研究者詳細 - 寺井　崇二

論文 - 寺井　崇二

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Diffuse Large B-cell Lymphoma with Severe Lactic Acidosis and Liver Failure: A Case Report and Literature Review.

Shun Yamazaki, Yusuke Watanabe, Kazuya Takahashi, Kentaro Tominaga, Satoshi Ikarashi, Takeshi Yokoo, Hiroteru Kamimura, Atsunori Tsuchiya, Shuji Terai

Internal medicine (Tokyo, Japan) 2024年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

Among causes of liver failure, liver failure due to lymphocytic infiltration is rare. Unlike typical liver failure, some cases present with severe lactic acidosis and a poor prognosis. We herein report a case of diffuse large B-cell lymphoma with severe lactic acidosis and liver failure. We further discuss the characteristics of similar cases in the literature, suggesting that intrahepatic infiltration by hematological malignant cells should be considered as a differential diagnosis in the presence of severe lactic acidosis and liver failure. This study underscores the importance of early recognition and serves as a reference for future cases.

DOI： 10.2169/internalmedicine.4450-24

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自験例から考察したHBV de novo再活性化診療のピットフォール

木村究, 横尾健, 吉田智彰, 渡邉雄介, 木村成宏, 阿部寛幸, 上村博輝, 坂牧僚, 上村顕也, 土屋淳紀, 寺井崇二

日本消化器病学会甲信越支部例会・日本消化器内視鏡学会甲信越支部例会抄録集 75回・97回 70 - 70 2024年10月

治療困難胆管結石に対する経口胆道鏡下治療の有用性

五十嵐聡, 林和直, 柴田理, 寺井崇二

Gastroenterological Endoscopy 66 ( Suppl.2 ) 2301 - 2301 2024年10月

「長期臨床経過を見据えた消化器疾患の治療・管理における工夫と課題」自己免疫性膵炎のステロイド治療導入後再燃例における臨床経過の検証

田中裕登, 柴田理, 五十嵐聡, 林和直, 寺井崇二

日本消化器病学会甲信越支部例会・日本消化器内視鏡学会甲信越支部例会抄録集 75回・97回 51 - 51 2024年10月

非切除肝門部領域胆管癌に対する内視鏡的胆管ステント留置術の検討

林和直, 柴田理, 五十嵐聡, 寺井崇二

Gastroenterological Endoscopy 66 ( Suppl.2 ) 2292 - 2292 2024年10月

Maid gene dysfunction promotes hyperobesity via the reduction of adipose tissue inflammation in Mc4r gene-deficient mice. 国際誌

Kyutaro Koyama, Akira Sakamaki, Shinichi Morita, Itsuo Nagayama, Marina Kudo, Yuto Tanaka, Naruhiro Kimura, Yoshihisa Arao, Hiroyuki Abe, Kenya Kamimura, Shuji Terai

Scientific reports 14 ( 1 ) 21126 - 21126 2024年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

The onset and progression mechanisms of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are being studied. We developed and analyzed a new mouse model of obesity by combining maternal Id-like molecule (Maid) and melanocortin-4 receptor (Mc4r) gene deletions. Four mice, each at 12 and 28 weeks of age, were analyzed for each genotype: Maid gene knockout, Mc4r gene knockout, combined Mc4r and Maid gene knockout, and Mc4r gene knockout with a high-fat diet. Mice with a combined deficiency of Mc4r and Maid gene showed significantly more severe obesity compared to all other genotypes, but no liver fibrosis or a decline in metabolic status were observed. In visceral white adipose tissue, Maid and Mc4r gene knockout mice had fewer CD11c-positive cells and lower mRNA expression of both inflammatory and anti-inflammatory cytokines. Furthermore, Maid and Mc4r gene knockout mice showed lower expression of adipocytokines in visceral white adipose tissue and uncoupling protein-1 in scapular brown adipose tissue. The expression of adipocytokines and uncoupling protein-1 is regulated by sympathetic nerve signaling that contribute severe obesity in Maid and Mc4r gene knockout mice. These mechanisms contribute hyperobesity in Maid and Mc4r gene knockout mice.

DOI： 10.1038/s41598-024-72217-1

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症候性巨大肝嚢胞に対する嚢胞内洗浄併用の塩酸ミノサイクリン硬化療法が長期的効果を呈した1例

小川和也, 上村顕也, 石井壮一, 遠藤沙織, 石川夏生, 阿部寛幸, 坂牧僚, 寺井崇二

日本消化器病学会雑誌 121 ( 9 ) 769 - 776 2024年9月

記述言語：日本語出版者・発行元：(一財)日本消化器病学会

肝嚢胞は,増大して圧迫症状や閉塞性黄疸などをきたし,症候性となることがある.内科的治療として嚢胞穿刺排液,硬化療法があるが,再発率が高い.今回われわれは,15年以上の経過で徐々に増大して圧迫症状と閉塞性黄疸をきたした症候性巨大肝嚢胞に対して,嚢胞穿刺排液と嚢胞内洗浄を併用する塩酸ミノサイクリンによる経皮的硬化療法を施行し,著明な嚢胞縮小効果と症状改善を認めた症例を経験したので報告する.(著者抄録)

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2024&ichushi_jid=J01118&link_issn=&doc_id=20240919370009&doc_link_id=%2Fck8syokb%2F2024%2F012109%2F009%2F0769-0776%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fck8syokb%2F2024%2F012109%2F009%2F0769-0776%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

PCPE-1, a brown adipose tissue-derived cytokine, promotes obesity-induced liver fibrosis. 国際誌

Yung Ting Hsiao, Yohko Yoshida, Shujiro Okuda, Manabu Abe, Seiya Mizuno, Satoru Takahashi, Hironori Nakagami, Ryuichi Morishita, Kenya Kamimura, Shuji Terai, Tin May Aung, Ji Li, Takaaki Furihata, Jing Yuan Tang, Kenneth Walsh, Akihito Ishigami, Tohru Minamino, Ippei Shimizu

The EMBO journal 2024年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

Metabolic dysfunction-associated steatohepatitis (MASH, previously termed non-alcoholic steatohepatitis (NASH)), is a major complication of obesity that promotes fatty liver disease. MASH is characterized by progressive tissue fibrosis and sterile liver inflammation that can lead to liver cirrhosis, cancer, and death. The molecular mechanisms of fibrosis in MASH and its systemic control remain poorly understood. Here, we identified the secreted-type pro-fibrotic protein, procollagen C-endopeptidase enhancer-1 (PCPE-1), as a brown adipose tissue (BAT)-derived adipokine that promotes liver fibrosis in a murine obesity-induced MASH model. BAT-specific or systemic PCPE-1 depletion in mice ameliorated liver fibrosis, whereas, PCPE-1 gain of function in BAT enhanced hepatic fibrosis. High-calorie diet-induced ER stress increased PCPE-1 production in BAT through the activation of IRE-1/JNK/c-Fos/c-Jun signaling. Circulating PCPE-1 levels are increased in the plasma of MASH patients, suggesting a therapeutic possibility. In sum, our results uncover PCPE-1 as a novel systemic control factor of liver fibrosis.

DOI： 10.1038/s44318-024-00196-0

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Urinary NGAL in gastrointestinal diseases can be used as an indicator of early infection in addition to acute kidney injury marker. 国際誌

Yuichi Kojima, Atsunori Tsuchiya, Masaki Mito, Yusuke Watanabe, Yuzo Kawata, Kentaro Tominaga, Shuji Terai

JGH open : an open access journal of gastroenterology and hepatology 8 ( 8 ) e70009 2024年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND AND AIM: Neutrophil gelatinase-associated lipocalin (NGAL) is characterized by increased expression before the rise in serum creatinine and has been used as a biomarker for the early prediction of acute kidney injury (AKI). However, there have been no comprehensive analyses of its significance in gastrointestinal diseases. This study aimed to analyze the usefulness of measuring urinary NGAL levels in patients with gastrointestinal diseases. METHODS: This study included 171 patients with a wide range of gastrointestinal diseases. Urinary NGAL levels were measured in all patients within 24 h of admission and 72 h later. RESULTS: Urinary NGAL levels were higher in patients with acute pancreatitis and acute cholangitis/cholecystitis than in those with other diseases. Although lower than in these diseases, urinary NGAL tends to be higher in inflammatory bowel diseases, such as ulcerative colitis and Crohn's disease, as well as in acute and chronic liver diseases, and is higher in liver cirrhosis as the Child-Pugh grade increases. Furthermore, we found that the group with higher urinary NGAL levels, which continued to increase over time, had worse hospital stays and prognosis. CONCLUSION: Urinary NGAL could be used as an indicator of infectious diseases rather than an indicator of AKI in inflammatory bowel diseases and cirrhosis, and could predict the prognosis of patients with gastrointestinal diseases.

DOI： 10.1002/jgh3.70009

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【肝臓リハビリテーションの現状と問題点】

寺井崇二, 吉治仁志, 川口巧, 清水雅仁, 辻哲也

肝臓 65 ( 8 ) 351 - 367 2024年8月

Diagnosis and resolution of olmesartan-associated sprue-like enteropathy confirmed by capsule endoscopy: a case report and literature review.

Erina Kodama, Yuzo Kawata, Shun Yamazaki, Takanori Igarashi, Yuichi Kojima, Kentaro Tominaga, Junji Yokoyama, Terasu Honma, Shuji Terai

Clinical journal of gastroenterology 2024年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

Herein, we describe a case of olmesartan-associated sprue-like enteropathy, in which improvement in villous atrophy was confirmed using small bowel capsule endoscopy. The patient was a 69-year-old woman who had persistent watery diarrhea (20 bowel movements/day) for 1 year and experienced a weight loss of 10 kg in the same period. Abdominal computed tomography revealed no abnormalities, and blood test results revealed no inflammatory reactions. Upper endoscopy and colonoscopy revealed villous atrophy in the duodenum and terminal ileum. As the patient was administered olmesartan for a long time and capsule endoscopy showed villous atrophy throughout the small bowel, she was diagnosed with olmesartan-associated sprue-like disease. Following the discontinuation of the medication, symptoms of diarrhea soon improved, and repeat capsule endoscopy indicated improvement in small intestinal villous atrophy. Olmesartan-associated sprue-like enteropathy should be considered a differential diagnosis in patients with severe chronic watery diarrhea. Our report is the first in which capsule endoscopy was performed multiple times over a long period for follow-up observation of improvements in the small intestine. In addition, our literature review regarding capsule endoscopy for olmesartan-associated enteritis might aid clinicians in the early diagnosis of the condition and the assessment of treatment efficacy.

DOI： 10.1007/s12328-024-02023-9

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Automatic ROI Selection with Reliability Evaluation Method for Cirrhosis Detection using Ultrasound Images 査読

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

IEEJ Transactions on Electrical and Electronic Engineering 19 ( 7 ) 2024年7月

Inflammation of the liver, HCC development and HCC establishment 招待査読

Tatsuo Kanda, Reina Sasaki-Tanaka, Shuji Terai

Hepatology International 2024年6月

Fibulin-4 as a potential extracellular vesicle marker of fibrosis in patients with cirrhosis. 国際誌

Masaru Kumagai, Atsunori Tsuchiya, Yuan Yang, Nobutaka Takeda, Kazuki Natsui, Yui Natusi, Kei Tomiyoshi, Fusako Yamazaki, Yohei Koseki, Hiroki Shinchi, Naoko Imawaka, Ryo Ukekawa, Takahiro Nishibu, Hiroyuki Abe, Takako Sasaki, Koji Ueda, Shuji Terai

FEBS open bio 2024年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

Chronic liver injury leads to decreased liver function and increased fibrosis. Fibrosis is not only associated with the development of portal hypertension and carcinogenesis, but with the occurrence of events and a poor prognosis, highlighting the importance of non-invasive fibrosis assessment in patients. In the present study, we searched for markers related to liver fibrosis via proteomic analysis of small extracellular vesicles (sEVs). In the discovery cohort, proteomic analysis was carried out in the sEVs extracted from the sera of 5 patients with decompensated cirrhosis, 5 patients with compensated cirrhosis, and 5 controls without liver disease. Interestingly, in this cohort, fibulin-4 was significantly associated with cirrhosis while in the validation cohort [formed by 191 patients: 7 patients without disease, 16 patients without liver disease (other diseases), 38 patients with chronic liver disease (CLD), 75 patients with cirrhosis of Child-Pugh class A (36 without hepatocellular carcinoma [HCC], 29 with HCC), and 65 patients with cirrhosis of Child-Pugh class B-C (39 without HCC, 26 with HCC)], fibulin-4/CD9 levels increased with cirrhosis progression. Furthermore, the fibulin-4/CD9 ratio was significantly higher in patients with varices. Immunostaining also revealed strong fibulin-4 expression in cholangiocytes within the fibrous areas and mesothelial cells in liver tissue blood vessels. Taken together, our results suggest that fibulin-4, essential for lysyl oxidase activation, might be a new liver fibrosis marker found in the sEVs of patients with cirrhosis.

DOI： 10.1002/2211-5463.13842

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胆膵内視鏡検査・治療における工夫とトラブルシューティング当院における副乳頭アプローチカニュレーション

名古屋拓郎, 小川光平, 五十嵐聡, 林和直, 寺井崇二

ENDOSCOPIC FORUM for digestive disease 39 ( 2 ) 154 - 154 2024年6月

小川光平, 名古屋拓郎, 五十嵐聡, 林和直, 寺井崇二

ENDOSCOPIC FORUM for digestive disease 39 ( 2 ) 148 - 148 2024年6月

Platelet-rich plasma-derived extracellular vesicles improve liver cirrhosis in mice. 国際誌

Yuichirou Maeda, Yusuke Watanabe, Natsuki Ishikawa, Tomoaki Yoshida, Naruhiro Kimura, Hiroyuki Abe, Akira Sakamaki, Hiroteru Kamimura, Takeshi Yokoo, Kenya Kamimura, Atsunori Tsuchiya, Shuji Terai

Regenerative therapy 26 1048 - 1057 2024年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: Cirrhosis remains a significant clinical challenge due to its poor prognosis and limited treatment options, creating a high unmet medical need for the development of novel therapies. In this study, we analyzed the effects of a novel approach to treat cirrhosis using platelet-rich plasma-derived extracellular vesicles (PRPEV) in mice. METHODS: PRPEV were collected from platelet-rich plasma using ultrafiltration, and their proteomes were analyzed. The carbon tetrachloride (CCl4)-induced cirrhosis model of mice was used to evaluate the effect of PRPEV administration and compared with the control group (n = 8). In vitro and in vivo mechanistic analyses of PRPEV administration were confirmed using real time-PCR and immunostaining. RESULTS: Gene ontology analysis based on the proteome revealed that PRPEV contain many factors associated with EV and immune responses. In vitro, PRPEV polarize macrophages into an anti-inflammatory phenotype. Following PRPEV administration, there was a decrease in serum alanine aminotransferase levels and reduction in liver fibrosis, while mRNA levels of regenerative factors were upregulated and transforming growth factor β-1 was downregulated. Furthermore, the number of anti-inflammatory macrophages in the liver increased. CONCLUSIONS: PRPEV may contribute to hepatocyte proliferation, anti-inflammation, and anti-fibrogenesis in the liver. This novel concept paves the way for cirrhosis treatment.

DOI： 10.1016/j.reth.2024.10.010

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胆膵内視鏡検査・治療における工夫とトラブルシューティング当院における副乳頭アプローチカニュレーション

名古屋拓郎, 小川光平, 五十嵐聡, 林和直, 寺井崇二

ENDOSCOPIC FORUM for digestive disease 39 ( 2 ) 154 - 154 2024年6月

小川光平, 名古屋拓郎, 五十嵐聡, 林和直, 寺井崇二

ENDOSCOPIC FORUM for digestive disease 39 ( 2 ) 148 - 148 2024年6月

Novel scale for evaluating the therapeutic efficacy of per-oral endoscopic myotomy in achalasia.

Kazuya Takahashi, Hiroki Sato, Yuto Shimamura, Hirofumi Abe, Hironari Shiwaku, Junya Shiota, Chiaki Sato, Kenta Hamada, Masaki Ominami, Yoshitaka Hata, Hisashi Fukuda, Ryo Ogawa, Jun Nakamura, Tetsuya Tatsuta, Yuichiro Ikebuchi, Shuji Terai, Haruhiro Inoue

Journal of gastroenterology 2024年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Symptom scales for achalasia after per-oral endoscopic myotomy (POEM) are lacking. This study aimed to propose a new scale based on the conventional Eckardt score (c-ES) and evaluate persistent symptoms that impair patients' quality of life (QOL) post-POEM. METHODS: Dysphagia, regurgitation, and chest pain frequencies were assessed using a 6-point scale modified-ES (m-ES) after POEM, with "occasional" symptoms on the c-ES further subdivided into three-period categories on m-ES. Symptom severity was further evaluated using a 5-point scale ranging from 1 to 5 points, with a score ≥ 3 points defined as persistent symptoms impairing QOL. We analyzed the correlation between the m-ES and severity score, diagnostic performance of the m-ES for persistent symptoms, and overlaps between each residual symptom. RESULTS: Overall, 536 patients (median follow-up period, 2.9 years) post-POEM were included in this multicenter study. Significant correlations were observed between the m-ES and severity scores for dysphagia (r = 0.67, p < 0.01), regurgitation (r = 0.73, p < 0.01), and chest pain (r = 0.85, p < 0.01). Twenty-six patients (4.9%) had persistent symptoms post-POEM, and 23 of them had m-ES-specific symptom frequency ≥ once a month, which was determined as the optimal frequency threshold for screening persistent symptoms. The total m-ES predicted persistent symptoms more accurately than the total c-ES (area under the curve: 0.95 vs. 0.79, p < 0.01). Furthermore, dysphagia and chest pain were the major residual symptoms post-POEM covering 91.4% of regurgitation. CONCLUSIONS: The new post-POEM scale successfully evaluated the QOL-based patient symptom severities. Our study implied the possibility of a simpler scale using residual dysphagia and chest pain.

DOI： 10.1007/s00535-024-02119-6

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