS. METHODS: Two hundred ninety-two patients with pancreatic adenocarcinoma who presented at Kindai University Hospital for EUS-FNA and CH-EUS between June 2009 and August 2013 were retrospectively evaluated. This was a single-center retrospective analysis of prospectively collected data held in a registry. The overall sensitivity of EUS-FNA for the diagnosis of pancreatic adenocarcinoma was calculated. The sensitivities of cytology, histology, and the combination of cytology and histology were also evaluated. These variables were individually evaluated according to the presence or absence of an avascular area on CH-EUS to assess whether the diagnostic sensitivity of EUS-FNA for pancreatic adenocarcinoma was related to the presence of an avascular area within the tumors. RESULTS: The overall sensitivity of EUS-FNA was 90.8% (265/292). The sensitivities of EUS-FNA for lesions with and without an avascular area were 72.9% (35/48) and 94.3% (230/244), respectively, with the difference being statistically significant (P < .001). CONCLUSIONS: EUS-FNA has lower sensitivity for pancreatic adenocarcinoma with avascular areas on CH-EUS.

DOI： 10.1016/j.gie.2017.05.052

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DOI： 10.1016/j.gie.2017.03.049

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DOI： 10.1016/j.gie.2017.03.1140

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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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BACKGROUND AND AIM: Endoscopic ultrasonography (EUS)-guided choledochoduodenostomy (EUS-CDS) is increasingly used in the treatment of malignant distal biliary obstruction. Standardized use of this technique requires improvements in instruments, including more convenient and safer devices. The present study was designed to evaluate the resistance force to migration (RFM) of a newly designed laser-cut metal stent and the feasibility of EUS-CDS using this stent. METHODS: This experimental study used a porcine model of biliary dilatation involving five male pigs. The new stent is a fully covered laser-cut stent with anti-migration anchoring hooks. The RFM of the new stents was compared with those of three commercially available covered metal stents using a phantom model. In the animal study, after ligation of Vater's ampulla with endoscopic clips, the dilated common bile duct was punctured under EUS guidance, followed by EUS-CDS using the new stent. One week after the procedure, the stents were removed endoscopically and the fistulas were assessed after the pigs were killed. Technical feasibility and clinical outcomes were evaluated. RESULTS: Among the four stents, the new stent had the highest RFM. Metal stent placement was successful in all five pigs, with no procedure-related complications occurring during and 1 week after endoscopic intervention. All stents remained in place without migration and were removed easily using a snare. At necropsy, fistulas were created between the bile duct and duodenum in all pigs. CONCLUSION: EUS-CDS using a newly designed metal stent was feasible and effective in this porcine model of biliary dilatation.

DOI： 10.1111/den.12741

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Repeated pancreatic juice cytology via endoscopic nasopancreatic drainage (ENPD) has a high diagnostic yield and might be useful for the diagnosis of early-stage pancreatic cancer. A 67-year-old man presented with a pancreatic cyst occasionally detectable in the body of the pancreas by ultrasonography (US). No obvious pancreatic tumor was detected by US, computed tomography (CT), magnetic resonance cholangiopancreatography, and endoscopic ultrasound (EUS) (although the latter did reveal a weak, low echoic area). Endoscopic retrograde pancreatography showed irregular narrowing of the main pancreatic duct (MPD) at the pancreatic body. Pancreatic juice cytology was also performed, but did not give evidence of a malignancy. Therefore, the patient was followed up. CT and EUS performed after 3 months showed the same findings as did endoscopic retrograde pancreatography; however, the results of repeated pancreatic juice cytology performed via ENPD tube revealed a suspected malignancy on 2 of 6 occasions. Therefore, we performed a central pancreatectomy. Histopathological examination of a resected specimen revealed carcinoma in situ in the narrow MPD at the body of the pancreas. In the current case, repeated pancreatic juice cytology via ENPD was effective. A weak low echoic area around the MPD stricture on EUS might be related to the inflammatory change accompanying carcinoma in situ of the pancreas.

DOI： 10.1159/000481240

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AIM: To assess the long-term outcomes of this procedure after removal of self-expandable metal stent (SEMS). The efficacy and safety of endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) with SEMS were also assessed. METHODS: Between January 2010 and April 2015, 12 patients with acute calculous cholecystitis, who were deemed unsuitable for cholecystectomy, underwent EUS-GBD with a SEMS. EUS-GBD was performed under the guidance of EUS and fluoroscopy, by puncturing the gallbladder with a needle, inserting a guidewire, dilating the puncture hole, and placing a SEMS. The SEMS was removed and/or replaced with a 7-Fr plastic pigtail stent after cholecystitis improved. The technical and clinical success rates, adverse event rate, and recurrence rate were all measured. RESULTS: The rates of technical success, clinical success, and adverse events were 100%, 100%, and 0%, respectively. After cholecystitis improved, the SEMS was removed without replacement in eight patients, whereas it was replaced with a 7-Fr pigtail stent in four patients. Recurrence was seen in one patient (8.3%) who did not receive a replacement pigtail stent. The median follow-up period after EUS-GBD was 304 d (78-1492). CONCLUSION: EUS-GBD with a SEMS is a possible alternative treatment for acute cholecystitis. Long-term outcomes after removal of the SEMS were excellent. Removal of the SEMS at 4-wk after SEMS placement and improvement of symptoms might avoid migration of the stent and recurrence of cholecystitis due to food impaction.

DOI： 10.3748/wjg.v23.i4.661

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BACKGROUND AND AIM: The study aims to evaluate contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) for the differential diagnosis of submucosal tumors (SMT) of the upper gastrointestinal tract. METHODS: Between June 2008 and May 2015, 157 consecutive patients with submucosal lesions of the upper gastrointestinal tract were evaluated by CH-EUS. This was a single-center retrospective analysis of prospectively collected data in a registry. The data from 73 patients who later underwent surgical resection were analyzed in this study. Surgical specimens served as the final diagnoses. The two CH-EUS variables of blood flow (hyper-enhancement vs hypo-enhancement) and homogeneity of enhancement pattern were evaluated. RESULTS: The final diagnoses were 58 gastrointestinal stromal tumors (GISTs) and 15 benign SMTs (two lipomas, five leiomyomas, five schwannomas, two glomus tumors, and one ectopic pancreas). On CH-EUS, 49 of 58 (84.5%) GISTs presented with hyper-enhancement, whereas 4 of 15 (26.7%) benign SMTs showed hyper-enhancement; 21 of 58 (36.2%) GISTs showed inhomogeneous contrast enhancement, while only 2 of 15 (13.3%) benign SMTs demonstrated inhomogeneous contrast enhancement. If hyper-enhancement was considered to indicate GISTs, the sensitivity, specificity, and accuracy were 84.5%, 73.3%, and 82.2%, respectively. If inhomogeneous enhancement was considered to indicate GISTs, the sensitivity, specificity, and accuracy were 36.2%, 86.7%, and 46.6%, respectively. In lesions of less than 2 cm, hyper-enhancement was a more sensitive indicator of GISTs than inhomogeneous enhancement. CONCLUSIONS: Hyper-enhancement and inhomogeneous enhancement were found to be a characteristic of GISTs. CH-EUS was useful for discrimination of benign SMTs from GISTs.

DOI： 10.1111/jgh.13766

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INTRODUCTION: Clarithromycin (CAM)-based triple therapy comprising proton pump inhibitors and amoxicillin is administered as first-line eradication treatment against Helicobacter pylori infection. However, the eradication rate achieved with CAM-based triple therapy has decreased to <80% owing to the emergence of CAM-resistant strains. This prospective randomized study aimed to compare the efficacy of CAM-based and metronidazole (MNZ)-based triple therapy in terms of H. pylori eradication. METHODS: H. pylori-positive patients were treated with CAM-based triple therapy comprising esomeprazole and amoxicillin (EAC group) or with MNZ-based triple therapy comprising esomeprazole and amoxicillin (EAM group). RESULTS: H. pylori eradication rates achieved in the intention-to-treat (ITT) and per protocol (PP) analyses were 70.6 and 72.7%, respectively, in the EAC group. Eradication rates obtained via ITT and PP analyses were 91.7 and 94.3%, respectively, in the EAM group. In the EAC group, eradication rates were significantly lower in patients harboring CAM-resistant strains than in those harboring CAM-sensitive strains. In contrast, eradication rates were comparable between patients harboring CAM-resistant strains and those harboring CAM-sensitive strains in the EAM group. CONCLUSION: MNZ-based triple therapy consisting of esomeprazole and amoxicillin is superior to CAM-based triple therapy containing esomeprazole and amoxicillin as first-line eradication treatment against H. pylori.

DOI： 10.1159/000481224

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BACKGROUND: Although the stem cell marker Bmi1 is overexpressed in many malignancies, its role in inflammation-associated cancer is unclear. Colitis-associated cancer (CAC) is caused by chronic intestinal inflammation and often results from refractory inflammatory bowel disease (IBD). METHODS: To assess the involvement of Bmi1 in the development of CAC, we analyzed the gene expression of colon tissues collected from 111 patients with IBD and CAC. RESULTS: In the colonic mucosa of patients with ulcerative colitis, the expression of Bmi1 correlated significantly with the expression of inflammatory cytokines such as IL-6, IL-17, IL-23, and tumor necrosis factor α (TNF-α). In the colonic mucosa of patients with Crohn's disease, the expression of Bmi1 correlated significantly with the expression of TNF-α and IL-23. The expression of Bmi1 was enhanced in the colonic mucosae of refractory IBD, suggesting that Bmi1 expression might be related to increased cancer risk. In addition, patients with high Bmi1 expression showed significantly lower response rates upon subsequent anti-TNF-α therapy as compared to patients with low Bmi1 expression. In human CAC specimens, the expression of Bmi1 was upregulated in nontumor tissues as well as tumors. CONCLUSIONS: Bmi1 expression is related to a refractory clinical course of IBD and upregulated in refractory IBD and CAC. Measurement of Bmi1 expression is a promising approach for the advanced treatment and personalized management of IBD patients.

DOI： 10.1159/000481225

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INTRODUCTION: Endoscopic submucosal dissection (ESD) has been widely used in the resection of superficial esophageal cancers. Since its use has been extended to cases involving large esophageal tumors occupying nearly the whole or the whole circumference of the lumen, the occurrence of esophageal stricture has increased. Although endoscopic injection of triamcinolone (TA) is widely used for the prevention of postoperative stricture, a significant number of patients still develop stricture after TA injection therapy. METHODS: We performed a retrospective study to identify the clinical parameters that predispose post-ESD patients to esophageal stricture after TA injection therapy. RESULTS: A total of 207 patients who were diagnosed with superficial esophageal cancer and subsequently underwent ESD were enrolled in this study. Among these patients, 53 patients and 57 lesions bearing mucosal defects covering greater than two-thirds of the esophageal circumference after ESD were treated with TA injection therapy. The rate of esophageal stricture was found to be highest in cases involving mucosal defects that covered more than seven-eighths of the circumference. CONCLUSION: Endoscopic TA injection is not sufficient for preventing esophageal stricture in patients bearing mucosal defects covering more than seven-eighths of the esophageal circumference after ESD.

DOI： 10.1159/000481223

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OBJECTIVES: This study evaluated whether quantitative perfusion analysis with contrast-enhanced harmonic (CH) endoscopic ultrasonography (EUS) characterizes pancreatic tumors, and compared the hemodynamic parameters used to diagnose pancreatic carcinoma. METHODS: CH-EUS data from pancreatic tumors of 76 patients were retrospectively analyzed. Time-intensity curves (TIC) were generated to depict changes in signal intensity over time, and 6 parameters were assessed: baseline intensity, peak intensity, time to peak, intensity gain, intensity at 60 s (I60), and reduction rate. These parameters were compared between pancreatic carcinomas (n = 41), inflammatory pseudotumors (n = 14), pancreatic neuroendocrine tumors (n = 14), and other tumors (n = 7). All 6 TIC parameters and subjective analysis for diagnosing pancreatic carcinoma were compared. RESULTS: Values of peak intensity and I60 were significantly lower and time to peak was significantly longer in the groups with pancreatic carcinomas than in the other 3 tumor groups (p < 0.05). Reduction rate was significantly higher in pancreatic carcinomas than in pancreatic neuroendocrine tumors (p < 0.05). Areas under the receiver-operating characteristic curves for the diagnosis of pancreatic carcinoma using subjective analysis, baseline intensity, peak intensity, intensity gain, I60, time to peak, and reduction rate, were 0.817, 0.664, 0.810, 0.751, 0.845, 0.777, and 0.725, respectively. I60 was the most accurate parameter for differentiating pancreatic carcinomas from the other groups, giving values of sensitivity/specificity of 92.7/68.6% when optimal cutoffs were chosen. CONCLUSIONS: In pancreatic carcinomas, TIC patterns were markedly different from the other tumor types, with I60 being the most accurate diagnostic parameter. Quantitative perfusion analysis is useful for differentiating pancreatic carcinomas from other pancreatic tumors.

DOI： 10.1159/000481231

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BACKGROUND AND AIMS: Risk factors for pancreatic ductal adenocarcinoma (PDAC) include diabetes mellitus, chronic pancreatitis, obesity, a family history of pancreatic cancer, and a history of smoking or alcohol consumption. The aim of this study was to evaluate the association between risk factors for PDAC and malignant intraductal papillary mucinous neoplasm (IPMN). METHODS: The study included 134 consecutive patients with IPMN who underwent surgical resection at Kindai University Hospital between April 2009 and March 2015. Data on the presence or absence of mural nodules (MNs) and risk factors for PDAC were evaluated. Multivariable logistic regression analysis was performed with malignant IPMN as the outcome variable and MNs and risk factors for PDAC as explanatory variables. RESULTS: The odds ratio of malignant IPMN to MNs was 3.88 (95% confidence interval [CI] 1.53-9.84; p = 0.004), whereas that of malignant IPMN to smoking history was 1.66 (95% CI 0.74-3.71; p = 0.22). When the presence of MNs was considered as a predictive factor for malignancy, the sensitivity and specificity were 88.5 and 32.1%, respectively, whereas when the presence of both smoking history and MNs was considered, the specificity improved to 73.2%, with a decrease in sensitivity to 42.3%. CONCLUSIONS: The presence of both a smoking history and MNs was a valuable predictive factor for malignant IPMN with high specificity. A smoking history should be considered before surgical resection in addition to the presence of MNs.

DOI： 10.1159/000481234

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Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has been widely used for diagnosis of both inflammatory and tumor lesions located in and adjacent to the gastrointestinal tract. EUS-FNA has been considered to be a safe technique with few complications, as shown in recent review articles in which EUS-FNA-related morbidity and mortality rates were reported to be <1%. It should be noted, however, that needle tract seeding, although uncommon, can occur after diagnostic EUS-FNA and that this complication affects the prognosis of patients. Although an accurate value for the frequency of needle tract seeding caused by EUS-FNA has not been reported, the numbers of case reports on needle tract seeding have been rapidly increasing, especially in Japan. These case reports regarding EUS-FNA-related needle tract seeding prompted us to reevaluate the safety of EUS-FNA because this complication may have a significant influence on patients' prognoses. In this review, we summarize the clinical features and outcomes of needle tract seeding after EUS on the basis of the previously reported cases and provide useful information to prevent and reduce this serious complication.

DOI： 10.1159/000481235

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BACKGROUND: Colonoscopic removal of adenomatous polyps or early cancer prevents death from colorectal cancer. Endoscopic submucosal dissection (ESD), which enables endoscopists to perform en bloc resection of flat or depressed colorectal tumors >20 mm, has recently been introduced and become a standard procedure in Japan. Although postoperative bleeding (POB) is a major complication associated with ESD, risk factors for POB have not been fully identified. METHODS: A total of 451 patients (509 lesions) who underwent colorectal ESD were retrospectively analyzed to identify clinical parameters associated with POB. RESULTS: POB occurred in 14 patients, and 7 of them had received antithrombotic therapy before ESD. Uni- and multivariate analyses revealed that antithrombotic therapy and rectal tumor location were strongly associated with POB following colorectal ESD. The incidence of POB was higher in patients on heparin bridge therapy (HBT) for the replacement of antithrombotic therapy than in patients with no HBT. Four of 7 patients (57.1%) on antithrombotic therapy experienced POB from the rectal lesions. CONCLUSION: Antithrombotic therapy and rectal lesions result in a higher POB incidence after colorectal ESD.

DOI： 10.1159/000481228

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BACKGROUND: Treatment of unresectable malignant hilar biliary stricture (UMHBS) is challenging, especially after failure of repeated transpapillary endoscopic stenting. Endoscopic ultrasonography-guided intrahepatic biliary drainage (EUS-IBD) is a recent technique for intrahepatic biliary decompression, but indications for its use for complex hilar strictures have not been well studied. The aim of this study was to assess the feasibility and safety of EUS-IBD for UMHBS after failed transpapillary re-intervention. METHODS: Retrospective analysis of all consecutive patients with UMHBS of Bismuth II grade or higher who, between December 2008 and May 2016, underwent EUS-IBD after failed repeated transpapillary interventions. The technical success, clinical success, and complication rates were evaluated. Factors associated with clinical ineffectiveness of EUS-IBD were explored. RESULTS: A total of 30 patients (19 women, median age 66 years [range 52-87]) underwent EUS-IBD for UMHBS during the study period. Hilar biliary stricture morphology was classified as Bismuth II, III, or IV in 5, 13, and 12 patients, respectively. The median number of preceding endoscopic interventions was 4 (range 2-14). EUS-IBD was required because the following procedures failed: duodenal scope insertion (n = 4), accessing the papilla after duodenal stent insertion (n = 5), or achieving desired intrahepatic biliary drainage (n = 21). Technical success with EUS-IBD was achieved in 29 of 30 patients (96.7%) and clinical success was attained in 22 of these 29 (75.9%). Mild peritonitis occurred in three of 30 (10%) and was managed conservatively. Stent dysfunction occurred in 23.3% (7/30). There was no procedure-related mortality. On multivariable analysis, Bismuth IV stricture predicted clinical ineffectiveness (odds ratio = 12.7, 95% CI 1.18-135.4, P = 0.035). CONCLUSIONS: EUS-IBD may be a feasible and effective rescue alternative with few major complications after failed transpapillary endoscopic re-intervention in patients with UMHBS, particularly for Bismuth II or III strictures.

DOI： 10.1007/s00464-017-5553-6

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The prophylactic closure of mucosal defects after endoscopic resection is known to prevent postoperative bleeding in colorectal lesions. However, closure of large mucosal defects is difficult with conventional clips only, and several closure techniques have been previously described; use of an Endoloop, 8-ring loop, or loop clip and a small incision around the mucosal defect. Given that the prophylactic closure requires much cost and time, the application should be limited to high-risk cases. Medication of antithrombotics or antiplatelet agents would be one of the reasonable indications for prophylactic closure of mucosal defects after endoscopic resection of colorectal tumors.

DOI： 10.1159/000481226

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：S. Karger AG  

DOI： 10.1159/000481236

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BACKGROUND: Endoscopic ultrasound (EUS)-guided biliary drainage (BD) is a well-recognized alternative BD method after unsuccessful endoscopic transpapillary drainage. EUS-guided hepaticogastrostomy (HGS) with antegrade stenting (AGS) was recently applied to the treatment of malignant obstructive jaundice. OBJECTIVE: To assess the efficacy and safety of HGS combined with AGS for treatment of malignant biliary stricture-induced obstructive jaundice. DESIGN: Retrospective cohort study. SETTING: Single academic tertiary care center. PATIENTS: From January 2006 to December 2014, endoscopic retrograde cholangiopancreatography was attempted in patients with obstructive jaundice; it was successful in 641 patients and impossible in 154 patients (postsurgically altered anatomy or duodenal stenosis, n = 101; difficult cannulation, n = 53). In total, 145 patients underwent EUS-guided BD; HGS and HGS with AGS were attempted in 42 patients (Group A, January 2006-August 2011) and 37 patients (Group B, September 2011-December 2014), respectively. INTERVENTIONS: Under EUS and fluoroscopy guidance, HGS and HGS with AGS were performed via needle puncture, guidewire insertion, puncture-hole dilation, and stent placement. MAIN OUTCOME MEASUREMENTS: Groups A and B were compared in terms of technical success, functional success, adverse event rates, re-intervention rates, patient survival time, and time to stent dysfunction or patient death. The two groups were also compared in a subgroup analysis of only 28 patients who underwent chemotherapy. RESULTS: The technical success rate was significantly higher in Group A than B (97.6 vs. 83.8%, p = 0.03). The functional success rate was comparable between the two groups (90.2 vs. 90.3%), although the rate of adverse events was significantly higher in Group A than B (26.1 vs. 10.8%, p = 0.03). The re-intervention rate tended to be higher in Group A than B (16.7 vs. 8.1%, p = 0.25). Groups A and B did not differ significantly in terms of median overall patient survival (75 vs. 61 days, p = 0.70) or median time to stent dysfunction or patient death (68 vs. 63 days, p = 0.08). Among patients who underwent chemotherapy, there was no difference in overall patient survival time between the two groups (121 vs. 157 days, p = 0.08), although time to stent dysfunction or patient death was significantly shorter in Group A than B (71 vs. 95 days, p = 0.02). CONCLUSION: Although the technical success rate of HGS with AGS was lower than that of HGS, HGS with AGS was superior to HGS in terms of adverse event rate and stent patency in patients receiving chemotherapy.

DOI： 10.1159/000481233

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Language：Japanese   Publisher：Journal of Hepato-Biliary-Pancreatic Sciences  

Background: There have been no reports showing the incidence of anastomotic stenosis of continuous hepaticojejunostomy (HJ) and identifying its risk factors for patients who underwent pancreaticoduodenectomy (PD). Method: We retrospectively investigated 200 patients whose HJ was established by unified method, single layered continuous suture. HJ stenosis was diagnosed with endoscopic or radiologic examinations. Uni and multivariable unconditional logistic modeling were performed to explore the predictive factors and to estimate odds ratios (ORs) and their 95% confidence intervals (CIs). Results: Sixteen patients (8.0%) were diagnosed as HJ stenosis. Multivariable analysis showed that body mass index (BMI) (OR: 1.24; 95% CI: 1.03–1.51), absence of preoperative biliary stenting (OR: 11.10; 95% CI: 1.22–101.12), operative time (OR: 1.74 per one hour increase; 95% CI: 1.01–2.98), age (OR: 1.58 per 10 years increase; 95% CI: 0.88–2.85), and absence of nodal metastasis (OR: 3.43; 95% CI: 0.90–13.12) correlated with HJ stenosis. Among these, BMI and preoperative biliary stenting were associated with stenosis with a lower P-value than the others (P = 0.026 and 0.033, respectively). Conclusions: The incidence of HJ stenosis was 8.0%. Close attention would be needed especially for patients at high risk of HJ stenosis, such as high BMI or absence of preoperative biliary stenting.

DOI： 10.1002/jhbp.385

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AIM: To assess anti-migration potential of six biliary covered self-expandable metal stents (C-SEMSs) by using a newly designed phantom model. METHODS: In the phantom model, the stent was placed in differently sized holes in a silicone wall and retracted with a retraction robot. Resistance force to migration (RFM) was measured by a force gauge on the stent end. Radial force (RF) was measured with a RF measurement machine. Measured flare structure variables were the outer diameter, height, and taper angle of the flare (ODF, HF, and TAF, respectively). Correlations between RFM and RF or flare variables were analyzed using a linear correlated model. RESULTS: Out of the six stents, five stents were braided, the other was laser-cut. The RF and RFM of each stent were expressed as the average of five replicate measurements. For all six stents, RFM and RF decreased as the hole diameter increased. For all six stents, RFM and RF correlated strongly when the stent had not fully expanded. This correlation was not observed in the five braided stents excluding the laser cut stent. For all six stents, there was a strong correlation between RFM and TAF when the stent fully expanded. For the five braided stents, RFM after full stent expansion correlated strongly with all three stent flare structure variables (ODF, HF, and TAF). The laser-cut C-SEMS had higher RFMs than the braided C-SEMSs regardless of expansion state. CONCLUSION: RF was an important anti-migration property when the C-SEMS did not fully expand. Once fully expanded, stent flare structure variables plays an important role in anti-migration.

DOI： 10.3748/wjg.v22.i30.6917

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BACKGROUND AND AIMS: EUS-guided bile duct drainage (EUS-BD) is a well-recognized rescue biliary drainage method after unsuccessful ERCP. EUS-guided gallbladder drainage (EUS-GBD) was recently used to treat acute cholecystitis. The aim of this study was to assess the efficacy and safety of EUS-GBD for malignant biliary stricture-induced obstructive jaundice after unsuccessful ERCP as well as unsuccessful or impractical EUS-BD. METHODS: Between January 2006 and October 2014, 12 patients with obstructive jaundice due to unresectable malignant distal biliary stricture underwent EUS-GBD after ERCP failed. EUS-GBD was performed under the guidance of EUS and fluoroscopy by puncturing the gallbladder with a needle, inserting a guidewire, dilating the puncture hole, and placing a stent. The technical and functional success rates, adverse events rate, overall patient survival time, and stent dysfunction rate during patient survival were measured. RESULTS: The rates of technical success, functional success, adverse events, and stent dysfunction were 100%, 91.7%, 16.7%, and 8.3%, respectively. The median survival time after EUS-GBD was 105 days (range 15 - 236 days). CONCLUSIONS: EUS-GBD is a possible alternative route for decompression of the biliary system when ERCP is unsuccessful.

DOI： 10.1016/j.gie.2015.12.024

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BACKGROUND: Interventional endoscopic ultrasound (EUS)-guided procedures such as EUS-guided celiac ganglia neurolysis (EUS-CGN) and EUS-guided broad plexus neurolysis (EUS-BPN) were developed to treat abdominal cancer-associated pain; however, these procedures are not always effective. The aim of this study was to explore predictors of pain response in EUS-guided neurolysis for pancreatic cancer-associated pain. METHODS: This was a retrospective analysis of prospectively collected data of 112 consecutive patients who underwent EUS-BPN in our institution. EUS-CGN was added in cases of visible celiac ganglia. The neurolytic-spread area was divided into six sections and evaluated by post-procedural computed tomography scanning. Pain intensity was assessed using a visual analog scale (VAS), and a decrease in VAS scores by ⩾3 points after neurolysis was considered a good pain response. Univariable and multivariable logistic regression analyses were performed to explore predictors of pain response at 1 and 4 weeks, and complications. RESULTS: A good pain response was obtained in 77.7% and 67.9% of patients at 1 and 4 weeks, respectively. In the multivariable analysis of these patients, the combination method (EUS-BPN plus CGN) was a significant positive predictive factor at 1 week (odds ratio = 3.69, p = 0.017) and 4 weeks (odds ratio = 6.37, p = 0.043). The numbers of neurolytic/contrast spread areas (mean ± SD) were 4.98 ± 1.08 and 4.15 ± 1.12 in patients treated with the combination method and single method, respectively (p < 0.001). There was no significant predictor of complications. CONCLUSIONS: EUS-BPN in combination with EUS-CGN was a predictor of a good pain response in EUS-guided neurolysis for pancreatic cancer-related pain. The larger number of neurolytic/contrast spread areas may lead to better outcomes in patients receiving combination treatment.

DOI： 10.1177/1756283X16644248

PubMed

J-GLOBAL

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Endoscopic ultrasonography (EUS) is widely used to evaluate pancreaticobiliary diseases, especially pancreatic masses. EUS has a good ability to detect pancreatic masses, but it is not sufficient for the differential diagnosis of various types of lesions. In order to address the limitations of EUS, new techniques have been developed to improve the characterization of the lesions detected by EUS. EUS-guided fine needle aspiration (EUS-FNA) has been used for diagnosing pancreatic tumors. In order to improve the histological diagnostic yield, a EUS-FNA needle with a core trap has recently been developed. Contrast-enhanced harmonic EUS is a new imaging modality that uses an ultrasonographic contrast agent to visualize blood flow in fine vessels. This technique is useful in the diagnosis of pancreatic solid lesions and in confirming the presence of vascularity in mural nodules for cystic lesions. EUS elastography analyzes several different variables to measure tissue elasticity, color patterns, and strain ratio, using analytical techniques such as hue-histogram analysis, and artificial neural networks, which are useful for the diagnosis of chronic pancreatitis and pancreatic cancer.

DOI： 10.14366/usg.15042

PubMed

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We report a successful endoscopic ultrasonography-guided drainage of a huge infected multilocular walled-off necrosis (WON) that was treated by a modified single transluminal gateway transcystic multiple drainage (SGTMD) technique. After placing a wide-caliber fully covered metal stent, follow-up computed tomography revealed an undrained subcavity of WON. A large fistula that was created by the wide-caliber metal stent enabled the insertion of a forward-viewing upper endoscope directly into the main cavity, and the narrow connection route within the main cavity to the subcavity was identified with a direct view, leading to the successful drainage of the subcavity. This modified SGTMD technique appears to be useful for seeking connection routes between subcavities of WON in some cases.

DOI： 10.3748/wjg.v22.i21.5132

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DOI： 10.1016/j.gie.2016.03.771

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Acute obstructive suppurative cholangitis (AOSC) due to biliary lithiasis is a life-threatening condition that requires urgent biliary decompression. Although endoscopic retrograde cholangiopancreatography (ERCP) with stent placement is the current gold standard for biliary decompression, it can sometimes be difficult because of failed biliary cannulation. In this retrospective case series, we describe three cases of successful biliary drainage with recovery from septic shock after urgent endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) was performed for AOSC due to biliary lithiasis. In all three cases, technical success in inserting the stents was achieved and the patients completely recovered from AOSC with sepsis in a few days after EUS-CDS. There were no procedure-related complications. When initial ERCP fails, EUS-CDS can be an effective life-saving endoscopic biliary decompression procedure that shortens the procedure time and prevents post-ERCP pancreatitis, particularly in patients with AOSC-induced sepsis.

DOI： 10.3748/wjg.v22.i16.4264

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

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BACKGROUND AND STUDY AIM: Comparison of fundamental B-mode endoscopic ultrasonography (FB-EUS) and contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) in the differential diagnosis of pancreatic cysts according to presence of mural nodules. PATIENTS AND METHODS: Between April 2007 and April 2012, FB-EUS and CH-EUS data were prospectively collected from 581 consecutive patients with pancreatic cysts, and were retrospectively analyzed from 70 with subsequent cyst resection. Presence and height of mural nodules as detected on FB-EUS and CH-EUS were evaluated, and thence accuracies of both methods for diagnosing mucinous versus nonmucinous and malignant versus benign cysts. RESULTS: On pathological examination 48 cysts were mucinous and 22 were nonmucinous; 30 cysts were malignant (high grade dysplasia or invasive carcinoma) and 40 were benign. If presence of a mural nodule was considered to indicate a mucinous cyst, FB-EUS and CH-EUS accuracies did not differ significantly (respectively: sensitivity 85 % vs. 79 %; specificity 46 % vs. 96 %; accuracy 73 % vs. 84 %, P = 0.057). If presence of mural nodule was considered to indicate malignancy, CH-EUS was significantly more accurate than FB-EUS (respectively: sensitivity 97 % vs. 97 %; specificity 75 % vs. 40 %; accuracy 84 % vs. 64 %, P = 0.0001). For diagnosing malignancy by evaluating mural nodule height, the area under the receiver operating characteristic (AUROC) was 0.84 and 0.93 for FB-EUS and CH-EUS, respectively (P = 0.028). Presence of a mural nodule of height ≥ 4 mm on CH-EUS was a sign of malignancy (false-positive fraction 0.2; true-positive fraction 0.93; odds ratio 56.0). CONCLUSIONS: CH-EUS is more accurate than FB-EUS for diagnosing malignant pancreatic cysts.

DOI： 10.1055/s-0034-1393564

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

DOI： 10.1055/s-0042-109059

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Language：Japanese   Publisher：Surgery Today  

Purpose: To clarify the incidence, clinicopathological features and prognosis of pancreatic invasive ductal carcinomas (IDCs) with different tumor origin sites in the pancreatic duct. Methods: Based on the relationship between the invasive cancer area (ICA) and the main pancreatic duct (MPD), IDCs less than 2 cm in diameter were classified into two groups: type I, in which the ICA and MPD were separated, and type II, in which the MPD passed through the ICA. The clinicopathological findings and prognosis of each type were compared in a total of 37 patients. Results: The incidences of IDC types I and II were 18.9 and 81.1 %, respectively. Although there was no difference in local invasion, both node involvement and venous invasion tended to occur more frequently in type I IDC, and the three-year survival rate was significantly lower for type I (28.6 %) than type II (71.8 %) IDC. Conclusions: The prognosis of IDCs that originated in the branching pancreatic duct (BPD) distant from the MPD (type I) was worse than the prognosis of IDCs that originated in either the MPD or the BPD close to the MPD (type II). These data suggest that the progression and degree of malignancy of IDCs may vary depending on the site of tumor origin in the pancreatic duct.

DOI： 10.1007/s00595-014-1075-1

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Language：Japanese   Publisher：Cancer Prevention Research  

Inactivation of methylcytosine dioxygenase, ten-eleven translocation (TET) is known to be associated with aberrant DNA methylation in cancers. Tumors with a CpG island methylator phenotype (CIMP), a distinct subgroup with extensive DNA methylation, show characteristic features in the case of colorectal cancer. The relationship between TET inactivation and CIMP in colorectal cancers is not well understood. The expression level of TET family genes was compared between CIMP-positive (CIMP-P) and CIMP-negative (CIMP-N) colorectal cancers. Furthermore, DNA methylation profiling, including assessment of the TET1 gene, was assessed in colorectal cancers, as well as colon polyps. The TET1 was silenced by DNA methylation in a subset of colorectal cancers as well as cell lines, expression of which was reactivated by demethylating agent. TET1 methylation was more frequent in CIMP-P (23/55, 42%) than CIMP-N (2/113, 2%, P < 0.0001) colorectal cancers. This trend was also observed in colon polyps (CIMP-P, 16/40, 40%; CIMP-N, 2/24, 8%; P = 0.002), suggesting that TET1 methylation is an early event in CIMP tumorigenesis. TET1 methylation was significantly associated with BRAF mutation but not with hMLH1 methylation in the CIMP-P colorectal cancers. Colorectal cancers with TET1 methylation have a significantly greater number of DNA methylated genes and less pathological metastasis compared to those without TET1 methylation (P = 0.007 and 0.045, respectively). Our data suggest that TET1 methylation may contribute to the establishment of a unique pathway in respect to CIMP-mediated tumorigenesis, which may be incidental to hMLH1 methylation. In addition, our findings provide evidence that TET1 methylation may be a good biomarker for the prediction of metastasis in colorectal cancer.

DOI： 10.1158/1940-6207.CAPR-14-0306

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Language：Japanese   Publisher：Journal of Hepato-Biliary-Pancreatic Sciences  

Background The Japanese Society of Hepato-Biliary-Pancreatic Surgery launched the clinical practice guidelines for the management of biliary tract and ampullary carcinomas in 2008. Novel treatment modalities and handling of clinical issues have been proposed after the publication. New approaches for editing clinical guidelines, such as the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, also have been introduced for better and clearer grading of recommendations. Methods Clinical questions (CQs) were proposed in seven topics. Recommendation, grade of recommendation and statement for each CQ were discussed and finalized by evidence-based approach. Recommendation was graded to grade 1 (strong) and 2 (weak) according to the concept of GRADE system. Results The 29 CQs covered seven topics: (1) prophylactic treatment, (2) diagnosis, (3) biliary drainage, (4) surgical treatment, (5) chemotherapy, (6) radiation therapy, and (7) pathology. In 27 CQs, 19 recommendations were rated strong and 11 recommendations weak. Each CQ included the statement of how the recommendation was graded. Conclusions This guideline provides recommendation for important clinical aspects based on evidence. Future collaboration with cancer registry will be a key for assessment of the guidelines and establishment of new evidence. Free full-text articles and a mobile application of this guideline are available via http://www.jshbps.jp/en/guideline/biliary-tract2.html.

DOI： 10.1002/jhbp.233

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Language：Japanese  

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Language：Japanese   Publisher：Hepato-Gastroenterology  

Background/Aims: This study evaluated the efficacy and safety of transnasal endoscopy (TNE) with flexible spectral imaging color enhancement (FICE) for detection of superficial cancer in the pharyngeal and esophageal regions for high-risk populations. Methodology: Patients who previously had head and neck or esophageal squamous cell carcinoma were enrolled. Screening was conducted using TNE with conventional white-light endoscopy (WLE) followed by FICE chromoendoscopy. For observation of the pharyngeal region, the Valsalva maneuver was employed. Results: 99 patients were eligible. Six esophageal cancers were detected in four patients (4.0%). The sensitivity, specificity, and accuracy for the detection of cancer were 25.0% (95% CI, 3.4-71.0), 97.8% (95% CI, 92.1-99.8), and 94.9% (95% CI, 88.4-98.1), respectively for WLE; 100% (95% CI, 451%-100%), 96.8% (95% CI, 90.7%-99.3%), and 96.9% (95% CI, 89.3%-99.1%), respectively for FICE chromoendoscopy. Pain in the nose and nasal hemorrhage were observed in 3 (3.0%) and 2 patients (2.0%), respectively. Following the Valsalva maneuver, endoscopic scores significantly increased from a mean of 1.1 (0.8-1.4) to 2.0 (1.3-2.6) (p<0.05). Conclusions: TNE with the Valsalva maneuver is a promising screening method for the pharyngeal and esophageal regions. TNE with FICE chromoendoscopy for detecting pharyngeal and esophageal cancer was more sensitive than WLE. © H.G.E. Update Medical Publishing S.A.

DOI： 10.5754/hge14489

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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：(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：Gastroenterology  

Background & Aims Cells of tumors associated with chronic inflammation frequently have altered patterns of DNA methylation, including hepatocellular carcinomas. Chronic hepatitis has also been associated with aberrant DNA methylation, but little is known about their relationship. Methods Pyrosequencing was used to determine the methylation status of cultured Huh7.5.1 hepatoma cells after hepatitis C virus (HCV) infection. We also studied mice with severe combined immunodeficiency carrying the urokinase-type plasminogen activator transgene controlled by an albumin promoter (urokinase-type plasminogen activator/severe combined immunodeficient mice), in which up to 85% of hepatocytes were replaced by human hepatocytes (chimeric mice). Mice were given intravenous injections of hepatitis B virus (HBV) or HCV, liver tissues were collected, and DNA methylation profiles were determined at different time points after infection. We also compared methylation patterns between paired samples of hepatocellular carcinomas and adjacent nontumor liver tissues from patients. Results No reproducible changes in DNA methylation were observed after infection of Huh7.5.1 cells with HCV. Livers from HBV- and HCV-infected mice had genome-wide, time-dependent changes in DNA methylation, compared with uninfected urokinase-type plasminogen activator/severe combined immunodeficient mice. There were changes in 160 ± 63 genes in HBV-infected and 237 ± 110 genes in HCV-infected mice. Methylation of 149 common genes increased in HBV- and HCV-infected mice; methylation of some of these genes also increased in hepatocellular carcinoma samples from patients compared with nontumor tissues. Expression of Ifng, which is expressed by natural killer cells, increased significantly in chimeric livers, in concordance with induction of DNA methylation, after infection with HBV or HCV. Induction of Ifng was reduced after administration of an inhibitor of natural killer cell function (anti-asialo GM1). Conclusions In chimeric mice with humanized livers, infection with HBV and HCV appears to activate a natural kill cell-dependent innate immune response. This contributes to the induction and accumulation of aberrant DNA methylation in human hepatocytes. © 2014 by the AGA Institute.

DOI： 10.1053/j.gastro.2013.10.056

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

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Language：Japanese   Publisher：Investigational New Drugs  

Background. Pancreatic neuroendocrine tumors (NETs) are rare but are frequently diagnosed at advanced stages and require systemic therapy. Patients and methods. This multicenter, open-label, phase II study evaluated sunitinib in Japanese patients with well-differentiated pancreatic NET. Patients received sunitinib 37.5 mg/day on a continuous daily dosing (CDD) schedule. The primary endpoint was clinical benefit rate (CBR; percentage of complete responses [CRs] plus partial responses [PRs] plus stable disease [SD] ≥24 weeks). Secondary endpoints included objective response rate (ORR), tumor shrinkage, progression-free survival (PFS) probability, safety, pharmacokinetics, and biomarkers. Results. Twelve patients received treatment. The CBR was 75 % (95 % confidence interval [CI], 43-94) and included 6 patients with a PR and 3 with SD. The ORR was 50 % (95 % CI, 21-79). PFS probability was 91 % (95 % CI, 54-99) at 6 months and 71 % (95 % CI, 34-90) at 12 months. Commonly reported treatment-emergent (all-causality), any-grade adverse events included diarrhea (n = 10), hand-foot syndrome and hypertension (both n = 8), fatigue and headache (both n = 7), and neutropenia (n = 6). No deaths on study were reported; one death due to disease progression occurred >28 days after end of treatment. Sunitinib on a CDD schedule resulted in sustained drug concentrations without accumulation across cycles. Tumor responses in all 12 patients did not appear to correlate with decreases in chromogranin A levels. Conclusions. Sunitinib 37.5 mg/day on a CDD schedule demonstrated antitumor activity in Japanese patients with unresectable, well-differentiated pancreatic NET. Commonly reported adverse events were consistent with the known safety profile of sunitinib. © 2012 The Author(s).

DOI： 10.1007/s10637-012-9910-y

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

急性胆嚢炎に対するドレナージ治療として、EUS下穿刺術を応用したEUS下胆嚢ドレナージ術(EUS-GBD)が報告されている。EUS観察下で胃前庭部または十二指腸球部より腫大した胆嚢を穿刺する。穿刺後、生理食塩水にて胆嚢内を洗浄した上で、胆嚢内にガイドワイヤーをコイリングする要領で留置し、続いて穿刺孔を拡張する。最後に経鼻ドレナージチューブ、両端ピッグテイルステントあるいは金属ステントを留置する。新しい手技のため、報告が少ないが、手技成功率97〜100%、臨床症状改善率100%と良好な成績が得られている。主な偶発症として、胆汁性腹膜炎気腹症、ステントの迷入、逸脱がある。今後、EUS-GBDは経皮経肝胆嚢ドレナージ術、経皮経肝胆嚢吸引穿刺法、内視鏡的経鼻胆嚢ドレナージ術、内視鏡的胆嚢ステント留置術と同様、急性胆嚢炎に対する治療選択肢となりうる。(著者抄録)

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Language：Japanese   Publisher：日本胆道学会  

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Language：Japanese   Publisher：Carcinogenesis  

The impact of alcohol on the risk of stomach cancer is controversial. Although aldehyde dehydrogenase 2 (ALDH2) Glu504Lys (rs671) polymorphism has a strong effect on acetaldehyde metabolism, little is known about its impact on stomach cancer risk when combined with alcohol drinking. This case-control study included a total of 697 incident stomach cancer case subjects and 1372 non-cancer control subjects who visited Aichi Cancer Center between 2001 and 2005. We estimated odds ratios (OR) and 95% confidence intervals (CI) for ALDH2 genotypes and alcohol consumption using logistic regression models after adjustment for potential confounders, including Helicobacter pylori infection. The ALDH2 504Lys allele was associated with the risk of stomach cancer, with adjusted ORs of 1.40 (95% CI, 1.11-1.76) for Glu/Lys and 1.73 (1.12-2.68) for Lys/Lys compared with Glu/Glu. Heavy drinking was associated with risk (OR 1.72, 1.17-2.52) after adjustment for ALDH2 genotype and other confounders. Moreover, ORs for heavy drinking were 1.28 (0.77-2.12) for those with ALDH2 Glu/Glu and 3.93 (1.99-5.79) for those with the ALDH2 Lys allele relative to non-drinkers with the Glu/Glu genotype (P for interaction = 0.0054). In conclusion, ALDH2 and alcohol drinking showed interaction for risk factors of stomach cancer, indicating that acetaldehyde plays a role in stomach carcinogenesis. ©The Author 2013.Published by Oxford University Press. All rights reserved.

DOI： 10.1093/carcin/bgt080

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Language：Japanese   Publisher：Japan Gastroenterological Endoscopy Society  

A 52-year-old man was referred to our hospital with intermittent abdominal pain. He had consumed raw fish 1 day prior to the onset of his symptom. Abdominal ultrasonography and computed tomography were conducted, which indicated thickening of the ileal wall and accumulation of ascites. Based on his clinical history and these images, enteric anisakiasis was suspected. He then underwent double-balloon enteroscopy (DBE) via the anal approach. DBE revealed edematous mucosa in the ileum and an Anisakis sp. larva invading the ileal wall. The entire larva was successfully retrieved using biopsy forceps, following which his symptoms completely resolved. Thus, we believe that, when enteric anisakiasis is suspected, DBE should be performed for diagnosis and endoscopic extraction.

DOI： 10.11280/gee.55.1643

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Other Link： http://search.jamas.or.jp/link/ui/2013245244

Language：Japanese   Publisher：Endoscopy  

A prospective clinical study was conducted to evaluate the safety, feasibility, and efficacy of endoscopic ultrasound (EUS)-guided choledochoduodenostomy (CDS) with direct metallic stent placement using a prototype forward-viewing echoendoscope. The indication for EUS - CDS in this study was lower biliary obstruction only, and not failed endoscopic biliary drainage, because the aim was to evaluate EUS - CDS for first-line biliary drainage therapy. The technical and functional success rates were 94 % (17 /18) and 94 % (16 /17), respectively. Early complications (focal peritonitis) were encountered in two patients (11 %). No patients developed late complications. EUS - CDS with direct metallic stent placement using a forward-viewing echoendoscope was generally feasible and effective for malignant distal biliary tract obstruction. The forward-viewing echoendoscope was useful, especially for deploying the metallic stent. © Georg Thieme Verlag KG Stuttgart - New York.

DOI： 10.1055/s-0032-1326076

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DOI： 10.1111/j.1872-034X.2012.01083.x

PubMed

Language：Japanese   Publisher：Asian Pacific Journal of Cancer Prevention  

Background: Cigarette smoking is a well-established risk factor of pancreatic cancer (PC). Although an association between nicotine dependence phenotype, namely time to first cigarette (TTFC) after waking, and the risk of several smoking-related cancers has been reported, an association between TTFC and PC risk has not been reported. We assessed the impact of smoking behavior, particularly TTFC, on PC risk in a Japanese population. Materials and Methods: We conducted a case-control study using 341 PC and 1,705 non-cancer patients who visited Aichi Cancer Center in Nagoya, Japan. Exposure to risk factors, including smoking behavior, was assessed from the results of a self-administered questionnaire. The impact of smoking on PC risk was assessed with multivariate logistic regression analysis adjusted for potential confounders to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results: Cigarettes per day (CPD) and/or smoking duration were significantly associated with PC risk, consistent with previous studies. For TTFC and PC risk, we found only a suggestive association: compared with a TTFC of more than 60 minutes, ORs were 1.15 (95%CI, 0.65-2.04) for a TTFC of 30-60 minutes and 1.35 (95%CI, 0.85-2.15) for that of 0-30 minutes (p trend=0.139). After adjustment for CPD or smoking duration, no association was observed between TTFC and PC. Conclusions: In this study, we found no statistically significant association between TTFC and PC risk. Further studies concerning TTFC and PC risk are warranted.

DOI： 10.7314/APJCP.2013.14.7.4409

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Language：Japanese   Publisher：Journal of Epidemiology  

Background: Although several reports have described a possible association between DNA repair genes and pancreatic cancer (PC) in smokers, this association has not been fully evaluated in an Asian population. We assessed the impact of genetic polymorphisms in the base excision repair (BER) pathway on PC risk among Japanese. Methods: This case-control study compared the frequency of 5 single-nucleotide polymorphisms (SNPs) of BER genes, namely rs1052133 in OGG1, rs1799782 and rs25487 in XRCC1, rs1130409 in APE1, and rs1136410 in PARP1. SNPs were investigated using the TaqMan assay in 185 PC cases and 1465 controls. Associations of PC risk with genetic polymorphisms and gene-environment interaction were examined with an unconditional logistic regression model. Exposure to risk factors was assessed from the results of a self-administered questionnaire. We also performed haplotype-based analysis. Results: We observed that the minor allele of rs25487 in XRCC1 was significantly associated with PC risk in the per-allele model (odds ratio = 1.29, CI = 1.01-1.65; trend P = 0.043). Haplotype analysis of XRCC1 also showed a statistically significant association with PC risk. No statistically significant interaction between XRCC1 polymorphisms and smoking status was seen.Conclusions: Our findings suggest that XRCC1 polymorphisms affect PC risk in Japanese. © 2012 by the Japan Epidemiological Association.

DOI： 10.2188/jea.JE20120010

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Language：Japanese  

PubMed

Language：Japanese   Publisher：Gut  

Background and aims: The majority of gastrointestinal stromal tumors (GISTs) have KIT mutations; however, epigenetic abnormalities that could conceivably potentiate the aggressiveness of GISTs are largely unidentified. Our aim was to establish epigenetic profiles associated with the malignant transformation of GISTs. Methods: Methylation of four tumor suppressor genes, RASSF1A, p16, CDH1, and MGMT was analyzed in GISTs. Additionally, genome-wide DNA methylation profiles were compared between small, malignant-prone, and malignant GISTs using methylated GpG island amplification microarrays (MCAM) in a training set (n=40). Relationships between the methylation status of genes identified by MCAM and clinical features of the disease were tested in a validation set (n=75). Results: Methylation of RASSF1A progressively increased from small to malignant GISTs. p16 was specifically methylated in malignant-prone and malignant GISTs. MCAM analysis showed that more genes were methylated in advanced than in small GISTs (average of 473 genes vs 360 genes, respectively, P=0.012). Interestingly, the methylation profile of malignant GISTs was prominently affected by their location. Two genes, REC8 and PAX3, which were newly-identified via MCAM analysis, were differentially methylated in small and malignant GISTs in the training and validation sets. Patients with methylation of at least REC8, PAX3, or p16 had a significantly poorer prognosis (P=0.034). Conclusion: Our results suggest that GIST is not, in epigenetic terms, a uniform disease and that DNA methylation in a set of genes is associated with aggressive clinical behavior and unfavorable prognosis. The genes identified may potentially serve as biomarkers for predicting aggressive GISTs with poor survivability.

DOI： 10.1136/gut.2011.241034

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Language：Japanese   Publisher：International Journal of Molecular Epidemiology and Genetics  

Although several reports have described a possible association between insulin-like growth factors-1 (IGF-1) and pancreatic cancer (PC) risk, this association has not been evaluated in the non-Caucasian population. To assess the impact of IGF-1 polymorphisms on PC risk in Japanese, we conducted a case-control study which compared the frequency of ten single nucleotide polymorphisms (SNPs) and haplotypes of IGF-1. SNPs were investigated using the TaqMan method in 176 patients with PC and 1402 control subjects. Exposure to risk factors was assessed from the results of a self-administered questionnaire. Associations and gene-environment interactions were examined using an unconditional logistic regression model. We did not observe any significant main effect of IGF-1 loci, but did find interactions between rs5742714 and past and/or current body-mass index (BMI) status. Among patients with BMI ≥ 25 at age 20, an increased PC risk was observed with the addition of the minor allele for rs5742714 (trend P = 0.048) and rs6214 (P = 0.043). Among patients with current BMI ≥ 25, an increased or decreased PC risk was observed with the addition of the minor allele for rs5742714 (trend P = 0.046), rs4764887 (P = 0.031) and rs5742612 (P = 0.038). Haplotype analysis of IGF-1 showed a significant association among patients who were either or both previously or currently overweight. These findings suggest that IGF-1 polymorphisms may affect the development of PC in the Japanese population in combination with obesity. Further studies to confirm these findings are warranted.

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Language：Japanese   Publisher：Cancer Science  

The insulin-like growth factor (IGF) signaling system plays a central role in cellular growth, differentiation and proliferation. Although the association between IGF1 gene polymorphisms and cancer risk has been evaluated for several carcinomas, this association has not yet been examined for stomach cancer. We investigated the association between IGF1 polymorphisms and the risk of stomach cancer in a Japanese population. A total of 703 patients with stomach cancer and 1462 non-cancer control subjects were enrolled in this case-control study. Associations between polymorphisms of 10 IGF1 loci and the risk of stomach cancer were evaluated using odds ratios (OR) and 95% confidence intervals (CI) in multiple logistic regression models. We observed that the C allele in rs1520220 and the G allele in rs4764887 were significantly associated with stomach cancer risk in the per-allele model after adjusting for other risk factors (OR: 1.14 [95% CI: 1.00-1.30] and OR: 1.18 [95% CI: 1.02-1.36], respectively). We also observed a positive and dose-dependent association between the number of risk alleles and stomach cancer risk (P-trend: 0.019) when examining the two loci in the same model. These associations were still seen after adjusting for potential confounders, including sex, age, smoking status, history of diabetes and family history of stomach cancer. We did not find any significant interaction between these factors and the number of risk alleles. In conclusion, we observed a significant association between IGF1 polymorphisms and stomach cancer risk among a Japanese population. Examination of the biological significance of IGF1 is warranted. © 2011 Japanese Cancer Association.

DOI： 10.1111/j.1349-7006.2011.02062.x

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Language：Japanese   Publisher：Journal of Japanese Society of Gastroenterology  

We describe a 54-year old woman with oxaliplatin-induced autoimmune hemolytic anemia and review the clinical features of similar published cases. The present patient had metastatic colon cancer and was admitted to our hospital with a floating sensation and general malaise on day 4 after undergoing the last of 4 cycles of a 7 th round of chemotherapy with XELOX. Laboratory data revealed 4.6g/d/ hemoglobin and 8.77 mg/d/ creatinine. Direct and indirect Coombs tests of a blood sample for blood transfusion were both positive. We diagnosed immune hemolysis with acute renal failure based on the clinical course and blood samples showing haptoglobin <10mg/d/. We treated her with hemodialysis, plasmapheresis and immune suppression with prednisolone, which improved the anemia and renal failure.

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Language：Japanese   Publisher：Cancer Epidemiology Biomarkers and Prevention  

Background: Although several studies have investigated the association between ABO blood type and risk of gastric cancer (GC), atrophic gastritis (AG), and Helicobacter pylori (HP) infection, no study has investigated these associations by using ABO genotype. Methods: We conducted a case-control study in 703 patients with GC and 1,465 noncancer patients. Wealso conducted a cross-sectional study by using 1,406 of these 1,465 controls, who were examined for pepsinogens and anti-HP IgG antibody levels in serum. ABO genotype was determined from single nucleotide polymorphisms in ABO gene. We used rs8176719 to mark the O allele, and rs8176746 and rs8176747 to mark the B allele. ORs and 95% CIs were calculated by a multivariate logistic model. Results: We observed significant associations between ABO genotype and GC, AG, and HP infection. ORs (95% CIs) of GC were 0.70 (0.50-0.99) for OO and 0.53 (0.36-0.77) for BO relative to AA genotype. An increased risk of GC was observed with addition of the A allele (P trend < 0.001), and a decreased risk with that of the B allele (P trend = 0.023). An OR of AG was 0.73 (95% CI, 0.53-0.99) for blood type B relative to blood type A, and an OR of HP infection was 0.39 (95% CI, 0.17-0.87) for BB relative to AA genotype. Conclusion: This study identified a statistically significant association between ABO genotype and GC risk. In addition, ABO gene locus may influence AG prevalence and HP infection. Impact: Further studies are necessary to confirm these findings. ©2011 AACR.

DOI： 10.1158/1055-9965.EPI-11-0213

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Language：Japanese   Publisher：American Journal of Gastroenterology  

Objectives: Endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) has recently been reported as an alternative to percutaneous transhepatic biliary drainage (PTBD) in cases of biliary obstruction, when endoscopic biliary drainage (EBD) is unsuccessful. However, prospective studies of EUS-CDS have not yet been performed. We conducted a prospective study to evaluate the safety, feasibility, and efficacy of EUS-CDS in patients with malignant lower biliary tract obstruction. Methods: A prospective study to confirm the safety of EUS-CDS was carried out in 6 patients, followed by a trial to evaluate the feasibility and efficacy of EUS-CDS in 12 additional patients. We placed a plastic stent from the duodenal bulb into the extrahepatic bile duct under EUS guidance using an oblique viewing echoendoscope, needle knife, guidewire, and biliary dilators. Results: The site of extrahepatic bile duct puncture was the common hepatic duct in 15 patients and the common bile duct in 3 patients. Mean diameter of the punctured extrahepatic bile ducts was 10 mm (range: 6-20 mm). Technical and functional success rates were 94% (17/18) and 100% (17/17), respectively. Median procedure time was 30 min (range: 10-52 min). Median duration to first oral intake after the procedure was 1 day (range: 1-3 days). Early complications were encountered in three (17%) patients, including focal peritonitis in two patients and hemobilia in one patient. During the follow-up period (median: 163 days; range: 46-484 days), 12 stent occlusion events were observed in nine patients. Re-intervention with exchange of the occluded stent was successful in 8 of 12 (66%) times. Severe early and late complications were not encountered in any patients in this study. Median duration of stent patency by Kaplan-Meier analysis was 272 days. Conclusions: EUS-CDS is safe, feasible, and effective as an alternative to PTBD and EBD in cases of malignant distal biliary tract obstruction. Prospective randomized studies are needed to compare the safety and efficacy of various kinds of endoscopic devices used in EUS-CDS and to compare EUS-CDS with PTBD or EBD. © 2011 by the American College of Gastroenterology.

DOI： 10.1038/ajg.2011.84

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Language：Japanese   Publisher：Cancer Science  

Several studies have investigated a possible association between the ABO blood group and the risk of pancreatic cancer (PC), but this association has not been fully evaluated in Asian populations. The present study aimed to assess the impact of genotype-derived ABO blood types, particularly ABO alleles, on the risk of PC in a Japanese population. We conducted a case-control study using 185 PC and 1465 control patients who visited Aichi Cancer Center in Nagoya, Japan. Using rs8176719 as a marker for the O allele, and rs8176746 and rs8176747 for the B allele, all participants' two ABO alleles were inferred. The impact of ABO blood type on PC risk was examined by multivariate analysis, with adjustment for potential confounders to estimate odds ratios (OR) and 95% confidence intervals (CI). An increased risk of PC was observed with the addition of any non-O allele (trend P=0.012). Compared with subjects with the OO genotype, those with AO and BB genotypes had significantly increased OR of 1.67 (CI, 1.08-2.57) and 3.28 (CI, 1.38-7.80), respectively. Consistent with earlier reports showing a higher risk of PC for individuals with the non-O blood type, the previously reported protective allele (T) for rs505922 was found to be strongly correlated (r2=0.96) with the O allele. In conclusion, this case-control study showed a statistically significant association between ABO blood group and PC risk in a Japanese population. Further studies are necessary to define the mechanisms by which the ABO gene or closely linked genetic variants influence PC risk. © 2011 Japanese Cancer Association.

DOI： 10.1111/j.1349-7006.2011.01907.x

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Language：Japanese   Publisher：American Journal of Pathology  

Liver metastasis is a fatal step in the progression of colorectal cancer (CRC); however, the epigenetic evolution of this process is largely unknown. To decipher the epigenetic alterations during the development of liver metastasis, the DNA methylation status of 12 genes, including 5 classical CpG island methylator phenotype (CIMP) markers, was analyzed in 62 liver metastases and in 78 primary CRCs (53 stage I-III; 25 stage IV). Genome-wide methylation analysis was also performed in stage I-III CRCs and in paired primary and liver metastatic cancers. Methylation frequencies of MGMT and TIMP3 increased progressively from stage I-III CRCs to liver metastasis (P = 0.043 and P = 0.028, respectively). The CIMP-positive cases showed significantly earlier recurrence of disease than did CIMPnegative cases with liver metastasis (P = 0.030), whereas no such difference was found in stage I-III CRCs. Genomewide analysis revealed that more genes were methylated in stage I-III CRCs than in paired stage IV samples (P = 0.008). Hierarchical cluster analysis showed that stage I-III CRCs and stage IV CRCs were clustered into two distinct subgroups, whereas most paired primary and metastatic cancers showed similar methylation profiles. This analysis revealed distinct methylation profiles between stage I-III CRCs and stage IV CRCs, whichmayreflect differences in epigenetic evolution during progression of the disease. In addition, most methylation status in stage IV CRCs seems to be established before metastasis. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

DOI： 10.1016/j.ajpath.2010.12.045

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Language：Japanese   Publisher：International Journal of Cancer  

Aberrant DNA methylation is involved in colon carcinogenesis. Although the CpG island methylator phenotype (CIMP) is defined as a subset of colorectal cancers (CRCs) with remarkably high levels of DNA methylation, it is not known whether epigenetic processes are also involved in CIMP-negative tumors. We analyzed the DNA methylation profiles of 94 CRCs and their corresponding normal-appearing colonic mucosa with 11 different markers, including the five classical CIMP markers. The CIMP markers were frequently methylated in proximal CRCs (p < 0.01); however, RASSF1A methylation levels were significantly higher in distal CRCs, the majority of which are CIMP-negative (p < 0.05). Similarly, methylation levels of RASSF1A and SFRP1 in the normal-appearing mucosae of distal CRC cases were significantly higher than those in the proximal CRC cases (p < 0.05). They were also positively correlated with age (RASSF1A, p < 0.01; SFRP1, p < 0.01). Microarray-based genome-wide DNA methylation analysis of 18 CRCs revealed that 168 genes and 720 genes were preferentially methylated in CIMP-negative distal CRCs and CIMP-positive CRCs, respectively. Interestingly, more than half of the hypermethylated genes in CIMP-negative distal CRCs were also methylated in the normal-appearing mucosae, indicating that hypermethylation in CIMP-negative distal CRCs is more closely associated with age-related methylation. By contrast, more than 60% of the hypermethylated genes in CIMP-positive proximal CRCs were cancer specific (p < 0.01). These data altogether suggest that CpG island promoters appear to be methylated in different ways depending on location, a finding which may imply the presence of different mechanisms for the acquisition of epigenetic changes during colon tumorigenesis. © 2010 UICC.

DOI： 10.1002/ijc.25225

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Language：Japanese   Publisher：Gastroenterology  

Background & Aims: Corticosteroids are now widely accepted as a treatment for autoimmune pancreatitis (AIP). However, the molecular mechanism by which steroid treatment improves AIP remains largely unknown. The aim of this study was to elucidate cellular mechanisms by which corticosteroids improve both pancreatic exocrine function and histopathology in AIP. Methods: Pancreatic exocrine function was evaluated by the secretin-stimulated function test and pancreatic biopsy specimens were processed for histologic analysis at the time of diagnosis and 3 months after initiation of steroid treatment. Expression and localization of proteins was assayed by immunohistochemistry. Analysis of immunoglobulin (Ig)G4-positive plasma cells was used to verify inflammation in AIP. Results: The number of IgG4-positive plasma cells in pancreatic sections was decreased by steroid treatment, indicating reduced inflammation. Fluid, bicarbonate (HCO3-), and digestive enzyme secretions all were impaired in most patients with AIP. Corticosteroids improved both HCO3- and digestive enzyme secretion. A large fraction of the cystic fibrosis transmembrane conductance regulator (CFTR), which plays a central role in pancreatic duct HCO3- secretion, was mislocalized to the cytoplasm of duct cells before treatment. Corticosteroids corrected the localization of CFTR to the apical membrane, accounting for the improved HCO3- secretion. Steroid treatment resulted in regeneration of acinar cells, accounting for restored digestive enzyme secretion. Conclusions: Corticosteroids reduce inflammation and restore both digestive enzyme and HCO3- secretion in patients with AIP by regenerating acinar cells and correcting CFTR localization in pancreatic duct cells. Mislocalization of CFTR may explain aberrant HCO3- secretion in other forms of pancreatitis. © 2010 AGA Institute.

DOI： 10.1053/j.gastro.2010.01.001

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Language：Japanese   Publisher：Journal of Hepato-Biliary-Pancreatic Sciences  

Background: Autoimmune pancreatitis (AIP) is often misdiagnosed as pancreatic cancer (PC). Both conditions accumulate 18F- fluorodeoxyglucose (FDG), so FDG positron emission tomography (FDG-PET) is not discriminatory. This study aimed to evaluate the pattern of FDG accumulation, and the change in FDG uptake after steroid treatment in AIP and PC. Methods: We compared FDG-PET patterns between 18 patients with AIP and 20 patients with PC, and also evaluated the short-term changes in FDG uptake after steroid therapy. Results: FDG uptake was observed in 88.9% in AIP and 90.0% in PC. FDG uptake in extra-abdominal lymph nodes was seen more frequently in AIP, and uptake in salivary glands, eyes and biliary ducts was seen only in AIP. Follow-up PET was performed in 6 AIP patients and in 3 PC patients. Changes in SUVmax after steroid therapy were estimated within 1 week in 5 AIP patients and in all 3 PC patients, retrospectively. In 4 AIP patients, the change in SUV max was more than 10%. On the other hand, in PC, SUVmax increased or remained almost unchanged (within 10%). Conclusions: FDG-PET pattern at baseline, and a decrease in FDG uptake after a short steroid trial can be useful for discriminating AIP from PC. © Japanese Society of Hepato-Biliary-Pancreatic Surgery and Springer 2009.

DOI： 10.1007/s00534-009-0172-9

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：MOSBY-ELSEVIER  

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膵癌術後合併症の膵切除後膵液瘻(POPF)はときに重篤な経過をたどるが、内視鏡的ドレナージはPOPFの治療において外科的治療と並ぶ重要な治療の一つである。内視鏡的ドレナージには、経乳頭的に主膵管内にドレナージチューブを留置して持続吸引を行うTrans-papillary drainageと、EUSガイド下に膵液貯留腔にドレナージを置くEUS-guided drainageがあり、それぞれの長所短所を理解したうえで、状況に応じた使い分けが求められる、EUS-guided drainageの時期は、急性膵炎後のWalled Off Necrosis(WON)に対するEUS-guided drainageの適応が発症4週間以降であることを踏まえ、術後4週間を待たれる症例が多いが、近年4週間以内の早期ドレナージの有効性も報告されており、症例に応じて4週間を待つことなく、EUS-guided drainageを行うことも考慮に入れるべきである。いずれの処置も適応が正しいかどうか、処置後合併症の対応、外科的ドレナージへのconversionの時期を含め、常に外科と内科で密にディスカッションを行い、患者にとってもっともよい治療法を施設として選択できるように取り組むことが肝要である。(著者抄録)

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

膵癌術後合併症の膵切除後膵液瘻(POPF)はときに重篤な経過をたどるが、内視鏡的ドレナージはPOPFの治療において外科的治療と並ぶ重要な治療の一つである。内視鏡的ドレナージには、経乳頭的に主膵管内にドレナージチューブを留置して持続吸引を行うTrans-papillary drainageと、EUSガイド下に膵液貯留腔にドレナージを置くEUS-guided drainageがあり、それぞれの長所短所を理解したうえで、状況に応じた使い分けが求められる、EUS-guided drainageの時期は、急性膵炎後のWalled Off Necrosis(WON)に対するEUS-guided drainageの適応が発症4週間以降であることを踏まえ、術後4週間を待たれる症例が多いが、近年4週間以内の早期ドレナージの有効性も報告されており、症例に応じて4週間を待つことなく、EUS-guided drainageを行うことも考慮に入れるべきである。いずれの処置も適応が正しいかどうか、処置後合併症の対応、外科的ドレナージへのconversionの時期を含め、常に外科と内科で密にディスカッションを行い、患者にとってもっともよい治療法を施設として選択できるように取り組むことが肝要である。(著者抄録)

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

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

胆管挿管をマスターすることは内視鏡的逆行性胆管膵管造影(ERCP)関連主義の基本中の基本である。胆管挿管の基本は、乳頭部の形態が千差万別であり全く同じものは一つとして存在しないことをまず認識し、これまでに多くの先人が胆管挿管に対する検討を行い、蓄積してきた多くの知見を学び、対峙した乳頭の形態、大きさ、口側隆起の形態から乳頭内の胆管と膵管の合流形式を予想し、その症例でとりうるスコープポジションと胆管挿管との兼ね合いを理解し、難渋することも頭に入れ、挿管のストラテジーを組み立てることが挿管成功率の向上につながり、挿管困難症例克服の重要な鍵となる。すべての処置を愛護的に行うことは言うまでもなく、ERCP歴がある症例はスコープの挿入前に上記内容を把握することが胆管挿管成功につながることは言うまでもなく遂行すべきである。(著者抄録)

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Language：Japanese   Publisher：日本胆道学会  

本症例は、胆嚢腺筋腫症におけるRokitansky-Aschoff sinus(RAS)内に進展し、一部で浸潤を認めるpT2(SS)胆嚢癌の1例である。胆嚢内にpolypoidに増殖する乳頭型腫瘍を呈し、内部で領域性に異なる増殖パターンを呈した。病理学的に、乳頭型腺癌の組織像を呈し、不整な乳頭腺管状構築をとりながら増殖している領域と充実性の構造を示し、密な腫瘍細胞の増殖を認める領域に分かれていた。造影ハーモニックEUSでは、腫瘤は造影早期より腫瘍血管構造が描出された後、均一かつ強く濃染される領域と少し遅れて内部に太く蛇行する異常血管が緩徐に造影され、その後不均一に造影される領域に2分された。本症例の胆嚢癌は、異なる組織成分の存在を示唆する興味深い造影ハーモニックEUS画像を呈した。(著者抄録)

DOI： 10.11210/tando.32.775

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Venue：大阪国際交流センター, 大阪  

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