研究者詳細 - 寺井　崇二

論文 - 寺井　崇二

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MC4R遺伝子及びMaid遺伝子両欠損マウスを用いた新規脂肪肝モデルマウスの検討

森田真一, 坂牧僚, 永山逸夫, 大越麻理奈, 小山究太郎, 田中裕登, 大脇崇史, 小田知友美, 柴田理, 木村淳史, 阿部寛幸, 上村顕也, 寺井崇二

肝臓 61 ( Suppl.3 ) A876 - A876 2020年11月

Efficacy and Safety of the Radiotherapy for Liver Cancer: Assessment of Local Controllability and its Role in Multidisciplinary Therapy. 国際誌

Marina Ohkoshi-Yamada, Kenya Kamimura, Osamu Shibata, Shinichi Morita, Motoki Kaidu, Toshimichi Nakano, Katsuya Maruyama, Atsushi Ota, Hirotake Saito, Nobuko Yamana, Tomoya Oshikane, Yukiyo Goto, Natsumi Yoshimura, Satoshi Tanabe, Hisashi Nakano, Madoka Sakai, Yuto Tanaka, Yohei Koseki, Yoshihisa Arao, Hiroyuki Abe, Toru Setsu, Akira Sakamaki, Takeshi Yokoo, Hiroteru Kamimura, Hidefumi Aoyama, Shuji Terai

Cancers 12 ( 10 ) 2020年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

This study investigated the efficacy and safety of radiotherapy as part of multidisciplinary therapy for advanced hepatocellular carcinoma (HCC). Clinical data of 49 HCC patients treated with radiotherapy were assessed retrospectively. The efficacy of radiotherapy was assessed by progression-free survival, disease control rate, and overall survival. Safety was assessed by symptoms and hematological assay, and changes in hepatic reserve function were determined by Child-Pugh score and albumin-bilirubin (ALBI) score. Forty patients underwent curative radiotherapy, and nine patients with portal vein tumor thrombus (PVTT) underwent palliative radiotherapy as part of multidisciplinary therapy. Local disease control for curative therapy was 80.0% and stereotactic body radiotherapy was 86.7% which was greater than that of conventional radiotherapy (60.0%). Patients with PVTT had a median observation period of 651 days and 75% three-year survival when treated with multitherapy, including radiotherapy for palliative intent, transcatheter arterial chemoembolization, and administration of molecular targeted agents. No adverse events higher than grade 3 and no changes in the Child-Pugh score and ALBI score were seen. Radiotherapy is safe and effective for HCC treatment and can be a part of multidisciplinary therapy.

DOI： 10.3390/cancers12102955

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Blocking sphingosine 1-phosphate receptor 2 accelerates hepatocellular carcinoma progression in a mouse model of NASH. 査読国際誌

Tomoaki Yoshida, Atsunori Tsuchiya, Masaru Kumagai, Suguru Takeuchi, Shunsuke Nojiri, Takayuki Watanabe, Masahiro Ogawa, Michiko Itoh, Masaaki Takamura, Takayoshi Suganami, Yoshihiro Ogawa, Shuji Terai

Biochemical and biophysical research communications 530 ( 4 ) 665 - 672 2020年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

The role of sphingosine 1-phosphate (S1P) and its sphingosine-1-phosphate receptors (S1PRs) in non-alcoholic steatohepatitis (NASH) is unclear. We aimed to analyze the role of S1P/S1PRs in a Melanocortin-4 receptor (Mc4r)-deficient NASH murine model using FTY720, the functional antagonist of S1PR1, S1PR3, S1PR4, and S1PR5, and JTE-013, the antagonist of S1PR2. We observed that, compared to that in the control, the mRNA of S1pr1 tended to decrease, whereas those of S1pr2 and S1pr3 significantly increased in Mc4r-knockout (KO) mice subjected to a Western diet (WD). While the fat area did not differ, fibrosis progression differed significantly between control mice and mice in which liver S1PRs were blocked. Lipidomic and metabolomic analysis of liver tissues showed that JTE-013-administered mice showed elevation of S-adenosyl-l-methionine level, which can induce aberrant methylation due to reduction in glycine N-methyltransferase (GNMT) and elevation in diacylglycerol (DG) and triacylglycerol (TG) levels, leading to increased susceptibility to hepatocellular carcinoma (HCC). These phenotypes are similar to those of Gnmt-KO mice, suggesting that blocking the S1P/S1PR2 axis triggers aberrant methylation, which may increase DG and TG, and hepatocarcinogenesis. Our observations that the S1P/S1PR2 axis averts HCC occurrence may assist in HCC prevention in NASH.

DOI： 10.1016/j.bbrc.2020.07.099

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Screening and follow-up of chronic liver diseases with understanding their etiology in clinics and hospitals. 国際誌

Masahiro Ogawa, Atsunori Tsuchiya, Takayuki Watanabe, Toru Setsu, Naruhiro Kimura, Masato Matsuda, Yoshiki Hoshiyama, Hiroaki Saito, Tsutomu Kanazawa, Motoi Shiotani, Tatsuhiko Sato, Takuya Yagi, Koji Igarashi, Norihiko Yoshimura, Masaaki Takamura, Hidefumi Aoyama, Shuji Terai

JGH open : an open access journal of gastroenterology and hepatology 4 ( 5 ) 827 - 837 2020年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

Background and Aim: Considering the increasing prevalence of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis (NASH), the development of an effective screening and follow-up system that enables the recognition of etiological changes by primary physicians in clinics and specialists in hospitals is required. Methods: Chronic hepatitis B (HBV) and C (HCV), NASH, and alcoholic steatohepatitis (ASH) patients who were assayed for Mac-2-binding protein glycosylation isomer (M2BPGi) (n = 272) and underwent magnetic resonance elastography (MRE) (n = 119) were enrolled. Patients who underwent MRE were also tested by ultrasound elastography (USE) (n = 80) and for M2BPGi (n = 97), autotaxin (ATX) (n = 62), and platelet count (n = 119), and their fibrosis-4 (FIB-4) index was calculated (n = 119). Results: FIB-4 index >2, excluding HBV-infected patients, M2BPGi >0.5, ATX >0.5, and platelet count <20 × 104/μL were the benchmark indices, and we took into consideration other risk factors, such as diabetes mellitus and age, to recommend further examinations, such as USE, based on the local situation to avoid overlooking hepatocellular carcinoma (HCC) in the clinic. During specialty care in the hospital, MRE exhibited high diagnostic ability for fibrosis stages >F3 or F4; it could efficiently predict collateral circulation with high sensitivity, which can replace USE. We also identified etiological features and found that collateral circulation in NASH/ASH patients tended to exceed high-risk levels; moreover, these patients exhibited more variation in HCC-associated liver stiffness than the HBV and HCV patients. Conclusions: Using appropriate markers and tools, we can establish a stepwise, practical, noninvasive, and etiology-based screening and follow-up system in primary and specialty care.

DOI： 10.1002/jgh3.12406

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Refractory hemorrhagic esophageal ulcers by Candida esophagitis with advanced systemic sclerosis. 国際誌

Kazuki Natsui, Atsunori Tsuchiya, Shuji Terai

JGH open : an open access journal of gastroenterology and hepatology 4 ( 5 ) 1007 - 1008 2020年10月

記述言語：英語

A 64-year-old woman diagnosed with rheumatoid arthritis (RA) and systemic sclerosis (SSc) was admitted to our hospital with chief complaints of uncontrolled bleeding from esophageal ulcers and an inability to consume meals. For RA and SSc, she was treated with prednisolone and abatacept and was taking vonoprazan as prophylaxis for steroid-induced gastric ulcers. She was diagnosed with severe Candida esophagitis, with multiple large and small ulcers with bleeding, based on esophagogastroduodenoscopy and pathological findings. We performed comprehensive treatment; abatacept was discontinued, and total parenteral nutrition was initiated along with antifungal therapy. Improvement in the esophageal ulcers was observed. Although severe Candida esophagitis is a rare condition, we should keep in mind that severe Candida esophagitis can occur in patients with an immunosuppressive compromised host and esophageal movement disorders such as SSc. Regular follow up by endoscopy and prophylactic treatment to prevent severe esophagitis may be necessary.

DOI： 10.1002/jgh3.12353

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重症急性膵炎後Walled-off necrosisの内視鏡治療におけるLumen apposing metal stentの有効性

五十嵐聡, 林和直, 寺井崇二

Gastroenterological Endoscopy 62 ( Suppl.2 ) 2162 - 2162 2020年10月

急性膵炎およびその合併症治療の最前線新潟県における重症急性膵炎の予後改善を目指して Niigata SAP network

林和直, 五十嵐聡, 寺井崇二

日本消化器病学会雑誌 117 ( 臨増大会 ) A624 - A624 2020年10月

食道・胃静脈瘤治療の現状と今後の展望門亢症の病態から考えたEIS/EVLの長期予後

薛徹, 横山純二, 寺井崇二

日本門脈圧亢進症学会雑誌 26 ( 3 ) 68 - 68 2020年10月

【肝硬変のトータルマネジメント】肝腎症候群に対する治療海外での動向

坂牧僚, 薛徹, 阿部寛幸, 上村顕也, 高村昌昭, 寺井崇二

肝臓クリニカルアップデート 6 ( 2 ) 205 - 211 2020年10月

再生医療はどこまで進んだか(vol.17) 間葉系幹細胞投与による肝線維化改善、再生誘導効果基礎研究成果の臨床応用

寺井崇二, 土屋淳紀

医学のあゆみ 275 ( 4 ) 367 - 370 2020年10月

Translational researchを目指した下部消化管研究炎症性腸疾患に対する間葉系幹細胞(MSC)、エクソソーム療法の可能性の検討

川田雄三, 土屋淳紀, 寺井崇二

日本消化器病学会雑誌 117 ( 臨増大会 ) A602 - A602 2020年10月

肝性脳症〜わが国における現状と課題〜潜在性肝性脳症患者における呼気中水素・メタン分析の有用性の検討

坂牧僚, 横山邦彦, 小山究太郎, 森田真一, 阿部寛幸, 上村顕也, 高村昌昭, 横山純二, 寺井崇二

日本門脈圧亢進症学会雑誌 26 ( 3 ) 76 - 76 2020年10月

急性膵炎およびその合併症治療の最前線新潟県における重症急性膵炎の予後改善を目指して Niigata SAP network

林和直, 五十嵐聡, 寺井崇二

日本消化器病学会雑誌 117 ( 臨増大会 ) A624 - A624 2020年10月

Synchronous Double Bile Duct Cancers with Distinct Genetic Features.

Shinichi Morita, Takeshi Suda, Yoji Kishi, Toshimitsu Iwasaki, Nobuyoshi Hiraoka, Itsuo Nagayama, Takahiro Hoshi, Satoshi Abe, Kazuyoshi Yagi, Go Hasegawa, Toshihiko Ikarashi, Shuji Terai

Internal medicine (Tokyo, Japan) 59 ( 17 ) 2129 - 2134 2020年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

A 69-year-old man was referred to our hospital because of appetite loss. Imaging showed a nodular tumor in the perihilar bile duct and a second flat lesion in the distal bile duct. Right hepatopancreaticoduodenectomy was performed, and the histopathological findings demonstrated that the perihilar and distal lesions were moderately and poorly differentiated adenocarcinoma, respectively, and anatomically separated. Furthermore, the resected specimens showed no pancreaticobiliary maljunction. Histological and TP53 gene analyses in a rare case of synchronous double bile duct cancers suggest that there are various genetic pathways through which bile duct cancer develops, highlighting the complexity of its pathogenesis.

DOI： 10.2169/internalmedicine.4613-20

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Transcriptomic Dissection of Hepatocyte Heterogeneity: Linking Ploidy, Zonation, and Stem/Progenitor Cell Characteristics 査読

Takeshi Katsuda, Kazunori Hosaka, Juntaro Matsuzaki, Wataru Usuba, Marta Prieto-Vila, Tomoko Yamaguchi, Atsunori Tsuchiya, Shuji Terai, Takahiro Ochiya

Cellular and Molecular Gastroenterology and Hepatology 9 ( 1 ) 161 - 183 2020年9月

2D-Shear Wave ElastographyとTransient Elastographyの乖離症例の特徴

杉田萌乃, 横尾健, 荒生祥尚, 薛徹, 上村博輝, 坂牧僚, 上村顕也, 土屋淳紀, 高村昌昭, 寺井崇二

肝臓 61 ( Suppl.2 ) A695 - A695 2020年9月

健診受検者における年齢層別NAFLDの解析と高齢者の意識変化

横尾健, 佐藤公俊, 丹羽佑輔, 荒生祥尚, 薛徹, 上村博輝, 坂牧僚, 上村顕也, 土屋淳紀, 高村昌昭, 寺井崇二

肝臓 61 ( Suppl.2 ) A671 - A671 2020年9月

mALBI score/gradeからみたNASH薬物治療に対する肝予備能への影響

高村昌昭, 横尾健, 荒生祥尚, 薛徹, 上村博輝, 坂牧僚, 上村顕也, 土屋淳紀, 寺井崇二

肝臓 61 ( Suppl.2 ) A691 - A691 2020年9月

2D-Shear Wave ElastographyとTransient Elastographyの乖離症例の特徴

杉田萌乃, 横尾健, 荒生祥尚, 薛徹, 上村博輝, 坂牧僚, 上村顕也, 土屋淳紀, 高村昌昭, 寺井崇二

肝臓 61 ( Suppl.2 ) A695 - A695 2020年9月

mALBI score/gradeからみたNASH薬物治療に対する肝予備能への影響

高村昌昭, 横尾健, 荒生祥尚, 薛徹, 上村博輝, 坂牧僚, 上村顕也, 土屋淳紀, 寺井崇二

肝臓 61 ( Suppl.2 ) A691 - A691 2020年9月

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