研究者詳細 - 寺井　崇二

論文 - 寺井　崇二

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Achalasia and esophageal cancer: a large database analysis in Japan.

Hiroki Sato, Shuji Terai, Yuto Shimamura, Shinwa Tanaka, Hironari Shiwaku, Hitomi Minami, Chiaki Sato, Ryo Ogawa, Hiroshi Yokomichi, Haruhiro Inoue

Journal of gastroenterology 56 ( 4 ) 360 - 370 2021年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Achalasia has been reported to be associated with esophageal cancers (ECs). However, owing to the rarity of achalasia, details of achalasia-related ECs are not well investigated. METHOD: The incidence of ECs in Japanese patients with achalasia and achalasia-related esophageal motility disorders (EMDs) was estimated, and risk factors for achalasia-related ECs were determined. Characteristics of ECs and treatment courses were also analyzed. RESULTS: Between 2010 and 2019, 2714 Japanese patients with achalasia and achalasia-related EMDs were recorded in 7 high-volume centers; 24 patients (21 men, 3 women) developed ECs. The incidence of ECs was estimated at 0.078 and 0.28 per 100 person-years from the onset and the diagnosis of disease, respectively. Kaplan-Meier estimate suggested that, in addition to a long history of achalasia, advanced age, male sex, and regular alcohol consumption were statistically significant risk factors for EC development. A prevalence of 40 ECs (12.5% multiple lesions, and 22.7% metachronal lesions) was also noted, predominantly distributed over the thoracic esophagus. All were histologically diagnosed as squamous cell carcinoma. Superficial ECs were successfully treated with endoscopic treatment in all cases, except one. Achalasia-related Barret esophagus was extremely rare, and Barret adenocarcinoma was not detected in our cohort. CONCLUSION: The high relative risk of ECs was clarified in Japanese achalasia patients, although the absolute risk remained low. Therefore, surveillance endoscopy may be recommended in limited patients with several aforementioned risk factors determined. Superficial cancer can be treated with endoscopic treatment. Multiple and metachronal ECs should be screened.

DOI： 10.1007/s00535-021-01763-6

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The first case of balloon-occluded retrograde transvenous obliteration and partial splenic embolization for gastric varices in situs inversus abdominus.

Yusuke Watanabe, Akihiko Osaki, Nobuo Waguri, Shuji Terai

Clinical journal of gastroenterology 14 ( 2 ) 656 - 661 2021年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

Situs inversus abdominus is a congenital abnormality characterized by the mirror image positioning of the abdominal organs, making it difficult to diagnosis and treatment of many diseases. Here, we report a rare case of gastric varices in situs inversus abdominus patient. A 55-year-old man was diagnosed with F2-shaped gastric varices associated with alcoholic cirrhosis. Abdominal dynamic computed tomography showed situs inversus abdominus, and gastric varices with a gastrorenal shunt. Due to the complex anatomy, emergency interventional radiology during bleeding was extremely difficult. Therefore, after thorough consultation, we decided to treat gastric varices prophylactically by balloon-occluded retrograde transvenous obliteration. After treatment, the patient's clinical course was generally good, with no adverse events, and the gastric varices disappeared. It is important to assess anatomical positioning using three-dimensional reconstruction computed tomography images before treatment, to adequately prepare, including selecting appropriate devices (i.e., catheters and sheath). Although preventive treatment of gastric varices is controversial, in cases with anatomical complexity, preventive treatment with sufficient preparation would be recommended. To the best of our knowledge, there are no reports of treatment for gastric varices in situs inversus abdominus patient. This case will serve as a reference for successful treatment in future cases.

DOI： 10.1007/s12328-020-01332-z

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Paris II and Rotterdam criteria are the best predictors of outcomes in patients with primary biliary cholangitis in Japan. 国際誌

Naruhiro Kimura, Masaaki Takamura, Nobutaka Takeda, Yusuke Watanabe, Yoshihisa Arao, Masahumi Takatsuna, Suguru Takeuchi, Hiroyuki Abe, Toru Setsu, Hiroteru Kamimura, Akira Sakamaki, Kenya Kamimura, Atsunori Tsuchiya, Shuji Terai

Hepatology international 15 ( 2 ) 437 - 443 2021年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Biochemical response to treatment in patients with primary biliary cholangitis (PBC) reflects prognosis. However, the best predictive criteria to detect biochemical response remain undetermined. In addition, because these criteria need > 6 months until definition, parameters that can estimate its results before initiating treatment are needed. METHODS: We conducted a single-center retrospective study on 196 patients with PBC, followed up for at least 12 months after initiating treatment. RESULTS: Kaplan-Meier analysis showed that Paris II (p = 0.002) and Rotterdam criteria (p = 0.001) could estimate the overall survival of PBC patients, whereas Paris II (p = 0.001), Rotterdam (p = 0.001), and Rochester criteria (p= 0.025) could estimate liver-related deaths. Cox hazard analysis revealed Paris II and Rotterdam criteria as significantly independent predictors of overall survival (hazard ratio (HR) 3.948, 95% CI 1.293-12.054, p = 0.016 and HR 6.040, 95% CI 1.969-18.527, p = 0.002, respectively) and liver-related deaths (HR 10.461, 95% CI 1.231-88.936, p = 0.032 and HR 10.824, 95% CI 1.252-93.572, p = 0.032, respectively). The results of Paris II criteria could be estimated by serum prothrombin time (Odds ratio (OR) 1.052, 95% CI 1.008-1.098, p = 0.021) and alanine transaminase level (OR 0.954, 95% CI 0.919-0.991, p = 0.014) whereas, those of Rotterdam criteria could be estimated by serum albumin level (OR 3.649, 95% CI 1.098-12.128, p = 0.035) at the time of diagnosis. CONCLUSIONS: This study highlights the best prediction criteria and pre-treatment parameters that facilitate the prognosis of PBC patients.

DOI： 10.1007/s12072-021-10163-0

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Analysis of the safety of pretransplant corticosteroid therapy in patients with acute liver failure and late-onset hepatic failure in Japan. 国際誌

Takuro Hisanaga, Isao Hidaka, Isao Sakaida, Nobuaki Nakayama, Akio Ido, Naoya Kato, Yasuhiro Takikawa, Kazuaki Inoue, Masahito Shimizu, Takuya Genda, Shuji Terai, Hirohito Tsubouchi, Hajime Takikawa, Satoshi Mochida, Intractable Hepato-Biliary Disease Study Group Of Japan

JGH open : an open access journal of gastroenterology and hepatology 5 ( 4 ) 428 - 433 2021年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

Background and Aim: In Japan, corticosteroids have been commonly used as a part of multidisciplinary therapy for patients with acute liver failure and late-onset hepatic failure. However, there is controversy regarding the development of infections and other complications. In this study, the influence of corticosteroids on patient outcomes after liver transplantation was investigated. Methods: This study included 167 patients with acute liver failure and late-onset hepatic failure who underwent liver transplantation between 2010 and 2015. The effects of pretransplant corticosteroid therapy on patient outcomes were evaluated using a database constructed by the subcommittee for fulminant hepatitis in the Intractable Hepato-Biliary Diseases Study Group of Japan. Results: The subacute type and the median total bilirubin levels were higher in those receiving corticosteroids than in those not receiving corticosteroids. Although infections tended to be higher in patients receiving corticosteroids, pretransplant corticosteroid administration did not affect the survival rates. The duration from corticosteroid initiation to liver transplantation was longer in patients who developed infections. The survival rates, however, did not differ between patients with and without infections. Conclusions: Corticosteroids were administered to patients with poor prognoses. Otherwise, the overall outcome in those administered corticosteroids was not significantly different from that in those administered without corticosteroids. Although infectious complications tended to occur, they were generally controllable and nonfatal. Pretransplant corticosteroid therapy may be permissible, with regarding for infections and performed within the minimum duration.

DOI： 10.1002/jgh3.12508

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当センターでの肝炎医療コーディネーター養成の現状と院内非専門医対策について

薛徹, 荒生祥尚, 廣川光, 寺井崇二

肝臓 62 ( Suppl.1 ) A242 - A242 2021年4月

新潟県における自治体肝炎ウイルス検診の現状

薛徹, 菊田玲, 中島徹, 荒生祥尚, 中山均, 寺井崇二

肝臓 62 ( Suppl.1 ) A230 - A230 2021年4月

臨床応用を目指したバイオマーカー研究の最前線急性肝障害条件下での血中セロトニン量の病態・予後予測バイオマーカーとしての有用性の検討

薛徹, 上村顕也, 寺井崇二

肝臓 62 ( Suppl.1 ) A170 - A170 2021年4月

肝移植の現状と課題当県での肝障害症例を対象としたネットワークの運用と、アンケート調査からみた県内の肝障害診療の現状と今後の啓発の必要性

薛徹, 寺井崇二

肝臓 62 ( Suppl.1 ) A113 - A113 2021年4月

新潟県における自治体肝炎ウイルス検診の現状

薛徹, 菊田玲, 中島徹, 荒生祥尚, 中山均, 寺井崇二

肝臓 62 ( Suppl.1 ) A230 - A230 2021年4月

当センターでの肝炎医療コーディネーター養成の現状と院内非専門医対策について

薛徹, 荒生祥尚, 廣川光, 寺井崇二

肝臓 62 ( Suppl.1 ) A242 - A242 2021年4月

肝疾患におけるビックデータとAI(人工知能)の臨床応用ディープラーニングを活用したPBC多施設データから予測する高齢者PBCの介入の必要性の検討

上村博輝, 高村昌昭, 寺井崇二

肝臓 62 ( Suppl.1 ) A208 - A208 2021年4月

肝疾患移行期医療の現状と問題点先天性心疾患術後に肝線維化悪化に影響を及ぼす因子の解析

山崎文紗子, 上村博輝, 寺井崇二

肝臓 62 ( Suppl.1 ) A167 - A167 2021年4月

多発肝転移、リンパ節転移を伴う直腸原発神経内分泌腫瘍に対して集学的治療が有効であった一例当院での症例群の検討と共に

小川和也, 阿部寛幸, 上村顕也, 寺井崇二

肝臓 62 ( Suppl.1 ) A266 - A266 2021年4月

point shear wave elastographyを利用した肝線維化のheterogeneityの検証

横尾健, 杉田萌乃, 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

超音波医学 48 ( Suppl. ) S713 - S713 2021年4月

肝再生の可能性と障壁 HMGB1の部分ペプチドを用いた慢性肝疾患に対するセルフリー治療の開発

土屋淳紀, 野尻俊介, 寺井崇二

肝臓 62 ( Suppl.1 ) A69 - A69 2021年4月

【肝類洞壁細胞研究における新知見】肝の炎症、線維化と類洞壁細胞間葉系幹細胞を用いた新規治療法の開発

渡邉雄介, 土屋淳紀, 寺井崇二

肝胆膵 82 ( 4 ) 525 - 529 2021年4月

肝癌に対する局所療法としての放射線療法の安全性と有効性の検証

山田麻理奈, 上村顕也, 柴田理, 森田真一, 寺井崇二

肝臓 62 ( Suppl.1 ) A338 - A338 2021年4月

Small extracellular vesicles derived from interferon-γ pre-conditioned mesenchymal stromal cells effectively treat liver fibrosis. 国際誌

Suguru Takeuchi, Atsunori Tsuchiya, Takahiro Iwasawa, Shunsuke Nojiri, Takayuki Watanabe, Masahiro Ogawa, Tomoaki Yoshida, Katsunori Fujiki, Yuta Koui, Taketomo Kido, Yusuke Yoshioka, Mayu Fujita, Junichi Kikuta, Tohru Itoh, Masaaki Takamura, Katsuhiko Shirahige, Masaru Ishii, Takahiro Ochiya, Atsushi Miyajima, Shuji Terai

NPJ Regenerative medicine 6 ( 1 ) 19 - 19 2021年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

Mesenchymal stromal cells (MSCs) are used for ameliorating liver fibrosis and aiding liver regeneration after cirrhosis; Here, we analyzed the therapeutic potential of small extracellular vesicles (sEVs) derived from interferon-γ (IFN-γ) pre-conditioned MSCs (γ-sEVs). γ-sEVs effectively induced anti-inflammatory macrophages with high motility and phagocytic abilities in vitro, while not preventing hepatic stellate cell (HSC; the major source of collagen fiber) activation in vitro. The proteome analysis of MSC-derived sEVs revealed anti-inflammatory macrophage inducible proteins (e.g., annexin-A1, lactotransferrin, and aminopeptidase N) upon IFN-γ stimulation. Furthermore, by enabling CX3CR1+ macrophage accumulation in the damaged area, γ-sEVs ameliorated inflammation and fibrosis in the cirrhosis mouse model more effectively than sEVs. Single cell RNA-Seq analysis revealed diverse effects, such as induction of anti-inflammatory macrophages and regulatory T cells, in the cirrhotic liver after γ-sEV administration. Overall, IFN-γ pre-conditioning altered sEVs resulted in efficient tissue repair indicating a new therapeutic strategy.

DOI： 10.1038/s41536-021-00132-4

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Modulation of serotonin in the gut-liver neural axis ameliorates the fatty and fibrotic changes in non-alcoholic fatty liver. 国際誌

Masayoshi Ko, Kenya Kamimura, Takashi Owaki, Takuro Nagoya, Norihiro Sakai, Itsuo Nagayama, Yusuke Niwa, Osamu Shibata, Chiyumi Oda, Shinichi Morita, Atsushi Kimura, Ryosuke Inoue, Toru Setsu, Akira Sakamaki, Takeshi Yokoo, Shuji Terai

Disease models & mechanisms 14 ( 3 ) 2021年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

The etiology of non-alcoholic fatty liver disease (NAFLD) consists of various factors, including neural signal pathways. However, the molecular mechanisms of the autonomic neural signals influencing NAFLD progression have not been elucidated. Therefore, we examined the involvement of the gut-liver neural axis in NAFLD development and tested the therapeutic effect of modulation of this axis in this study. To test the contribution of the gut-liver neural axis, we examined NAFLD progression with respect to body weight, hepatic steatosis, fibrosis, intestinal tight junction, microbiota and short-chain fatty acids in NAFLD models of choline-deficient defined L-amino-acid and high-fat diet-fed mice with or without blockades of autonomic nerves from the liver. Blockade of the neural signal from the liver to the gut in these NAFLD mice models ameliorated the progression of liver weight, hepatic steatosis and fibrosis by modulating serotonin expression in the small intestine. It was related to the severity of the liver pathology, the tight junction protein expression, microbiota diversity and short-chain fatty acids. These effects were reproduced by administrating serotonin antagonist, which ameliorated the NAFLD progression in the NAFLD mice models. Our study demonstrated that the gut-liver neural axis is involved in the etiologies of NAFLD progression and that serotonin expression through this signaling network is the key factor of this axis. Therefore, modulation of the gut-liver neural axis and serotonin antagonist ameliorates fatty and fibrotic changes in non-alcoholic fatty liver, and can be a potential therapeutic target of NAFLD.This article has an associated First Person interview with the first author of the paper.

DOI： 10.1242/dmm.048922

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Successful treatment of positive-sense RNA virus coinfection with autoimmune hepatitis using double filtration plasmapheresis. 国際誌

Hiroteru Kamimura, Kenya Kamimura, Atsunori Tsuchiya, Shuji Terai

BMJ case reports 14 ( 3 ) 2021年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

Double filtration plasmapheresis (DFPP) is an apheretic technique that selectively removes high molecular weight substances using a plasma component filter. DFPP has been used to treat positive-sense RNA virus infections, mainly chronic hepatitis C virus (HCV) infection, because of its ability to directly eliminate viral particles from blood plasma from 2008 to about 2015, before direct-acting antiviral agents was marketed. This effect has been termed virus removal and eradication by DFPP. HCV is a positive-sense RNA virus similar to West Nile virus, dengue virus and the SARS and Middle East respiratory syndrome coronaviruses. SARS-CoV-2 is classified same viral species. These viruses are all classified in Family Flaviviridae which are family of single-stranded plus-stranded RNA viruses. Viral particles are 40-60 nm in diameter, enveloped and spherical in shape. We present a rare case of HCV removal where an RNA virus infection that copresented with virus-associated autoimmune hepatitis was eliminated using DFPP. Our results indicate that DFPP may facilitate prompt viraemia reduction and may have novel treatment applications for SARS-CoV-2, that is, use of therapeutic plasma exchange for fulminant COVID-19.

DOI： 10.1136/bcr-2020-236984

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