記述言語：英語   掲載種別：研究論文（学術雑誌）  

Amoebic colitis is a parasitic gastrointestinal disease caused by Entamoeba histolytica (E. histolytica). In Japan, metronidazole (MNZ) monotherapy is often used and most cases are effective. However, we report a case of MNZ-insufficient amoebic colitis caused by residual cysts. A 73-year-old man had been staying in Southeast Asia for over a decade. He had undergone a screening colonoscopy and ulcerative lesions were observed in the cecum, and a biopsy confirmed amoeba parasites. The patient was treated with MNZ monotherapy. However, he forgot to take the medicine for several days, and the ulcerative lesions persisted. The patient was referred to our facility, and we performed a colonoscopy and confirmed trophozoites. Since we considered that previous treatment failure was due to the low oral dosage, we re-prescribed MNZ. A colonoscopy after 6 months showed that the ulcerative lesions persisted. We clinically diagnosed MNZ-insufficient amoebic colitis caused by residual cysts and prescribed MNZ and paromomycin (PRM) each for 10 days. One year later, no ulcerative lesions were observed. MNZ-insufficient amoebic colitis should be considered, when ulcerative lesions remain after MNZ administration and PRM is effective drug against cysts, and we propose a combination therapy of PRM to MNZ.

DOI： 10.1007/s12328-024-02083-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1055/a-2408-8685

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1055/a-2418-3257

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1055/a-2239-2558

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1055/a-2440-6432

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1055/a-2468-6484

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1055/a-2480-3803

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1055/a-2420-7965

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1055/a-2496-2899

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1055/a-2291-9399

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1055/a-2253-8912

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1055/a-2271-4124

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1055/a-2387-4238

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Peroral cholangioscopy (POCS) is valuable for assessing malignant biliary strictures; however, biliary drainage prior to POCS often hinders accurate diagnosis. Objectives: This retrospective study aimed to investigate the feasibility of POCS using a newly developed cholangioscope, CHF-B290, during initial endoscopic retrograde cholangiopancreatography (ERCP) for malignant biliary strictures. Methods: This multicenter retrospective study included patients who underwent initial ERCP for malignant biliary strictures at two institutions between January 2018 and March 2022. Patients who underwent initial ERCP with POCS were classified into the POCS group, and those without POCS were classified into the non-POCS group. To prevent post-POCS cholangitis, the original irrigation system for CHF-B290 was used in all POCS examinations. The primary endpoint was the rate of post-ERCP biliary infections, and the secondary endpoints were other ERCP-related complications, including pancreatitis, bleeding, and perforation. Results: Overall, 53 and 94 patients were included in the POCS and non-POCS groups, respectively. For the primary endpoint, the rate of post-ERCP biliary infection was not significantly different between the two groups (1.9% vs. 5.3%, p = 0.42). For the secondary endpoints, no significant differences were observed in the rates of post-ERCP pancreatitis (5.7% vs. 6.4%, p = 1.00) and other ERCP-related complications. The overall complication rate was 9.4% in the POCS group and 13% in the non-POCS group (p = 0.60). Conclusions: POCS during the initial ERCP for malignant biliary strictures is feasible.

DOI： 10.3390/diagnostics14222589

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: This retrospective study aimed to investigate the role of an additional high mechanical index (MI) setting scan during the post-vascular phase (PVP) in detecting deep-seated hepatocellular carcinoma (HCC) lesions. METHODS: A total of 805 confirmed HCCs, which underwent Sonazoid-based contrast-enhanced ultrasound (CEUS) between January 2014 and October 2021, were included. Low MI scan was initially employed for lesion detection during the PVP, followed by high MI scan. Propensity score matching (PSM) was utilized to address confounding variables. RESULTS: Of the 805 study lesions, 668 were detected as perfusion defects at the initial low MI setting, while 137 remained undetected. Among these 137 undetected lesions, 77 were identified at the subsequent high MI setting, whereas 60 remained undetected. Lesions that were larger (18.69 ± 11.27 mm vs. 16.55 ± 7.42 mm, p = 0.006), more superficial (6.06 ± 2.41 cm vs. 7.40 ± 2.74 cm, p < 0.001), and hypoechoic (482/668 vs. 62/137, p < 0.001) were detectable at the initial low MI setting. Male patients benefited more from the additional high MI scan (63/97 vs. 14/40, p < 0.001). Lesions identified with additional high MI were larger (18.30 ± 8.76 mm vs. 14.30 ± 4.34 mm, p < 0.001) and deeper than undetected ones (8.48 ± 2.48 cm vs. 6.02 ± 2.43 cm, p < 0.001). After PSM, depth was shown to be an independent predictor in multivariate analysis (odds ratio: 1.557, 95% confidence interval: 1.249-1.941). The depth cutoff was 7.75 cm, with a sensitivity of 0.681, specificity of 0.851, and area under the curve of 0.774. CONCLUSIONS: The additional high MI setting scan during the PVP of Sonazoid-based CEUS leads to enhanced detection of deep-seated HCCs.

DOI： 10.1007/s10396-024-01507-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/den.14949

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

DOI： 10.3390/tomography10100117

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The aims of this study were to identify clinically significant biomarkers of a response to atezolizumab plus bevacizumab (ATZ + BV) therapy and to develop target strategies against unresectable hepatocellular carcinoma (u-HCC). METHOD: We first investigated the potential of circulating tumor DNA (ctDNA) to serve as a biomarker for predicting the therapeutic outcome in 24 u-HCC patients treated with ATZ + BV therapy. Next, we analyzed levels of immune-related cytokines in blood samples from 134 u-HCC patients who received ATZ + BV. For this, serum immune-related molecules or cancer-immune cycle-related molecules that have been reported in HCC patient sera, namely CD274, LAG-3, CCL2, 4, 5, CXCL1, 9, 10, 12, 13, CX3CL1, CCR5, IFNγ and IL-6, 8 were measured using enzyme-linked immunosorbent assay. RESULTS: More than 1% of variant read frequency (VRF) mutations were found in TP53, APC, PIK3CA and VHL, although with no correlation with treatment response. Among the 15 cytokines evaluated, CXCL9 and LAG-3 levels were significantly different between patients with objective response (OR), stable disease (SD), and progressive disease (PD) following ATZ + BV treatment. Receiver-operating characteristic curve analyses of CXCL9 (cut-off value: 419.1 pg/ml) and LAG-3 (cut-off value: 3736.3 pg/ml) indicated areas of 0.779 and 0.697, respectively, for differentiating PD from non-PD and OR from non-OR. In multivariate analysis of progression-free survival (PFS) and overall survival (OS), high serum CXCL9 (hazard ratio (HR) and 95% confidence interval (CI): 0.412 (0.251-0.677) (p = 0.0005) for PFS and 0.252 (0.125-0.508) (p = 0.0001) for OS), and low serum LAG-3 (HR and 95% CI 0.419 (0.249-0.705) (p = 0.0011) for PFS and 0.294 (0.140-0.617) (p = 0.0012) for OS) were independent positive predictive factors. CONCLUSION: Although, as far as we examined, no ctDNA mutations in blood were found to be related to ATZ + BV treatment efficacy, serum CXCL9 and LAG-3 levels, which are related to the cancer-immune cycle, were associated with treatment efficacy and could be predictive markers of the efficacy of ATZ + BV treatment in HCC patients.

DOI： 10.1007/s12072-024-10680-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: Cold snare polypectomy (CSP) is a common, simple, and safe procedure; however, it has a high rate of unclear margins. We analyzed the risk factors for unclear margins of colorectal polyp. METHODS: We retrospectively investigated colorectal polyps treated with CSP between July 2021 and July 2022, excluding those that could not be retrieved or pathologically nonneoplastic and hyperplastic polyps without margin evaluation. The clinicopathological features and risk factors for unclear margins were analyzed. Furthermore, the polyps were divided into two groups: those resected by experts and those resected by trainees. A 1 : 1 propensity score matching was performed. After matching, the risk factors for unclear margins in each group were analyzed as secondary outcomes. RESULTS: We analyzed 237 patients with 572 polyps; the margins were negative in 58.6% (negative group) and unclear in 41.4% (unclear group). The unclear margin was significantly higher at straddling folds (P = 0.0001), flexure points (P = 0.005), and in the procedures performed by trainees (P < 0.0001). Altogether, 198 propensity score matched pairs were explored for secondary outcomes. There were no significant differences in risk factors for unclear margins in the expert group, while in the trainee group, the unclear margin was significantly higher at the straddling folds (P = 0.0004) and flexure points (P = 0.005). CONCLUSIONS: We demonstrated that straddling folds, flexure points, and procedures performed by the trainees were significant risk factors for unclear margins, and we hypothesized that the rate of unclear margins will reduce as the trainees accumulate experience at difficult sites.

DOI： 10.1097/MEG.0000000000002845

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本胆道学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Pancreatic ductal adenocarcinoma (PDAC) has a high mortality rate; therefore, the development of effective treatments is a priority. The stimulator of interferon genes (STING) pathway enhances tumor immunity by inducing the production of type 1 interferon (IFN) and proinflammatory cytokines and chemokines and promoting the infiltration of cytotoxic T cells. To assess the function of STING on pancreatic tumorigenesis, Ptf1aER-Cre/+ LSL-KrasG12D/+ p53loxP/loxP mice (KPC mice) and Ptf1aER-Cre/+ LSL-KrasG12D/+ p53loxP/loxP/STING-/- mice (KPCS mice) were generated. However, STING deletion did not affect pancreatic tumorigenesis in mice. Because STING is expressed not only in immune cells but also in cancer-associated fibroblasts (CAFs), we evaluated the STING function in PDAC CAFs. A mouse STING agonist 5,6-Dimethyl-9-oxo-9H-xanthene-4-acetic acid (DMXAA) was administered to KPC mice and CAFs from KPC mice and the resulting immune response was evaluated. DMXAA activated STING in PDAC CAFs in KPC mice, promoting cytotoxic T cell infiltration by secreting proinflammatory cytokines and enhancing tumor immunity. We next generated STING-deficient PDAC cells and subcutaneous tumors in which STING was expressed only in CAFs by performing bone marrow transplantation and assessed the antitumor effect of STING-activated CAFs. The administration of DMXAA to subcutaneous tumors expressing STING only in CAFs sustained the antitumor effect of DMXAA. About half of human PDACs lacked STING expression in the cancer stroma, suggesting that STING activation in PDAC CAFs exerts an antitumor effect, and STING agonists can be more effective in tumors with high than in those with low STING expression in the stroma.

DOI： 10.1038/s41598-024-68061-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/den.14888

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIMS: Intestinal Behçet disease is typically associated with ileocecal punched-out ulcers and significant morbidity and mortality. Intestinal ultrasound is a noninvasive imaging technique for disease monitoring. However, no previous reports have compared intestinal ultrasound with endoscopic ulcer activity or histopathological findings for intestinal Behçet disease. We evaluated the usefulness of intestinal ultrasound for assessing the activity of ileocecal ulcers in intestinal Behçet disease. METHODS: We retrospectively compared intestinal ultrasound findings with 73 corresponding endoscopic images and 6 resected specimens. The intestinal ultrasound findings were assessed for 7 parameters (bowel wall thickness, vascularity [evaluated using the modified Limberg score with color Doppler], bowel wall stratification, white-plaque sign [strong hyperechogenic lines or spots], mesenteric lymphadenopathy, extramural phlegmons, and fistulas), and endoscopic ulcer activity was classified into active, healing, and scar stages. Histopathological findings were evaluated by consensus among experienced pathologists. RESULTS: Bowel wall thickness (P< 0.001), vascularity (P< 0.001), loss of bowel wall stratification (P= 0.015), and white-plague sign (P= 0.013) were significantly exacerbated in the endoscopic active ulcer stage. Receiver operating characteristic curve analysis revealed that a bowel wall thickness of > 5.5 mm (sensitivity 89.7%, specificity 85.3%) was potentially useful for detecting active lesions. When compared with histopathological findings, an increase in bowel wall thickness reflected the ulcer marginal ridge, and the white-plaque sign reflected the ulcer bottom. CONCLUSIONS: Intestinal ultrasound is useful for monitoring intestinal ulcer activity in intestinal Behçet disease.

DOI： 10.5217/ir.2023.00129

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: This study aims to evaluate the efficacy and safety of lenvatinib radiofrequency ablation (RFA) sequential therapy for certain hepatocellular carcinoma (HCC) patients. METHODS: One hundred and nineteen patients with unresectable HCC in the intermediate stage with Child-Pugh A were retrospectively recruited in a multicenter setting. Those in the lenvatinib RFA sequential therapy group received lenvatinib initially, followed by RFA and the retreatment with lenvatinib. The study compared overall survival (OS), progression-free survival (PFS), tumor response, and adverse events (AEs) between patients undergoing sequential therapy and lenvatinib monotherapy. RESULTS: After propensity score matching, 25 patients on sequential therapy and 50 on monotherapy were evaluated. Independent factors influencing OS were identified as sequential therapy, modified albumin-bilirubin (mALBI) grade, and relative dose intensity (%) with hazard ratios (HRs) of 0.381 (95% confidence interval [CI], 0.186-0.782), 2.220 (95% CI, 1.410-3.493), and 0.982 (95% CI, 0.966-0.999), respectively. Stratified analysis based on mALBI grades confirmed the independent influence of treatment strategy across all mALBI grades for OS (HR, 0.376; 95% CI, 0.176-0.804). Furthermore, sequential therapy was identified as an independent factor of PFS (HR, 0.382; 95% CI, 0.215-0.678). Sequential therapy significantly outperformed monotherapy on survival benefits (OS: 38.27 vs. 18.96 months for sequential therapy and monotherapy, respectively, p = 0.004; PFS: 13.80 vs. 5.32 months for sequential therapy and monotherapy, respectively, p < 0.001). Sequential therapy was significantly associated with complete response by modified Response Evaluation Criteria in Solid Tumors (odds ratio, 63.089). Ten of 119 patients experienced grade 3 AEs, with no AE beyond grade 3 observed. CONCLUSION: Lenvatinib RFA sequential therapy might offer favorable tolerability and potential prognostic improvement compared to lenvatinib monotherapy.

DOI： 10.1111/hepr.14089

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

To establish clinical prediction models of vessels encapsulating tumor clusters (VETC) pattern using preoperative contrast-enhanced ultrasound (CEUS) and gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid magnetic resonance imaging (EOB-MRI) in patients with hepatocellular carcinoma (HCC). A total of 111 resected HCC lesions from 101 patients were included. Preoperative imaging features of CEUS and EOB-MRI, postoperative recurrence, and survival information were collected from medical records. The best subset regression and multivariable Cox regression were used to select variables to establish the prediction model. The VETC-positive group had a statistically lower survival rate than the VETC-negative group. The selected variables were peritumoral enhancement in the arterial phase (AP), hepatobiliary phase (HBP) on EOB-MRI, intratumoral branching enhancement in the AP of CEUS, intratumoral hypoenhancement in the portal phase of CEUS, incomplete capsule, and tumor size. A nomogram was developed. High and low nomogram scores with a cutoff value of 168 points showed different recurrence-free survival rates and overall survival rates. The area under the curve (AUC) and accuracy were 0.804 and 0.820, respectively, indicating good discrimination. Decision curve analysis showed a good clinical net benefit (threshold probability > 5%), while the Hosmer-Lemeshow test yielded excellent calibration (P = 0.6759). The AUC of the nomogram model combining EOB-MRI and CEUS was higher than that of the models with EOB-MRI factors only (0.767) and CEUS factors only (0.7). The nomogram verified by bootstrapping showed AUC and calibration curves similar to those of the nomogram model. The Prediction model based on CEUS and EOB-MRI is effective for preoperative noninvasive diagnosis of VETC.

DOI： 10.5582/bst.2024.01112

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Although the combination of atezolizumab and bevacizumab (ATZ + BEV) is a standard treatment for advanced hepatocellular carcinoma (HCC), strategies for addressing treatment failure and prognostic factors of post-progression survival (PPS) remain unestablished. METHODS: We conducted a multicentre retrospective study to evaluate PPS following ATZ + BEV treatment in patients with advanced HCC. We classified the patients into three groups: BCLC stage B and BCLC stage C without or with new extrahepatic lesions (BCLCp-C1 and BCLCp-C2, respectively) at the time of progression. RESULTS: Of the 204 patients who started ATZ + BEV treatment between October 2020 and September 2022, 110 showed disease progression, with 33, 55 and 22 showing the BCLCp-B, BCLCp-C1 and BCLCp-C2 stages of the disease, respectively. Specifically, patients with the BCLCp-B stage of the disease showed better overall survival than those with the BCLCp-C1 and BCLCp-C2 stages (hazard ratios: 1.93 [95% confidence interval, CI, 1.06-3.51] and 2.64 [95% CI, 1.32-5.30] for HCC stages BCLCp-C1 and BCLCp-C2, respectively). Via multivariable analysis, we identified the BCLCp-C1 and BCLCp-C2 stages, as well as performance status, Child-Pugh class and alpha-fetoprotein as poor prognostic factors for PPS. CONCLUSIONS: BCLCp-B1 stage was identified as a better prognostic factor for PPS following ATZ + BEV treatment compared with BCLCp-C1 and BCLCp-C2 stages. This may help in making decisions regarding subsequent treatment after ATZ + BEV.

DOI： 10.1111/liv.15825

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The differential diagnosis of solid pancreatic lesions (SPLs) using B-mode endoscopic ultrasonography (EUS) is challenging. Detective flow imaging (DFI) offers the potential for detecting low-flow vessels in the pancreas, thus enhancing diagnostic accuracy. This retrospective study aimed to investigate DFI-EUS findings of SPLs and analyze their differential diagnostic accuracy for pancreatic cancer. We included 104 patients with pathologically confirmed SPLs who underwent EUS between April 2021 and June 2023. Expert endosonographers, blinded to the patients' clinical data, evaluated images obtained through B-mode, eFLOW, and DFI-EUS. The frame rate and vessel detection sensitivity were compared between eFLOW and DFI, and the diagnostic criteria for pancreatic cancer were established. The visualization rate for vessels in SPLs was significantly higher with DFI-EUS (96%) compared to eFLOW (27%). Additionally, DFI showed a superior frame rate, sensitivity (99%), and accuracy (88%) for detecting pancreatic cancer, although with a modest specificity (43%). On DFI-EUS, characteristics such as hypovascularity, peritumoral vessel distribution, or spotty vessel form were suggestive of pancreatic cancer. DFI-EUS significantly improved the visualization of vascular structures within the SPLs, highlighting its efficacy as a diagnostic modality for pancreatic cancer.

DOI： 10.3390/diagnostics14090882

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：英語  

In clinical cases of pancreas divisum, endoscopic retrograde cholangiopancreatography often necessitates cannulation of the pancreatic duct through the minor papilla. Nevertheless, this procedure can be challenging because of the small size of the minor papilla and the difficulty in visualizing the ductal orifice. A new image-enhanced endoscopy technique called texture and color enhancement imaging (TXI) has been developed, which enhances texture, brightness, and color compared with white-light imaging, resulting in subtle differences in the surface mucosa. Herein, we describe the case of a 73-year-old man with pancreas divisum in whom TXI was useful in identifying the orifice of the minor papilla. He was referred to our hospital with repetitive acute exacerbation of chronic pancreatitis. Since contrast-enhanced computed tomography revealed a pancreatic stone in the main pancreatic duct, endoscopic retrograde cholangoepancreatography was performed as a therapeutic intervention. Despite the initial difficulty in identifying the orifice of the minor papilla on white-light imaging, TXI enhanced its visibility successfully, enabling dorsal pancreatic duct cannulation via the minor papilla. Subsequently, endoscopic pancreatic sphincterotomy was performed and a 6Fr plastic stent was placed. Post-endoscopic therapy, the patient's abdominal pain was relieved. TXI was useful in identifying the minor papilla orifice and led to successful cannulation.

DOI： 10.1002/deo2.358

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DOI： 10.22541/au.171189338.87013934/v1

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND AIM: Gastrointestinal stromal tumors (GISTs) are treated as malignant gastric subepithelial lesions (SELs), and resection is recommended. However, small gastric SELs < 20 mm with no malignant features are monitored without histopathological examination, and the frequency of malignancy is unknown. This study aimed to clarify the clinicopathological findings and clinical course of gastric SELs < 20 mm measured by endoscopic ultrasound (EUS). METHODS: This retrospective cohort study included consecutive patients with small gastric SELs < 20 mm diagnosed using EUS at a tertiary referral center between 2009 and 2021. The clinical course after diagnosis using EUS-guided fine-needle aspiration (EUS-FNA) was reviewed. RESULTS: Among 333 patients with small gastric SELs, 104 patients with 105 lesions underwent EUS-FNA. The pathological diagnosis was confirmed in 87 patients. GISTs were the most common pathology (47%). Among the 87 patients, 43 underwent therapeutic interventions, including tumor resection and chemotherapy. In groups of tumor resection, the pathological tumor size on the resected specimen was significantly larger than the size measured by EUS (19.5 mm vs 15.0 mm, P < 0.001), and 37% of resected SELs were 20 mm or over. No recurrence was observed after tumor resection during a mean follow-up period of 40 months. CONCLUSIONS: Approximately 40% of small gastric SELs were malignant tumors, such as GIST, with most of them requiring treatment. Additionally, considering that the EUS measurement is 5 mm smaller than the pathological tumor diameter, further examinations, such as systematic EUS-FNA, may be required for SEL, including those smaller than 20 mm.

DOI： 10.1111/jgh.16534

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: Japanese guidelines recommend posttreatment endoscopy once or twice a year after endoscopic submucosal dissection (ESD) for early gastric cancer. However, the impact of endoscopy intervals on metachronous gastric cancer (MGC) remains unclear, especially the difference between 1-year and half-a-year intervals. We aimed to investigate this difference. METHODS: This study retrospectively investigated 2429 patients who underwent gastric ESD between May 2001 and June 2019 at our hospital. Patients who developed MGC were classified based on those who underwent the previous endoscopy within at least 7 months (short-interval group) and within 8-13 months (regular-interval group). Propensity score matching (PSM) was used to adjust for possible confounders. The primary outcome was the proportion of MGC beyond curative ESD criteria established in the guidelines. RESULTS: A total of 216 eligible patients developed MGC. The short- and regular-interval groups included 43 and 173 patients, respectively. Overall, no patients in the short-interval group had MGC beyond curative ESD criteria, while 27 patients in the regular-interval group did. The proportion of MGC beyond curative ESD criteria was significantly lower in the short-interval group than in the regular-interval group before (P = 0.003) and after (P = 0.028) PSM. Although not significant, the short-interval group tended to have a higher stomach preservation rate than the regular-interval group (P = 0.093). CONCLUSION: Our study indicated a possible benefit of biannual surveillance endoscopy in the early post-ESD period.

DOI： 10.1111/den.14599

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記述言語：英語  

Miwa and colleagues report on their experience with a newly developed peroral cholangioscope that is effective for the removal of difficult stones in the common bile duct and the cystic duct. The scope offers a large working channel and a high mobility bending section, increasing the efficacy of electrohydraulic lithotripsy.

DOI： 10.1002/jhbp.1385

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1055/a-1930-6258

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1055/a-2109-0561

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: An esophageal diverticulum is a relatively rare disease, with reports of treatment for esophageal cancer in the diverticulum even rarer. CASE PRESENTATION: The case involved a 72-year-old male with a chief complaint of dysphagia. He was diagnosed with an esophageal diverticulum (Zenker's diverticulum) measuring 10 cm in diameter. Five years later, an upper gastrointestinal endoscopy revealed an iodine-unstained 0-IIb lesion of 20 mm in diameter with type B1 vessels in the diverticulum. An endoscopic biopsy and CT revealed it to be squamous cell carcinoma, cT1a-EP/LPM N0 M0, cStage 0. Because the lesion was in the diverticulum and endoscopic resection was difficult with the risk of perforation, surgical resection was set as the course of treatment. Diverticulectomy was performed via a cervical approach, using a stapler, and the patient was discharged on the 16th day without any complications. The pathological diagnosis was pTis-EP, ly0, v0, R0. CONCLUSIONS: We think this case is very rare and diverticulectomy of early esophageal cancer in the diverticulum is available and safe.

DOI： 10.1186/s44215-023-00123-5

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: This was a prospective, multicenter, single-arm intervention, against historical controls, study of the efficacy of a vonoprazan-based 7-day triple regimen with metronidazole (VPZ-AMPC-MNZ) as a first-line therapy for eradicating clarithromycin-resistant Helicobacter pylori (H. pylori). METHODS: We enrolled 35 patients positive for clarithromycin-resistant H. pylori, as assessed by culture, without a history of eradication. These 35 patients were prospectively eradicated with VPZ-AMPC-MNZ. As historical controls, we also assessed 98 patients with clarithromycin-resistant H. pylori from our prior prospective studies, who achieved H. pylori eradication with a 7-day triple regimen including clarithromycin (VPZ-AMPC-CAM). A preplanned analysis was performed as a superiority study against the historical controls (VPZ-AMPC-MNZ compared to VPZ-AMPC-CAM). In each regimen, vonoprazan was used at 20 mg bid, amoxicillin at 750 mg bid, metronidazole at 250 mg bid, and clarithromycin at 200 mg or 400 mg bid for 7 days. We assessed the outcome of eradication therapy using a 13C-urea breath test or H. pylori stool antigen test. We evaluated safety using patient questionnaires. RESULTS: The intention-to-treat (ITT) and per-protocol (PP) eradication rates of VPZ-AMPC-MNZ were both 100% (95% confidence interval (95% CI) 90.0-100%, n = 35). The eradication rates of VPZ-AMPC-CAM were 76.5% (95% CI 66.9-84.5%, n = 98) in the ITT analysis and 77.3% (95% CI 67.7-85.2%, n = 97) in the PP analysis. The eradication rate of VPZ-AMPC-MNZ was significantly higher than that of VPZ-AMPC-CAM in both the ITT (p = 0.00052) and PP (p = 0.00095) analyses. CONCLUSIONS: The findings suggest that 7-day VPZ-AMPC-MNZ was superior to 7-day VPZ-AMPC-CAM as a first-line regimen for eradicating clarithromycin-resistant H. pylori. We suggest VPZ-AMPC-MNZ as the standard first-line regimen for eradication of clarithromycin-resistant H. pylori in Japan.

DOI： 10.3390/jcm12175443

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記述言語：日本語   出版者・発行元：(一社)日本胆道学会  

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記述言語：日本語   出版者・発行元：(一社)日本胆道学会  

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記述言語：日本語   出版者・発行元：(一社)日本膵臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本膵臓学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: Irinotecan and trifluridine/tipiracil (FTD/TPI) are fourth-line treatment options after third-line nivolumab for advanced gastric cancer (AGC). However, the efficacy and safety of irinotecan and FTD/TPI in the fourth-line setting after third-line nivolumab remains unclear. This study aimed to evaluate the efficacy and safety of irinotecan and FTD/TPI in the fourth-line setting after third-line nivolumab. PATIENTS AND METHODS: We identified 137 AGC patients treated with nivolumab as third-line treatment in our institute between October 2017 and July 2021. Of these, we recruited 19 AGC patients who initiated irinotecan and 23 AGC patients who initiated FTD/TPI in the fourth-line setting until September 2021. RESULTS: The median overall survival was 5.83 months for irinotecan and 6.31 months for FTD/TPI. Median time-to-treatment failure was 2.07 months for irinotecan and 1.64 months for FTD/TPI. While the frequency of all-grade diarrhea was higher in irinotecan (36% vs. 17%), grade ≥3 neutropenia tended to be higher in FTD/TPI (21% vs. 35%). CONCLUSION: Irinotecan and FTD/TPI may be clinically useful as fourth-line treatments after nivolumab.

DOI： 10.21873/anticanres.16452

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1111/den.14570

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND AIM: Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) is widely used in the management of biliary obstructions; however, literature on guidewire manipulation is lacking. This study aimed to assess the utility and optimal conditions of the loop technique for guidewire manipulation during EUS-HGS. METHODS: Consecutive patients who underwent EUS-HGS between April 2015 and January 2022 were included in this study. Patient characteristics and procedural details were retrospectively analyzed. Guidewire manipulations were classified as conventional technique or loop technique, based on the shape of the guidewire tip. RESULTS: A total of 52 patients (Median age: 73 years, 38 male and 14 female) underwent EUS-HGS. The median guidewire insertion time was 49 s and the median overall procedure time was 20.5 min. The initial guidewire direction was toward the peripheral side in 23 patients (44%). Technical success rate of the EUS-HGS was 100%. Twenty patients (38%) underwent the procedure using the loop technique and 32 (62%) with the conventional technique. In the logistic regression analysis, an angle between the bile duct and needle of >70° was independently associated with use of the loop technique (OR 9.84; 95% CI: 2.24-43.13; P <0.01). CONCLUSION: This study revealed the utility of the loop technique in EUS-HGS. This technique is recommended if the bile duct is punctured at an angle >70°.

DOI： 10.1002/jgh3.12903

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/den.14530

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Immune checkpoint inhibitors (ICIs) are effective for advanced hepatocellular carcinoma (HCC). However, there are few reports on the correlation between the clinical efficacy of ICIs and the development of immune-related adverse events (irAEs) in patients with HCC. The aim of this study was to investigate the association between irAE development and survival in patients with HCC treated with atezolizumab plus bevacizumab. PATIENTS AND METHODS: We enrolled 150 patients with advanced HCC treated with atezolizumab plus bevacizumab between October 2020 and October 2021 at 5 territorial institutions. We compared the efficacy of atezolizumab plus bevacizumab between patients who experienced irAEs (irAE group) and those who did not (non-irAE group). RESULTS: Thirty-two patients (21.3%) developed irAEs of any grade. Grade 3/4 irAEs were observed in 9 patients (6.0%). The median progression-free survivals (PFS) in the irAE and non-irAE groups were 273 and 189 days, respectively (P = .055). The median overall survivals (OS) in the irAE and non-irAE groups were not reached and 458 days, respectively (P = .036). Grade 1/2 irAEs significantly prolonged PFS (P = .014) and OS (P = .003). Grade 1/2 irAEs were significantly associated with PFS (hazard ratio [HR], 0.339; 95% confidence interval [CI], 0.166-0.691; P = .003) and OS (HR, 0.086; 95% CI, 0.012-0.641; P = .017) on multivariate analysis. CONCLUSION: The development of irAEs was associated with increased survival in a real-world population of patients with advanced HCC treated with atezolizumab plus bevacizumab. Grade 1/2 irAEs were strongly correlated with PFS and OS.

DOI： 10.1093/oncolo/oyad090

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記述言語：英語  

A 45-year-old man underwent esophagogastroduodenoscopy because of symptoms of laryngopharyngeal discomfort. We found a protruded reddish lesion adjacent to the ectopic gastric mucosa (EGM) in the cervical esophagus, and a biopsy revealed that it was a tubular adenocarcinoma. We diagnosed the patient with intramucosal cancer and performed endoscopic submucosal dissection. Esophageal endoscopic submucosal dissection was performed under general anesthesia using a conventional procedure. The resected tumor measured 23 × 14 mm and was adjacent to the EGM. Histologically, the tumor cells showed moderately well-differentiated adenocarcinoma confined to the muscularis mucosa with no lymphovascular infiltration. Immunohistochemically, the tumor cells were positive for intestinal markers, namely MUC2 and CD10, and negative for gastric markers, namely MUC5AC and MUC6. The patient had no post-endoscopy submucosal dissection stenosis and remained disease-free without local recurrence. EGM of the cervical esophagus develops from the columnar epithelium during embryonic development. There are few reports on endoscopic submucosal dissection for mucosal cancer. Of these, immunostaining was performed in three cases. All were positive for MUC5AC and MUC6 and negative for MUC2 and CD10. Usually, EGM shows gastric type epithelium, but occasional cases with intestinal metaplasia, which show positivity for MUC2 and CD10, have been reported. Therefore, we consider this to be an extremely rare case of esophageal adenocarcinoma arising from intestinal metaplasia within the EGM.

DOI： 10.1002/deo2.141

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記述言語：英語  

DOI： 10.1093/ibd/izad023

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: In women with inflammatory bowel disease, at least 3 months of preconception corticosteroid-free remission (CFREM) is recommended by experts in current consensus statements. However, data are lacking on the appropriate preconception remission period. We investigated the appropriate preconception CFREM period in women with ulcerative colitis to reduce maternal disease activity and adverse pregnancy outcomes (ie, preterm birth, low birth weight, and small for gestational age). METHODS: We retrospectively examined 141 pregnancies in women with ulcerative colitis at 2 institutions. We categorized the patients into 3 subgroups by their preconception CFREM period (≥3 months, >0 to <3 months, and non-CFREM). We also investigated disease activity during pregnancy and postpartum and adverse pregnancy outcomes in each group. RESULTS: During pregnancy, the rate of active disease was significantly lower in the ≥3 months and >0 to <3 months CFREM groups compared with that in the non-CFREM group (P < .001 and P = .0257, respectively). Postpartum, the rate of active disease was significantly lower in the ≥3 months CFREM group compared with that in the non-CFREM group (P = .0087). The preconception CFREM period of ≥3 months was an independent inhibitory factor for active disease during pregnancy and postpartum (adjusted odds ratio, 0.15; P = .0035; and adjusted odds ratio, 0.33; P = .027, respectively). Adverse pregnancy outcomes were less common in the >3 months CFREM group compared with those in the other groups, but this difference was not significant. CONCLUSIONS: A preconception CFREM period of more than 3 months may be appropriate for better maternal and adverse pregnancy outcomes, as recommended in consensus statements.

DOI： 10.1093/ibd/izac270

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: To date, no interventional trial has assessed the efficacy and safety of vonoprazan and high-dose (500 mg four times daily, 2000 mg/day) amoxicillin dual therapy in terms of Helicobacter pylori eradication. We explored whether this was an appropriate first-line treatment. METHODS: This prospective, dual-center, single-arm interventional study was performed in Japan. Twenty H. pylori-positive patients lacking any eradication history were treated with vonoprazan 20 mg twice daily and amoxicillin 500 mg four times daily (qid) for 7 days. Eradication was evaluated using a stool H. pylori antigen test. We evaluated safety using patient questionnaires. This study was registered in the jRCT database (jRCT031200128). RESULTS: The intention-to-treat and per-protocol eradication rates were 90% (95% confidence interval [CI] 68.3-98.8%, n = 20) and 94.4% (95% CI 72.7-99.9%, n = 18) respectively. No significant adverse event was recorded. CONCLUSION: Vonoprazan/high-dose amoxicillin dual therapy can be a safe standard first-line therapy. We are now undergoing a randomized controlled trial comparing dual therapy and vonoprazan-based triple therapy.

DOI： 10.1002/jgh3.12852

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Endoscopic resection (ER) is feasible for treating well-circumscribed dysplasia in patients with ulcerative colitis (UC). However, long-term prognosis of ER for high-grade dysplasia (HGD) in patients with UC remains unclear. We aimed to evaluate the long-term prognoses of ER for HGD compared with low-grade dysplasia (LGD) and verify the feasibility of ER and follow-up with surveillance colonoscopy for HGD. METHODS: An observational, single-center retrospective study included 38 and 22 patients with LGD and HGD who were followed-up with surveillance colonoscopy after ER. We evaluated the cumulative incidence rate of metachronous HGD or colorectal cancer (CRC) and identified the characteristics of metachronous dysplasia. RESULTS: The median follow-up period was 56 months, and surveillance colonoscopies were performed 3.6 times (mean). The 5-year cumulative incidence rate of HGD/CRC was relatively high in HGD (24.6%) than in LGD (13.7%), but the difference was not significant (p = .16). In HGD cases, six metachronous dysplasia lesions (two LGD and four HGD) were detected 11.6-40.5 months after ER. However, these patients did not progress to CRC. All metachronous lesions were well-circumscribed and with no invisible dysplasia surrounding them; they were 'endoscopically resectable' lesions. Two of the four metachronous HGD lesions were treated endoscopically and two, by colectomy. No synchronous HGD or CRC was detected in the colectomy specimens. CONCLUSIONS: Our results suggest that ER and follow-up with surveillance colonoscopy is feasible in patients with HGD when histological complete resection is achieved.

DOI： 10.1080/00365521.2022.2107878

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Endoscopic full-thickness resection (EFTR) without laparoscopic assistance (pure EFTR) is an emerging, less invasive treatment for gastrointestinal stromal tumors (GISTs). However, the technique has seldom been performed outside China because of concerns regarding pneumoperitoneum, maintenance of endoscopic view, and endoscopic suturing. This study aimed to evaluate the efficacy and safety of endoscopic resection with one-port placement (EROPP) for gastric GISTs. METHODS: This retrospective study included 17 patients with gastric GISTs originating from the muscularis propria who underwent EROPP between 2019 and 2022. One camera port was inserted in the umbilicus before initiating the endoscopic procedure to maintain intra-abdominal pressure, which was monitored and adjusted via this port. While allowing for conversion to laparoscopic surgery if needed, EFTR was performed as follows: (1) circumferential incision of the mucosal and submucosal layers around the lesion was performed by typical endoscopic submucosal dissection; (2) an intentional perforation and subsequent seromuscular resection was made using dental floss and an endo-clip for traction; and (3) closure of the gastric full-thickness defect was performed with an over-the-scope clip (OTSC) after peroral retrieval of the specimen. We retrospectively assessed the short-term outcomes and safety. RESULTS: All procedures were completed successfully without conversion to laparoscopic surgery. The median size of the resected tumors was 23 mm (range, 8-35 mm), the median resection time was 36 min (range, 22-95 min), and closure time was 18 min (range, 10-45 min). The rates of en bloc and complete resection were 100% and 88%, respectively. In 2 cases, another port was added to aspirate the leaking fluid or check the condition of the endoscopic closure. All gastric defects were endoscopically closed, mainly using OTSCs. The recovery course for all patients was uneventful, and no adverse events were reported. CONCLUSIONS: EROPP is a safe and minimally invasive treatment for gastric GISTs and appears to be suitable for introducing EFTR procedures.

DOI： 10.1159/000532012

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Serrated polyps have recently been reported in patients with ulcerative colitis (UC); however, their prevalence and detailed characteristics remain unclear. METHODS: The prevalence and clinicopathological and biological characteristics of serrated polyps in patients with UC were retrospectively examined in a single tertiary inflammatory bowel disease center in Japan from 2000 to 2020. RESULTS: Among 2035 patients with UC who underwent total colonoscopy, 252 neoplasms, including 36 serrated polyps (26 in colitis-affected segments, 10 in colitis-unaffected segments), were identified in 187 patients with UC. The proportion of serrated polyps was 1.8% (36/2035). Serrated polyps in colitis-affected segments were common with extensive colitis (88%), history of persistent active colitis (58%), and long UC duration (12.1 years). Serrated polyps in colitis-affected segments were more common in men (88%). Of the 26 serrated polyps in colitis-affected segments, 15, 6, and 5 were categorized as sessile serrated lesion-like dysplasia, traditional serrated adenoma-like dysplasia, and serrated dysplasia not otherwise specified, respectively. Sessile serrated lesion-like dysplasia was common in the proximal colon (67%) and with BRAF mutation (62%), whereas traditional serrated adenoma-like dysplasia and serrated dysplasia not otherwise specified were common in the distal colon (100% and 80%, respectively) and with KRAS mutations (100% and 75%, respectively). CONCLUSIONS: Serrated polyps comprised 14% of the neoplasias in patients with UC. Serrated polyps in colitis-affected segments were common in men with extensive and longstanding colitis, suggesting chronic inflammation in the development of serrated polyps in patients with UC.

DOI： 10.1371/journal.pone.0282204

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Pregnancy is a known risk factor for amebic enteritis, which develops into potentially fatal fulminant amebic enteritis in some cases. We describe a case of a 27-year-old non-immunosuppressed pregnant woman with fulminant amebic enteritis complicated with cytomegalovirus enteritis. She improved with intensive care and intravenous metronidazole and ganciclovir but eventually required subtotal colectomy for intestinal stenosis. It is difficult to diagnose amebic enteritis, especially in a non-endemic area. Amebic enteritis must be considered as a differential diagnosis for refractory diarrhea with bloody stools in women in the perinatal period, even those without immunosuppression.

DOI： 10.2169/internalmedicine.0839-22

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND AIMS: Superficial duodenal epithelial tumors are emerging targets for endoscopic submucosal dissection (ESD). However, it is unknown how competence is achieved in duodenal ESD. This study aimed to elucidate the learning curve for duodenal ESD. METHODS: This retrospective observational study included 100 consecutive patients who underwent duodenal ESD by a single endoscopist between March 2014 and September 2021. The primary outcome was to define the learning curve for duodenal ESD by an endoscopist with sufficient non-duodenal ESD experience. Cumulative sum (CUSUM) curve analysis was used to assess the learning curve in terms of procedural speed. Comparative analyses of phases identified using the CUSUM method were performed. RESULTS: In total, 98 patients were included in the analysis. Evaluation of the cumulative sum curve revealed four distinct phases in the graph: phase I, cases 1-25 (learning phase); phase II, cases 26-47 (proficiency phase); phase III, cases 48-72 (mastery phase); and phase IV, cases 73-98 (after introduction of general anesthesia). The median procedural speed was significantly faster in phase II than in phase I (11.1 mm2 /min vs 7.0 mm2 /min, P = .002). Clinically significant intraoperative perforation tended to decrease through phase II to phase IV (22.7%, 12.0%, and 3.8% in phases II, III, and IV, respectively). Delayed perforation occurred only in phases I and II. CONCLUSIONS: Duodenal ESD requires 25 cases to gain proficiency and 50 to achieve mastery even for an endoscopist with extensive non-duodenal ESD experience.

DOI： 10.1111/jgh.15995

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記述言語：日本語   出版者・発行元：(株)東京医学社  

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J02312&link_issn=&doc_id=20230124070006&doc_link_id=10.24479%2Fendo.0000000527&url=https%3A%2F%2Fdoi.org%2F10.24479%2Fendo.0000000527&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：日本語   出版者・発行元：(株)医学書院  

＜文献概要＞第81回食道色素研究会において全国13施設から提示された習慣的喫煙,飲酒歴のない食道表在癌104例110病変と,横浜市立大学附属市民総合医療センターの習慣的喫煙・飲酒歴のある食道表在癌544例767病変を対象として,習慣的喫煙,飲酒歴のない食道表在癌の臨床病理学的特徴を明らかにした.それらの特徴は,(1)女性に多く,(2)重複がんは少なく,(3)多発ヨード不染帯は少なく,(4)GERDを伴うことが多く,(5)胸部中部食道(Mt)後壁の局在が多く,(6)0-IIa型が多く,(7)病理組織学的に上皮内癌成分が"表層分化型"である病変が多い,ことであった.

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

DOI： 10.1007/s12328-022-01696-4

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その他リンク： https://link.springer.com/article/10.1007/s12328-022-01696-4/fulltext.html

掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

Abstract

Mucinous cystadenocarcinoma (MCAC) with malignant ascites is rare. We report a case of a 28-year-old woman who presented with epigastric pain. The ascites in the Douglas fossa was identified at a nearby gynecology clinic. Computed tomography showed a multiloculated cystic lesion (9.5 × 6.4 cm) in the tail of the pancreas, which was diagnosed as mucinous cystic neoplasm on imaging. Staging laparoscopy was performed, and rapid cytology of ascites revealed adenocarcinoma, leading to a diagnosis of unresectable MCAC. Subsequently, combination chemotherapy with gemcitabine plus S-1 was initiated. Although there were no remarkable changes in the imaging findings, the peritoneal dissemination node was not consistently recognized in any of the imaging findings, and distal pancreatectomy was performed. A peritoneal dissemination node was not observed in the laparotomy findings, but the peritoneal lavage cytology was positive. The postoperative pathological result was non-invasive MCAC, and the ascites was suspected to be caused by cyst rupture. The patient has been recurrence-free, including the reappearance of ascites, for &gt; 8 years after adjuvant therapy with S-1. Although careful follow-up will be required in the future, the very good prognosis in this case suggests that MCAC with malignant ascites without obvious peritoneal dissemination should be considered for surgical resection.

DOI： 10.1007/s12328-022-01639-z

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その他リンク： https://link.springer.com/article/10.1007/s12328-022-01639-z/fulltext.html

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: In this study, we investigated the impact of simple measurement of psoas muscle index (PMI) on the tolerability of sorafenib treatment of switch from sorafenib to regorafenib. METHOD: This retrospective study enrolled 109 patients with Child-Pugh A hepatocellular carcinoma (HCC) treated with sorafenib. Pretreatment PMI was calculated by measuring and multiplying the greatest anterior/posterior and transverse diameters of the psoas muscles on axial computed tomography images at the L3 vertebral level, and normalizing the sum of bilateral psoas muscle areas by the square of the height in meters. We, then, statistically analyzed the association between PMI and adverse events (AEs) to treatment, tolerability of sorafenib, time to treatment failure (TTF), and prognosis in patients stratified according to PMI. RESULT: Patients were divided into high PMI (n = 41) and low PMI (n = 68) groups based on the cutoff PMI values (men: 7.04 cm2/m2; women: 4.40 cm2/m2) determined by receiver operating characteristic curve analysis to determine sorafenib tolerability. Frequencies of all types of severe AEs were higher in the low PMI group (50.0%) than in the high PMI group (29.3%; P = 0.045). The high PMI group (51.2%) had greater tolerance to sorafenib than the low PMI group (25.0%; P = 0.007). Moreover, in multivariable analysis, PMI was associated with sorafenib tolerability (odds ratio 0.26; P = 0.008) and was a prognostic factor affecting TTF (hazard ratio 1.77; P = 0.021). CONCLUSION: PMI might be a predictive marker of tolerance to treatment and TTF in HCC patients receiving sorafenib treatment.

DOI： 10.1097/MEG.0000000000002346

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND AIMS: Endoscopic resection (ER) is feasible for well-circumscribed tumors in patients with ulcerative colitis (UC); however, the specific manner for diagnosis of the tumor border is unclear. We evaluated the efficacy of magnifying endoscopy (ME) for the diagnosis of tumor borders in UC. METHODS: We analyzed endoscopically or surgically resected tumors in UC patients in whom both chromoendoscopy (CE) and ME were performed, retrospectively. We classified the tumors based on tumor border visibility and evaluated tumor's characteristics and ER outcomes. RESULTS: We examined 100 tumors from 76 UC patients (66 distinct and 34 indistinct on CE). In 22 (65%) indistinct tumors on CE, ME improved the tumor border visibility. Compared with distinct tumors on CE, nonpolypoid and large tumors were more common in indistinct tumors on CE. In indistinct tumors even on ME, flat or depressed morphologies and type V pit were more frequently than in other groups. Sixty-five distinct tumors on CE and 18 distinct tumors on ME alone were treated endoscopically, and their R0 resection rate were 91% and 95% (p > 0.99). CONCLUSIONS: ME can improve the tumor border visibility in UC, and ER is feasible for tumors whose border can be visualized on ME.

DOI： 10.1016/j.dld.2022.03.003

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1002/ccr3.5981

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その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ccr3.5981

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Lenvatinib is approved as a first-line treatment for unresectable HCC. The therapeutic duration of lenvatinib is limited by resistance, but the underlying mechanism is unclear. To establish lenvatinib-resistant cells, Hep3B cells were initially treated with 3 µM lenvatinib. The concentration was gradually increased by 1 µM or 0.5 µM per week and it reached to 7.5 µM 2 months after the initial exposure to lenvatinib. The biological characteristics of these cells were analyzed by ERK activation in the MAPK signaling pathway and a human phospho-receptor tyrosine kinase (RTK) antibody array. Factors possibly related to lenvatinib resistance were analyzed using inhibitors, and cell proliferation was analyzed. We established lenvatinib-resistant HCC cells (LR cells) by long-term exposure to lenvatinib. Lenvatinib reduced ERK activation in the parent cells, but not in the LR cells. RTK array analysis showed that the activities of EGFR and insulin-like growth factor 1 receptor (IGF1R)/insulin receptor (INSR) were significantly increased in LR cells, whereas the activities of other RTKs were unchanged. Erlotinib, a widely used EGFR inhibitor, downregulated ERK activation in LR cells. The proliferation of LR cells will also be affected when lenvatinib is combined with erlotinib to treat LR cells. In contrast, inhibition of IGFR/INSR did not affect ERK activation or cell proliferation. Scavenging of reactive oxygen species (ROS) ameliorated the enhanced EGFR activation in LR cells. Lenvatinib resistance was induced by enhanced EGFR activation, possibly via ROS accumulation, in lenvatinib- resistant cells. These findings may enable the development of lenvatinib combination therapies for HCC.

DOI： 10.1038/s41598-022-12076-w

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To assess the utility of measurement of the computed tomography (CT) attenuation value (CTav) in predicting tumor necrosis in hepatocellular carcinoma (HCC) patients who achieve a complete response (CR), defined using modified Response Evaluation Criteria in Solid Tumors (mRECIST), after lenvatinib treatment. METHOD: We compared CTav in arterial phase CT images with postoperative histopathology in four patients who underwent HCC resection after lenvatinib treatment, to determine CTav thresholds indicative of histological necrosis (N-CTav). Next, we confirmed the accuracy of the determined N-CTav in 15 cases with histopathologically proven necrosis in surgical specimens. Furthermore, the percentage of the tumor with N-CTav, i.e., the N-CTav occupancy rate, assessed using Image J software in 30 tumors in 12 patients with CR out of 571 HCC patients treated with lenvatinib, and its correlation with local recurrence following CR were examined. RESULTS: Receiver operating characteristic (ROC) curve analysis revealed an optimal cut-off value of CTav of 30.2 HU, with 90.0% specificity and 65.0% sensitivity in discriminating between pathologically identified necrosis and degeneration, with a CTav of less than 30.2 HU indicating necrosis after lenvatinib treatment (N30-CTav). Furthermore, the optimal cut-off value of 30.6% for the N30-CTav occupancy rate by ROC analysis was a significant indicator of local recurrence following CR with 76.9% specificity and sensitivity (area under the ROC curve; 0.939), with the CR group with high N30-CTav occupancy (≥30.6%) after lenvatinib treatment showing significantly lower local recurrence (8.3% at 1 year) compared with the low (&lt;30.6%) N30-CTav group (p &lt; 0.001, 61.5% at 1 year). CONCLUSION: The cut-off value of 30.2 HU for CTav (N30-CTav) might be appropriate for identifying post-lenvatinib necrosis in HCC, and an N30-CTav occupancy rate of &gt;30.6% might be a predictor of maintenance of CR. Use of these indicators have the potential to impact systemic chemotherapy for HCC.

DOI： 10.3390/curroncol29050266

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objectives: Recently, a novel clip device, SureClip® (Micro-Tech Co. Ltd., Nanjing, China), has been developed, which improved rotation and reopening performance. We aimed to assess the efficacy of the SureClip® in prophylactic closure of the mucosal break after endoscopic papillectomy (EP) for ampullary neoplasm. Methods: We retrospectively reviewed the medical records of 40 patients who underwent EP for ampullary neoplasms between October 2009 and March 2020. Prophylactic closure after resection was performed using the conventional clip between 2014 and 2018, and with the SureClip® after 2019. The baseline characteristics, techniques, outcomes, and complications of EP were analyzed. Results: The median age of the patients (25 males and 15 females) was 70 years. The en block resection rate was 82.5% and the curative resection rate was 80.0%. Histologically, 11 (27.5%) patients had malignancy. Prophylactic closure was performed in 29 (72.5%) patients (17 conventional clips, 12 SureClip®). Complications occurred in 18 (45.0%) patients, including postprocedure bleeding in 9 (22.5%) patients. However, no postprocedure bleeding was observed in the patients who received prophylactic closure using the SureClip® (p = 0.038). All other factors were not significantly correlated with postprocedure bleeding. The duration of hospital stay after EP was significantly shorter in patients treated with the SureClip® compared to those treated with a conventional clip or without clips (p < 0.05). Conclusions: In the present study, prophylactic clipping of the mucosal break using the SureClip® was effective in preventing bleeding after EP.

DOI： 10.1002/deo2.51

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記述言語：日本語   出版者・発行元：(一社)日本胃癌学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To assess the impact of clinical factors on the safety and efficacy of atezolizumab plus bevacizumab (ATZ + BV) treatment in patients with unresectable hepatocellular carcinoma (u-HCC). METHOD: Ninety-four u-HCC patients who were treated with ATZ + BV at multiple centers were enrolled. We defined Child-Pugh (CP)-A patients who received ATZ + BV treatment as a first line therapy as the 'meets the broad sense of the IMbrave150 criteria' group (B-IMbrave150-in, n = 46), and patients who received ATZ + BV treatment as a later line therapy or CP-B patients (regardless of whether ATZ + BV was a first line or later line therapy) as the B-IMbrave150-out group (n = 48). Patients were retrospectively analyzed for adverse events (AEs) and treatment outcomes according to their clinical characteristics, including neutrophil lymphocyte ratio (NLR) at baseline. RESULTS: The overall incidence of AEs was 87.2% (82/94 patients). The frequency of interruption of ATZ + BV treatment due to fatigue was higher in CP-B than CP-A patients (p = 0.030). Objective response (OR) rates of the B-IMbrave150-in group (28.3%, 39.1%) were significantly higher than those of the B-IMbrave150-out group (8.3%, 18.8%; p = 0.0157, 0.0401) using Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST, respectively. In multivariate analysis, NLR (hazard ratio (HR), 4.591; p = 0.0160) and B-IMbrave150 criteria (HR, 4.108; p = 0.0261) were independent factors associated with the OR of ATZ + BV treatment using RECIST. CONCLUSION: In real-world practice, ATZ + BV treatment might offer significant benefits in patients who meet B-IMbrave150 criteria or have low NLR.

DOI： 10.1111/hepr.13732

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Helicobacter pylori (HP) infection causes chronic inflammation and atrophy of the gastric mucosa and thus a high risk of gastric cancer (GC). With the increasing success of HP infection treatment, a larger number of GCs that develop after eradication can be assessed. Several studies have shown that epithelium with low-grade atypia (ELA) is a frequent characteristic of these GCs, but the origin of this condition is unknown. In this study, we compared the mucin phenotype, cellular proliferation, and p53 staining in ELA and cancerous tissues obtained from patients with GC with and without HP eradication. METHODS: The study population consisted of 23 patients with GC that developed after successful HP eradication therapy (eradicated group) and 24 patients with GC and HP infection (infected group). The prevalence of ELA was determined by hematoxylin and eosin staining. Tumor tissue and ELA samples were further analyzed by immunohistochemical staining for Muc5AC, Muc2, p53, and Ki-67. RESULTS: The ELA coverage rate was significantly higher in the eradicated group than in the infected group. Gastric-type mucin was frequently expressed by the ELA, and the mucin phenotypes of ELA and cancerous areas differed in 75% of cases. The Ki-67 labeling index was consistently lower in ELA than in the cancerous mucosa. Fourteen of 21 (66.7%) cancerous lesions, but only 3 ELA samples, were p53-positive. CONCLUSION: In most cases, ELA on the surfaces of GCs seems to have originated from normal gastric cells, not from cancer cells.

DOI： 10.1159/000521875

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Endoscopic resection, especially endoscopic submucosal dissection (ESD), is increasingly performed in elderly patients with early gastric cancer, and lesions beyond the expanded indications are also resected endoscopically in some patients. It is essential to assess whether gastric ESD is safe and suitable for elderly patients and investigate what type of lesions carry an increased risk of ESD-related complications. AIM: To assess the efficacy and feasibility of gastric ESD for elderly patients, and define high-risk lesions and prognostic indicators. METHODS: Among a total of 1169 sessions of gastric ESD performed in Kanagawa Cancer Center Hospital from 2006 to 2014, 179 sessions (15.3%) were performed in patients aged ≥ 80 years, and 172 of these sessions were done in patients with a final diagnosis of gastric cancer. These patients were studied retrospectively to evaluate short-term outcomes and survival. The short-term outcomes included the rates of en bloc resection and curative resection, complications, and procedure-related mortality. Curability was assessed according to the Japanese Gastric Cancer Treatment Guidelines 2010. Fisher's exact test was used to statistically analyze risk factors. Clinical characteristics of each group were compared using Fisher's exact test and Mann-Whitney U test. Survival rates at each time point were based on Kaplan-Meier estimation. Overall survival rates were compared between patients with gastric cancer in each group with use of the log-rank test. To identify prognostic factors that jointly predict the hazard of death while controlling for model overfitting, we used the least absolute shrinkage and selection operator (LASSO) Cox regression model including factors curative/ noncurative, age, gender, body mass index, prognostic nutritional index, Charlson comorbidity index (CCI), Glasgow prognostic score, neutrophil-to-lymphocyte ratio, and antithrombotic agent use. We selected the LASSO Cox regression model that resulted in minimal prediction error in 10-fold cross-validation. P < 0.05 was considered statistically significant. RESULTS: The en bloc dissection rate was 97.1%, indicating that a high quality of treatment was achieved even in elderly patients. As for complications, the rates of bleeding, perforation and aspiration pneumonitis were 3.4%, 1.1% and 0.6%, respectively. These complication rates indicated that ESD was not associated with a particularly higher risk in elderly patients than in nonelderly patients. A dissection incision > 40 mm, lesions associated with depressions, and lesions with ulcers were risk factors for post-ESD bleeding, and location of the lesion in the upper third of the stomach was a risk factor for perforation in elderly patients (P < 0.05). Location of the lesion in the lower third of the stomach tended to be associated with a higher risk of bleeding. The overall survival (OS) did not differ significantly between curative and noncurative ESD (P = 0.69). In patients without additional surgery, OS rate was significantly lower in patients with a high CCI (≥ 2) than in those with a low CCI (≤ 1) (P < 0.001). CONCLUSION: Gastric ESD is feasible even in patients aged ≥ 80 years. Observation without additional surgery after noncurative ESD is reasonable, especially in elderly patients with CCI ≥ 2.

DOI： 10.4253/wjge.v14.i1.49

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS: There is a paucity of comparative data on the use of sorafenib and lenvatinib for unresectable hepatocellular carcinoma. We assessed the real-world treatment outcomes between using sorafenib and lenvatinib for unresectable hepatocellular carcinoma in the multiple molecular-targeted therapy era. METHODS AND RESULTS: We enrolled 386 patients treated with sorafenib or lenvatinib as the first-line therapy for unresectable hepatocellular carcinoma at multiple centers. Propensity score matching was performed to adjust for differences in baseline and tumor characteristics between the two groups. Propensity score matching identified 110 patients in each treatment group. The median overall survival was similar between lenvatinib and sorafenib (14.8 and 13.0 months, respectively; P = 0.352). The median progression-free survival was longer with lenvatinib than with sorafenib (7.6 and 3.9 months, respectively; P < 0.001). The overall response rate (P < 0.001) and disease control rate (P = 0.015), as defined by the modified Response Evaluation Criteria in Solid Tumors, were significantly better with lenvatinib than with sorafenib. The median overall survival was longer in patients who received subsequent treatment than in those who did not in the sorafenib group (23.1 and 5.7 months, respectively; P < 0.001), whereas the median overall survival with or without subsequent treatment did not differ significantly in the lenvatinib group (17.8 and 14.7 months, respectively; P = 0.439). CONCLUSION: Overall survival with sorafenib and lenvatinib was not significantly different. However, patients who received subsequent treatments had longer overall survival than those who received only first-line treatment with sorafenib, whereas lenvatinib did not show this effect.

DOI： 10.1002/jgh3.12691

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The present study aimed to evaluate the efficacy and safety of combined lenvatinib (first-line systemic therapy) and radiofrequency ablation (RFA) therapy in patients with intermediate-stage hepatocellular carcinoma with beyond up-to-seven criteria and Child-Pugh Class A liver function (CP A B2-HCC). METHODS: Twenty-two patients with CP A B2-HCC were enrolled in the study. The patients had no history of systemic treatment. For the initial lenvatinib administration in this study, all of the patients had an adequate course of treatment (no less than two weeks) and were administered the recommended dose. Of them, 13 were treated by means of lenvatinib monotherapy (monotherapy group), while the 9 patients with no contraindication to RFA operation and who had consented to RFA received initial lenvatinib plus subsequent RFA (combination group). The clinical outcomes that were considered to evaluate the treatments included tumor response, prognosis (recurrence and survivals), and possible adverse events (serum liver enzymes and clinically visible complications). RESULTS: The combination group exhibited a higher object response rate (9/9, 100%) as best tumor response than the monotherapy group (10/13, 76.9%). Longer progression-free survival (PFS) (12.5 months) and overall survival (OS) (21.3) were demonstrated in the combination group than in the monotherapy group (PFS: 5.5 months; OS:17.1 months). The combination group achieved a higher PFS rate (1-year: 74.1%) and OS rate (2-year: 80%) than the monotherapy group (1-year PFS rate: 0%; 2-year OS rate: 25.6%; for PFS, p<0.001; for OS, p=0.022). The treatment strategy was the independent factor for PFS (HR: 18.215 for monotherapy, p =0.010), which was determined by Cox regression analysis, suggesting that a combination strategy may reduce tumor progression when compared to the use of lenvatinib alone. There were no statistically significant intergroup differences that were observed in terms of adverse events, with the exception of ALT elevation (p=0.007) in the combination group. CONCLUSION: Our newly proposed combination therapy may potentially be effective and safe for CP A B2-HCC beyond up-to-seven criteria. A larger scale, multicenter, prospective study is warranted to confirm our findings.

DOI： 10.3389/fonc.2022.843680

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Hepatocellular carcinoma (HCC) has the third-highest incidence in cancers and has become one of the leading threats to cancer death. With the research on the etiological reasons for cirrhosis and HCC, early diagnosis has been placed great hope to form a favorable prognosis. Non-invasive medical imaging, including the associated contrast media (CM)-based enhancement scan, is taking charge of early diagnosis as mainstream. Meanwhile, it is notable that various CM with different advantages are playing an important role in the different imaging modalities, or even combined modalities. For both physicians and radiologists, it is necessary to know more about the proper imaging approach, along with the characteristic CM, for HCC diagnosis and treatment. Therefore, a summarized navigating map of CM commonly used in the clinic, along with ongoing work of agent research and potential seeded agents in the future, could be a needed practicable aid for HCC diagnosis and prognosis.

DOI： 10.3389/fonc.2022.921667

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BioMed Central Ltd  

Background: In clinical practice, many hepatocellular carcinoma (HCC) patients in Barcelona Clinical Liver Cancer (BCLC) stage A4–B1 cannot receive the curative treatments of liver transplantation, resection, and radiofrequency ablation (RFA), which are the recommended options according to liver cancer guidelines. Our aim is to study the feasibility of RFA and stereotactic body radiotherapy (SBRT) as a curative treatment for different multifocal HCCs in BCLC stage A4–B1 patients. Methods: From September 2014 to August 2019, 39 multifocal HCC lesions (median diameter: 16.6 mm) from 15 patients (median age: 73 years) were retrospectively selected. Among them, 23 were treated by RFA and the other 16 by SBRT because of predictable insufficiency and/or risk related to RFA performance. The indicators for evaluating this novel therapy were the tumor response, prognosis (recurrence and survival), and adverse effects (deterioration of laboratory test values and severe complications). Results: The median follow-up duration was 31.3 months (range: 15.1–71.9 months). The total patients with a one-year complete response, stable disease, or disease progression were 11, 1, and 3, respectively. In total, 8 and 2 patients had confronted intrahepatic or local recurrence, respectively. The one-year progression-free survival rate and local control rate were 80% (12/15 patients) and 97.4% (38/39 lesions), respectively. The median time to progression was 20.1 (2.8–45.1) months. The one- and two-year survival rates were 100 and 88.9%, respectively. In up to five months’ observation, no patient showed severe complications. Seven, four, and two patients had slight changes in their white blood cells, platelet count, or albumin–bilirubin grade, respectively. Conclusions: For patients with BCLC stage A4–B1, RFA and SBRT treatment for different multifocal HCCs may be a potential option because of the favorable prognosis and safety. However, before its application in clinical practice, prospective, controlled, large-scale studies are needed to further confirm our conclusions.

DOI： 10.1186/s12885-021-08897-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Nature Research  

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

DOI： 10.1038/s41598-021-86457-y

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記述言語：日本語   出版者・発行元：日本消化器病学会-関東支部  

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記述言語：日本語   出版者・発行元：日本消化器病学会-関東支部  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Vonoprazan (VPZ), a new potassium-competitive acid blocker, has been approved and used for Helicobacter pylori eradication in Japan. To date, many studies, as well as several systematic reviews and meta-analyses (MAs), have compared VPZ-based 7-day triple therapy with proton pump inhibitor (PPI)-based therapy. An MA of randomized controlled trials (RCTs) comparing first-line VPZ- with PPI-based triple therapy, the latter featuring amoxicillin (AMPC) and clarithromycin (CAM), found that approximately 30% of patients hosted CAM-resistant H. pylori; however, the reliability was poor because of high heterogeneity and a risk of selection bias. VPZ-based triple therapy is superior to PPI-based triple therapy for patients with CAM-resistant H. pylori, but not for those with CAM-susceptible H. pylori. An MA of non-RCTs found that second-line VPZ-based triple therapies were slightly (~2.6%) better than PPI-based triple therapies (with AMPC and metronidazole). However, the reliability of that MA was also low because of selection bias, confounding variables and a risk of publication bias; in addition, it is difficult to generalize the results because of a lack of data on antibiotic resistance. VPZ-based triple therapy (involving AMPC and sitafloxacin) was more effective than PPI-based triple therapy in a third-line setting, but a confirmatory RCT is needed. Non-RCT studies indicated that VPZ-based triple therapy involving CAM and metronidazole may be promising. Any further RCTs must explore the antibiotic-resistance status when evaluating the possible superiority of a potassium-competitive acid blocker.

DOI： 10.5009/gnl20242

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Endoscopic ultrasonography has become a routine procedure in clinical practice and is widely accepted as a safe procedure. Previous studies have reported that severe bleeding rarely occurs even when performing fine-needle aspiration biopsy. Severe hemorrhage following non-interventional endoscopic ultrasonography has never been reported. We herein report a case of hemorrhagic shock due to hemoperitoneum caused by a ruptured right gastroepiploic artery consequent to a diagnostic endoscopic ultrasonography. The patient was administered two antithrombotic agents. An extensive diagnostic workup contributed to the correct diagnosis, which led to a successful treatment by transcatheter arterial embolization. Endoscopists should be aware of this rare, but potentially fatal, adverse event of endoscopic ultrasonography.

DOI： 10.1007/s12328-021-01466-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Cigarette smoking, alcohol consumption, and Lugol-voiding lesions (LVLs) are the major causative risk factors of esophageal squamous cell carcinoma (ESCC); however, reports on ESCC cases unrelated to these risk factors are very limited. Here, we investigated the clinicopathological features and etiology of such cases. METHODS: We retrospectively analyzed 704 consecutive superficial ESCC tumors of 512 patients who were treated with endoscopic submucosal dissection. The enrolled patients were divided into two groups-the very low-risk (VLR)-group and risk (R)-group-based on the presence of the abovementioned risks. Clinical, endoscopic, and pathological characteristics and genetic findings were assessed in both groups. RESULTS: The VLR-group consisted of 21 (4.1%) patients, who were characteristically female. Patients in the VLR-group presented gastroesophageal reflux disease (GERD), hiatal hernia, and non-open-type atrophic gastritis, and were negative for Helicobacter pylori. We found unique endoscopic features-frequently observed in the posterior wall of the middle thoracic esophagus-with a linear shape that closely resembled the erosion-like form of GERD. Additionally, histopathological examination showed that these tumors presented atypical nuclei limited to the basal and parabasal layer, sequential to the surrounding changes that presented pathological chronic inflammation of esophagitis. Evaluation of somatic mutations in cancer-related genes using next-generation sequencing revealed that the positive carcinogenic potential (TP53 mutation) of the tumors was relatively frequent in the VLR-group. CONCLUSIONS: Our study suggests that ESCC without major causative factors is related to GERD, with no remarkable oncogenic difference.

DOI： 10.1007/s00535-021-01815-x

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Public Library of Science (PLoS)  

Isocitrate dehydrogenase 1 and 2 (<italic>IDH1/2</italic>) mutations and their key effector 2-hydroxyglutarate (2-HG) have been reported to promote oncogenesis in various human cancers. To elucidate molecular mechanism(s) associated with <italic>IDH1/2</italic> mutations, we established mouse embryonic fibroblasts (MEF) cells and human colorectal cancer cells stably expressing cancer-associated IDH1^R132C or IDH2^R172S, and analyzed the change in metabolic characteristics of the these cells. We found that IDH1/2 mutants induced intracellular 2-HG accumulation and inhibited cell proliferation. Expression profile analysis by RNA-seq unveiled that glucose transporter 1 (Glut1) was induced by the IDH1/2 mutants or treatment with 2-HG in the MEF cells. Consistently, glucose uptake and lactate production were increased by the mutants, suggesting the deregulation of glucose metabolism. Furthermore, PI3K/Akt/mTOR pathway and Hif1α expression were involved in the up-regulation of Glut1. Together, these results suggest that Glut1 is a potential target regulated by cancer-associated <italic>IDH1/2</italic> mutations.

DOI： 10.1371/journal.pone.0257090

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.jiph.2021.08.016

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掲載種別：研究論文（学術雑誌）   出版者・発行元：MDPI AG  

A 67-year-old male with type 2 diabetes (T2DM) was diagnosed with postoperative intrahepatic recurrence for hepatocellular carcinoma (HCC). Nine sessions of transarterial chemoembolization (TACE) proved ineffective, and the patient was diagnosed as having TACE-refractory disease and received seven cycles of atezolizumab–bevacizumab combination therapy. After that, the patient developed hyperglycemia with the HbA1c elevation and the marked fasting serum C-peptide reduction and was diagnosed with developed immune-mediated diabetes (IMD) (T2DM exacerbation with insulin-dependent diabetes development). Subsequently, the hepatobiliary enzyme levels, which were high before the systemic therapy, worsened. Thus, we clinically diagnosed an exacerbation of liver injury due to TACE-induced liver injury complicated by drug-induced liver injury such as immune-mediated hepatotoxicity (IMH). Meanwhile, after contrast-enhanced computed tomography revealed complete response, contrast-enhanced ultrasound was performed to assess intrahepatic recurrence. We found that the latter modality allowed earlier and more definitive diagnosis of intrahepatic recurrence of HCC. Subsequently, despite systemic therapy discontinuation and steroids administration, the liver injury worsened, and the patient died. The autopsy revealed intrahepatic recurrence of HCC and extensive arterial obstruction by the beads used for TACE within the liver, which indicated that disturbed circulation was the primary cause of the liver injury and histopathologically confirmed IMD, but not IMH.

DOI： 10.3390/diagnostics11081394

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記述言語：日本語   出版者・発行元：(一社)日本胆道学会  

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記述言語：日本語   出版者・発行元：(一社)日本膵臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本膵臓学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Endoscopic submucosal dissection (ESD) is the treatment of choice for colorectal superficial neoplasia, but certain anatomical locations are challenging even for skilled endoscopists. Ileocecal valve (ICV) is considered a technically challenging site for ESD. OBJECTIVE: Aim of this study was to analyze efficacy and safety of Endoscopic Submucosal Dissection in the treatment of colorectal neoplasia involving the ileocecal valve (ICV) DESIGN: Retrospective study. PATIENTS: We retrospectively evaluated 1507 consecutive patients undergoing ESD at two tertiary referral centres for ESD (Italy and Japan) from January 2008 to March 2020. MAIN OUTCOME MEASURES: Demographic, clinical, procedural, and follow-up data was collected, analysed, and compared between patients with ileocecal valve lesions (ICVL) and patients with non-ICVL. RESULTS: Overall, 1507 patients were enrolled (872 M, 57.8%), of these 53 patients had lesions involving the ICV. Mean age was 70.2 years (range, 53-83 years). En-bloc resection was achieved in 52 (98%) patients. The median specimen size of ICVL was 36.4 mm (range, 8-80 mm), significantly smaller than non-ICVL (p = 0.005). Procedure time was significantly longer in the ICVL group, (71.3 vs. 58.9 min; p = 0.03). Non Granular Type Laterally Spreading Tumors (LST-NG) were significantly more frequent in the ICVL group compared to rectum (52.8% vs. 25.7; p = 0.0001). En-bloc resection rate in the ileocecal region did not differ significantly between groups (p = 0.20). Complications such as perforation and postoperative occurred respectively in 3/53 (5.7%) and 1/53 (2%) patient, and were treated conservatively. At first surveillance colonoscopy performed at 6 months, recurrent adenoma was detected in 2/53 patients (3.9%). CONCLUSIONS: ESD is safe and effective for the treatment of colorectal neoplasia involving the ileocecal valve if performed by expert endoscopist in referral centres.

DOI： 10.1016/j.dld.2021.03.005

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

ABSTRACT: The Coronavirus disease 2019 pandemic continues to spread worldwide. Because of the absence of reliable rapid diagnostic systems, patients with symptoms of Coronavirus disease 2019 are treated as suspected of the disease. Use of computed tomography findings in Coronavirus disease 2019 are expected to be a reasonable method for triaging patients, and computed tomography-first triage strategies have been proposed. However, clinical evaluation of a computed tomography-first triage protocol is lacking.The aim of this study is to investigate the real-world efficacy and limitations of a computed tomography-first triage strategy in patients with suspected Coronavirus disease 2019.This was a single-center cohort study evaluating outpatients with fever who received medical examination at Yokohama City University Hospital, prospectively registered between 9 February and 5 May 2020. We treated according to the computed tomography-first triage protocol. The primary outcome was efficacy of the computed tomography-first triage protocol for patients with fever in an outpatient clinic. Efficacy of the computed tomography-first triage protocol for outpatients with fever was evaluated using sensitivity, specificity, positive predictive value, and negative predictive value. We conducted additional analyses of the isolation time of feverish outpatients and final diagnoses.In total, 108 consecutive outpatients with fever were examined at our hospital. Using the computed tomography-first triage protocol, 48 (44.9%) patients were classified as suspected Coronavirus disease 2019. Nine patients (18.8%) in this group were positive for severe acute respiratory syndrome coronavirus 2 using polymerase chain reaction; no patients in the group considered less likely to have Coronavirus disease 2019 tested positive for the virus. The protocol significantly shortened the duration of isolation for the not-suspected versus the suspected group (70.5 vs 1037.0 minutes, P < .001).Our computed tomography-first triage protocol was acceptable for screening patients with suspected Coronavirus disease 2019. This protocol will be helpful for appropriate triage, especially in areas where polymerase chain reaction is inadequate.

DOI： 10.1097/MD.0000000000026161

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会-関東支部  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To estimate the role of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced MRI (EOB-MRI) in predicting hypervascularization outcome of non-hypervascular hypointense hepatic lesions in high-risk patients for hepatocellular carcinoma (HCC). METHODS: Under the premise of non-hyperenhance in arterial phase (AP) and hypointensity in hepatobiliary phase (HBP) of EOB-MRI, 29 fresh lesions from 22 patients with chronic viral hepatitis (median (range) age: 69(57-82) years) were prospectively enrolled. During continuously followed-up by EOB-MRI, lesional vascularity in AP, the signal intensity (SI) ratios of lesions-to-parenchyma in HBP images (post-contrast ratio) and adjusted enhancement with reference of unenhanced images (EOB enhancement ratio) were examined. RESULTS: After 644 (220-2912) days of follow-up, 20 lesions changed into hyperenhancement in AP of EOB-MRI (hypervascularized group), while nine remained non-hyperenhanced (maintained non-hypervascular group). There is no statistical difference of post-contrast ratio at the initial detection. The post-contrast ratios in hypervascularized group were different between each follow-up time point when followed-up ≥ three (P < 0.01) and four (P < 0.05) times, and exposed a linear downward trend with time. Between the hypervascularized and maintained non-hypervascular groups, there were significant differences in the post-contrast ratio at endpoint for three-times' follow-up (P < 0.001); and at the second (P = 0.037), third follow-up time points (P = 0.005), endpoint (P = 0.005) for four-times' follow-up. EOB enhancement ratio showed inter-group difference only at endpoint for three-times' follow-up (P = 0.008). CONCLUSION: For non-hypervascular, HBP hypointense hepatic lesions, decreasing trend of SI in HBP may early predict unfavorable hypervascularized outcome.

DOI： 10.1007/s00261-020-02881-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: This study aimed to compare the value of Sonazoid contrast-enhanced ultrasound (SCEUS) with gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid magnetic resonance imaging (EOB-MRI) for histological grading diagnosis, especially for early hepatocellular carcinoma (eHCC). METHODS: A total of 163 histopathologically confirmed HCC lesions were retrospectively collected, including 71 eHCCs (27 hypervascular, 44 non-hypervascular) and 92 advanced HCCs (adHCC) (73 hypervascular, 19 non-hypervascular). We performed SCEUS to evaluate the lesions' vascularity during the portal phase (PP) and the echogenicity during the post-vascular phase (PVP). EOB-MRI was used to determine the signal intensity between lesions and the surrounding liver parenchyma on unenhanced T1-weighted images (pre-contrast ratio) in the hepatobiliary phase (HBP) (post-contrast ratio). RESULTS: For the PP and PVP of SCEUS (for all lesions), the pre-and post-contrast ratios of EOB-MRI (for all hypervascular lesions) showed statistical differences in the diagnosis of some (but not all) histological grades. For the diagnosis of eHCC, isoechogenicity in the PVP achieved the best diagnostic efficacy [area under the receiver operating characteristic curve (AUC) =0.892]. Whether used independently or in a combination of any form, all indicators failed to produce a higher diagnostic efficacy than PVP. Post- (≥0.610) and pre-contrast ratios (≥0.981) yielded acceptable diagnostic efficacy, with, respectively, accuracy levels of 69.3% and 75.5% and AUC values of 0.719 and 0.736. For eHCC diagnosis, the post-contrast ratio (≥0.625) and combined diagnosis using pre- (≥0.907) and post-contrast ratios (≥0.609) revealed the highest sensitivity (92.6%) for hypervascular lesions and perfect specificity (100%) for non-hypervascular lesions. CONCLUSIONS: Unenhanced T1-weighted images and the HBP of EOB-MRI [regardless of the vascularity in the arterial phase (AP)], and the PP and PVP of SCEUS showed their value in the histological grading diagnosis of HCC. In particular, isoechogenicity in the PVP may have promising diagnostic utility for eHCC.

DOI： 10.21037/qims-20-685

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1111/cas.14828

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その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/cas.14828

記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Ultrasound (US) is a cost-effective and noninvasive procedure without radiation exposure, with real-time evaluation and high spatial resolution. Although it is useful for the detection of gallbladder (GB) polyps, including gallbladder cancer, adenoma, and benign polyps, conventional US is insufficient for differential diagnosis because it is not capable of evaluating hemodynamic information, unlike computed tomography or magnetic resonance imaging. With recent technological advances in US equipment and contrast agents, Doppler imaging and contrast-enhanced ultrasonography (CEUS) are being used to characterize GB polyps, and several reports on evaluation of the vascularity of GB polyp have been published. In this review, we aimed to report the latest developments in the hemodynamic diagnosis of GB polyps based on previous reports, with an emphasis on CEUS, and to evaluate the efficacy for differential diagnosis. The information in this article is expected to enable early diagnosis and prompt surgical treatment for gallbladder cancer.

DOI： 10.1007/s10396-020-01008-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: By analyzing possible factors contributing to imaging misevaluation of arterial phase (AP) vascularity, we aimed to provide a more proper way to detect AP hypervascularity of hepatocellular carcinomas (HCCs) using the noninvasive imaging modalities magnetic resonance imaging (MRI) and contrast-enhanced ultrasound (CEUS). METHODS: We retrospectively recruited 164 pathologically confirmed HCC lesions from 128 patients. Using CEUS with Sonazoid (SCEUS) and gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid MRI (EOB-MRI), AP vascularity of the lesions was evaluated and inconsistencies in interpretation were examined. Indicators of margin, echogenicity, and halo and mosaic signs of lesions on grayscale US; depth of lesions on SCEUS; and tumoral homogeneity, signal contrast ratio of lesions to the surrounding area on precontrast and AP images on EOB-MRI, and histological grade were investigated. RESULTS: When precontrast images were used to adjust the AP enhancement ratio, the proportion of inconsistent interpretations of AP vascularity declined from 26.2% (43/164; 29 non-hypervascularity instances using EOB-MRI and 14 using SCEUS) to 16.5% (27/164; 7 using EOB-MRI and 20 using SCEUS). Greater lesion depth (P = 0.017), ill-defined tumoral margin (P = 0.028), absence of halo sign (P = 0.034), and histologically early HCC (P = 0.007) on SCEUS, and small size (P = 0.012) and heterogeneity (P = 0.013) of lesions and slight enhancement (low AP enhancement ratio) (P = 0.018 and 0.009 before and after adjustment) on EOB-MRI, may relate to undetectable hypervascularity. CONCLUSIONS: SCEUS and EOB-MRI may show discrepancies in evaluating AP vascularity in the case of deep, ill-defined, heterogeneous, slightly enhanced lesions, and histologically early HCCs. We recommend adjusting AP with precontrast images in EOB-MRI, and combining both modalities to detect hypervascularity.

DOI： 10.1007/s10396-021-01086-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND AIMS: Colorectal neoplasms with submucosal fibrosis are the most challenging targets of endoscopic resection. Water pressure endoscopic submucosal dissection (WP-ESD) is a recently introduced procedure that has several advantages over conventional endoscopic submucosal dissection (C-ESD). This study aimed to assess the efficacy and safety of WP-ESD for fibrotic colorectal neoplasms. METHODS: This retrospective observational study investigated 133 colorectal neoplasms expected to have submucosal fibrosis, which were resected by WP-ESD or C-ESD between April 2012 and April 2020. Eighty-seven lesions after endoscopic or surgical treatment, 18 with biopsy scar with fold convergence, and 28 in patients with ulcerative colitis were included. The differences in treatment outcomes, including procedure time and adverse events proportions, between the WP-ESD and C-ESD groups were analyzed. Clinical courses after perforation using WP-ESD were also evaluated, including postprocedural multidetector computed tomography (MDCT) findings obtained immediately after WP-ESD. RESULTS: Severe submucosal fibrosis was observed in 96 lesions (72.2%). The median procedure time was significantly shorter in the WP-ESD than in the C-ESD group (43.5 minutes [Interquartile range (IQR) 32.8-73] vs 72 minutes [IQR 45-105]; P =.0041). The multivariate analysis revealed WP-ESD as an independent factor for a short procedure time (odds ratio 2.90; 95% confidence interval 1.28-6.55). The proportions of post-ESD electrocoagulation syndrome (PEECS) (11.6% vs 13.1%) and perforation (20.4% vs 22.8%) were similar between the groups. Four of 11 patients with perforation using WP-ESD showed fluid collection on postprocedural MDCT images. CONCLUSIONS: WP-ESD can shorten procedure time for treating fibrotic colorectal neoplasms.

DOI： 10.1016/j.gie.2021.03.026

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

ABSTRACT: Oral direct-acting antiviral (DAA) treatment leads to >95% sustained virological response (SVR) and could be clinically useful in regression of liver fibrosis in chronic hepatitis C virus (HCV) infection. We evaluated if ledipasvir/sofosbuvir or sofosbuvir + ribavirin is associated with regression of fibrosis in HCV patients who achieved SVR.In this prospective cohort study performed at 3 sites in Japan, patients with genotype 1 and genotype 2 were given standard treatment of ledipasvir 90 mg/sofosbuvir 400 mg and sofosbuvir 400 mg + 200-1000 mg/day ribavirin, respectively, for 12 weeks. Liver fibrosis was assessed using Mac-2-binding protein glycosylation isomer (M2BPGi) and other fibrosis markers (platelet count, Fib-4 index, liver stiffness measurement [LSM]) in patients who achieved SVR.A total of 98.1% of (n = 101/103) patients in genotype 1 cohort and 100% (n = 16/16) in the genotype 2 cohort achieved SVR12. Based on per-protocol analysis, M2BPGi levels showed a significant decrease (-2.2  cut-off index [COI], P < .0001) at week 48 after treatment initiation. Forty-three patients showed a significant decrease in Fib-4 index (-1.2, P < .0001), and 44 patients showed improvement in LSM (-5.9 kPa, P < .0001).Achievement of SVR after antiviral therapy was associated with fibrosis regression. M2BPGi correlated well with LSM at week 48 after treatment initiation, supporting the sustainable benefit of HCV therapy.

DOI： 10.1097/MD.0000000000025110

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Radiotherapy is one of the available curative therapies for hepatocellular carcinoma (HCC). We investigate the use of contrast-enhanced ultrasound using Sonazoid (SCEUS) in evaluating the efficacy of radiotherapy for HCC. We enrolled 59 patients with 59 HCCs in this retrospective study. Tumor size and tumor vascularity were evaluated using SCEUS before and 1, 3, 7, 10, and 13 months after radiotherapy. The median follow-up period was 44.5 months (range: 16-82 months). Of the HCCs, 95% (56/59) had no local recurrence, while 5% (3/59) did. At 13 months after radiotherapy, in cases with no local recurrence, SCEUS showed a reduction in tumor vascularity in all cases, while tumor size reduction (>30% reduction, compared with pre-radiotherapy) was observed in 82.1% (46/56). In all three cases of local recurrence, vascularity and tumor size reduction were not observed during the follow-up period and residual HCCs were demonstrated pathologically. Compared with cases with local recurrence, tumor size reduction and reduction in tumor vascularity (p < 0.001) were significantly greater in cases with no local recurrence at 13 months after radiotherapy. SCEUS may be useful in evaluating radiotherapy efficacy for HCC.

DOI： 10.3390/diagnostics11030486

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: Superficial nonampullary duodenal epithelial tumors (SNADETs) have become frequently detected and referred for endoscopic resection (ER). However, optimal treatment methods and long-term outcomes after ER of SNADETs have not been fully elucidated. We aimed to clarify them by analyzing our large cohort of patients with SNADETs. MATERIALS AND METHODS: We enrolled 190 consecutive tumors from 189 patients undergoing ER between January 2004 and September 2019. Cases were stratified into endoscopic submucosal dissection (ESD), conventional endoscopic mucosal resection, (CEMR) and underwater endoscopic mucosal resection (UEMR). Baseline characteristics and short-term outcomes were compared between the groups. Long-term outcomes were also investigated with a median follow-up of 36 months. RESULTS: ESD significantly exceeded CEMR (96.4% vs. 52.9%; p = .0026) and UEMR (96.4% vs. 50.0%; p = .0008) in complete resection rates for 11- to 20-mm lesions; the differences were not significant for lesions ≤10 mm. Local recurrence only occurred in patients with an incomplete resection. Only patients with submucosal invasion died from the primary neoplasms. The 3- and 5-year disease-free survivals were 91.3% and 83.5%. CONCLUSIONS: While tumors ≤10 mm seem to be good indications for endoscopic mucosal resection, ESD should be considered for larger tumors to better achieve complete resection. Patients with submucosal invasive carcinomas have a great risk of cancer death. Therefore, a close follow-up and an additional treatment are desirable.

DOI： 10.1080/00365521.2020.1867896

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: Gastrointestinal endoscopy (GIE) is useful for the early detection and treatment of many diseases; however, GIE is considered a high-risk procedure in the coronavirus disease 2019 (COVID-19) pandemic era. This study aimed to explore the rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity in saliva and gastrointestinal fluids to which endoscopy medical staff are exposed. METHODS: The study was a single-center cross-sectional study. From June 1 to July 31, 2020, all patients who underwent GIE at Yokohama City University Hospital were registered. All patients provided 3 mL of saliva. For upper GIE, 10 mL of gastric fluid was collected through the endoscope. For lower GIE, 10 mL of intestinal fluid was collected through the endoscope. The primary outcome was the positive rate of SARS-CoV-2 in saliva and gastrointestinal fluids. We also analyzed serum-specific antibodies for SARS-CoV-2 and patients' background information. RESULTS: A total of 783 samples (560 upper GIE and 223 lower GIE samples) were analyzed. Polymerase chain reaction (PCR) on saliva samples did not show any positive results in either upper or lower GIE samples. However, 2.0% (16/783) of gastrointestinal fluid samples tested positive for SARS-CoV-2. No significant differences in age, sex, purpose of endoscopy, medication, or rate of antibody test positivity were found between PCR positive and PCR negative cases. CONCLUSIONS: Asymptomatic patients, even those with no detectable virus in their saliva, had SARS-CoV-2 in their gastrointestinal tract. Endoscopy medical staff should be aware of infection when performing procedures. The study was registered as UMIN000040587.

DOI： 10.1111/den.13945

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: Clinicopathologic characteristics and treatment outcomes of mixed-histological-type (MT) early gastric cancers (EGCs) treated with endoscopic submucosal dissection (ESD) have not been sufficiently elucidated. We aimed to clarify them in comparison with pure-histological-type EGCs. METHODS: We used 3022 consecutive EGCs in 2281 patients treated with ESD from our prospectively maintained database. Cases were stratified into four groups according to the final diagnosis of the resected specimen are as follows: 2780 pure differentiated-type (DT), 127 DT-predominant MT (D-MT), 87 pure undifferentiated-type (UDT), and 28 UDT-predominant MT (U-MT). Clinicopathologic characteristics and treatment outcome were compared between pure DT and D-MT, and between pure UDT and U-MT separately. Risk factors for deep submucosal invasion, lymphovascular invasion, and a final diagnosis of MT were identified using multivariate analysis. RESULTS: Both D-MT (41.7 vs. 92.0%; P < 0.0001) and U-MT (35.7 vs. 75.9%; P = 0.0002) showed a significantly lower curative resection rate than their pure histologic counterparts. Multivariate analysis revealed that MT was an independent risk factor for deep submucosal (OR 6.55; 95% CI, 4.18-10.14) and lymphovascular (OR 4.74; 95% CI, 2.72-8.29) invasion. Preoperative biopsy results that did not show well-differentiated tubular adenocarcinoma (OR 28.2; 95% CI, 18.9-42.9) were an independent risk factor for a final diagnosis of MT. CONCLUSIONS: MT poses a greater risk for noncurative resection regardless of the predominant histologic types, reflecting more aggressive malignant potential. Although a biopsy examination rarely shows MT, clinicians should consider the possibility of MT when a biopsy examination does not show well-differentiated tubular adenocarcinoma.

DOI： 10.1097/MEG.0000000000001894

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND AIM: Endoscopic resection is feasible for superficial tumors in patients with ulcerative colitis; however, endoscopic resection options have not been evaluated comprehensively. We evaluated the efficacy and safety of endoscopic submucosal dissection and endoscopic mucosal resection, and decision making regarding endoscopic resection options for patients with ulcerative colitis. METHODS: Endoscopically treated tumors from patients with ulcerative colitis were analyzed retrospectively. We evaluated en bloc and R0 resection, adverse events, local tumor recurrence, and metachronous lesion occurrence rates. RESULTS: We examined 102 tumors (mean size, 12 mm; non-polypoid, 55 tumors) from 74 patients with ulcerative colitis, of whom, 39 and 63 underwent endoscopic submucosal dissection and endoscopic mucosal resection, respectively. The R0 resection rate was significantly higher for endoscopic submucosal dissection (97%) than for endoscopic mucosal resection (80%) (P = 0.0015). For 11-20-mm tumors, the R0 resection rate was significantly higher for endoscopic submucosal dissection (94%) than for endoscopic mucosal resection (55%) (P = 0.0027); the endoscopic submucosal dissection and endoscopic mucosal resection R0 rates did not differ for ≤ 10-mm tumors. The non-polypoid tumor R0 resection rates were significantly higher for endoscopic submucosal dissection (100%) than for endoscopic mucosal resection (65%) (P < 0.001) and did not differ regarding the polypoid tumor R0 resection rates (75% vs 86%, P = 0.49). Four patients experienced intraoperative perforation during endoscopic submucosal dissection. No local recurrences occurred. Metachronous high-grade dysplasia occurred in three patients during surveillance. CONCLUSIONS: In patients with ulcerative colitis, endoscopic submucosal dissection is suitable for ≥ 11-mm and non-polypoid tumors, whereas endoscopic mucosal resection is acceptable for ≤ 10-mm tumors.

DOI： 10.1111/jgh.15207

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS: To assess the safety, efficacy, and prognostic impact of clinical factors associated with lenvatinib treatment in highly advanced hepatocellular carcinoma (HCC) with tumor thrombus in the main portal vein trunk (VP4) or tumor with more than 50% liver occupation (tm50%LO). METHODS: A total of 61 highly advanced HCC patients (41 patients with tm50%LO and 20 patients with VP4) who were treated with lenvatinib at multicenter were enrolled and retrospectively analyzed for treatment outcomes according to their clinical status, including tumor morphology. RESULTS: The most frequent grade ≥3 adverse event in tm50%LO HCC was elevated aspartate aminotransferase (17.1%). Objective response rates were 37.5% and 0% in tm50%LO HCC patients with Child-Pugh grade (CP)-A and CP-B, respectively, and 26.7% and 0% in VP4 HCC patients with CP-A and CP-B, respectively. Estimated median progression-free survival and overall survival were 132 days and 229 days, and 101 days and 201 days in patients with tm50%LO and VP4, respectively. In multivariate analysis, modified albumin-bilirubin grade (hazard ratio 0.372, 95% CI 0.157-0.887; p = 0.0241) and tumor morphology (hazard ratio 0.322, 95% CI 0.116-0.889; p = 0.0287) were independently associated with progression-free survival in patients with tm50%LO HCC. In VP4 HCC, median progression-free survival was worse in CP-B (57 days) than in CP-A patients (137 days, p = 0.0462). CONCLUSIONS: Lenvatinib treatment offers a benefit in highly advanced HCC (tm50%LO or VP4) patients with good liver function or nodular-type tumor. The various characteristics identified in this study might be useful as indicators of lenvatinib treatment in highly advanced HCC with tm50%LO or VP4, which are considered very refractory cancers.

DOI： 10.1111/hepr.13592

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記述言語：日本語   出版者・発行元：日本消化器病学会-関東支部  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND AIM: To assess the efficacy and safety of 7-day Helicobacter pylori rescue treatment consisting of a vonoprazan (VPZ), metronidazole (MNZ), and sitafloxacin (STFX) regimen (VPZ-MNZ-STFX therapy) in patients with penicillin allergy. METHODS: This was a registered prospective intervention study. Patients with penicillin allergy who were diagnosed with H. pylori infection and had a history of H. pylori eradication were eligible for inclusion. Seventeen patients were prospectively treated with VPZ 20 mg bid, MNZ 250 mg bid, and STFX 100 mg bid for 7 days. Safety was evaluated using a questionnaire on adverse effects. RESULTS: The eradication rate of 7-day VPZ-MNZ-SFTX therapy was 88.2% (95% confidence interval: 63.6-98.5%; n = 17) in both intention-to-treat and per-protocol analyses. On the questionnaire, 25% of patients reported experiencing diarrhea, with a score of 2 or 3. All patients undergoing VPZ-MNZ-STFX therapy completed 100% of their medication course. CONCLUSION: Rescue H. pylori eradication with VPZ-MNZ-STFX therapy is effective and well tolerated in patients with penicillin allergy (UMIN000016335, jRCTs031180133).

DOI： 10.1002/jgh3.12492

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Baishideng Publishing Group Co  

BACKGROUND The oral nucleos(t)ide analogue, entecavir (ETV) was demonstrated to reduce the rate of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV)- associated liver cirrhosis. However, the reduction of HCC differs in various regions of the world. AIM To investigate the reduction of HCC development due to ETV therapy by metaanalysis. METHODS We surveyed the differences in HCC development following ETV treatment based on published articles using PubMed (2004-2019). RESULTS The regions with the most marked reduction in HCC development due to ETV therapy were Spain (1.0%/year) and Canada (Southern part, 1.3%/year), and the most ineffective areas were South Korea (3.6%-3.8%/year), China (3.3%/year), Taiwan (2.4%-3.1%/year), and Hong Kong (2.8%/year). Following ETV administration, the incidence of HCC in genotype D regions (1.89% ± 0.28%/year, mean ± SE) was significantly lower than that in genotype C regions (2.91% ± 0.24%/year, P &lt
0.01). With regard to the initial HBV-DNA level, in genotype C patients (average: 5.61 Log10IU/mL) this was almost the same as that in genotype D patients (average: 5.46 Log10IU/mL). Moreover, there was no association between the prevalence ratio of HBV and the incidence of HCC on ETV treatment. CONCLUSION The effectiveness of ETV in preventing HCC development in HBV-associated liver cirrhosis is genotype-dependent.

DOI： 10.4254/wjh.v13.i1.144

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Lippincott Williams and Wilkins  

The Morisky Medication Adherence Scale is a clinically relevant tool used to evaluate medication adherence. In the current study, the validity and reliability of a Japanese version of the Morisky Medication Adherence Scale and factors related to low adherence were investigated in patients with ulcerative colitis. The original English version was translated into Japanese and then 3 institutions in Japan administered that Japanese version to 428 patients taking medication. Factor validity, internal consistency, and correlations between the Morisky Medication Adherence Scale and adherence were calculated on the basis of patients' own reports of skipped medication, and known group validity between clinically different groups was assessed. Logistic regression was used to assess relationships between low adherence and other factors. The Morisky Medication Adherence Scale identified 184 of 428 patients (43.0%) who exhibited low adherence. Confirmed factor analysis indicated one-dimensionality of the scale. Cronbach's α was 0.74. The Morisky Medication Adherence Scale score was significantly correlated with self-reported missed medication. Patients who were on concomitant induction therapy exhibited significantly better Morisky Medication Adherence Scale scores than those who were not. Patients with low adherence reported difficulty taking medicine, having proctitis, and ulcerative colitis duration of less than 5 years, and were of younger age. The Japanese Morisky Medication Adherence Scale yielded clinically relevant measures of adherence in patients with ulcerative colitis and may promote further international comparative studies.

DOI： 10.1097/SGA.0000000000000533

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掲載種別：研究論文（学術雑誌）  

Aim To evaluate the safety and efficacy of the administration of radiofrequency ablation (RFA) and stereotactic body radiotherapy (SBRT) in the short term to the same patients in Barcelona Clinical Liver Cancer (BCLC) stages 0–B1. Methods From April 2014 to June 2019, we retrospectively reviewed BCLC stage 0–B1 patients with fresh hepatocellular carcinoma (HCC) lesions that were repeatedly treated by RFA (control group, n = 72), and by RFA and subsequent SBRT (case group, n = 26). Propensity score matching (PSM) was performed to reduce the selection bias between two groups. Recurrence, survival, Child–Pugh scores and short-term side effects (fever, bleeding, skin change, abdominal pain and fatigue) were recorded and analyzed. Results After PSM, 21 patients remained in each group. Seventeen and 20 patients in the case and control groups experienced recurrence. For these patients, the median times to progression and follow-up were 10.7 and 35.8 months, respectively. After PSM, the 1-year progression-free survival rate in case and control groups were 66.7% and 52.4%, respectively (P = 0.313). The inter-group overall survival (OS) was comparable (3 and 5-year OS rates in case groups were 87.3% and 74.8%, while rates in control groups were 73.7% and 46.3%, respectively; P = 0.090). The short-term side effects were mild, and the incidence showed no inter-group difference. The 1-year rates of the Child–Pugh score deterioration of ≥2 in case and control groups were 23.8% and 33.3% (P > 0.05), respectively. Conclusion The short-term administration of RFA and SBRT to the same BCLC stage 0–B1 patients may be feasible and effective because of their good prognosis and safety.

DOI： 10.1371/journal.pone.0245076

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Society of Internal Medicine  

DOI： 10.2169/internalmedicine.6755-20

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Baishideng Publishing Group Co  

BACKGROUND In hepatocellular carcinoma (HCC), detection and treatment prior to growth beyond 2 cm are important as a larger tumor size is more frequently associated with microvascular invasion and/or satellites. In the surveillance of very small HCC nodules (&lt
2 cm in maximum diameter, Barcelona clinical stage 0), we demonstrated that the tumor markers alpha-fetoprotein and PIVKA-II are not so useful. Therefore, we must survey with imaging modalities. The superiority of magnetic resonance imaging (MRI) over ultrasound (US) to detect HCC was confirmed in many studies. Although enhanced MRI is now performed to accurately diagnose HCC, in conventional clinical practice for HCC surveillance in liver diseases, unenhanced MRI is widely performed throughout the world. While, MRI has made marked improvements in recent years. AIM To make a comparison of unenhanced MRI and US in detecting very small HCC that was examined in the last ten years in patients in whom MRI and US examinations were performed nearly simultaneously. METHODS In 394 patients with very small HCC nodules, those who underwent MRI and US at nearly the same time (on the same day whenever possible or at least within 14 days of one another) at the first diagnosis of HCC were selected. The detection rate of HCC with unenhanced MRI was investigated and compared with that of unenhanced US. RESULTS The sensitivity of unenhanced MRI for detecting very small HCC was 95.1% (97/102, 95% confidence interval: 90.9-99.3) and that of unenhanced US was 69.6% (71/102, 95% confidence interval: 60.7-78.5). The sensitivity of unenhanced MRI for detecting very small HCC was significantly higher than that of unenhanced US (P &lt
0.001). Regarding the location of HCC in the liver in patients in whom detection by US was unsuccessful, S7-8 was identified in 51.7%. CONCLUSION Currently, unenhanced MRI is a very useful tool for the surveillance of very small HCC in conventional clinical follow-up practice.

DOI： 10.4254/wjh.v13.i6.699

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Spandidos Publications  

The aim of the present study was to evaluate the long-term outcomes and the impact of repeated conventional transarterial chemoembolization (C-TACE) and transarterial chemoembolization with epirubicin-loaded superabsorbent polymer embolics (SAP-TACE) on liver function in TACE-naïve patients with unresectable hepatocellular carcinoma (HCC). Overall, 155 consecutive patients with HCC received either C-TACE or SAP-TACE. The first cohort (n=71), treated between 2011 and 2014, received C-TACE
the second cohort (n=84), treated between 2014 and 2016, received SAP-TACE. Overall survival and deterioration of liver function were compared between the two cohorts. The 1-, 2- and 3-year overall survival rates and median survival times were 74, 50, 35% and 26 months in the C-TACE cohort and 75, 60, 39% and 28 months in the SAP-TACE cohort, respectively. There were no significant differences between the two groups (P=0.289). Age &lt
70 years, Child-Pugh class A, alpha-feto-protein &lt
400 ng/ml and des-gamma-carboxy prothrombin &lt
1,000 mAU/ml were identified as favorable prognostic factors in multivariate analysis. In the subgroup of patients with a Child-Pugh score of 5, survival was 29 months for C-TACE vs. 55 months for SAP-TACE (P&lt
0.05). In the C-TACE cohort, the median Child-Pugh score was 6 after 3 cycles and 7 after 5 cycles of TACE, and the score worsened significantly (before vs. 3 cycles, P&lt
0.05
before vs. 5 cycles, P&lt
0.05). In the SAP-TACE cohort, the median Child-Pugh score was 6 after 3 and 5 cycles of TACE, and the score did not worsen during the treatment cycles. There were no differences in overall survival between repeated C-TACE and SAP-TACE in TACE-naïve patients with HCC. However, liver function deterioration was more evident in patients treated with C-TACE than in those treated with SAP-TACE.

DOI： 10.3892/mco.2021.2281

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.4103/EUS-D-20-00211

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Japan  

For an esophageal submucosal mass suspicious of granular cell tumor (GCT) based on gross appearance and endoscopic ultrasound findings, a sufficient number of biopsy specimens is required for a definite diagnosis using immunohistochemical examination. When the specimen obtained by forceps biopsy is insufficient, endoscopic ultrasound-fine needle aspiration (EUS-FNA) is believed to be an useful alternative. However, it may be difficult to obtain an adequate amount of tumor material using EUS-FNA. Mucosal incision-assisted biopsy (MIAB) is a simple method that can collect larger amounts of specimens. This procedure is helpful for physicians who encounter the problem of obtaining an adequate amount of biopsy material from esophageal tumors suspicious for GCT. We present a case of esophageal GCT that was successfully diagnosed through MIAB.

DOI： 10.1007/s12328-021-01535-y

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記述言語：英語  

Thrombotic microangiopathy (TMA) is a serious complication following kidney transplantation. Although intestinal TMA is a major organ injury and causes abdominal pain, diarrhea and bloody stools, the clinical and endoscopic characteristics of small intestinal TMA remain unclear. Here, we report a drug-induced small intestinal TMA, which did not meet the laboratory-defined TMA criteria but was diagnosed by balloon-assisted enteroscopy (BAE). A 32-year-old woman who underwent kidney transplantation at the age of 10 years complained of abdominal pain, diarrhea and bloody stools one month after starting everolimus (EVE) as an immunosuppressant. Although she did not meet the diagnostic criteria for TMA serologically, BAE revealed a circumferential ulcer in the jejunum, and the pathological findings of a biopsy specimen showed microvascular thrombi, compatible with intestinal TMA. Her symptoms improved upon the discontinuation of EVE, demonstrating that EVE can cause drug-induced intestinal TMA. The present case suggests that BAE should be performed when abdominal pain, diarrhea, and bloody stools occur in patients receiving immunosuppressive medication following kidney transplantation, even if there is no evidence of TMA according to the laboratory definition.

DOI： 10.20524/aog.2020.0561

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：{MDPI} {AG}  

<jats:p>The mechanism of H. pylori-induced atrophy and metaplasia has not been fully understood. Here, we demonstrate the novel role of Apoptosis signal-regulating kinase 1 (ASK1) and downstream MAPKs as a regulator of host immune responses and epithelial maintenance against H. pylori infection. ASK1 gene deficiency resulted in enhanced inflammation with numerous inflammatory cells including Gr-1+CD11b+ myeloid-derived suppressor cells (MDSCs) recruited into the infected stomach. Increase of IL-1β release from apoptotic macrophages and enhancement of TH1-polarized immune responses caused STAT1 and NF-κB activation in epithelial cells in ASK1 knockout mice. Dysregulated immune and epithelial activation in ASK1 knockout mice led to dramatic expansion of gastric progenitor cells and massive metaplasia development. Bone marrow transplantation experiments revealed that ASK1 in inflammatory cells is critical for inducing immune disorder and metaplastic changes in epithelium, while ASK1 in epithelial cells regulates cell proliferation in stem/progenitor zone without changes in inflammation and differentiation. These results suggest that H. pylori-induced immune cells may regulate epithelial homeostasis and cell fate as an inflammatory niche via ASK1 signaling.</jats:p>

DOI： 10.3390/microorganisms8121995

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会-関東支部  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会-関東支部  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会-関東支部  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Clinical trials of direct-acting antivirals for patients with decompensated cirrhosis have been conducted, but there is limited information on the medicinal applications in clinical settings. We aimed to evaluate the safety and efficacy of sofosbuvir/velpatasvir for decompensated cirrhotic patients with genotypes 1 and 2 in real-world clinical practice. METHODS: A prospective, multicenter study of 12-week sofosbuvir/velpatasvir was conducted for patients with decompensated cirrhosis at 33 institutions. RESULTS: The cohort included 71 patients (52 genotype 1, 19 genotype 2): 7 with Child-Pugh class A, 47 with class B, and 17 with class C (median score 8; range 5-13). The albumin-bilirubin (ALBI) score ranged from - 3.01 to - 0.45 (median - 1.58). Sixty-nine patients (97.2%) completed treatment as scheduled. The overall rate of sustained virologic response at 12 weeks post-treatment (SVR12) was 94.4% (67/71). SVR12 rates in the patients with Child-Pugh classes A, B, and C were 85.7%, 97.9%, and 88.2%, respectively. Among 22 patients with a history of hepatocellular carcinoma treatment, 20 (90.9%) achieved SVR12. The Child-Pugh score and ALBI grade significantly improved after achieving SVR12 (p = 7.19 × 10-4 and 2.42 × 10-4, respectively). Notably, the use of diuretics and branched-chain amino acid preparations significantly reduced after achieving SVR12. Adverse events were observed in 19.7% of the patients, leading to treatment discontinuation in two patients with cholecystitis and esophageal varices rupture, respectively. CONCLUSION: Twelve weeks of sofosbuvir/velpatasvir in real-world clinical practice yielded high SVR rates and acceptable safety profiles in decompensated cirrhotic patients with genotypes 1 and 2. Achievement of SVR not only restored the liver functional reserve but also reduced or spared the administration of drugs for related complications. TRIAL REGISTRATION: UMIN registration no, 000038587.

DOI： 10.1007/s40121-020-00329-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: In hepatocellular carcinoma (HCC), detection and treatment prior to growth beyond 2 cm are relevant as a larger tumor size is more frequently associated with microvascular invasion and/or satellites. AIM: To examine the impact of the tumor marker alpha-fetoprotein (AFP) or PIVKA-II in detecting very small HCC nodules (≤ 2 cm in maximum diameter, Barcelona stage 0) in the large number of very small HCC. The difference in the behavior of these tumor markers in HCC development was also examined. METHODS: A total of 933 patients with single-nodule HCC were examined. They were subdivided into 394 patients with HCC nodules ≤ 2 cm in maximum diameter and 539 patients whose nodules were > 2 cm. The rates of patients whose AFP and PIVKA-II showed normal values were examined. RESULTS: The positive ratio of the marker PIVKA-II was significantly different (P < 0.0001) between patients with nodules ≤ 2 cm in diameter and those with nodules > 2 cm, but there was no significant difference in AFP (P = 0.4254). In the patients whose tumor was ≤ 2 cm, 50.5% showed normal levels in AFP and 68.8% showed normal levels in PIVKA-II. In 36.4% of those patients, both AFP and PIVKA-II showed normal levels. The PIVKA-II-positive ratio was markedly increased with an increase in the tumor size. In contrast, the positivity in AFP was increased gradually and slowly. CONCLUSION: In the surveillance of very small HCC nodules (≤ 2 cm in diameter, Barcelona clinical stage 0) the tumor markers AFP and PIVKA-II are not so useful.

DOI： 10.4254/wjh.v12.i11.1046

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Postoperative delayed bleeding (PDB) after gastric endoscopic submucosal dissection (ESD) is the most common adverse event in patients receiving antithrombotics even with second-look endoscopy. Moreover, with the increasing prevalence of cardiovascular and cerebrovascular diseases in an aging population with associated lifestyle-related diseases, an increasing number of patients receive antithrombotics. Several attempts have been made to prevent PDB in aging population; however, a consensus has yet to be reached. AIM: To examine the efficacy of third-look endoscopy (TLE) for PDB prevention. METHODS: One hundred patients with early gastric neoplasms receiving antithrombotics were prospectively enrolled and subjected to ESD with TLE between February 2017 and July 2019. The primary endpoint was PDB rate, which was compared with our preset threshold. Furthermore, we divided the bleeding period into early-and late-onset PDB (E-PDB and L-PDB, respectively) and analyzed its rate. As a secondary analysis, we compared PDB rates with those of a historical control group, using propensity score matching, and calculated the PDB rates per antithrombotic agent use in each group. RESULTS: In total, 96 patients and 114 specimens were finally evaluated. The overall PDB rate was 7.9% (9/114) [90%CI: 4.7-13.1, P = 0.005], while the late-and early-onset PDB rates (L-PDB and E-PDB) were 5.3% [90%CI: 2.7-9.9, P < 0.0001] and 2.6% [90%CI: 1.1-6.4, P = 0.51], respectively. Propensity score matching generated 58 matched pairs for TLE and control groups. No differences were found in overall PDB incidence (10.3% vs 20.7%, P = 0.12), whereas L-PDB occurrence significantly differed (5.2% vs 17.2%, P = 0.04) between groups. Considering antithrombotics' use, the overall PDB rate was higher for direct oral anticoagulants and multiple antithrombotics in the control group, while L-PDB incidence was lower in the TLE group for these agents (8.7% vs 23.1% and 5.0% vs 29.4%, respectively). CONCLUSION: TLE for gastric ESD reduces overall PDB, and especially L-PDB incidence, among patients receiving antithrombotics.

DOI： 10.3748/wjg.v26.i41.6475

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We investigated whether or not nitric oxide synthase 3 (NOS3) rs2070744 genotypes can affect the response for lenvatinib treatment in patients with hepatocellular carcinoma (HCC). We evaluated the relation of the NOS3 rs2070744 genotypes to the tumor response, progression-free survival (PFS), and overall survival (OS) as the response for lenvatinib. We also examined the association between fibroblast growth factor receptor (FGFR) gene polymorphisms, a potential feature of lenvatinib, and the response. There were no significant differences between the studies for either PFS or OS, even though patients with the TT genotype had a longer mean PFS (hazard ratio [HR] 0.60; p = 0.069) and mean OS (HR 0.46; p = 0.075) than those with the TC/CC genotypes. However, patients with a single-nucleotide polymorphism (SNP) combination pattern of the NOS3 rs2070744 TC/CC and FGFR4 rs351855 CT/TT genotypes had a significantly shorter mean PFS (HR 2.56; p = 0.006) and mean OS (HR 3.36; p = 0.013) than those with the other genotypes. The NOS3 rs2070744 genotypes did not influence the clinical response. However, the SNP combination pattern of the NOS3 rs2070744 and FGFR4 rs351855 genotypes may be helpful as treatment effect predictors and prognostic factors for HCC patients treated with lenvatinib.

DOI： 10.1038/s41598-020-73930-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND AIMS: Although colorectal endoscopic submucosal dissection (ESD) has become a standardized procedure worldwide, the difficulty of the procedure is well known. However, there have been no studies assessing the causes of treatment interruption. The present study aimed to evaluate the factors involved in the interruption of colorectal ESD. METHODS: We retrospectively analyzed 1116 consecutive superficial colorectal neoplasms of 1012 patients who were treated with ESD between August 2008 and September 2018. The clinicopathological characteristics and treatment outcomes were analyzed. RESULTS: Interrupted ESD was reported in 14 lesions (1.3%) of the total study population. Univariate analysis of clinical characteristics indicated that age, 0-I macroscopic-type tumor, and tumor location on the left side colon were risk factors for interruption. Multivariate analysis revealed that 0-I macroscopic-type tumor was the sole preoperative independent risk factor for interruption. Univariate analysis revealed that the presence of muscle-retracting sign (MRS), deep submucosal tumor invasion, and intermediate invasive growth pattern represented the etiology of interruption. Multivariate analysis indicated that MRS can be a sole key sign for the interruption. Additionally, the resectability and curability of 0-I type tumors were significantly inferior to those of predominantly lateral spreading tumors. Observations of 0-I macroscopic-type tumors, MRS, and submucosal deep invasion were significantly more frequent in interrupted cases. Conventional endoscopic images without magnification endoscopy were more associated with interruption than irregular surfaces or Vi pit patterns in cases with 0-I type tumors. CONCLUSION: ESD of 0-I type tumors is highly disruptive, and undiagnosable submucosal infiltration can reduce the curability.

DOI： 10.1007/s00464-020-08042-0

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The undifferentiated-type (UDT) component profoundly affects the clinical course of early gastric cancers (EGCs). However, an accurate preoperative diagnosis of the histological types is unsatisfactory. To date, few studies have investigated whether the UDT component within mixed-histological-type (MT) EGCs can be recognized preoperatively. AIM: To clarify the histopathological characteristics of the endoscopically-resected MT EGCs for investigating whether the UDT component could be recognized preoperatively. METHODS: This was a single-center retrospective study. First, we attempted to clarify the histopathological characteristics of the endoscopically-resected MT EGCs with emphasis on the UDT component. Histopathological examination investigated each lesion's UDT component: (1) Whole mucosal layer occupation of the UDT component; (2) UDT component exposure to the surface of the mucosa; and (3) existence of a clear border between the differentiated-type and UDT components. Then, preoperative endoscopic images with magnifying endoscopy with narrow-band imaging (ME-NBI) were examined to identify whether the endoscopic UDT component finding was recognizable within the area where it was present in the histopathological examination. The preoperative biopsy results and comparative relationships between endoscopic and histopathological findings were also examined. RESULTS: In the histopathological examination, the whole mucosal layer occupation of the UDT component and exposure of the UDT component to the mucosal surface were observed in 67.3% (33/49) and 79.6% (39/49) of samples, respectively. A clear distinction of the border between the differentiated-type and UDT components could not be drawn in 65.3% (32/49) of MT lesions. In the endoscopic examination, the preoperative endoscopic images showed that only 24.5% (12/49) of MT EGCs revealed the UDT component within the area where it was present histopathologically. Histopathological UDT predominance was the single significant factor associated with the presence of the endoscopic UDT component finding (61.5% vs 11.1%, P = 0.0009). Only 26.5% (13/49) of the lesions were diagnosed from the pretreatment biopsy as having a UDT component. Combined results of the pretreatment biopsy and ME-NBI showed the preoperative presence of the UDT component in 40.8% (20/49) of MT EGCs. CONCLUSION: Recognition of a UDT component within MT EGCs is difficult even when pretreatment biopsy and ME-NBI are combined. Endoscopic resection plays a significant role in both treatment and diagnosis.

DOI： 10.3748/wjg.v26.i36.5450

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記述言語：日本語   出版者・発行元：日本消化器病学会-関東支部  

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記述言語：日本語   出版者・発行元：日本消化器病学会-関東支部  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background and Aim: Endoscopic duodenal stenting for patients with malignant gastric outlet obstruction (GOO) has been widespread; however, clinical trials evaluating the structures of duodenal stents are lacking. Thus, we aimed to investigate the clinical outcomes of a highly flexible duodenal stent for GOO patients. Methods: A prospective study of duodenal stenting for GOO patients from five hospitals between August 2017 and August 2018 was performed. WallFlex Duodenal Soft were used in all procedures. The primary endpoint was clinical success, defined as an improvement in the GOO scoring system. Results: The study enrolled 31 patients (12 women, 19 men) with GOO, with a median age of 70 (range 52-90) years. Primary diseases were pancreatic cancer, gastric cancer, biliary tract cancer, and others in 14, 10, 3, and 4 patients, respectively. The technical success rate was 97%, and the clinical success rate was 87%. Simultaneous biliary drainage was performed in 19% of patients. Adverse events occurred in three patients. Chemotherapy was given in 41% of clinically successful cases, and the median overall survival time after stent placement was 82 days (range, 30-341 days), and. Stent dysfunction occurred in 30% of clinically successful cases (stent ingrowth in seven and stent overgrowth in one patient). The median time to stent dysfunction was 157 days (range, 11-183 days). Six patients were treated with additional stent placement after dysfunction. Conclusion: Placement of a highly flexible duodenal stent is an effective and safe treatment for patients with GOO (UMIN-CTR 000028783).

DOI： 10.1002/jgh3.12326

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Therapeutic endoscopic ultrasound has become widespread as an effective procedure for biliary drainage; however, it is rarely used to remove foreign bodies such as a biliary stent. A 57-year-old man was referred to our hospital for a benign biliary stricture in the left hepatic duct after hepatectomy. Initially, a 7-Fr plastic stent was placed in the left hepatic duct with the distal end set above the papilla, and it was replaced with an 8.5-Fr stent as the stricture remained after 3 months. Endoscopic retrograde cholangiopancreatography was performed to retrieve the plastic stent 3 months later; however, the stent could not be moved because the proximal flap was caught in the stricture. Attempts using various devices failed to retrieve the stent; thus, endoscopic ultrasound-guided hepaticogastrostomy was performed to create a route for stent retrieval. Eventually, the plastic stent was successfully retrieved with biopsy forceps through a fully covered self-expandable metallic stent located in a transgastric fistula. We propose our new method involving endoscopic ultrasound-guided hepaticogastrostomy for endoscopic stent retrieval that fails via the transpapillary route.

DOI： 10.1007/s12328-020-01184-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The therapeutic effect of regorafenib was previously demonstrated in patients with advanced hepatocellular carcinoma (HCC) and Child-Pugh classification A (CP-A) whose disease progressed during sorafenib treatment in a phase III trial. However, treatment options are limited for patients with advanced HCC other than CP-A. In this study, we aimed to evaluate the therapeutic effect of regorafenib on advanced HCC patients including those with Child-Pugh classification B (CP-B).We retrospectively analyzed the medical records of 21 patients with advanced HCC who were treated with regorafenib after sorafenib monotherapy at our hospital from July 2017 to April 2018 and were followed up until September 2019. Patients were classified according to liver function and adverse events experienced during sorafenib treatment and were started on regorafenib with a pre-defined reduced starting dose along with a dose reduction and schedule change based on the judgement of the attending physician.At regorafenib initiation, 13 and 8 patients were classified as CP-A and CP-B, respectively. In all patients with CP-B, the starting dose of regorafenib was reduced, and the pre-defined starting-dose sets were applied to 17 (81%) patients. The median duration of regorafenib treatment in patients with CP-A and CP-B were 4.1 months and 2.0 months, respectively, with no significant difference. The median overall survival from regorafenib initiation (OS-r) and sorafenib initiation (OS-s) was 13.2 months and 30.9 months, respectively. In subgroup analysis, OS-r was 16.3 months in patients with CP-A and 10.1 months with CP-B with no significant difference (P = .44), whereas OS-r was 16.3 months in patients with modified albumin-bilirubin Grade 1/2a and 13.2 months in patients with Grade 2b, with no significant difference. There was no clear difference in the incidence rate of ≥grade 3 adverse events between CP-A and CP-B. OS-r and OS-s were significantly correlated.Even patients with impaired liver function achieved the desired therapeutic effects by safely reducing the starting dose of regorafenib according to both impaired liver function and adverse events during pretreatment. Regorafenib may be considered to be an effective treatment after sorafenib monotherapy in patients with impaired liver function.

DOI： 10.1097/MD.0000000000021191

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：日本消化器病学会-関東支部  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一社)日本膵臓学会  

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記述言語：英語  

BACKGROUND: In a phase III trial of lenvatinib as first-line treatment for advanced unresectable hepatocellular carcinoma (uHCC), the drug proved non-inferior to sorafenib in terms of the overall survival, but offered better progression-free survival. However, the effects of lenvatinib in uHCC patients with a tumor thrombus in the main portal vein and/or a high tumor burden (tumor occupancy more than 50% of the total liver volume), remain unclear, because these were set as exclusion criteria in the aforementioned trial. CASE SUMMARY: A 53-year-old man (case 1) and 66-year-old woman (case 2) with uHCC presented to us with a tumor thrombus in both the main portal vein and inferior vena cava, a high tumor burden accompanied by a tumor diameter greater than > 100 mm, and distant metastasis, with the residual liver function classified as grade 2A according to the modified Albumin-Bilirubin grading. We started both patients on lenvatinib. The therapeutic effect, as evaluated by the modified Response Evaluation Criteria in Solid Tumors, was rated as partial response in both case 1 and case 2 (at 8 wk and 4 wk after the start of lenvatinib administration, respectively). The therapeutic effect was sustained for 6 mo in case 1 and 20 mo in case 2. Fever occurred as an adverse event in both case 1 and 2, and hyperthyroidism and thrombocytopenia in only case 2, neither of which, however, necessitated treatment discontinuation. CONCLUSION: Even in hepatocellular carcinoma patients with poor prognostic factors, if the liver function is well-preserved, lenvatinib is effective and safe.

DOI： 10.12998/wjcc.v8.i12.2574

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Ovid Technologies (Wolters Kluwer Health)  

DOI： 10.1097/meg.0000000000001788

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Persistent Helicobacter pylori (H. pylori) infection causes chronic inflammation, atrophy of the gastric mucosa, and a high risk of developing gastric cancer. In recent years, awareness of eradication therapy has increased in Japan. As H. pylori infections decrease, the proportion of gastric cancers arising from H. pylori uninfected gastric mucosa will increase. The emergence of gastric cancer arising in H. pylori uninfected patients though rarely reported, is a concern to be addressed and needs elucidation of its clinicopathological features. AIM: To evaluate the clinicopathological features of early gastric cancer in H. pylori-uninfected patients. METHODS: A total of 2462 patients with 3375 instances of early gastric cancers that were treated by endoscopic submucosal dissection were enrolled in our study between May 2000 and September 2019. Of these, 30 lesions in 30 patients were diagnosed as H. pylori-uninfected gastric cancer (HpUIGC). We defined a patient as H. pylori-uninfected using the following three criteria: (1) The patient did not receive treatment for H. pylori, which was determined by investigating medical records and conducting patient interviews; (2) Lack of endoscopic atrophy; and (3) The patient was negative for H. pylori after being tested at least twice using various diagnostic methods, including serum anti-H. pylori-IgG antibody, urease breath test, rapid urease test, and microscopic examination. RESULTS: The frequency of HpUIGC was 1.2% (30/2462) for the patients in our study. The study included 19 males and 11 females with a mean age of 59 years. The location of the stomach lesions was divided into three sections; upper third (U), middle third (M), lower third (L). Of the 30 lesions, 15 were U, 1 was M, and 14 were L. Morphologically, 17 lesions were protruded and flat elevated type (0-I, 0-IIa, 0-IIa + IIc), and 13 lesions were flat and depressed type (0-IIb, 0-IIc). The median tumor diameter was 8 mm (range 2-98 mm). Histological analysis revealed that 22 lesions (73.3%) were differentiated type.The HpUIGC lesions were classified into fundic gland type adenocarcinoma (7 cases), foveolar type well-differentiated adenocarcinoma (8 cases), intestinal phenotype adenocarcinoma (7 cases), and pure signet-ring cell carcinoma (8 cases). Among 30 HpUIGCs, 24 lesions (80%) were limited to the mucosa; wherein, the remaining 6 lesions showed submucosal invasion. One of the submucosal invasive lesions showed more than 500 μm invasion. The mucin phenotype analysis identified 7 HpUIGC with intestinal phenotype and 23 with gastric phenotype. CONCLUSION: We elucidated the clinicopathological characteristics of HpUIGC, revealing recognition not only undifferentiated-type but also differentiated-type. In addition, intestinal phenotype tumors were also observed and could be an important tip.

DOI： 10.3748/wjg.v26.i20.2618

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Perineural invasion (PNI) is one of the major pathological characteristics of pancreatic ductal adeno-carcinoma (PDAC), which is mediated by invading cancer cells into nerve cells. Herein, we identify the overexpression of Interleukin-13 Receptor alpha2 (IL-13Rα2) in the PNI from 236 PDAC samples by studying its expression at the protein levels by immunohistochemistry (IHC) and the RNA level by in situ hybridization (ISH). We observe that ≥75% samples overexpressed IL-13Rα2 by IHC and ISH in grade 2 and 3 tumors, while ≥64% stage II and III tumors overexpressed IL-13Rα2 (≥2+). Interestingly, ≥36 % peripancreatic neural plexus (PL) and ≥70% nerve endings (Ne) among PNI in PDAC samples showed higher levels of IL-13Rα2 (≥2+). IL-13Rα2 +ve PL and Ne subjects survived significantly less than IL-13Rα2 -ve subjects, suggesting that IL-13Rα2 may have a unique role as a biomarker of PNI-aggressiveness. Importantly, IL-13Rα2 may be a therapeutic target for intervention, which might not only prolong patient survival but also help alleviate pain attributed to perineural invasion. Our study uncovers a novel role of IL-13Rα2 in PNI as a key factor of the disease severity, thus revealing a therapeutically targetable option for PDAC and to facilitate PNI-associated pain management.

DOI： 10.3390/cancers12051294

PubMed

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掲載種別：研究論文（学術雑誌）   出版者・発行元：MDPI AG  

We attempted to establish an ultrasound (US) imaging-diagnostic system for histopathological grades of differentiation of hepatocellular carcinoma (HCC). We conducted a retrospective study of histopathologically confirmed 200 HCCs, classified as early (45 lesions), well- (31 lesions), moderately (68 lesions) or poorly differentiated (diff.) (56 lesions) HCCs. We performed grayscale US to estimate the presence/absence of halo and mosaic signs, Sonazoid contrast-enhanced US (CEUS) to determine vascularity (hypo/iso/hyper) of lesion in arterial and portal phase (PP), and echogenicity of lesion in post-vascular phase (PVP). All findings were of significance for the diagnosis of some (but not all) histological grades (p &lt; 0.001–0.05). Combined findings with a relatively high diagnostic efficacy for early, poorly and moderately diff. HCC were a combination of absence of halo sign and isoechogenicity in PVP of CEUS (accuracy: 93.0%, AUC: 0.908), hypovascularity in PP (accuracy: 78.0%, area under the curve (AUC): 0.750), and a combination of isovascularity in PP and hypoechogenicity in PVP (accuracy: 75.0%, AUC: 0.739), respectively. On the other hand, neither any individual finding nor any combination of findings yielded an AUC of over 0.657 for the diagnosis of well-diff. HCC. Our study provides encouraging data on Sonazoid CEUS in the histological differential diagnosis of HCC, especially in early HCC, and the effectiveness of this imaging method should be further proved by prospective, large sample, multicenter studies.

DOI： 10.3390/diagnostics10050321

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/den.13648

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The aim of this study is to clarify whether trans-abdominal ultrasound (TAUS) can reflect actual intestinal conditions in Crohn's disease (CD) as effectively as water-immersion ultrasound (WIUS) does. This retrospective study enrolled 29 CD patients with 113 intestinal lesions. Five ultrasound (US) parameters (distinct presence/indistinct presence/disappearance of wall stratification in the submucosal and mucosal layers; thickened submucosal layer; irregular mucosal surface; increased fat wrapping around the bowel wall; and fistula signs) that may indicate different states in CD were determined by TAUS and WIUS for the same lesion. Using WIUS as a reference standard, the sensitivity, specificity, and accuracy of TAUS were calculated. The degree of agreement between TAUS and WIUS was evaluated by the kappa coefficient. All US parameters of TAUS had an accuracy >70% (72.6-92.7%). The highest efficacy of TAUS was obtained for fistula signs (sensitivity, specificity, and accuracy values were 63.6%, 96.0%, and 92.7%, respectively). All US parameters between TAUS and WIUS had a definitive (p ≤ 0.001) and moderate-to-substantial consistency (kappa value = 0.446-0.615). The images of TAUS showed substantial similarity to those of WIUS, suggesting that TAUS may function as a substitute to evaluate the actual intestinal conditions of CD.

DOI： 10.3390/diagnostics10050267

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

40歳男性が上腹部痛と発熱で救急外来を受診した.CTで空腸憩室と周囲脂肪織濃度上昇に加えて限局性の腸管外ガス像を認め,穿通性小腸憩室炎を疑った.腹部症状が軽度で,腸管外ガスが限局していたため手術は行わず,保存的に治療したところ軽快し,再発はない.小腸憩室炎はまれであり,診断には注意深いCT読影が必要である.穿通性小腸憩室炎を保存的治療で軽快させた本邦からの既報告はなく,貴重であるため報告する.(著者抄録)

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01118&link_issn=&doc_id=20200421270008&doc_link_id=130007830099&url=http%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F130007830099&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

DOI： 10.1007/s12072-020-10019-z

PubMed

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その他リンク： http://link.springer.com/article/10.1007/s12072-020-10019-z/fulltext.html

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Direct-acting anti-virals (DAAs) have markedly improved the effectiveness of anti-viral therapy for chronic hepatitis C (CHC) patients. In a phase III trial in Japan, treatment with the NS3/4A protease inhibitor glecaprevir and the NS5A inhibitor pibrentasvir (G/P) resulted in a small number of patients with refractory factors. We aimed to evaluate the effectiveness and safety of G/P, especially among patients with these refractory factors, and the influence of these factors on treatment. METHODS: In a prospective, multicenter study involving 33 medical institutions, 1439 patients were treated with G/P, and their efficacy, safety, and most frequent adverse effects (AEs) were analyzed. RESULTS: Overall SVR12 rates were 99.1% (1397/1410) in the per-protocol-analysis, and genotype sustained virologic response SVR12 rates were: genotype 1, 99.4% (707/711); genotype 2, 99.4% (670/674); genotype 3, 80.0% (16/20). DAA-naïve patients (p = 0.008) with HCV genotype except 3 (genotype 1 vs. 3, p = 2.68 × 10-5; genotype 2 vs. 3, p = 3.28 × 10-5) had significantly higher SVR12 rates. No significant difference was observed between CKD stage 1-3 (99.1% [1209/1220]) and chronic kidney disease (CKD) stage 4-5 (98.9% [188/190]) patients, or between cirrhotic (99.0% [398/402]) and non-cirrhotic (99.1% [999/1008]) patients. Multiple logistic regression analysis revealed that genotype 3 [OR 33.404, 95% CI (7.512-148.550), p value (p = 4.06 × 10-5)] and past experience of IFN-free DAAs [OR 3.977, 95% CI (1.153-13.725), p value (p = 0.029)] were both significantly independent predictors of non-SVR12. AEs were reported in 28.2% of patients, and 1.6% discontinued treatment owing to drug-related AEs. AEs were significantly higher in CKD stage 4-5 (41.6% [79/190]) than CKD stage 1-3 (26.1% [319/1220]) patients (p = 2.00 × 10-5). AEs were also significantly higher in cirrhotic (38.6% [155/402]) than in non-cirrhotic (24.1% [243/1008]) (p = 2.91 × 10-18) patients. CONCLUSIONS: G/P regimen is highly effective and safe to treat CHC patients even with refractory factors such as CKD and advanced liver fibrosis. However, patients with past experience of IFN-free DAA treatment and genotype 3, CKD stage 4 or 5, and advanced liver fibrosis should be more closely observed.

DOI： 10.1007/s12072-020-10019-z

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掲載種別：研究論文（学術雑誌）   出版者・発行元：MDPI AG  

Predictive biomarkers of the response of hepatocellular carcinoma (HCC) to Lenvatinib therapy have not yet been clarified. The aim of this study was to identify clinically significant biomarkers of response to Lenvatinib therapy, to target strategies against HCC. Levels of circulating angiogenic factors (CAFs) were analyzed in blood samples collected at baseline and after introducing lenvatinib, from 74 Child-Pugh class A HCC patients who received lenvatinib. As CAF biomarkers, serum vascular endothelial growth factor (VEGF), fibroblast growth factor 19 (FGF19), FGF23, and angiopoietin-2 (Ang-2) were measured using enzyme-linked immunosorbent assays. Results: Significantly increased FGF19 (FGF19-i) levels and decreased Ang-2 (Ang-2-d) levels were seen in Lenvatinib responders as compared to non-responders (ratio of FGF19 level at 4 weeks/baseline in responders vs. non-responders: 2.09 vs. 1.32, respectively, p = 0.0004; ratio of Ang-2 level at four weeks/baseline: 0.584 vs. 0.810, respectively, p = 0.0002). Changes in FGF23 and VEGF levels at four weeks versus baseline, however, were not significantly different in responders versus non-responders. In multivariate analysis, the combination of serum FGF19-i and Ang-2-d was the most independent predictive factor for Lenvatinib response (Odds ratio, 9.143; p = 0.0012). Furthermore, this combination biomarker showed the greatest independent association with progression-free survival (Hazard ratio, 0.171; p = 0.0240). Early changes in circulating FGF19 and Ang-2 levels might be useful for predicting clinical response and progression-free survival in HCC patients on Lenvatinib therapy.

DOI： 10.3390/cancers12020293

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

According to cancer genome sequences, more than 90% of cases of pancreatic ductal adenocarcinoma (PDAC) harbor active KRAS mutations. Digital PCR (dPCR) enables accurate detection and quantification of rare mutations. We assessed the dynamics of circulating tumor DNA (ct-DNA) in patients with advanced PDAC undergoing chemotherapy using dPCR. KRAS G12/13 mutation was assayed by dPCR in 47 paired tissue- and ct-DNA samples. The 21 patients were subjected to quantitative ct-DNA monitoring at 4 to 8-week intervals during chemotherapy. KRAS mutation was detected in 45 of those 47 patients using tissue DNA. In the KRAS mutation-negative cases, next-generation sequencing revealed KRAS Q61K and NRAS Q61R mutations. KRAS mutation was detected in 23/45 cases using ct-DNA (liver or lung metastasis, 18/19; mutation allele frequency [MAF], 0.1%-31.7%; peritoneal metastasis, 3/9 [0.1%], locally advanced, 2/17 [0.1%-0.2%]). In the ct-DNA monitoring, the MAF value changed in concordance with the disease state. In the 6 locally advanced cases, KRAS mutation appeared concurrently with liver metastasis. Among the 6 cases with liver metastasis, KRAS mutation disappeared during the duration of stable disease or a partial response, and reappeared at the time of progressive disease. The median progression-free survival was longer in cases in which KRAS mutation disappeared after an initial course of chemotherapy than in those in which it was continuously detected (248.5 vs 50 days, P < .001). Therefore, ct-DNA monitoring enables continuous assessment of disease state and could have prognostic utility during chemotherapy.

DOI： 10.1111/cas.14245

PubMed

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記述言語：日本語   出版者・発行元：神奈川県医師会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose: To assess the safety, efficacy and prognostic impact of clinical factors related to lenvatinib treatment in Child-Pugh class A (CP-A) and class B (CP-B) patients with unresectable hepatocellular carcinoma (u-HCC). Methods: Patients with u-HCC who were treated with lenvatinib at multiple centers in Japan were retrospectively analyzed for treatment outcomes according to their respective CP status. Radiological objective response (OR) was assessed using modified response evaluation criteria in solid tumors (mRECIST) guidelines. Results: Baseline demographic parameters were comparable between 126 (69.6%) patients with CP-A disease and 55 patients (30.4%) with CP-B disease. Frequency of lenvatinib-related adverse events, including decreased appetite (P=0.034), diarrhea (P=0.040), elevated serum bilirubin (P=0.016) and vomiting (P=0.009), were higher in CP-B than in CP-A patients. Relative dose intensity (RDI) was significantly higher in CP-A (0.69) than CP-B patients (0.50, P <0.001). Furthermore, OR rate (44.0%) was markedly higher in CP-A5 patients as compared to CP-A6 (25.5%), CP-B7 (22.2%), and CP-B8 patients (5.3%), respectively (P=0.002). In multivariable analysis, performance status (0 vs 1, 2, P=0.026), CP class (A vs B, P=0.045) and RDI (≥0.7 vs <0.7, P=0.034) were identified as factors associated with response to lenvatinib treatment. Overall survival (OS) at 12 months was significantly different between CP-A (66.3%) and CP-B patients (30.0%, P=0.002), and between CP 5-7 (59.2%) and CP 8 patients (34.8%, P=0.003). In multivariable analysis, CP class (A vs B, P=0.007) and Barcelona clinic liver cancer (BCLC) stage (B vs C, P=0.002) were associated with OS following lenvatinib treatment. Conclusion: Lenvatinib treatment offers significant benefits in patients with good liver function in real-world practice. The various characteristics identified in this study might be helpful as clinical predictors of response to lenvatinib and survival in clinical practice. Further studies are required to address eligibility for lenvatinib treatment in CP 7 patients.

DOI： 10.2147/CEG.S256691

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：HELLENIC SOC GASTROENTEROLOGY  

Background Endoscopic resection is recommended for non-ampullary duodenal neuroendocrine tumors (NAD-NETs) <= 10 mm in diameter and confined to the submucosal layer, without lymph node or distant metastasis. However, the efficacy and safety of endoscopic submucosal dissection (ESD) for NAD-NET remains unclear. The aim of this study was to assess the short-term efficacy and safety and the long-term outcomes of ESD for NAD-NET.Methods Eight patients with 8 NAD-NETs who underwent ESD between 2015 and 2018 were included. The indications for ESD were: i) tumor <= 10 mm in diameter; ii) NET G1; iii) confined to the submucosal layer; and iv) without lymph node or distant metastasis. We retrospectively assessed the short- and long-term outcomes and safety.Results The median patient age was 69 (48-76) years. All tumors were located in the duodenal bulb and showed 0-Is morphology. The median size was 6.4 (3-9.3) mm. The rates of en bloc resection, histologically free horizontal and vertical margins, and curative resection were 100%, 88%, and 88%, respectively. Intraoperative and postoperative perforation each occurred in 13% of patients, all of whom were treated conservatively and avoided emergent surgery. Delayed bleeding was not observed. No local, lymph node or distant recurrence was observed during a median follow-up period of 34 (18.5-62.5) months.Conclusions The rates of en bloc and curative resection, and histologically free margins were sufficiently high. Although intraoperative and postoperative perforations occurred, emergency surgery was not needed. The results show that ESD is an efficacious and safe treatment for NAD-NET.

DOI： 10.20524/aog.2020.0477

Web of Science

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.jcmgh.2019.09.001

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose: This study evaluated the usefulness of intraprocedural contrast-enhanced ultrasound (CEUS)/ultrasound (US) fusion imaging using a perflubutane-based contrast agent combined with preprocedural auto sweep three-dimensional US to obtain volume data for guidance and evaluation of the therapeutic efficacy of radiofrequency ablation (RFA).Methods: This uncontrolled clinical trial included 50 hepatocellular carcinomas (HCCs) with a mean diameter of 15.3 mm that had been treated by RFA. The efficacy of RFA was evaluated by CEUS/US fusion imaging during the procedure. If the ablation was deemed to be inadequate, further ablation was performed until adequate ablation was achieved. Contrast-enhanced computed tomography (CECT) or contrast-enhanced magnetic resonance imaging (CEMRI) was performed a month after RFA, and the images obtained using each modality were reviewed to evaluate the efficacy of RFA.Results: Thirty-three of the 50 lesions were evaluated by CEUS/US fusion imaging as having been adequately ablated after the first RFA procedure. The ablation was evaluated as inadequate in the remaining 17 lesions, for which additional ablation was performed. Ninety-eight (49/50) of all HCCs were evaluated as having been eventually adequately ablated on intraprocedural CEUS/US fusion imaging. The concordance rate for evaluations between intraprocedural CEUS/US fusion imaging and CECT/CEMRI performed 1 month after RFA was 88% (44/50). The kappa value for agreement between the two methods of evaluation was 0.792.Conclusion: Intraprocedural fusion imaging combining CEUS and auto sweep three-dimensional US appears to be a useful modality for RFA guidance and evaluation of therapeutic efficacy of RFA in patients with HCC.

DOI： 10.1080/02656736.2020.1729422

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND & AIMS: To explore the ability of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid magnetic resonance imaging (EOB-MRI)/ultrasound (US) fusion imaging (FI) to improve the prognosis of radiofrequency ablation (RFA) by ablating the characteristic findings of hepatocellular carcinoma (HCC) in hepatobiliary phase (HBP) imaging. METHODS: We retrospectively recruited 115 solitary HCC lesions with size of (15.9 ± 4.6) mm. They were all treated by RFA and preoperative EOB-MRI. According to the modalities guiding RFA performance, the lesions were grouped into contrast enhanced US (CEUS)/US guidance group and EOB-MRI/US FI guidance group. For the latter group, the ablation scope was set to cover the HBP findings (peritumoral hypointensity and irregular protruding margin). The presence of HBP findings, the modalities guided RFA, the recurrence rate were observed. RESULTS: After an average follow-up of 377 days, local tumor progression (LTP) and intrahepatic distant recurrence (IDR) were 14.8% and 38.4%, respectively. The lesions having HBP findings exhibited a higher recurrence rate (73.7%) than the lesions without HBP findings (42.9%) (p = 0.002) and a low overall recurrence-free curve using the Kaplan-Meier method (p = 0.038). Using EOB-MRI/US FI as guidance, there was no difference in the recurrence rate between the groups with and without HBP findings (p = 0.799). In lesions with HBP findings, RFA guided by EOB-MRI/US FI (53.8%) produced a lower recurrence rate than CEUS/US (84.0%) (p = 0.045). CONCLUSIONS: The intraprocedurally application of EOB-MRI/US FI to determine ablation scope according to HBP findings is feasible and beneficial for prognosis of RFA.

DOI： 10.1080/02656736.2020.1825837

PubMed

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記述言語：日本語   出版者・発行元：日本消化器病学会-関東支部  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/jgh.14690

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objectives: Transabdominal ultrasonography is a common and accurate tool for managing Crohn's disease (CD); however, the significance of the resulting data is poorly understood. This study was performed to determine the association between bowel wall thickness evaluated by water-immersion ultrasonography and macroscopic severity, namely, refractory inflammation and subsequent fibrosis in CD surgical specimens.Materials and methods: We retrospectively evaluated 100 segments of colon and small intestine from 27 patients with CD. The resected specimens were placed in saline postoperatively, and bowel wall thickness was measured by water-immersion ultrasonography and compared with macroscopic findings. Correlations between bowel wall thickness and macroscopic findings were assessed using analysis of variance and receiver operating characteristic curves.Results: According to the progression of macroscopic severity, the mean bowel wall thickness was increased as follows: macroscopically intact: 4.1 mm, longitudinal ulcer scars: 5.4 mm, longitudinal open ulcers: 6.0 mm, large ulcers: 6.4 mm, cobblestone-like lesions: 7.1 mm, and fibrotic strictures: 7.4 mm. For all lesions except longitudinal ulcer scars, the bowel wall thickness was significantly thicker than that of macroscopically-intact areas (p < .001). According to receiver operating characteristic curves, bowel wall thickness >4.5 mm was associated with CD lesions, and thickness >5.5 mm was associated with more severe lesions.Conclusions: The bowel wall thickness of CD lesions was evaluated by water-immersion ultrasonography correlated with macroscopic disease severity.

DOI： 10.1080/00365521.2019.1683224

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DOI： 10.1097/MEG.0000000000001595

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DOI： 10.1186/s12885-019-6198-8

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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DOI： 10.1007/s12328-019-00976-w

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1002/jum.14926

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AVES  

Background/Aims: The aim of this study was to determine the correlation between low-dose ramosetron pretreatment and gastric emptying using a novel, non-invasive technique for measuring gastric emptying, namely, the continuous real-time 13C breath test (BreathID system: Exalenz Bioscience Ltd., Israel). Materials and Methods: Twelve healthy male volunteers participated in this randomized two-way crossover study. The subjects fasted overnight and were randomly assigned to receive the test meal (200 kcal per 200 mL) after an hour pre-treatment with 5 µg ramosetron or the test meal alone. Gastric emptying was monitored for 4 hours after administration of the test meal with the 13C-acetic acid breath test performed continuously using the BreathID system. Using Oridion Research Software (β version), T 1/2, T lag, GEC and the regression-estimated constants (β and κ) were calculated. The differences in the parameters measured at two time-points were analyzed using Wilcoxon’s signed-rank test. Results: There was a significant difference in the calculated parameter β. No significant differences in the calculated parameters T 1/2, T lag, GEC or κ were observed between the test meal with ramosetron group and the test meal alone group. Conclusion: This study showed that ramosetron pre-treatment enhances the early gastric emptying of liquid nutrients.

DOI： 10.5152/TJG.2015.4768

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS: Early tumor recurrence (ETR) after hepatic resection is a crucial predictor of poor prognosis in patients with hepatocellular carcinoma (HCC). The aim of this study was to identify clinically significant serum microRNAs (miRNAs) involved in the ETR of HCC. METHODS: We compared expression profiles of circulating miRNAs from serum samples between five HCC patients with ETR (recurrence within 12 months after hepatectomy) and five HCC patients without recurrence using microarray analysis of miRNA. The identified miRNA associated with ETR was further verified in 121 HCC patients, 73 liver disease patients, and 15 health controls by real-time quantitative reverse transcription-polymerase chain reaction (PCR). RESULTS: Of the approximately 2000 miRNAs analyzed, we identified 15 miRNAs for which expression levels correlated significantly with ETR. Of these miRNAs, we further investigated expression of miRNA-1246 (miR-1246). Quantitative PCR confirmed that miR-1246 was upregulated in HCC with ETR, compared to the level in HCC without ETR (P < 0.001). Serum miR-1246 showed a receiver operating characteristic curve area of 0.762, with 77.4% specificity and 54.1% sensitivity in discriminating HCC patients with ETR from HCC patients without ETR. Altered expression of miR-1246 was associated with aggressive tumor characteristics, including tumor-node-metastasis classification (P = 0.0413), tumor differentiation (P = 0.0419), and portal vein invasion (P = 0.0394). Moreover, multivariate Cox regression analysis identified serum miR-1246 level as an independent risk factor for overall survival (hazard ratio, 2.784; 95% confidence interval, 1.528-5.071; P = 0.0008). CONCLUSION: Circulating miR-1246 in serum has strong potential as a novel ETR and prognostic biomarker for HCC.

DOI： 10.1111/hepr.13338

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記述言語：日本語   出版者・発行元：(NPO)日本食道学会  

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/hep.30591

Scopus

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s00261-018-1833-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/jgh.14456

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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DOI： 10.1007/s00535-018-1500-0

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

症例は92歳男性。入院前9ヵ月間にS状結腸軸捻転症で6回の緊急入院を繰り返した。重度の認知症で手術は困難であり、毎回内視鏡的整復術、減圧術で治療していた。7回目の入院時に重度の粘膜虚血性変化を認めたが、保存的治療で改善した。家族と十分に相談した上で再発予防目的に経皮的内視鏡的結腸瘻造設術(PEC)を施行した。合併症はなく、術後は他病死するまでの3年間無再発であった。合併症を有する高齢者に多いS状結腸軸捻転症は根治的手術が困難なため内視鏡的治療が行われることが多いが、その再発率が高いことが課題である。繰り返すS状結腸軸捻転症に対してPECは有用な治療選択肢となりうると考えられた。(著者抄録)

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J00192&link_issn=&doc_id=20181126340005&doc_link_id=10.11280%2Fgee.60.2393&url=https%3A%2F%2Fdoi.org%2F10.11280%2Fgee.60.2393&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1080/00365521.2018.1511825

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Tokyo  

Purpose: We evaluated the efficacy of fusion imaging combining contrast-enhanced ultrasonography (CEUS) images and arterial phase contrast-enhanced CT (CECT) or hepatobiliary phase magnetic resonance imaging with gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (EOB-MRI) images for the early evaluation of the effectiveness of radiofrequency ablation (RFA) for small hypervascular hepatocellular carcinoma (HCC) with iso-echoic or unclear margins on conventional US. Methods: Forty HCCs (22 iso-echoic and 18 unclear margin lesions) with mean diameters of 13.7 mm were treated using RFA under the guidance of fusion imaging with CEUS. The adequacy of RFA was evaluated using fusion imaging with CEUS 1 day after RFA. CECT or EOB-MRI was performed 1 month after RFA. We reviewed the images obtained using both modalities. Results: When the 1-month CECT or EOB-MRI scans were used as the reference standard, the sensitivity, specificity, and accuracy of the 1-day fusion imaging for the diagnosis of the adequate ablation of these HCCs were 97, 100, and 98%, respectively
the kappa value for the agreement between the findings using the two modalities was 0.655. Conclusion: Fusion imaging with CEUS appears to be a useful method for the early evaluation of the efficacy of RFA for the treatment of HCCs with iso-echoic or unclear margins on conventional US.

DOI： 10.1007/s10396-018-0861-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Celsius Publishing House  

Background/Aims: The aim of this study was to investigate the efficacy and safetyof the oral fluoropyrimidine derivativeS-1 in elderly patients with unresectable pancreatic cancer. Methods: Patients were eligible if they were at least 70 years old and had unresectable pancreatic carcinoma. S-1 was administered orally twice daily after meals at doses of 80, 100, and 120 mg/day forbody surface areasfor 28 consecutive days, followed by a 14-day rest period. Administration was repeated until the appearance of disease progression or unacceptable toxicity. Results: Twenty-one patients were enrolledin this study. Five patients (23.8%) achieved a partial response (95% CI, 8.2-47.2%),stable disease was observed in 9 patients (42.9%), and progressive disease was observed in 5 patients (23.8%).The disease control rate was 66.7%. The median time to progression and overall survivaltime were 3.7 months (95% CI, 2.3-6.5 months) and 7.3 months (95% confidence interval, 4.9-12.1 months), respectively. Toxicity was generally mild, and the most common grade 3/4 toxicities were neutro-penia (14.3%), anemia (14.3%), leucopenia (9.5%), thrombocytopenia (9.5%), anorexia (9.5%), and diarrhea (9.5%). There were no treatment-related deaths. Conclusions: Monotherapy with S-1 is an effective and well-tolerated regimen for elderly patients with unresectable pancreatic cancer.

DOI： 10.21614/sgo-23-3-191

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記述言語：日本語   出版者・発行元：(一社)日本膵臓学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Pancreatic ductal adenocarcinoma (PDA) has a 5-year survival rate of less than 5% and is the sixth leading cause of cancer death. Although KRAS mutations are one of the major driver mutations in PDA, KRAS mutation alone is not sufficient to induce invasive pancreatic cancer in mice model. HER2, also known as ERBB2, is a receptor tyrosine kinase, and overexpression of HER2 is associated with poor clinical outcomes in pancreatic cancer. However, no report has shown whether HER2 and its downstream signaling contributes to the pancreatic cancer development. By immunohistochemical analysis in human cases, HER2 protein expression was detected in 40% of PDAs and 29% of intraductal papillary mucinous carcinomas, another type of pancreatic cancer. In a mouse model, we showed overexpression of activated HER2 (HER2 NT ) in the pancreas, in which cystic neoplastic lesions resembling intraductal papillary mucinous neoplasm-like lesions in humans had developed. We also found that HER2 NT cooperated with oncogenic Kras to accelerate the development of pancreatic intraepithelial neoplasms. In addition, using pancreatic organoids in 3D cultures, we found that organoids cultured from HER2 NT /Kras double transgenic mice showed proliferative potential and tumorigenic ability cooperatively. HER2-signaling inhibition was suggested to be an new therapeutic target in some types of PDAs.

DOI： 10.1038/s41598-018-24375-2

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記述言語：英語   出版者・発行元：Blackwell Publishing  

DOI： 10.1111/den.13026

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Blackwell Publishing Ltd  

Background: The eradication rate of vonoprazan-based first-line triple therapy (combined with clarithromycin and amoxicillin) (V-AC) was reported to be 97.6% in patients with clarithromycin (CAM)-susceptible Helicobacter pylori in a phase III study, whereas our real-world, prospective, multicenter cohort study yielded an eradication rate &lt
90%. Objective: To validate the eradication rate of V-AC using CAM-susceptible testing in a multicenter, prospective, randomized trial. Methods: We included 147 treatment-naïve H. pylori-positive patients [41 with CAM-resistant infections and 106 with CAM-susceptible infections]. The CAM-susceptible group patients were randomized to either the V-AC group (vonoprazan 20 mg bid, amoxicillin 750 mg bid, and clarithromycin 200 or 400 mg bid) or PPI-AC group (lansoprazole 30 mg, rabeprazole 10 mg, or esomeprazole 20 mg bid
amoxicillin 750 mg bid
and clarithromycin 200 or 400 mg bid). All CAM-resistant H. pylori were eradicated by V-AC, as measured by the urea breath test around 8 weeks after eradication. Safety was evaluated by patient questionnaires. Results: The intention-to-treat and per-protocol eradication rates of V-AC in the CAM-susceptible H. pylori-infected patients were 87.3% (95% confidence interval 75.5%-94.7%) and 88.9% (77.4%-95.8%). The respective eradication rates of PPI-AC were 76.5% (62.5%-87.2%) and 86.7% (73.2%-94.9%). No significant difference was observed between the V-AC and PPI-AC regimes in terms of the intention-to-treat (P =.21) or per-protocol (P =.77) analyses. The questionnaire scores did not differ significantly between the groups. Both the intention-to-treat and per-protocol eradication rates of V-AC in the CAM-resistant patients were 82.9% (67.9%-92.8%). Conclusion: The eradication rate of V-AC treatment in the CAM-susceptible H. pylori-infected patients was &lt
90%, as was that by PPI-AC, thus V-AC is not ideal regimen in CAM-susceptible H. pylori. However, the 82.9% eradication rate of V-AC in the CAM-resistant infections may indicate the potential of V-AC with modified dose, dosing interval, and treatment duration. (UMIN000016337).

DOI： 10.1111/hel.12456

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記述言語：英語   出版者・発行元：(一社)日本胃癌学会  

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.gie.2017.10.038

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DOI： 10.1007/s10120-017-0734-5

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：英語   出版者・発行元：Georg Thieme Verlag  

DOI： 10.1055/s-0043-121134

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BioMed Central Ltd.  

Correction: Unfortunately, the original article [1] contained an error incorporated during production. A duplicated version of Table1 was published in place of Table2. Table2 has been corrected in the original article and is also included correctly below.

DOI： 10.1186/s12876-017-0733-3

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記述言語：日本語   出版者・発行元：(公社)神奈川県医師会  

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Hindawi Limited  

<italic>Background</italic>. Vonoprazan affords more clinical benefits than proton pump inhibitors (PPIs) during the healing of gastroduodenal ulcers. However, it remains controversial whether vonoprazan is more effective than PPIs when used to heal artificial ulcers arising after endoscopic submucosal dissection (ESD). <italic>Aim</italic>. This study investigated the effects of vonoprazan compared with esomeprazole on the healing of post-ESD artificial ulcers. <italic>Methods</italic>. Sixty patients who underwent gastric ESD between May 2015 and May 2017 were randomized to treatment with vonoprazan (V group) or esomeprazole (E group) for 8 weeks. Upper endoscopy was performed at 4 and 8 weeks after ESD, and drug effects were estimated based on the ulcer healing rates and shrinkage rates. <italic>Results</italic>. Fifty-three patients were analyzed. The respective 4- and 8-week ulcer healing rates did not differ significantly between V and E groups (8.0 versus 11.5%, <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mi>P</mml:mi><mml:mo>=</mml:mo><mml:mn>0.669</mml:mn></mml:math>; 88.9 versus 84.6%, <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mi>P</mml:mi><mml:mo>=</mml:mo><mml:mn>0.420</mml:mn></mml:math>). Similarly, the respective 4- and 8-week ulcer shrinkage rates did not differ significantly between V and E groups (96.8 versus 97.5%, <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M3"><mml:mi>P</mml:mi><mml:mo>=</mml:mo><mml:mn>0.656</mml:mn></mml:math>; 100 versus 100%, <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M4"><mml:mi>P</mml:mi><mml:mo>=</mml:mo><mml:mn>0.257</mml:mn></mml:math>). <italic>Conclusion</italic>. The healing of artificial ulcers after ESD did not differ using vonoprazan or esomeprazole. Both vonoprazan and esomeprazole were effective when used to promote artificial ulcer healing after ESD.

DOI： 10.1155/2018/1615092

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その他リンク： http://downloads.hindawi.com/journals/grp/2018/1615092.xml

記述言語：日本語  

DOI： 10.11280/gee.60.2393

J-GLOBAL

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1155/2018/8046838

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background/Aim: Although IL-6-mediated activation of the signal transduction and activator of transcription 3 (STAT3) axis is involved in inflammation and cancer, the role of STAT3 in Helicobacter-associated gastric inflammation and carcinogenesis is unclear. This study investigated the role of STAT3 in gastric inflammation and carcinogenesis and examined the molecular mechanism of Helicobacter-induced gastric phenotypes. Methods: To evaluate the contribution of STAT3 to gastric inflammation and carcinogenesis, we used wild-type (WT) and gastric epithelial conditional Stat3-knockout (Stat3Δgec ) mice. Mice were infected with Helicobacter felis and euthanized at 18 months postinfection. Mouse gastric organoids were treated with recombinant IL-6 (rIL-6) or rIL-11 and a JAK inhibitor (JAKi) to assess the role of IL-6/STAT3 signaling in vitro. Results: Inflammation and mucous metaplasia were more severe in WT mice than in Stat3Δgec mice. The epithelial cell proliferation rate and STAT3 activation were increased in WT mice. Application of rIL-6 and rIL-11 induced expression of intestinal metaplasia-associated genes, such as Tff2; this induction was suppressed by JAKi administration. Conclusions: Loss of STAT3 signaling in the gastric mucosa leads to decreased epithelial cell proliferation, atrophy, and metaplasia in the setting of Helicobacter infection. Therefore, activation of STAT3 signaling may play a key role in Helicobacter-associated gastric carcinogenesis.

DOI： 10.1155/2018/9050715

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.7150/jca.24236

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The platinum-based chemotherapy regimen FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin) is currently used as a standard treatment for patients with unresectable pancreatic cancer. FOLFIRINOX is associated with severe toxicities, including neutropenia, febrile neutropenia, and anorexia; however, there are currently no reliable biomarkers to predict its efficacy and safety. Several studies of patients with various cancers have shown that tumor expression of excision repair cross-complementing (ERCC) proteins and glutathione S-transferase Pi (GSTPi) correlates with the response to platinum-based chemotherapies. Therefore, in this study, we examined the associations between expression of ERCC proteins and GSTPi and the safety and efficacy of FOLFIRINOX in 34 patients with unresectable pancreatic cancer. ERCC1, ERCC2, ERCC4, and GSTPi expression were examined by immunohistochemical staining of tumor specimens and the results were correlated with overall survival, progression-free survival, response rate, disease control rate, and the frequency of grade 3-4 neutropenia and non-hematologic toxicities. We found that ERCC1, ERCC2, ERCC4, and GSTPi were expressed in tumor samples from 64%, 24%, 18%, and 64% of patients, respectively. Notably, there were no statistically significant associations between the expression pattern of any of the proteins and either the clinical outcomes or the frequency of grade 3-4 neutropenia or grade 3-4 anorexia. Collectively, these data indicate that tumor expression of ERCC1, ERCC2, ERCC4, and GSTPi does not predict the safety or efficacy of FOLFIRINOX in patients with pancreatic cancer.

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記述言語：英語  

Stomach cancer rarely develops in patients with familial adenomatous polyposis (FAP), and Helicobacter pylori infection may increase the risk of FAP-related gastric cancer. We describe the case of a 64-year-old woman who developed multiple synchronous early gastric cancers without H. pylori infection. Nine cancer lesions were successfully treated by endoscopic submucosal dissection. An immunohistochemical analysis revealed that the tumors were positive for mucin (MUC)2, MUC6, and CDX2, but negative for MUC5AC, suggesting that the tumors were gastrointestinal mixed type. Periodical endoscopic surveillance is important for the detection of cancers at an early stage.

DOI： 10.2169/internalmedicine.8735-16

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DOI： 10.1055/s-0043-118003

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OXFORD UNIV PRESS  

In HCC patients who were unresponsive to chemoembolization with epirubicin, switching the chemotherapeutic regimen to a platinum-based anticancer drug should be considered as a treatment option.The aim of this prospective study was to evaluate the efficacy of transarterial chemoembolization using miriplatin, a platinum-based anticancer drug, as a retreatment regimen for hepatocellular carcinoma (HCC) unresponsive to chemoembolization using epirubicin.
Between April 2013 and December 2014, we enrolled 57 consecutive chamoembolization-na &lt; ve patients with unresectable HCC, and performed chemoembolization with epirubicin. Treatment effect, necrotizing rate of the target nodules, was evaluated at 1-3 months after treatment using contrast-enhanced CT or MRI. We subsequently included retreatment chemoembolization with miriplatin for patients whose treatment effect was &lt; 50% after chemoembolization with epirubicin. The treatment effect after chemoembolization with miriplatin and the liver function before and after chemoembolization were evaluated.
Eighteen patients of the 57 showed a treatment effect &lt; 50% after chemoembolization with epirubicin, and were switched to chemoembolization with miriplatin. The treatment effect after chemoembolization with miriplatin was a parts per thousand 50% in four (22%) patients. Four of the remaining 14 (78%) patients who had &lt; 50% necrosis exhibited deterioration of the liver function after chemoembolization with miriplatin. Univariate analysis indicated that an alpha-fetprotein-L3 level &lt; 10% and a serum albumin level a parts per thousand 3.6 g/dl were predictive factors of therapeutic response after chemoembolization with miriplatin (P &lt; 0.05). However, there was no predictive factor regarding the deterioration of liver function after chemoembolization with miriplatin.
In unresectable HCC patients who were unresponsive to chemoembolization with epirubicin, switching the chemotherapeutic regimen to a platinum-based anticancer drug in retreatment chemoembolization should be considered as a treatment option. Trial registration: UMIN 000015887.

DOI： 10.1093/jjco/hyx131

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMED CENTRAL LTD  

Background: Although Helicobacter-induced gastric inflammation is the major predisposing factor for gastric carcinogenesis, the precise mechanism by which chronic gastritis causes gastric cancer remains unclear. Intestinal and spasmolytic polypeptide-expressing metaplasia (SPEM) is considered as precancerous lesions, changes in epithelial tissue stem/progenitor cells after chronic inflammation has not been clarified yet. In this study, we utilized three-dimensional gastric epithelial cell culture systems that could form organoids, mimicking gastric epithelial layer, and characterized the changes in epithelial cells after chronic Helicobacter felis infection.
Methods: We used three mice model; 1) long-term H. felis infection, 2) H. felis eradication, and 3) MNU chemical carcinogenesis model. We performed cRNA microarray analysis after organoid culture, and analyzed the effects of chronic gastric inflammation on tissue stem cells, by the size of organoid, mRNA expression profile and immunohistochemical analysis.
Results: The number of organoids cultured from gastric epithelial cells was significantly higher in organoids isolated from H. felis-infected mice compared with those from uninfected gastric mucosa. Based on the mRNA expression profile, we found that possible stem cell markers such as Cd44, Dclk1, and genes associated with the intestinal phenotype, such as Villin, were increased in organoids isolated from H. felis-infected mucosa compared with the control. The upregulation of these genes were cancelled after H. felis eradication. In a xenograft model, tumors were generated only from organoids cultured from carcinogen-treated gastric mucosa, not from H. felis infected mucosa or control organoids.
Conclusions: Our results suggested that, as a possible mechanism of gastric carcinogenesis, chronic inflammation induced by H. felis infection increased the number of tissue stem/progenitor cells and the expression of stem cell markers. These findings suggest that chronic inflammation may alter the direction of differentiation toward undifferentiated state and that drawbacks may enable cells to redifferentiate to intestinal metaplasia or neoplasia.

DOI： 10.1186/s12876-017-0706-6

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DOI： 10.1002/ccr3.1151

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Background: Patients with inflammatory bowel disease (IBD) occasionally require central venous catheter (CVC) placement to support a therapeutic plan. Given that CVC can predispose patients to infection, this investigation was undertaken to assess the incidence, risk factors, and outcomes of CVC-related blood stream infection (CRBSI) in patients with IBD during routine clinical practice.
Methods: Data were compiled using retrospective chart reviews of 1367 patients treated at our IBD center between 2007 and 2012 during routine clinical practice. Among the 1367 patients, 314 who had received CVC placements were included. Patients with positive blood culture were considered as "definite" CRBSI, whereas "possible" CRBSI was defined as patients in whom fever alleviated within 48 hours post-CVC without any other infection. Patients' demographic variables including age, body mass index, serum albumin, duration of CVC placement, use of antibiotics, medications for IBD, and perioperative status between CRBSI and non-CRBSI subgroups were compared by applying a multivariate Poisson logistic regression model.
Results: Among the 314 patients with CVC placement, there were 83 CRBSI cases (26.4%). The average time to the onset of CRBSI was 22.5 days (range 4-105 days). The jugular vein access was found to be the most serious risk of CRBSI (risk ratio 2.041 versus subclavian vein). All patients with CRBSI fully recovered.
Conclusions: In this investigation, regardless of the patients' demographic features including immunosuppressive therapy, up to 30% of febrile IBD patients with CVC showed CRBSI. It is believed that CVC placement per se is a risk of CRBSI in patients with IBD.

DOI： 10.1097/MIB.0000000000001230

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

Pancreatic ductal adenocarcinoma (PDAC) is a life-threatening disease and there is an urgent need to develop improved therapeutic approaches. The role of c-Jun N-terminal kinase (JNK) in PDAC stroma is not well defined even though dense desmoplastic reactions are characteristic of PDAC histology. We aimed to explore the role of JNK in PDAC stroma in mice. We crossed Ptf1a(Cre/+);Kras(G12D/+) mice with JNK1(-/-) mice to generate Ptf1a(Cre/+);Kras(G12D/+);JNK1(-/-) (Kras;JNK1(-/-)) mice. Tumor weight was significantly lower in Kras;JNK1(-/-) mice than in Kras;JNK1(+/-) mice, whereas histopathological features were similar. We also transplanted a murine PDAC cell line (mPC) with intact JNK1 s.c. into WT and JNK1(-/-) mice. Tumor diameters were significantly smaller in JNK1(-/-) mice. Phosphorylated JNK (p-JNK) was activated in -smooth muscle actin (SMA)-positive cells in tumor stroma, and mPC-conditioned medium activated p-JNK in tumor-associated fibroblasts (TAF) in vitro. Relative expression of Ccl20 was downregulated in stimulated TAF. Ccl20 is an important chemokine that promotes CD8(+) T-cell infiltration by recruitment of dendritic cells, and the number of CD8(+) T cells was decreased in Kras;JNK1(+/-) mice compared with Kras;JNK1(-/-) mice. These results suggest that the cancer secretome decreases Ccl20 secretion from TAF by activation of JNK, and downregulation of Ccl20 secretion might be correlated with reduction of infiltrating CD8(+) T cells. Therefore, we concluded that inhibition of activated JNK in pancreatic tumor stroma could be a potential therapeutic target to increase Ccl20 secretion from TAF and induce accumulation of CD8(+) T cells, which would be expected to enhance antitumor immunity.

DOI： 10.1111/cas.13382

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BAISHIDENG PUBLISHING GROUP INC  

AIM
To investigated the relationship between postoperative bleeding following gastric endoscopic submucosal dissection (ESD) and individual antithrombotic agents.
METHODS
A total of 2488 gastric neoplasms in 2148 consecutive patients treated between May 2001 and June 2016 were studied. The antithrombotic agents were categorized into antiplatelet agents, anticoagulants, and other antithrombotic agents, and we included combination therapies [e.g., dual antiplatelet therapy (DAPT)]. The risk factors associated with post-ESD bleeding, namely, antithrombotic agents overall, individual antithrombotic agents, withdrawal or continuation of antithrombotic agents, and bleeding onset period (during the first six days or thereafter), were analyzed using univariate and multivariate analyses.
RESULTS
The en bloc resection and complete curative resection rates were 99.2% and 91.9%, respectively. Postoperative bleeding occurred in 5.1% cases. Bleeding occurred in 10.3% of the patients administered anti-thrombotic agents. Being male (p = 0.007), specimen size (p &lt; 0.001), and antithrombotic agent used (p &lt; 0.001) were independent risk factors for postoperative bleeding. Heparin bridging therapy (HBT) (p = 0.002) and DAPT/multidrug combinations (p &lt; 0.001) were independent risk factors associated with postoperative bleeding. The bleeding rate of the antithrombotic agent continuation group was significantly higher than that of the withdrawal group (p &lt; 0.01). Bleeding within postoperative day (POD) 6 was significantly higher in warfarin (p = 0.015), and bleeding after POD 7 was significantly higher in DAPT/multidrug combinations (p = 0.007). No thromboembolic events were reported.
CONCLUSION
We must closely monitor patients administered HBT and DAPT/multidrug combinations after gastric ESD, particularly those administered multidrug combinations after discharge.

DOI： 10.3748/wjg.v23.i30.5557

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記述言語：日本語   出版者・発行元：(一社)日本胆道学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer International Publishing  

DOI： 10.1007/s11548-017-1647-9

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DOI： 10.1055/s-0043-105487

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記述言語：日本語   出版者・発行元：(一社)日本ヘリコバクター学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会-関東支部  

40歳女性。心窩部痛を主訴に近医を受診し、急性膵炎の診断で入院加療が行われたが、造影CTにて総胆管拡張を認めたため、精査加療目的で紹介となった。MRCPでは総胆管拡張と膵管内の腫瘤影を認め、EUSでは十二指腸壁外での胆管と膵管の合流を認め、膵管内には嵌頓膵石がみられた。膵管ステント留置を施行し、胆汁中の膵酵素はAMY、LIPが異常高値を示したが、胆汁細胞診では悪性所見を認めなかった。以上より、先天性胆道拡張症、膵胆管合流異常症および膵石嵌頓と診断され、入院6日目に膵石に対し内視鏡的乳頭括約筋切開術を施行した。術後は経過良好で、退院後に消化器外科を紹介され、分流術施行の運びとなった。

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2017&ichushi_jid=J04450&link_issn=&doc_id=20170621140056&doc_link_id=%2Fdw9poden%2F2017%2F009001%2F068%2F0168-0170%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdw9poden%2F2017%2F009001%2F068%2F0168-0170%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AVES  

Background/Aims: This study's purpose was to compare the efficacy of CO2-enhanced ultrasonography (US) with that of Sonazoid-enhanced US and conventional US in detecting local tumor residue after percutaneous radiofrequency (RF) ablation therapy for hepatocellular carcinoma.
Materials and Methods: Between February 2009 and March 2010, 141 lesions of 121 hepatocellular carcinoma patients were treated by percutaneous RF ablation, and 22 tumor residues were detected in 22 patients by contrast-enhanced computed tomography. These 22 patients were examined by conventional US, Sonazoid-enhanced US (0.5 mL/body of Sonazoid, intravenous administration), and CO2-enhanced US (10 mL of CO2, hepatic arterial administration).
Results: Tumor residue was confirmed by CO2-enhanced US in all the 22 patients (sensitivity: 100%) in 19 of the 22 patients by Sonazoid-enhanced US (sensitivity: 86%; 3 lesions that were not detected by this modality were located deeper than the sonographic depth (p=0.0109)), and in 17 of the 22 patients by conventional US (sensitivity: 77%; 5 lesions that were not detected by this modality were smaller in terms of the sonographic tumor size (p= 0.0278)).
Conclusion: Although CO2-enhanced US requires angiography, it was superior to both Sonazoid-enhanced US and conventional US for detecting tumor residues, particularly deep-seated ones, after percutaneous RF ablation.

DOI： 10.5152/tjg.2017.16641

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記述言語：日本語   出版者・発行元：(一社)日本膵臓学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BAISHIDENG PUBLISHING GROUP INC  

AIM
To evaluate whether pathologically early hepatocellular carcinoma (HCC) exhibited local tumor progression after radiofrequency ablation (RFA) less often than typical HCC.
METHODS
Fifty pathologically early HCCs [tumor diameter (mm): mean, 15.8; range, 10-23; follow-up days after RFA: median, 1213; range, 216-2137] and 187 typical HCCs [tumor diameter (mm): mean, 15.6; range, 6-30; follow-up days after RFA: median, 1116; range, 190-2328] were enrolled in this retrospective study. The presence of stromal invasion (namely, tumor cell invasion into the intratumoral portal tracts) was considered to be the most important pathologic finding for the diagnosis of early HCCs. Typical HCC was defined as the presence of a hyper-vascular lesion accompanied by delayed washout using contrastenhanced computed tomography or contrast-enhanced magnetic resonance imaging. Follow-up examinations were performed at 3-mo intervals to monitor for signs of local tumor progression. The local tumor progression rates of pathologically early HCCs and typical HCCs were then determined using the Kaplan-Meier method.
RESULTS
During the follow-up period for the 50 pathologically early HCCs, 49 (98%) of the nodules did not exhibit local tumor progression. However, 1 nodule (2%) was associated with a local tumor progression found 636 d after RFA. For the 187 typical HCCs, 46 (24.6%) of the nodules exhibited local recurrence after RFA. The follow-up period until the local tumor progression of typical HCC was a median of 605 d, ranging from 181 to 1741 d. Among the cases with typical HCCs, local tumor progression had occurred in 7.0% (7/187), 16.0% (30/187), 21.9% (41/187) and 24.6% (46/187) of the cases at 1, 2, 3 and 4 years, respectively. Pathologically early HCC was statistically associated with a lower rate of local tumor progression, compared with typical HCC, when evaluated using a log-rank test (P = 0.002).
CONCLUSION
The rate of local tumor progression for pathologically early HCCs after RFA was significantly lower than that for typical HCCs.

DOI： 10.3748/wjg.v23.i17.3111

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記述言語：英語   出版者・発行元：(一社)日本胃癌学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Dove Medical Press Ltd.  

Background: Overall, 30%–45% of patients with ulcerative colitis (UC) are non-adherent and have difficulties taking their medications
this non-adherence increases the risk of clinical relapse 1.4- to 5.5-fold. This study aimed to clarify the strategies patients employ to facilitate adherence and determine whether the strategies had an impact on good adherence. Methods: This was a cross-sectional survey using a self-administered questionnaire and review of medical records. Patients diagnosed as having UC and attending one of the outpatient clinics of four urban hospitals from June 2009 to December 2012 were enrolled. A questionnaire was developed to identify the strategies patients employ to facilitate adherence and then administered to patients with UC. Adherence to 5-aminosalicylic acid was calculated, and univariate and multiple logistic regression analyses were performed to determine the strategies that were associated with good adherence. Results: The final analyses included 671 participants (mean age 40.2 years
54.3% males). The valid response rate was 96.9%
186 (27.7%) participants were classified as non-adherent, the mean adherence rate being 86.1% (standard deviation [SD] 17.9). Seven strategies that patients employ to facilitate adherence were identified, the following two being significantly associated with good adherence: “I keep my medicines where I eat meals” and “I keep each day’s medicine in a pill case or something similar to make sure I have taken them”. Conclusion: The identified strategies might be used to develop a program to improve medication adherence in patients with UC.

DOI： 10.2147/PPA.S117841

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記述言語：英語   出版者・発行元：NATURE PUBLISHING GROUP  

DOI： 10.1038/srep39567

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PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

Objective We investigated the characteristic findings of regenerative nodules (RNs) for differentiating early hepatocellular carcinoma (HCC) from high-grade dysplastic nodules (HGDNs) using magnetic resonance imaging (MRI) with gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA; EOB-MRI) and contrast-enhanced ultrasonography (CEUS) in patients with chronic liver disease.
Subjects and methods Pathologically confirmed lesions (100 early HCCs, 7 HGDNs, and 20 RNs with a maximum diameter of more than 1 cm and mean maximal diameters of 15.5, 15.1, and 14.8 mm, respectively) were enrolled in this retrospective study. The signal intensities of these lesions during the hepatobiliary phase of EOB-MRI were investigated, and findings characteristic of RNs using this modality were also evaluated using CEUS.
Results Ninety-eight of the 100 early HCCs that were hypo-intense (n = 95), iso-intense (n = 2), or hyper-intense (n = 1) and the seven HGDNs that were hypo-intense (n = 6) or hyper-intense (n = 1) during the hepatobiliary phase of EOB-MRI exhibited centripetal vessels during the arterial dominant phase of CEUS, although one early HCC that was hypo-intense exhibited both centrifugal and centripetal vessels. Eighteen of the 20 RNs and one early HCC that were hyper-intense with a small central hypo-intensity and the remaining two RNs that were hyper-intense on EOB-MRI exhibited centrifugal vessels during the arterial dominant phase of CEUS. The small central hypo-intense area corresponded to central vascular structures in the lesion, such as the hepatic artery and portal vein running from the center to the periphery, when viewed using CEUS.
Conclusion Central vascular structures may be a characteristic finding of RNs when observed during the hepatobiliary phase of EOB-MRI and the arterial dominant phase of CEUS.

DOI： 10.1007/s10396-016-0750-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN SOC INTERNAL MEDICINE  

Objective We evaluated the safety and efficacy of vonoprazan-based amoxicillin and clarithromycin 7-day triple therapy (VAC) in comparison to proton pump inhibitor (PPI)-based (PAC) as a first-line treatment and vonoprazan-based amoxicillin and metronidazole 7-day triple therapy (VAM) in comparison to PPI-based (PAM) as a second-line treatment for the eradication of Helicobacter pylori in Japan.
Methods We performed a non-randomized, multi-center, parallel-group study to compare first-line VAC to PAC and second-line VAM to PAM. A pre-planned subgroup analysis on CAM resistance was also performed. Safety was evaluated with an adverse effects questionnaire (AEQ), which was completed by patients during therapy.
Results The first-line eradication rates (ER) in the intention-to-treat (ITT) and per protocol (PP) analyses were 84.9% (95% CI: 81.9-87.6%, n=623) and 86.4% (83.5-89.1%, n=612), respectively, for VAC and 78.8% (75.3-82.0%, n=608) and 79.4% (76.0-82.6%, n=603), respectively, for PAC. The ER of VAC was higher than that of PAC in the ITT (p=0.0061) and PP analyses (p=0.0013). The ERs for VAC in patients with CAM-resistant and CAM-susceptible bacteria were 73.2% (59.7-84.2%, n=56) and 88.9% (83.4-93.1%, n=180), respectively. PAC was associated with higher AEQ scores for diarrhea, nausea, headache, and general malaise. In the second-line ITT and PP analyses VAM achieved ERs of 80.5% (74.6-85.6%, n=216) and 82.4% (76.6-87.3%, n=211), respectively, while PAM achieved ERs of 81.5% (74.2-87.4%, n=146) and 82.1% (74.887.9%, n=145), respectively. No significant differences were observed in the ITT (p=0.89) or PP (p=1.0) analyses.
Conclusion The ER of first-line VAC was higher than that of PAC, but still &lt;90%. No difference was observed between second-line VAM and PAM. Vonoprazan-based triple therapy was safe and well tolerated.

DOI： 10.2169/internalmedicine.56.7833

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：HINDAWI LTD  

Background. Sorafenib is a first-line treatment option for advanced hepatocellular carcinoma (HCC) patients; however, survival predictors upon progression have not been well characterized. In the present study, we aimed to show the efficacy of multidisciplinary therapy for patients who had failed to respond to sorafenib treatment. Methods. Among 146 BCLC stage B or C HCC patients treated with sorafenib monotherapy between July 2009 and August 2014, the first radiological progression according to the modified RECIST was identified in 71 patients; factors predicting overall survival (OS) and survival postprogression (SPP) were analyzed in these patients. Results. The median OS and SPP for patients who failed to respond to sorafenib treatment were 10.5 and 6.2 months, respectively, and the SPP was strongly correlated with the OS (r = 0 982, P &lt; 0 01, and R-2 = 0 965). The independent predictors of OS and SPP were identical. The predictors of SPP were des-gammacarboxy prothrombin, progression of portal vein thrombosis, and subsequent second-line or additional treatment. Conclusions. SPP is closely associated with OS and might be notable in patients who have failed to respond to initial sorafenib treatment. Furthermore, interventions consisting of other treatment options upon the appearance of progression might prolong OS.

DOI： 10.1155/2017/5728946

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN SOC INTERNAL MEDICINE  

Objective The risk factors associated with severe erosive esophagitis are not well defined in Japan. We aimed to evaluate the risk factors associated with the endoscopic severity of esophageal mucosal injury.
Methods Eighty consecutive Japanese patients with severe erosive esophagitis [Los Angeles (LA) classification grade C or D] who had undergone upper endoscopies in the Gastroenterology Division of Omori Red Cross Hospital between June 2010 and March 2013 were retrospectively analyzed. For each case, a control with mild erosive esophagitis (LA classification grade A or B) who was matched by sex and age was randomly selected during the same period. Among the endoscopic findings, the condition of the gastroesophageal flap valve (GEFV) was graded according to Hill's classification. We identified the risk factors for severe erosive esophagitis using a multivariable logistic regression model.
Results A poor performance status (PS) (odds ratio [OR]=17.1201, 95% confidence interval [CI]=3.0268-140.3121, p=0.0008) and an abnormal GEFV (OR=3.0176, 95% CI=1.0589-9.4939, p=0.0385) were risk factors for severe erosive esophagitis, while the presence of open-type gastric mucosal atrophy (GMA) was inversely associated with severe erosive esophagitis (OR=0.2772, 95% CI=0.1087-0.6675, p=0.0040).
Conclusion Among patients with erosive esophagitis, a poor PS and an abnormal GEFV were associated while GMA was inversely associated with severe erosive esophagitis. Drug therapy alone or in combination with physical therapy may improve the therapeutic effect on severe erosive esophagitis in patients with a poor PS.

DOI： 10.2169/internalmedicine.56.8058

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japan Gastroenterological Endoscopy Society  

Background and Aim: The aim of the present study was to evaluate the efficacy and safety of sedation with a combination of propofol (PF) and dexmedetomidine (DEX) compared with sedation with benzodiazepines in esophageal endoscopic submucosal dissection (ESD). Methods: We retrospectively reviewed clinical data for 40 consecutive patients who had undergone esophageal ESD at the Yokohama City University Hospital between July 2012 and August 2014. Of these patients, 20 were sedated with benzodiazepines (conventional group) and another 20 patients were sedated with a combination of PF and DEX (combination group). Parameters for efficacy and safety of sedation were evaluated by comparisons between the two groups. Results: Median procedural times in the combination group were shorter than those in the conventional group (61min vs 89 min, P = 0.03), and the percentage of patients who showed restlessness in the combination group was significantly lower than that in the conventional group (25% vs 65%, P = 0.025). Incidences of hypotension and bradycardia in the combination group were higher than those in the conventional group (60% vs 15%, P=0.008, and 60% vs 15%, P = 0.008, respectively). Conclusion: This retrospective study suggests that a combination of PF and DEX may provide stable deep sedation with less body movement than benzodiazepines during esophageal ESD.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japan Society of Hepatology  

We report a case of primary hepatic neuroendocrine carcinoma in a 77-years-old male. He presented with right hypochondriac pain. The serum was negative for hepatitis B surface antigen, and for hepatitis C virus antibody. US demonstrated low echoic nodule. Plain CT showed a low density. MRI showed hyperintensity on diffusion weighted imaging. Tumor biopsy was performed for definitive diagnosis. The tumor was diagnosed pathologically as a small cell carcinoma. He presented with flushing and intermittent bronchial wheezing in the hospital course. The symptoms were diagnosed as carcinoid syndrome by elevated 5-HIAA levels in the urine. Primary hepatic neuroendocrine carcinoma is rare, and so we report this case which appears to be of primary hepatic neuroendocrine carcinoma with carcinoid syndrome.

DOI： 10.2957/kanzo.58.632

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Hellenic Society of Gastroenterology  

Background An ideal medication for acid-related diseases would offer prompt stopping of blood flow as well as efficient symptom resolution. The aim of this study was to investigate the gastric acid suppression potency of a single oral dose of rabeprazole alone, compared with administration of rabeprazole plus mosapride. Methods Twelve male volunteers, Helicobacter pylori (H. pylori)-negative, participated in this randomized, three-way crossover study. After a single oral administration of rabeprazole, rabeprazole with mosapride, or rabeprazole administered 1 h after mosapride, we monitored their intragastric pH constantly for 6 h. A 7-day washout period was allowed between each administration. Results The median 6-h intragastric pH after the administration of rabeprazole 1 h after mosapride was 4.41±1.22 (mean±s.d.), significantly higher than after rabeprazole alone 3.45±1.33, P=0.0376). There was no significant difference between the median 6-h pH after the administration of rabeprazole plus mosapride and that after rabeprazole alone (3.81±0.98 vs. 3.45±1.33, respectively
P=0.0927). Conclusion An oral dose of rabeprazole administered 1 h after mosapride increased the intragastric pH more rapidly than rabeprazole alone, in healthy, male, H. pylori-negative volunteers.

DOI： 10.20524/aog.2017.0161

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：HINDAWI LTD  

Aim. To assess the efficacy of 7-day first-line Helicobacter pylori eradication with vonoprazan (VPZ), clarithromycin (CAM), and metronidazole (MNZ) in patients with penicillin allergy. Methods. Patients with penicillin allergy, diagnosed with Helicobacter pylori infection and did not have history of Helicobacter pylori eradication, were eligible for the study. Twenty patients were prospectively treated with 20 mg VPZ twice daily, 200 or 400 mg CAM twice daily, and 250 mg MNZ twice daily for 7 days. We also collected the data from 30 patients retrospectively treated with proton pump inhibitor (PPI), CAM, and MNZ. Safety was evaluated in patients completing an adverse effect questionnaire. Results. Both the intention-to-treat and per-protocol effectiveness of VPZ-based eradication were 100% (95% CI: 86.1-100%; n = 20). The eradication rates of PPI-based regimen were 83.3% (95% CI: 65.3-94.4%) in the ITT and 82.7% (95% CI: 64.2-94.2%) in the PP analyses. Abdominal fullness was more frequent in VCM compared to PCM. However, all patients with VCM regimen had taken 100% of their course of medication. Conclusion. Triple therapy with VPZ, CAM, and MNZ is well tolerated and effective for eradicating Helicobacter pylori in patients allergic to penicillin. This study was registered in the UMIN Clinical Trials Registry as UMIN000016335.

DOI： 10.1155/2017/2019802

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会-関東支部  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3892/ol.2016.5168

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DOI： 10.1055/s-0042-117632

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

Patients receiving methotrexate (MTX) for the treatment of autoimmune disease are at a high risk of developing lymphoproliferative disorders (LPD), the so-called methotrexate-associated lymphoproliferative disorders (MTX-LPD). We recently performed abdominal ultrasonography (US) in a patient with rheumatoid arthritis (RA) who had developed hepatic dysfunction during the course of MTX therapy; the examination revealed multiple well-demarcated hepatic tumors with slightly irregular borders, the largest one measuring 9 cm in diameter. In view of the finding of portal and hepatic veins perforating the tumor, we suspected a diagnosis of malignant lymphoma and performed a hepatic tumor biopsy. Histopathological examination of the biopsy specimens revealed a diagnosis of diffuse large B-cell lymphoma, and we made a final diagnosis of MTX-LPD. MTX treatment was discontinued, which resulted in rapid resolution of the lesions. Resolution of MTX-LPD can be obtained just by discontinuation of MTX treatment. In patients receiving MTX therapy who are found to have hepatic tumors perforated by the portal vein and/or hepatic vein on abdominal US, it is advisable to perform hepatic tumor biopsy to facilitate differential diagnosis of MTX-LPD and enable a definite diagnosis.

DOI： 10.1007/s10396-016-0740-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

Helicobacter pylori induces chronic inflammation and intestinal metaplasia (IM) through genetic and epigenetic changes and activation of intracellular signaling pathways that contribute to gastric carcinogenesis. However, the precise mechanism of IM in gastric carcinogenesis has not been fully elucidated. We previously found that intestine-specific homeobox (ISX) mRNA expression increased in organoids cultured from Helicobacter-infected mouse mucosa. In this study, we elucidate the role of ISX in the development of IM and gastric carcinogenesis.
ISX expression was assessed in Helicobacter-infected mouse and human gastric mucosa. MKN45 gastric cancer cells were co-cultured with H. pylori to determine whether Helicobacter infection induced ISX expression. We established stable MKN45 transfected cells expressing ISX (Stable-ISX MKN45) and performed a spheroid colony formation assay and a xenograft model. We performed ISX immunohistochemistry in cancer and adjacent gastric tissues.
ISX expression was increased in mouse and human gastric mucosa infected with Helicobacter. The presence of IM and H. pylori infection in human stomach was correlated with ISX expression. H. pylori induced ISX mRNA and protein expression. CDX1/2, cyclinD1, and MUC2 were upregulated in Stable-ISX MKN45, whereas MUC5AC was downregulated. Stable-ISX MKN45 cells formed more spheroid colonies, and had high tumorigenic ability. ISX expression in gastric cancer and adjacent mucosa were correlated.
ISX expression induced by H. pylori infection may lead to IM and hyperproliferation of gastric mucosa through CDX1/2 and cyclinD1 expression, contributing to gastric carcinogenesis.

DOI： 10.1007/s00535-016-1176-2

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BAISHIDENG PUBLISHING GROUP INC  

The present report describes a rare case of a tumor composed of early gastric cancer and a duodenal neuroendocrine tumor (NET). A 78-year-old woman underwent esophagogastroduodenoscopy at a local institution for screening of the upper gastrointestinal tract which revealed a protruded tumor through the pyloric ring from the pyloric antrum. The tumor was too large to treat at the facility; consequently, she was referred to our hospital for further management. Esophagogastroduodenoscopy with tumor biopsy of the lesion revealed the diagnosis of early gastric cancer. Endoscopic submucosal dissection was performed with sufficient free margins in both vertical and horizontal directions. Histopathological findings showed NET confined to the submucosal layer and covered by well-differentiated adenocarcinoma. Immunohistochemical stainings showed that the two lesions existed continuously. While the possibility of a collision cancer was considered, it was suggested that the two lesions existed continuously. Finally, the tumor was diagnosed as gastric cancer composed of duodenal NET G1, with a lymphatic invasion of NET component.

DOI： 10.3748/wjg.v22.i36.8242

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy with poor prognosis and its incidence is increasing worldwide. Recently, several types of cells have been considered as the origin of ICC, namely cholangiocytes, liver progenitor cells, and hepatocytes. Here, we have established a novel mouse model of ICC by liver-specific Kras activation and Pten deletion. An activating mutation of Kras in combination with deletion of Pten was introduced in embryonic hepatic bipotential progenitor cells (so-called hepatoblasts) and mature hepatocytes using the Cre-loxP system. As a result, liver-specific Kras activation and homozygous Pten deletion cooperated to induce ICCs exclusively. In contrast, Kras activation in combination with heterozygous Pten deletion induced both ICCs and HCCs, whereas Kras activation alone resulted in HCCs but not ICCs. Furthermore, a cell-lineage visualization system using tamoxifen-inducible Cre-loxP demonstrated that the ICCs did not originate from hepatocytes but from cholangiocytes. Our data suggest that mice carrying liver-specific Kras activation in combination with homozygous Pten deletion should be useful for the investigation of therapeutic strategies for human ICC.

DOI： 10.1038/srep23899

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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DOI： 10.5152/tjg.2015.150359

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記述言語：日本語   出版者・発行元：(公社)神奈川県医師会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：TAYLOR & FRANCIS LTD  

Aim: In Japan, most of colorectal carcinoid tumors developed in rectum. The choice of treatment is important because surgical treatment may need to construct artificial anus. Although curative endoscopic resection (ER) is desirable from the point of quality of life, sufficient evidence of endoscopic treatment for rectal carcinoid tumors is not fully obtained.Methods: Between April 2001 and August 2013, 46 rectal carcinoid tumors in 46 patients who underwent either with endoscopic mucosal resection with a ligation device (EMR-L) or endoscopic submucosal dissection (ESD) were analyzed retrospectively. The rates of en bloc resection, positive for lateral and/or vertical margin, curative resection, local recurrence, additional treatments, overall and disease-specific survival rate after ER were evaluated during follow-up (median observation period 61.6 months).Results: Twenty-two lesions were treated by EMR-L and 24 lesions were treated by ESD. Both groups had similar mean tumor size (EMR-L: 6.2mm, ESD: 6.0mm). The rate of en bloc resection, negative for both lateral and vertical margins, and curative resection were, respectively, 73%, 63%, and 50% for EMR-L, 100%, 100%, and 83% for ESD. These results suggested that the rate of resectability and curability for ESD was significantly higher than EMR-L (p&lt;0.05). Complications such as perforation and bleeding did not occur in both groups. Fifteen patients were judged as non-curative and 3 patients underwent additional surgery and lymph node metastasis was evident in 1 patient. Remained 11 patients were carefully followed-up, and so far no obvious recurrence was found. Thirty-two patients (84%) were eligible for long-term follow-up and 5-year overall and disease-specific survival rates were 100% and 100%, respectively.Conclusion: The long-term outcomes of ER for rectal carcinoid tumors were excellent. ESD has advantage for resectability and curability compared with EMR-L; therefore, ESD is more favorable procedure as treatment for rectal carcinoid tumors.

DOI： 10.1080/00365521.2016.1216591

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会-関東支部  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会-関東支部  

81歳男。2013年8月、前医にて十二指腸乳頭部癌に対して胆管カバーメタリックステント(C-MS)が留置された。2014年5月、急性胆管炎および十二指腸狭窄のため前医に入院し、胆管C-MS内の多発性結石を指摘された。胆管C-MSの抜去と結石除去が行われた後、胆管C-MSと十二指腸MSがside-to-endの形で留置された。同年10月より胆管炎を繰り返し、前医にて経乳頭的ドレナージが試みられるも困難であったため、2015年1月に当科紹介となった。本例は、総胆管積み上げ結石の合併により胆管炎を繰り返しており、胆道ドレナージ法の変更が必要と判断されたため、EUS-BDを行う方針とした。穿刺可能な肝内胆管を認めなかったため、経十二指腸的なアプローチを選択したが、穿刺ルートに胆管C-MSが介在していたため、APCによる十二指腸MSのトリミングを行い、胆管C-MSを抜去した。術後合併症なく経過し、第21病日に軽快退院した。

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2015&ichushi_jid=J04450&link_issn=&doc_id=20151229110046&doc_link_id=%2Fdw9poden%2F2015%2F008701%2F055%2F0154-0156%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdw9poden%2F2015%2F008701%2F055%2F0154-0156%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会-関東支部  

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DOI： 10.4253/wjge.v7.i12.1055

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

Reducing blood flow in the liver during radiofrequency ablation causes enlargement of the ablation area. In this animal study, we evaluated the extended effects of radiofrequency ablation combined with transarterial embolization using various embolic agents.
We treated 38 radiofrequency ablation lesions after embolization in 13 pigs using the following embolic agents: gelatin sponge (Group A); iodized oil followed by gelatin sponge (Group B); 700-900 A mu m calibrated microspheres (Group C); and 100-300 A mu m calibrated microspheres (Group D). Lesion size and pathological evaluations of these ablation lesions were compared with those receiving radiofrequency ablation alone (control).
Both the long- and short-axis diameters of the ablation lesions for Groups A, B, C, and D were significantly longer than those of controls (long axis/short axis for Groups A, B, C, D, and controls were 27.2/23.2, 30.2/26.0, 28.2/22.2, 32.0/24.4, and 23.2 mm/18.5 mm, respectively) (P &lt; 0.05). The long-axis of the ablation lesion for Group D was significantly longer than those for both Groups A and C (P &lt; 0.05). At pathological examination, the central ablation lesions showed coagulative necrosis with a surrounding hemorrhagic rim, and the microspheres were fitted to occlude the small arteries in peripheral liver parenchyma in Groups C and D.
The extended effects of embolization with small microspheres may be stronger than those with large microspheres and were equal to those with iodized oil followed by gelatin sponge.

DOI： 10.1007/s00261-014-0332-5

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記述言語：英語   掲載種別：研究論文（国際会議プロシーディングス）  

DOI： 10.1186/2050-5736-3-S1-P47

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

Helicobacter pylori cagA-positive strain delivers the CagA oncoprotein into gastric epithelial cells and at the same time elicits stomach inflammation. To experimentally investigate the pathophysiological interplay between CagA and inflammation, transgenic mice systemically expressing the bacterial cagA gene were treated with a colitis inducer, dextran sulfate sodium (DSS). Compared with control mice, DSS-induced colitis was markedly deteriorated in cagA-transgenic mice. In the colonic epithelia of cagA-transgenic mice, there was a substantial decrease in the level of I kappa B, which binds and sequesters NF-kappa B in the cytoplasm. This I kappa B reduction was due to CagA-mediated inhibition of PAR1, which may stimulate I kappa B degradation by perturbing microtubule stability. Whereas the CagA-mediated I kappa B reduction did not automatically activate NF-kappa B, it lowered the threshold of NF-kappa B activation by inflammogenic insults, thereby contributing to colitis exacerbation in cagA-transgenic mice. CagA also activates inflammasomes independently of NF-kappa B signaling, which further potentiates inflammation. The incidence of colonic dysplasia was elevated in DSS-treated cagA-transgenic mice due to a robust increase in the number of pre-cancerous flat-type dysplasias. Thus, CagA deteriorated inflammation, whereas inflammation strengthened the oncogenic potential of CagA. This work revealed that H. pylori CagA and inflammation reinforce each other in creating a downward spiral that instigates neoplastic transformation.

DOI： 10.1038/srep10024

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：H G E UPDATE MEDICAL PUBLISHING S A  

Background/Aims: The aim of our study was to investigate the inhibitory effects on gastric acid secretion of a single oral dose of a proton pump inhibitor, esomeprazole 20 mg and omeprazole 20 mg. Methodology: A total of 14 Helicobacter pylori-negative male subjects participated in this study. Intragastric pH was monitored continuously for 6 hours after a single oral dose of omeprazole 20 mg and a single oral dose of esomeprazole 20 mg. Each administration was separated by a 7-day washout period. Results: During the 6-hour study period, the average pH after administration of esomeprazole was higher than that after the administration of omeprazole. Also during the 6-hour study period, each of pH &gt; 2, 3, 3.5, 4, and 5 was maintained for a longer duration after administration of esomeprazole 20 mg than after administration of omeprazole 20 mg (median: 75.4% vs. 53.8%, p = 0.0138; 52.1% vs. 33.4%, p = 0.0188; 45.8% vs. 28.2%, p = 0.0262; 42.5% vs. 20.7%, p = 0.0414; 35.8% vs. 11.6%, p = 0.0262; respectively). Conclusions: In Helicobacter pylori-negative healthy male subjects, single oral administration of esomeprazole 20 mg increased the intragastric pH more rapidly than single oral administration of omeprazole 20 mg.

DOI： 10.5754/hge13850

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記述言語：英語  

OBJECTIVE: We aimed to evaluate the efficacy and tolerability of hepatic arterial infusion chemotherapy (HAIC) using cisplatin as an alternative to sorafenib for the treatment of hepatocellular carcinoma (HCC) patients who had not responded to transarterial chemoembolization (TACE). METHODS: Medical records of 127 consecutive HCC patients without extrahepatic metastasis (cisplatin, n = 44; sorafenib, n = 83) who had not responded to prior TACE at four institutions were retrospectively reviewed. An inverse probability of treatment weighting using propensity scoring was used to adjust for the selection bias. RESULTS: Severe adverse events accounting for treatment discontinuation occurred in 2.3% of the patients in the cisplatin group and 32.5% of those in the sorafenib group. The median overall survival (OS) period was 11.2 months (95% CI 4.8-17.7) in the cisplatin group and 10.2 months (95% CI 8.8-11.5) in the sorafenib group, respectively. After an inverse probability of treatment weighting adjustment, the survival outcome of the HAIC treatment group was not inferior to that of the sorafenib treatment group (hazard ratio 0.758; 95% CI 0.471-1.219, P = 0.253). CONCLUSION: HAIC with cisplatin can be an alternative treatment for the selection of HCC patients who have not responded to prior TACE and cannot tolerate sorafenib.

DOI： 10.1111/1751-2980.12221

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/den.12300

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記述言語：日本語  

DOI： 10.11641/pde.86.1_216

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DOI： 10.1007/978-4-431-55651-0_6

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN SOC INTERNAL MEDICINE  

Objective Right-sided type colonic diverticulosis has been predominant in Japan, in contrast to European counties where the left-sided type is predominant. Considering the recent change in the dietary habits of Japanese people to a more Western diet in urban areas of Japan, the features of colonic diverticulosis may also change to reflect a more Western type. Therefore, we attempted to clarify the current situation.
Methods A total of 435 consecutive outpatients who agreed to a barium enema and complete examination were enrolled in this study.
Results 113 patients (26.0%) revealed colon diverticulosis; 50.4% of the patients had more than ten diverticula. The percentage of man with ten or more diverticula (67.4%) was significantly higher than that of women patients (40.0%, p &lt; 0.01). Among the 88 patients who had four or more diverticula, 39 patients (44.3%) were right-side dominant, 27 (30.7%) left-side dominant and 22 (25.0%) were both-sides. Thirteen (68.4%) of the 19 patients who had more than 30 diverticula were left-side dominant.
Conclusion The clinical features of colon diverticulosis in the patients living in Yokohama may be changing to reflect a more Western type, in particular decreased right-side dominance, increases in the left-side and both-sides dominant patients, and the emergence of patients with crowded diverticula in the left-side colon was observed.

DOI： 10.2169/internalmedicine.54.4813

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記述言語：英語   出版者・発行元：AVES  

DOI： 10.5152/tjg.2014.4114

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会-関東支部  

症例は55歳男性で、53歳時に4型進行胃癌に対し胃全摘術・Roux-en Y再建術を施行し、術後補助化学療法として、TS-1+クレスチン併用療法を施行した。食思不振、嘔吐が出現し、上部消化管内視鏡検査を行ったところ、食道空腸吻合部に狭窄を認めたが、粘膜生検では悪性所見を認めず術後瘢痕による良性狭窄と考えた。狭窄に対しバルーン拡張術を計3回施行したが症状改善を認めなかった。胸腹部造影CT検査で食道空腸吻合部の全周性壁肥厚を認め、PET-CTで同部位にFDGの集積を認め、胃癌吻合部再発が疑われ、EUS-FNAのため入院となった。上部消化管内視鏡検査で胸部食道に液体貯留あり、下部食道粘膜は全周性の狭窄を認め、内視鏡の通過は困難であった。胸腹部造影CTで食道空腸吻合部に造影効果の乏しい全周性壁肥厚を認め、コンベックス型超音波内視鏡で狭窄部食道壁の層構造は消失し低エコー性の腫瘤を形成していた。22G穿刺針で計3回穿刺した。病理組織学的所見は低分化腺癌で、胃癌再発に矛盾しない所見であった。EUS-FNAの結果より胃癌吻合部再発と診断し、全身化学療法を行った。術翌日より経口摂取可能となり、化学療法継続中である。

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2014&ichushi_jid=J04450&link_issn=&doc_id=20141216240022&doc_link_id=%2Fdw9poden%2F2014%2F008501%2F032%2F0088-0090%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdw9poden%2F2014%2F008501%2F032%2F0088-0090%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMED CENTRAL LTD  

Background: Non-adherence to aminosalicylates is observed among 30% to 45% of patients with ulcerative colitis and increases the risk of relapse. The Health Belief Model is a theoretical model that could offer a broader perspective to improve patients self-medication adherence. This study aimed to develop a screening instrument based on the Health Belief Model to screen patients with ulcerative colitis who had a high possibility of current non-adherence to aminosalicylates. The study was also designed to allow examination of factors of non-adherence.
Methods: A multicenter, cross-sectional study was conducted in outpatients diagnosed with ulcerative colitis and prescribed aminosalicylates. Non-adherence was defined as taking less than 80% of the prescribed dose. We hypothesized that there was a significant relationship between current aminosalicylate non-adherence and five components of the HBM: beliefs about taking aminosalicylates, disease characteristics, medication characteristics, abdominal symptoms, and sociodemographic characteristics. A logistic regression model was applied and the coefficients converted to a numeric scores in order to develop a screening instrument which could reliably discriminate non-adherent and adherent subjects.
Results: Non-adherence was observed in 127 (29.6%) of the 429 enrolled subjects. Lower perceptions of belief in taking aminosalicylates, absence of visible bleeding, eight daily tablets or less taken, and no concomitant use of thiopurines were related to non-adherence. We then developed a screening instrument comprising 22 items. When the cut-off point was set at 60, the instrument showed 85.0% sensitivity and 69.2% specificity with an area under the curve of 0.84 (95% confidence interval = 0.79 0.91).
Conclusions: The instrument appeared to be reliable for identifying patients with a high possibility of current non-adherence to aminosalicylates. Further, the instrument may provide useful information for detecting patients with a high possibility of current non-adherence and for assessing factors of non-adherence. On the other hand, we need to evaluate disease activity more strictly and examine whether it is included in the screening instrument in the future.

DOI： 10.1186/s12876-014-0220-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

OBJECTIVES: No previous reports have shown an association between location of diverticular disease (DD) and the irritable bowel syndrome (IBS).
METHODS: We included 1,009 consecutive patients undergoing total colonoscopy in seven centers in Japan from June 2013 to September 2013. IBS was diagnosed using Rome III criteria, and diverticulosis was diagnosed by colonoscopy with transparent soft-short-hood. Left-sided colon was defi ned as sigmoid colon, descending colon, and rectum. Right-sided colon was defi ned as cecum, ascending colon, and transverse colon. We divided the patients into IBS and non-IBS groups and compared characteristics.
RESULTS: Patient characteristics included mean age, 64.2 +/- 12.9 years and male: female ratio, 1.62: 1. Rightsided DD was identifi ed in 21.6% of subjects. Left-sided and bilateral DD was identifi ed in 6.6 and 12.0% of subjects, respectively. IBS was observed in 7.5% of subjects. Multiple logistic regression analysis showed left-sided DD (odds ratio, 3.1; 95% confi dence interval (CI): 1.4-7.1; P = 0.0060) and bilateral DD (odds ratio, 2.6; 95% CI, 1.3-5.2; P = 0.0070) were independent risk factors for IBS. Right-sided DD was not a risk factor for IBS.
CONCLUSIONS: Our data showed that the presence of left-sided and bilateral DD, but not right-sided disease, was associated with a higher risk of IBS, indicating that differences in pathological factors caused by the location of the DD are important in the development of IBS. Clarifying the specifi c changes associated with left-sided DD could provide a better understanding of the pathogenic mechanisms of IBS

DOI： 10.1038/ajg.2014.323

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記述言語：英語   出版者・発行元：AVES  

DOI： 10.5152/tjg.2014.5262

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記述言語：英語   出版者・発行元：AVES  

DOI： 10.5152/tjg.2014.4113

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MOSBY-ELSEVIER  

Background: To develop appropriate management strategies for patients who take low-dose aspirin, it is important to identify the risk factors for GI injury. However, few studies have described the risk factors for small-bowel injury in these patients.
Objective: To investigate factors influencing the risk of small-bowel mucosal breaks in individuals taking continuous low-dose aspirin.
Design: Capsule endoscopy data were collected prospectively from 5 institutions.
Setting: Yokohama City University Hospital and 4 other hospitals.
Patients: A total of 205 patients receiving treatment with low-dose aspirin for over 3 months.
Interventions: Colonoscopic and upper GI endoscopy had been performed in all of the patients before the capsule endoscope evaluation.
Main Outcome Measurements: Risk factors for small-bowel mucosal breaks.
Results: Of the 198 patients (141 male; mean age 71.9 years) included in the final analysis, 114 (57.6%) had at least 1 mucosal break. Multivariate analysis identified protein pump inhibitor (PPI) use (OR 2.04; 95% confidence interval [CI], 1.05-3.97) and use of enteric-coated aspirin (OR 4.05; 95% CI, 1.49-11.0) as independent risk factors for the presence of mucosal breaks.
Limitations: Cross-sectional study.
Conclusion: PPI use appears to increase the risk of small-bowel injury in patients who take continuous low-dose aspirin. Clinicians should be aware of this effect of PPIs; new strategies are needed to treat aspirin-induced gastroenteropathy.

DOI： 10.1016/j.gie.2014.03.024

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：H G E UPDATE MEDICAL PUBLISHING S A  

Background/Aims: The aim of this study was to deter,. mine the possible existence of a correlation between the gastric transit time (GTT) measured by video capsule endoscopy (VCE) and the parameters of gastric empty! ing determined using 13C breath test (BreathID system). Methods: Eight healthy male volunteers participated in this randomized; two-way crossover study. The subjects were randomly assigned to undergo VCE using the pillCam SB capsule endoscopy system or the 13C breath test for 4 hours after a test meal (400 kcal per 400 mL) containing 100 mg of 13C acetic acid administered after overnight fasting. The VCE images were analyzed and the GTT was determined using the proprietary RAPID software. The parameters, namely T lag, T1/2 and GEC were calculated using the Oridion Research Software (beta version). The GTT measured by VCE and the parameters of gastric emptying were compared statistically. Results: No significant correlation was observed between the GTT and T lag (p = 0.5263), T 1/2 (p = 0.4100) or GEC (p = 0.2410), as determined by calculation of the Spearman's rank correlation coefficient. Conclusions: GTT measured by VCE cannot serve as a substitute for the gastric emptying time measured by the 13C breath test.

DOI： 10.5754/hge13358

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記述言語：英語  

PURPOSE: To investigate the usefulness of contrast-enhanced three-dimensional ultrasonography (CE 3D US) for differential diagnosis of solid pancreatic lesions. METHODS: Eighty-five patients with solid pancreatic lesions who underwent CE 3D US were retrospectively analyzed. Sixty-four patients had pancreatic ductal adenocarcinoma (PDAC), 10 had mass-forming pancreatitis (MFP), and 11 had neuroendocrine tumor (NET). Two blinded readers evaluated the enhancement patterns using four features: vascularity in the arterial phase, vascularity in the venous phase, vessel location, and vessel form. Vascularity in both phases was classified as hypervascular, isovascular, or hypovascular. Vessel location was classified into peritumoral or intratumoral. Vessel form was classified into fine or irregular. Kappa values were used to assess inter-reader agreement. The institutional review board approved this study, and informed consent was obtained. RESULTS: Kappa values of the four features were 0.75, 0.72, 0.85, and 0.65, which were graded as good or excellent. The most typical combined enhancement pattern in PDAC was hypovascularity in both phases with peritumoral and irregular vessels; MFP was isovascular in both phases with intratumoral and fine vessels; and NETs were hypervascular in both phases with intratumoral and irregular vessels. The sensitivity and positive predictive value of the three patterns were 93.8% and 96.7% for the PDAC pattern, 80.0% and 100% for the MFP pattern, and 81.8%, and 69.2% for the NET pattern, respectively. The accuracy of these diagnostic criteria was 90.5%. CONCLUSION: CE 3D US allows detailed visualization of the enhancement patterns of various pancreatic lesions and can be used for the differential diagnosis.

DOI： 10.1007/s00261-014-0135-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OXFORD UNIV PRESS  

Leptin, secreted by the adipose tissue and known to be related to obesity, is considered to be involved in the onset and progression of colorectal cancer. However, the exact role of leptin in colorectal carcinogenesis is still unclear, as several controversial reports have been published on the various systemic effects of leptin. The aim of this study was to clarify the local and precise roles of leptin receptor (LEPR)-mediated signaling in colonic carcinogenesis using intestinal epithelium-specific LEPRb conditional knockout (cKO) mice. We produced and used colonic epithelium-specific LEPRb cKO mice to investigate the carcinogen-induced formation of aberrant crypt foci (ACF) and tumors in the colon, using their littermates as control. There were no differences in the body weight or systemic condition between the control and cKO mice. The tumor sizes and number of large-sized tumors were significantly lower in the cKO mice as compared with those in the control mice. On the other hand, there was no significant difference in the proliferative activity of the normal colonic epithelial cells or ACF formation between the control and cKO mice. In the control mice, marked increase of the LEPRb expression level was observed in the colonic tumors as compared with that in the normal epithelium; furthermore, signal transducer and activator of transcription (STAT3) was activated in the tumor cells. These findings suggest that STAT3 is one of the important molecules downstream of LEPRb, and LEPRb/STAT3 signaling controls tumor cell proliferation. We demonstrated the importance of local/regional LEPR-mediated signaling in colorectal carcinogenesis.

DOI： 10.1093/carcin/bgu135

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：H G E UPDATE MEDICAL PUBLISHING S A  

Background/Aims: The aim of this study was to comparatively examine the convenience of use of the QUEST and GerdQ questionnaires as self- administered diagnostic instruments. Methodology: This was a two-way crossover study conducted from December 2011 to April 2012. The subjects were 70 third-year nursing students of Yokohama Soei University in Yokohama, Japan. They were randomly assigned to fill in either of the study questionnaires first, and then the other on a later. Results: A significant difference was observed in the questionnaire completion time between the QUEST and GerdQ questionnaires (125.5 vs. 44 seconds, P &lt; 0.0001) and also in the number of subjects asking questions while completing the questionnaires (26 vs. 1 subject, respectively: P &lt; 0.0001). To detect GERD based on a QUEST score &gt;= 4 of ROC analysis revealed an area under the curve for the GerdQ score of 0.616. The sensitivity and specificity calculated using this cutoff value were 0.842 and 0.312, respectively. Conclusion: This study revealed that Japanese subjects may find it easier to complete the GerdQ than the QUEST questionnaire.

DOI： 10.5754/hge14396

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：H G E UPDATE MEDICAL PUBLISHING S A  

Background /Aims: The natural immunomodulator actoferrin is known to possess anti-inflammatory effects. However, there have been no studies examininig the mode of action of lactoferrin in protecting the esophageal mucosa against damage. We investigated the effect of lactoferrin on gastric acid secretion and in protecting against acute acid reflux-induced esophagitis in rats. Methodology: Male Wistar rats aged 8 weeks, weighing 210-240 g, were used for all the experiments. A gastric perfusion system was installed using the method of Ghosh et al. Lactoferrin was administered once via he caudate vein, starting 24 hours before an acute acid reflux (treatment mode), or saline (control). Statistical comparison of the parameters between the two test conditions was performed. Results: No significant differences in basal or stimulated gastric acid secretion, or in the serum gastrin level were observed between the two test conditions. Esophageal damage was attenuated by the improvement in the esophageal tissue weight and macroscopic scores. Significant reductions in the histological scores, myeloperoxidase activity and the levels of proinflammatory cytokines, tumor necrosis factor-a and interleukin-1 beta were also observed following lactoferrin administration. Conclusions: We concluded that lactoferrin exerts a protective effect against acute acid reflux-induced esophageal damage in rats.

DOI： 10.5754/hge13380

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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DOI： 10.5754/hge13136

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記述言語：英語  

PURPOSE: To retrospectively compare radiofrequency ablation (RFA) combined with the multikinase inhibitor sorafenib (hereafter, sorafenib-RFA) and RFA alone in the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Between January 2007 and December 2011, 16 patients (mean age, 72.8 years; age range 52-84 years; 10 men, six women) with HCC tumors less than 3 cm in diameter were included in the sorafenib-RFA group, and 136 patients (mean age, 72.1 years; age range, 51-86 years; 92 men, 44 women) with HCC tumors less than 3 cm in diameter were included in the RFA alone (control) group. Mean diameters of the greatest long-axis dimensions of HCC were 22.8 mm ± 4.6 (standard deviation) in the sorafenib-RFA group and 18.1 mm ± 4.4 in the control group. RFA was performed immediately after the 7-day administration of sorafenib. Propensity score matching analysis was used to adjust for potential biases. RESULTS: Fifteen of the 16 patients in the sorafenib-RFA group and 30 of the 136 patients in the control group were selected during propensity score matching. No significant differences between the sorafenib-RFA group (n = 15) and the control group (n = 30) were observed with regard to age, sex, etiology, Child-Pugh class, tumor size, puncture number, needle size, location at the liver margin, or location adjacent to a main vessel. The respective mean diameters of the greatest long- and short-axis dimensions of the RFA-induced ablated area were 46.3 mm ± 10.3 and 33.0 mm ± 6.9 in the sorafenib-RFA group and 32.9 mm ± 7.6 and 25.6 mm ± 5.7 in the control group; both of these dimensions were significantly larger in the sorafenib-RFA group (both P < .001). CONCLUSION: Sorafenib-RFA may be superior to standard RFA alone in the treatment of HCC tumors smaller than 3 cm in diameter.

DOI： 10.1148/radiol.14131640

PubMed