研究者詳細 - 寺井　崇二

Drug-eluting beads in hepatocellular carcinoma 査読

Hiroyuki Abe, Kenya Kamimura, Shuji Terai

THERAPEUTIC ADVANCES IN GASTROENTEROLOGY 10 ( 3 ) 337 - 338 2017年3月

Re-evaluation of phenotypic expression in differentiated-type early adenocarcinoma of the stomach 査読

Masato Hayakawa, Ken Nishikura, Yoichi Ajioka, Yutaka Aoyagi, Shuji Terai

PATHOLOGY INTERNATIONAL 67 ( 3 ) 131 - 140 2017年3月

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

A total of 313 cases of differentiated-type early gastric adenocarcinomas, including 113 cases of small-sized carcinoma (5 < x <= 10mm) and 121 cases of microcarcinoma (0 < x <= 5 mm), were examined immunohistochemically to clarify the phenotypic expressions. They were classified into four categories (gastric phenotype (G-type), intestinal phenotype, gastrointestinal phenotype, and null phenotype) by a two-step process: the phenotype based on an immunoprofile of mucin core proteins (MUCs) with CDX2 (w/.CDX2-assessment); and the phenotype of MUCs only (w/o. CDX2-assessment). CDX2 expression was observed in 89.1% (279/313); it was highly expressed in 87.6% (106/121) of microcarcinomas. MUC2 expression increased as tumor size increased (P < 0.05). Compared with w/o. CDX2-assessment, w/.CDX2-assessment showed significantly fewer G-type carcinomas (P < 0.05). Each phenotype marker was less expressed in the submucosal part than in the mucosal part. In conclusion, CDX2 was a sensitive marker for assessing intestinal phenotype. A large portion of the early differentiated-type adenocarcinomas expressed CDX2 from the very early stage of carcinogenesis, and the proportion of G-type was unexpectedly low. Lower expression of each phenotype marker was considered the cause of phenotype alteration during submucosal invasion.

DOI： 10.1111/pin.12506

当科におけるCrohn病に合併した胆石症の検討

林和直, 五十嵐聡, 水野研一, 本田穣, 橋本哲, 横山純二, 佐藤祐一, 山際訓, 寺井崇二

日本消化器病学会雑誌 114 ( 臨増総会 ) A335 - A335 2017年3月

他臓器癌合併IPMNの臨床像

五十嵐聡, 林和直, 水野研一, 本田穣, 橋本哲, 横山純二, 佐藤祐一, 山際訓, 寺井崇二

日本消化器病学会雑誌 114 ( 臨増総会 ) A372 - A372 2017年3月

膵癌非切除例における骨格筋量と体脂肪組成の評価による予後解析

中野応央樹, 川合弘一, 小林隆昌, 五十嵐聡, 林和直, 佐藤祐一, 寺井崇二

日本消化器病学会雑誌 114 ( 臨増総会 ) A271 - A271 2017年3月

自己免疫性肝疾患のパラダイムシフト原発性胆汁性胆管炎におけるMucosal-associated invariant T細胞の検討

薛徹, 山際訓, 寺井崇二

日本消化器病学会雑誌 114 ( 臨増総会 ) A135 - A135 2017年3月

Predictive factors of the pharmacological action of tolvaptan in patients with liver cirrhosis: a post hoc analysis 査読

Isao Sakaida, Shuji Terai, Koji Nakajima, Yoshiyuki Shibasaki, Sayaka Tachikawa, Hidetsugu Tsubouchi

JOURNAL OF GASTROENTEROLOGY 52 ( 2 ) 229 - 236 2017年2月

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

Background Tolvaptan has been approved in Japan for the treatment of hepatic edema. An important consideration in providing a clinical benefit to patients with liver cirrhosis is the improvement of ascites-related clinical symptoms. In the present post hoc analysis, we aimed to identify factors that were predictive of the potency of tolvaptan, and to examine the relationship between changes in initial urine volume and improvement in ascites-related clinical symptoms.
Methods This post hoc analysis was based on three previous phase 2 and 3 clinical trials of tolvaptan in patients with liver cirrhosis. Predictive factors associated with a change in initial urine volume were identified. A change of >= 500 mL from baseline confirmed the pharmacological action of tolvaptan treatment. The relationship between the change in initial urine volume and improvement in ascitesrelated clinical symptoms was also examined.
Results A total of 152 patients were enrolled in this study. Body weight and BUN were identified as predictive parameters. Among patients with a change in initial urine volume of >= 500 mL, 75 % demonstrated improvement in ascites-related clinical symptoms, while no improvement was seen in those with a change of >= 500 mL. None of the patients with initial urine volume of >= 500 mL showed resolution of symptoms.
Conclusions Change in urine volume was affected by both baseline body weight and BUN in tolvaptan-treated subjects. Higher urine output was associated with improvements in ascites-related clinical symptoms.

DOI： 10.1007/s00535-016-1233-x

Loss of peristalsis of the esophagus due to diffuse esophageal leiomyomatosis 査読

Kazuya Takahashi, Yui Ishii, Kazunao Hayashi, Satoshi Ikarashi, Hirokazu Kawai, Yuichi Sato, Shuji Terai

ENDOSCOPY 49 ( S 01 ) E95 - E96 2017年2月

lStatus of and candidates for cell therapy in liver cirrhosis: overcoming the "point of no return'' in advanced liver cirrhosis 査読

Shuji Terai, Atsunori Tsuchiya

JOURNAL OF GASTROENTEROLOGY 52 ( 2 ) 129 - 140 2017年2月

記述言語：英語出版者・発行元：SPRINGER JAPAN KK

The treatment of liver cirrhosis is currently being standardized and developed specifically to reduce activation of hepatic stellate cells (HSCs), inhibit fibrosis, increase degradation of matrix components, and reduce activated myofibroblasts. Cell therapy can be applied in the treatment of liver cirrhosis; however, the characteristic features of this therapy differ from those of other treatments because of the involvement of a living body origin and production of multiple cytokines, chemokines, matrix metalloproteinases (MMPs), and growth factors. Thus, cell therapies can potentially have multiple effects on the damaged liver, including alleviating liver cirrhosis and stimulating liver regeneration with affecting the host cells. Cell therapies initially involved autologous bone marrow cell infusion, and have recently developed to include the use of specific cells such as mesenchymal stem cells and macrophages. The associated molecular mechanisms, routes of administration, possibility of allogeneic cell therapy, and host conditions appropriate for cell therapies are now being extensively analyzed. In this review, we summarize the status and future prospects of cell therapy for liver cirrhosis.

DOI： 10.1007/s00535-016-1258-1

Phase 1 Clinical Study of siRNA Targeting Carbohydrate Sulphotransferase 15 in Crohn's Disease Patients with Active Mucosal Lesions 査読

Kenji Suzuki, Junji Yokoyama, Yusuke Kawauchi, Yutaka Honda, Hiroki Sato, Yutaka Aoyagi, Shuji Terai, Kazuichi Okazaki, Yasuo Suzuki, Yukinori Sameshima, Tsuneo Fukushima, Kazuyuki Sugahara, Raja Atreya, Markus F. Neurath, Kenichi Watanabe, Hiroyuki Yoneyama, Hitoshi Asakura

JOURNAL OF CROHNS & COLITIS 11 ( 2 ) 221 - 228 2017年2月

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

Background and Aims: Carbohydrate sulphotransferase 15 [CHST15] is a specific enzyme biosynthesizing chondroitin sulphate E that binds various pathogenic mediators and is known to create local fibrotic lesions. We evaluated the safety of STNM01, a synthetic double-stranded RNA oligonucleotide directed against CHST15, in Crohn's disease [CD] patients whose mucosal lesions were refractory to conventional therapy.
Methods: This was a randomized, double-blind, placebo-controlled, concentration-escalation study of STNM01 by a single-dose endoscopic submucosal injection in 18 CD patients. Cohorts of increasing concentration of STNM01 were enrolled sequentially as 2.5 nM [n = 3], 25 nM [n = 3], and 250 nM [n = 3] were applied. A cohort of placebo [n = 3] was included in each concentration. Safety was monitored for 30 days. Pharmacokinetics was monitored for 24 h. The changes from baseline in the segmental Simple Endoscopic Score for CD [SES-CD] as well as the histological fibrosis score were evaluated.
Results: STNM01 was well tolerated and showed no drug-related adverse effects in any cohort of treated patients. There were no detectable plasma concentrations of STNM01 at all measured time points in all treatment groups. Seven of nine subjects who received STNM01 showed reduction in segmental SES-CD at Day 30, when compared with those who received placebo. Histological analyses of biopsy specimens revealed that STNM01 reduced the extent of fibrosis.
Conclusion: Local application of STNM01 is safe and well tolerated in CD patients with active mucosal lesions.

DOI： 10.1093/ecco-jcc/jjw143

Lipoprotein-X in cholestatic patients causes xanthomas and promotes foam cell formation in human macrophages 査読

Luka Suzuki, Satoshi Hirayama, Mariko Fukui, Makoto Sasaki, Sadayuki Hiroi, Makoto Ayaori, Shuji Terai, Minoru Tozuka, Hirotaka Watada, Takashi Miida

JOURNAL OF CLINICAL LIPIDOLOGY 11 ( 1 ) 110 - 118 2017年2月

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

BACKGROUND: Lipoprotein-X (Lp-X) is an abnormal phospholipid-rich lipoprotein found in patients with cholestatic liver disease. Some patients exhibit skin xanthomas and severe hyperlipidemia.
OBJECTIVE: We investigated whether Lp-X induces foam cell formation in human-derived macrophages.
METHODS: To compare the atherogenic properties of Lp-X and modified LDL, we isolated Lp-X from 2 patients who had drug-induced cholestasis and xanthoma striata in the interphalangeal folds. We prepared oxidized LDL and acetylated LDL from healthy volunteers for the positive control experiments.
RESULTS: When human monocyte-derived macrophages were incubated with these lipoproteins, the isolated Lp-X induced more prominent lipid accumulation than oxidized LDL or acetylated LDL. One case underwent liver biopsy, with the bile ducts showing marked damage, fulfilling the criteria for vanishing bile duct syndrome. The other case was clinically diagnosed as drug-induced hypersensitivity syndrome. In both cases, Lp-X levels decreased markedly and the xanthomas disappeared completely after the improvement of cholestasis.
CONCLUSION: This study indicates that Lp-X induces foam cell formation in human-derived macrophages. Our findings strongly suggest that persistently elevated Lp-X may cause xanthomas. (C) 2016 National Lipid Association. All rights reserved.

DOI： 10.1016/j.jacl.2016.10.013

A novel technique for biliary biopsy using the sheath of a plastic stent and a non-return valve 査読

Shinichi Morita, Tsutomu Kanefuji, Takahiro Hoshi, Masaaki Kobayashi, Takeshi Suda, Takeshi Mizusawa, Shuji Terai

ENDOSCOPY 49 ( S 01 ) E9 - E10 2017年2月

Early Detection of Hepatocellular Carcinoma Recurrence Using the Highly Sensitive Fucosylated Fraction of Alpha-Fetoprotein 査読

Toru Setsu, Atsunori Tsuchiya, Takayuki Watanabe, Takuro Nagoya, Satoshi Ikarashi, Kazunao Hayashi, Junji Yokoyama, Satoshi Yamagiwa, Shuji Terai

Case Reports in Gastroenterology 11 ( 1 ) 142 - 147 2017年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：S. Karger AG

Alpha-fetoprotein (AFP)-L3 was originally reported as a hepatocellular carcinoma (HCC)-specific tumor marker, and recent accumulation of evidence has revealed that AFP-L3 frequency predicts the biological malignancy potential of HCC. However, AFP-L3 elevation from undetectable levels after curative treatment could not be discussed due to the difficulties of calculating AFP-L3 concentrations when serum AFP levels were low. Here, as a novel method, we used highly sensitive AFP-L3 frequency to predict HCC recurrence after curative treatment. Our cases illustrate that recognizing elevation of AFP-L3 from undetectable levels led to the early detection of recurrent HCC due to more careful surveillance.

DOI： 10.1159/000462969

Scopus

Immunohistochemical differentiation of eosinophilic esophageal myositis from eosinophilic esophagitis 査読

Hiroki Sato, Nao Nakajima, Go Hasegawa, Yuzo Kawata, Yuichi Sato, Kenji Suzuki, Terasu Honma, Shuji Terai

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 32 ( 1 ) 106 - 113 2017年1月

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-BLACKWELL

Background and AimEosinophilic esophagitis (EoE) is a Th2-mediated allergic disease of the esophageal epithelium, associated with antigen. We previously reported a case series for eosinophilic esophageal myositis (EoEM)a novel eosinophilic gastrointestinal disorder defined as eosinophilic infiltration localized in the esophageal muscle layerand diagnosed it by peroral endoscopic muscle biopsy. Here, we investigated the immunopathology of EoEM to differentiate it from EoE.
MethodsHistological analysis was performed for three cases of EoEM and EoE, respectively. The results were compared with those of two control samples (non-eosinophilic gastrointestinal disorder full-layer esophagus). Using immunofluorescence, we analyzed the expression of the chemokine receptor CCR3 and its ligands eotaxin-1 and eotaxin-3 to investigate the eosinophilic reaction. Additionally, we determined the expression patterns of desmoglein-1 in the esophageal epithelium, which shows dysregulated expression in EoE.
ResultsEosinophil infiltration was observed in the muscle layer (maximum number, 30, 36, 73/high-power field) and the epithelium (50, 44, 40/high-power field) for EoEM and EoE, respectively. In EoE esophageal epithelium, the number of eotaxin-3-positive epithelial cells was significantly increased together with CCR3-positive infiltrating cells. However, in EoEM, a number of eotaxin-1-positive and eotaxin-3-positive myocytes and vascular endothelial cells were increased in the esophageal muscle layer. A significant loss of desmoglein-1 expression was only observed in EoE, not in EoEM.
ConclusionsEotaxin-1 and eotaxin-3 expression on the smooth muscle and vessels plays a role in the pathogenesis of EoEM, while EoE shows an epithelial eotaxin-3-dominant immunoreaction. Thus, the EoEM immunological pattern displays clear differences from that of EoE.

DOI： 10.1111/jgh.13466

Training sample selection based on self-training for liver cirrhosis classification using ultrasound images 査読

Yusuke Fujita, Yoshihiro Mitani, Yoshihiko Hamamoto, Makoto Segawa, Shuji Terai, Isao Sakaida

THIRTEENTH INTERNATIONAL CONFERENCE ON QUALITY CONTROL BY ARTIFICIAL VISION 2017 10338 103380J 2017年

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）出版者・発行元：SPIE-INT SOC OPTICAL ENGINEERING

Ultrasound imaging is a popular and non-invasive tool used in the diagnoses of liver disease. Cirrhosis is a chronic liver disease and it can advance to liver cancer. Early detection and appropriate treatment are crucial to prevent liver cancer. However, ultrasound image analysis is very challenging, because of the low signal-to-noise ratio of ultrasound images. To achieve the higher classification performance, selection of training regions of interest (ROIs) is very important that effect to classification accuracy. The purpose of our study is cirrhosis detection with high accuracy using liver ultrasound images. In our previous works, training ROI selection by MILBoost and multiple-ROI classification based on the product rule had been proposed, to achieve high classification performance. In this article, we propose self-training method to select training ROIs effectively. Evaluation experiments were performed to evaluate effect of self-training, using manually selected ROIs and also automatically selected ROIs. Experimental results show that self-training for manually selected ROIs achieved higher classification performance than other approaches, including our conventional methods. The manually ROI definition and sample selection are important to improve classification accuracy in cirrhosis detection using ultrasound images.

DOI： 10.1117/12.2264076